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10th annual World Medical Innovation Forum (WMIF) Monday, Sept. 23–Wednesday, Sept. 25 at the Encore Boston Harbor in Boston

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10th annual World Medical Innovation Forum (WMIF) Monday, Sept. 23–Wednesday, Sept. 25 at the Encore Boston Harbor in Boston

Dr. Aviva Lev-Ari, PhD, RN, Founder

Leaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

will be in attendance

covering this event in REAL TIME for PharmaceuticalIntelligence.com and WMIF organizers

CLAIMER: Live coverage in REAL TIME on X.com for 9/23/2024

8AM to 3:40PM
at 3:40PM the handles
@Pharma_BI

@AVIVA1950

my two X.com accounts had exceeded tweeting volume capacity and were inactivated to verify if I am a person or a BOT. Account authentication reported SOmething went wrong, try later.

9/23/2024 contacted Customer Services at X.com for reactivated these two accounts

For Speaker’s quotes on 9/23/2024 from 4PM EST to end on the day

see below on WordPress.com by Date, Time, Session Name and Speaker Name

For Speaker’s quotes on 9/24/2024 from 8AM to 5:30PM

see below on WordPress.com by Date, Time, Session Name and Speaker Name

For Speaker’s quotes on 9/25/2024 from 8AM to 12:35PM

see below on WordPress.com by Date, Time, Session Name and Speaker Name

UPDATE on reactivation of handles on X.com will be posted, here.

Usage of X.com will resume after Handle reactivation by X.com

UPDATED on 9/26/2024

Unmet Needs Panel

https://www.youtube.com/watch?v=e6hk7yavBzk

100+ Mass General Brigham Leading Experts Identify

Top Unmet Needs in Healthcare

Project from Harvard Medical School-affiliated clinicians and scientists in the Mass General Brigham healthcare system stimulates new consideration, urgency regarding

innovation in life sciences, healthcare

Top 10 List Announced at World Medical Innovation Forum

BOSTON, MA September 25, 2024 – Some of the most vexing challenges and transformational opportunities in healthcare are included in a new list, “Top Unmet Needs in Healthcare” released by leading experts at Mass General Brigham. Identified by more than 100 Harvard Medical School faculty at Mass General Brigham, the findings range from the need to expand and accelerate rare disease treatment, to the coming “gray tsunami” of aging patients and the implications for patient care, delivery, and technology. The project, revealed at the 10th annual World Medical Innovation Forum, is meant to stimulate new consideration and urgency regarding solving and advancing these issues for improved patient care.

Views from Leading Clinicians, Researchers, and Practitioners in Academic Medicine

The Top Unmet Needs emerge from structured one-on-one discussions with more than 100 Harvard faculty who practice medicine and conduct research at Mass General Brigham, the largest hospital system-based research enterprise in the U.S., with an annual research budget exceeding $2 billion, and five of the nation’s top hospitals according to US News & World Report.

Through one-on-one discussions with these key opinion leaders from diverse clinical and research fields, and subsequent analyses by internal teams of experts, Mass General Brigham has identified the following top 10 unmet clinical needs:

#1. Preparing for the ‘Gray Tsunami’

The need for better tools and therapies aimed at caring for geriatric populations and maintaining geriatric independence, with a particular focus on expanded hospital-at-home capabilities, and the need to better understand the pathways that lead to chronic and acute disease in geriatric patients to enable better and more proactive treatment.

#2. Defining and Maintaining Brain Health

The need for a model of brain health and neurological care that clearly defines not only what brain health is but also integrates our current understanding of the mechanisms and phases of neuroinflammatory and neurodegenerative diseases; enables better and earlier diagnoses and treatment; and propels the development of therapies that target these mechanisms and phases.

#3. A Paradigm Shift in Cancer Treatment

The need for a new framework for therapeutic development in cancer that is focused on improving curability as opposed to an exclusive focus on the development of drugs for metastatic disease. This

framework also requires effective tools for early-stage cancer detection across the board in all cancers, but especially in lung, ovarian, pancreatic, and GI cancers (esophagus, stomach and colon).

#4. Targeting Fibrosis, a Shared Culprit in Disease

The need for therapeutics that target fibrosis (tissue scarring), which is responsible for a significant percentage of deaths worldwide, representing diseases of the lung, liver, kidney, heart, and skin.

#5. New Approaches for Infectious Disease in a Changing World

The need for novel strategies for the rapid diagnoses, treatment, and even prevention of antibiotic-resistant infections, and the need for the next generation of globally deployable vaccines to enable pandemic preparedness.

#6. Striving for Equity in Healthcare

The need to radically rethink how, when, and where patients interact with healthcare services to optimize healthcare access and efficiency without diminishing its effectiveness, and to proactively meet the needs of currently underserved populations.

#7. Riding the Wave of Clinical Data

The need to expand the scope of available clinical data to include historically understudied populations (including women) and to model and implement a cohesive, dynamic data “stream,” which flows as patients do between the different phases of health and clinical care, enabling comparisons of patients to their previously healthy selves and the development of AI/ML approaches to harness these data to improve diagnosis, prognosis, and treatment.

#8. A Systems-Level View of Human Disease

The need to rethink how we understand and treat disease — not only from an organ-specific standpoint but from a whole-body, systems-level view — and to fully elucidate the roles that inflammation and immune pathways play in autoimmune and infectious diseases and their effects on chronic and acute diseases in diverse human systems, such as the cardiovascular/circulatory and nervous systems.

#9. A New Approach to Psychiatric Disease

The need for novel treatments for psychiatric disease, improved biomarkers and minimally invasive and ambulatory ways of measuring them, and more productive interactions with industry to advance new therapies to the clinic. This includes hybrid therapies (therapies that combine elements such as talk therapy, novel biomarkers, and pharmacological treatments) as well as new diagnostic and treatment modalities, such as psychedelic therapeutics and precision psychiatry.

#10. Charting a Course in Rare Disease Treatment

The need for viable treatments for the 7,000 identified rare diseases, especially the roughly 70% of such diseases that are genetic and the effects of which are first observed in early childhood.

The Unmet Needs list also include the following honorable mentions which rose to significant rankings in the analysis:

Driving Innovation in Chronic Disease: Improved Diagnosis, Treatment, and Prevention

A New Era of Obesity Medicine

A New Generation of Pain Treatments

Unlocking Novel Treatments for the Skin

Overarching Themes

Addressing unmet clinical needs involves solving a number of common challenges, including commercialization hurdles, regulatory considerations, and funding. The Mass General Brigham project identified overarching themes to help address these challenges and support innovation across multiple sectors. These include:

Taking a systems view of human disease and the practice of system-medicine

Developing a global view of infectious disease, including antimicrobial resistance

An expansion in high-quality, real-world data that closes gaps in current data (particularly for women and other underserved populations) and ensures that data sets are sufficiently enabling for AI/ML

Improving health and healthcare across key populations, including geriatrics and rare genetic disease

Addressing major diseases of the brain, including both neurodegenerative and neuropsychiatric conditions; these include Alzheimer’s disease, Parkinson’s disease, ALS, as well as psychiatric and mental health disorders

Opening an era of precision medicine across disease areas that includes early diagnosis, treating staged disease, and biomarker discovery and utilization

Panel co-chairs José Florez, Physician-in-Chief and Co-Chair of the MGB Department of Medicine and the Jackson Professor of Clinical Medicine at Harvard Medical School, and Bruce Levy, Physician-In-Chief and Co-Chair of the MGB Department of Medicine and the Parker B. Francis Professor of Medicine at Harvard Medical School, noted how the observations of a broad and representative set of faculty help illuminate the innovation landscape ahead.

“As a leader in patient care and healthcare innovation, our goal is to build on the legacy of research and discovery that has shaped the hospitals of the Mass General Brigham healthcare system for more than a hundred years, and continue to bring breakthroughs forward that can help solve pressing needs,” said Dr. Florez.

Dr. Levy added that “This is a roadmap for the future that can inform discussions happening throughout the healthcare and investment ecosystem regarding the future of medicine.”

More than 2000 decision-makers from healthcare, industry, finance and government attended the World Medical Innovation Forum this week in Boston. A premier global event, the Forum highlights leading innovations in medicine and transformative advancements in patient care.

###

About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

Contact: Tracy Doyle Mass General Brigham Innovation

(262) 227-5514

Tdoyle5@mgb.org

SOURCE

From: “Doyle, Tracy” <tdoyle5@mgb.org>
Date: Thursday, September 26, 2024 at 10:19 AM
Cc: “Card, Matthew” <matthew.card@bofa.com>
Subject: Unmet Needs in Healthcare — Press Release and link to panel

@@@@@@@

Invitation as MEDIA

From: “Doyle, Tracy” <tdoyle5@mgb.org>
Date: Wednesday, August 14, 2024 at 4:04 PM
Cc: “Doyle, Tracy” <tdoyle5@mgb.org>, “Card, Matthew” <matthew.card@bofa.com>
Subject: Media Invite: World Medical Innovation Forum, Sept. 23-25, Boston — Hundreds of clinical experts, industry, investment leaders

Media Invite: World Medical Innovation Forum: Monday, Sept. 23—Wednesday, Sept. 25, Boston

At the intersection of innovation and investment in healthcare

Join Us!

Register Now: WMIF24 Media Registration

Mass General Brigham, one of the nation’s leading academic medical centers, is pleased to invite reporters to the 10^th annual World Medical Innovation Forum (WMIF) Monday, Sept. 23–Wednesday, Sept. 25 at the Encore Boston Harbor in Boston. The event features expert discussions of scientific and investment trends for some of the hottest areas in healthcare, including

GLP-1s,

the cancer care revolution,

generative AI-enabled care paths,

xenotransplant,

community health,

hospital at home, and

therapeutic psychedelics, among many others.

The agenda includes nearly 175 executive speakers from healthcare, pharma, venture, start-ups, and the front lines of care, including many of Mass General Brigham’s Harvard Medical School-affiliated researchers and clinicians who this year will host 20+ focused sessions. Bank of America, presenting sponsor of the Forum, will provide additional expert insights on the investment landscape associated with healthcare innovation.

Forum highlights include:

1:1 and panel interviews with leading CEOs and government officials including:

Stéphane Bancel, CEO, Moderna

Albert Bourla, PhD, CEO, Pfizer

Marc Casper, CEO, Thermo Fisher

Deepak Chopra, MD, Founder, The Chopra Foundation

Scott Gottlieb, MD, PhD, Former Commissioner, FDA (2017-2019)

Maura Healey, Governor, Commonwealth of Massachusetts

David Hyman, MD, CMO, Eli Lilly

Haim Israel, Head of Global Thematic Investing Research, BofA Global Research

Reshma Kewalramani, MD, CEO, Vertex

Anne Klibanski, MD, President and CEO, Mass General Brigham

Peter Marks, MD, PhD, Director, Center for Biologics Evaluation and Research, FDA

Tadaaki Taniguchi, MD, PhD, Chief Medical Officer, Astellas Pharma

Christophe Weber, CEO, Takeda

Renee Wegrzyn, PhD, Director, ARPA-H

Expert panels including:

Oncology’s New Paradigm

Gene Therapies for Rare Diseases

Future of Metabolic Therapies

Digital Transformation

Biologic Revolution in Radiotherapies

Cell Therapies for Autoimmune Diseases

Hospital Venture Funds

Leading biotech and venture speakers from companies including:

Abata Therapeutics

Atlas Venture

Be Biopharma

Everly Health

Flagship Pioneering

Fractyl Health

MindMed

Mirador Therapeutics

Regor Therapeutics

RH Capital

Transcend Therapeutics

Exclusive programming:

First Look – 15 rapid-fire presentations on the latest research from leading Mass General Brigham scientists

Un-Met Clinical Needs – 100+ key opinion leaders in healthcare weigh in on the top un-met clinical needs in medicine today

Emerging Tech Zone – Hands-on exploration of some of the latest digital and AI-based healthcare technologies

Our program keeps growing — explore the current Forum agenda and list of speakers.

FORUM AGENDA

SOURCE

https://2024.worldmedicalinnovation.org/agenda/

Monday, September 23, 2024

7:00 AM – 8:30 AM

Picasso Foyer

Continental Breakfast

7:00 AM – 5:00 PM

Rotunda

Registration

8:00 AM – 10:00 AM

Picasso Ballroom

First Look

First Look: 14 rapid fire presentations

Moderators

Giles Boland, MD

President, Brigham and Women’s Hospital and Brigham and Women’s Physicians Organization;

Philip H. Cook Distinguished Professor of Radiology, Harvard Medical School

Marcela del Carmen, MD

President, Massachusetts General Hospital and Massachusetts General Physicians Organization (MGPO);

Executive Vice President, Mass General Brigham;

Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Presenters

Natalie Artzi, PhD

Associate Professor of Medicine, Brigham and Women’s Hospital & Harvard Medical School

Yolonda Colson, MD, PhD

Chief, Division of Thoracic Surgery, Massachusetts General Hospital;

Hermes C. Grillo Professor of Surgery, Harvard Medical School

Nobuhiko Hata, PhD

Director, Surgical Navigation and Robotics Laboratory, Brigham and Women’s Hospital;

Professor of Radiology, Harvard Medical School

John Hanna, MD, PhD

Associate Professor, Brigham and Women’s Hospital & Harvard Medical School

Leigh Hochberg, MD, PhD

Director of Neurotechnology and Neurorecovery, Massachusetts General Hospital;

Senior Lecturer on Neurology, Harvard Medical School

Daphne Holt, MD, PhD

Director of the Resilience and Prevention Program, Massachusetts General Hospital;

Associate Professor of Psychiatry, Harvard Medical School

Ole Isacson, MD-PhD

Founding Director, Neuroregeneration Research Institute, McLean Hospital;

Professor of Neurology and Neuroscience, Harvard Medical School

Farouc Jaffer, MD, PhD

Director, Coronary Intervention, Massachusetts General Hospital;

Associate Professor of Medicine, Harvard Medical School

Albert Kim, MD

Assistant Physician, Mass General Cancer Center;

Assistant Professor, Harvard Medical School

Vesela Kovacheva, MD, PhD

Director of Translational and Clinical Research, Mass General Brigham;

Assistant Professor of Anesthesia, Harvard Medical School

Mark Poznansky, MD, PhD

Director, Vaccine and Immunotherapy Center, Massachusetts General Hospital;

Steve and Deborah Gorlin MGH Research Scholar;

Professor of Medicine, Harvard Medical School

Daniel Solomon, MD

Matthew H. Liang Distinguished Chair in Arthritis and Population Health, Brigham and Women’s Hospital;

Professor of Medicine, Harvard Medical School

Scott Solomon, MD

Director, Clinical Trials Outcomes Center;

Edward D. Frohlich Distinguished Chair in Cardiovascular Pathophysiology, Brigham and Women’s Hospital;

Professor of Medicine, Harvard Medical School

Guillermo Tearney, MD, PhD

Principal Investigator, Wellman Center for Photomedicine, Massachusetts General Hospital;

Remondi Family Endowed MGH Research Institute Chair;

Professor of Pathology, Harvard Medical School

Raul Uppot, MD

Interventional Radiologist, Massachusetts General Hospital;

Associate Professor, Harvard Medical School

David Walt, PhD

Professor of Pathology, Brigham and Women’s Hospital;

Hansjörg Wyss Professor of Biologically Inspired Engineering, Harvard Medical School

10:00 AM – 10:20 AM

Morning Break

10:20 AM – 10:30 AM

Initial Welcome Remarks

10:30 AM – 10:55 AM

Fireside

Fireside Chat

Moderator

Keith Flaherty, MD

Director of Clinical Research, Mass General Cancer Center;

Professor of Medicine, Harvard Medical School

Panelist

Albert Bourla, PhD

Chairman & CEO, Pfizer

11:00 AM – 11:45 AM

Medicine’s Hottest Topics – Block I of IV

Concurrent Events

11:00 AM – 11:45 AM

Oncology’s New Paradigm

Moderators

Keith Flaherty, MD

Director of Clinical Research, Mass General Cancer Center;

Professor of Medicine, Harvard Medical School

Jason Zemansky, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Jonathan Carlson, MD, PhD

Director of Chemistry, Center for Systems Biology, Massachusetts General Hospital;

Assistant Professor of Medicine, Harvard Medical School

Gad Getz, PhD

Director of Bioinformatics, Krantz Center for Cancer Research and Department of Pathology;

Paul C. Zamecnik Chair in Cancer Research, Mass General Cancer Center;

Professor of Pathology, Harvard Medical School

Russell Jenkins, MD, PhD

Krantz Family Center for Cancer Research, Massachusetts General Hospital;

Mass General Cancer Center, Center for Melanoma;

Assistant Professor of Medicine, Harvard Medical School

Gregory Simon

President, Simonovation

Shannon Stott, PhD

Associate Investigator, Krantz Family Center for Cancer Research and Mass General Cancer Center;

d’Arbeloff Research Scholar, Massachusetts General Hospital;

Associate Investigator, Krantz Family Center for Cancer Research Harvard Medical School

11:00 AM – 11:45 AM

GLP-1s: How Far Will They Go?

Moderators

Tazeen Ahmad

SMid-Cap Biotech Analyst, BofA Global Research

Fatima Cody Stanford, MD

Obesity Medicine Physician Scientist, Massachusetts General Hospital;

Associate Professor of Medicine and Pediatrics, Harvard Medical School

Panelists

Caroline Apovian, MD

Co-Director, Center for Weight Management and Wellness, Brigham and Women’s Hospital;

Professor of Medicine, Harvard Medical School

Vanita Aroda, MD

Director, Diabetes Clinical Research, Brigham and Women’s Hospital;

Associate Professor, Harvard Medical School

Paul LaViolette

Managing Partner & COO, SV Health Investors

11:00 AM – 11:45 AM

Generative AI: Breakthrough Research and Limitations

Moderators

Adam Landman, MD

Chief Information Officer & SVP, Digital, Mass General Brigham;

Associate Professor of Emergency Medicine, Harvard Medical School

Alec Stranahan, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Katherine Andriole, PhD

Director of Academic Research and Education, Mass General Brigham Data Science Office;

Associate Professor, Harvard Medical School

David Blumenthal, MD

Professor of Practice of Public Health and Health Policy, Harvard TH Chan School of Public Health;

Research Fellow, Harvard Kennedy School of Government;

Samuel O. Thier Professor of Medicine, Emeritus, Harvard Medical School

Faisal Mahmood, PhD

Associate Professor, Brigham and Women’s Hospital & Harvard Medical School

William Morris, MD

Chief Medical Information Officer, Google Cloud

11:00 AM – 11:45 AM

Gene and Cell Therapy’s Unlimited Potential

Moderators

Roger Hajjar, MD

Director, Gene & Cell Therapy Institute, Mass General Brigham

Charlie Yang, PhD

Large/SMid-Cap Biotech and Major Pharma Analyst, BofA Global Research

Nathan Yozwiak, PhD

Head of Research, Gene and Cell Therapy Institute, Mass General Brigham

Panelists

Samarth Kulkarni, PhD

CEO, CRISPR Therapeutics

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research, FDA

Marcela Maus, MD, PhD

Director of Cellular Therapy and Paula O’Keeffe Chair in Cancer Research, Krantz Family Center for Cancer Research and Mass General Cancer Center;

Associate Director, Gene and Cell Therapy Institute, Mass General Brigham;

Associate Professor, Harvard Medical School

Joanne Smith-Farrell, PhD

CEO & Director, Be Biopharma

11:00 AM – 11:45 AM

Xenotransplant: Game Changing Organ Replacement

Moderators

Jason Gerberry

Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research

Joren Madsen, MD, PhD

Director, MGH Transplant Center;

Paul S. Russell/Warner-Lambert Professor of Surgery, Harvard Medical School

Panelists

Tatsuo Kawai, MD, PhD

Director of the Legorreta Center for Clinical Transplantation Tolerance,

A.Benedict Cosimi Chair in Transplant Surgery, Massachusetts General Hospital;

Professor of Surgery, Harvard Medical School

Richard Pierson III, MD

Scientific Director, Center for Transplantation Sciences, Massachusetts General Hospital;

Professor of Surgery, Harvard Medical School

Leonardo Riella, MD, PhD

Medical Director of Kidney Transplantation, Massachusetts General Hospital;

Harold and Ellen Danser Endowed Chair in Transplantation, Harvard Medical School

11:45 AM – 12:00 PM

Break

12:00 PM – 12:45 PM

Lunch and Medicine’s Hottest Topics – Block II of IV

Concurrent Events

12:00 PM – 12:45 PM

Future of Cancer Care

Moderator

Alec Stranahan, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Gerard Doherty, MD

Surgeon-in-Chief, Mass General Brigham Cancer;

Surgeon-in-Chief, Brigham and Women’s Hospital;

Moseley Professor of Surgery, Harvard Medical School

Daphne Haas-Kogan, MD

Chief, Enterprise Radiation Oncology, Mass General Brigham;

Professor, Harvard Medical School

Benjamin Kann, MD

Assistant Professor, Brigham and Women’s Hospital & Harvard Medical School

David Ryan, MD

Physician-in-Chief, Mass General Brigham Cancer;

Professor of Medicine, Harvard Medical School

12:00 PM – 12:45 PM

Generative AI Enabled Care Paths

Moderators

Adam Ron

Health Care Facilities and Managed Care Analyst, BofA Global Research

Marc Succi, MD

Executive Director, Mass General Brigham MESH Incubator;

Associate Chair of Innovation & Commercialization, Mass General Brigham Radiology;

Assistant Professor, Harvard Medical School

Panelists

Christopher Longhurst, MD

Chief Medical & Digital Officer, UC San Diego Health

Rebecca Mishuris, MD

Chief Medical Information Officer, Mass General Brigham;

Member of the Faculty, Harvard Medical School

Shiv Rao, MD

CEO & Founder, Abridge

Alkesh Shah

Head of US Equity Software Research, BofA Global Research

12:00 PM – 12:45 PM

Transforming Care in a Resource Limited Era

Moderator

Niyum Gandhi

CFO & Treasurer, Mass General Brigham

Panelists

Fritz François, MD

Executive Vice President and Vice Dean, Chief of Hospital Operations, NYU Langone Health

Susan Huang, MD

EVP, Chief Executive, Providence Clinical Network, Providence Southern CA

Ron Walls, MD

Chief Operating Officer, Mass General Brigham;

Neskey Family Professor of Emergency Medicine, Harvard Medical School

12:00 PM – 12:45 PM

Cardiovascular Pipeline Renewal

Moderators

Jason Gerberry

Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research

Calum MacRae, MD, PhD

Vice Chair for Scientific Innovation, Department of Medicine, Brigham and Women’s Hospital;

Professor of Medicine, Harvard Medical School

Panelists

Lotte Bjerre Knudsen, DMSc

Chief Scientific Advisor, Novo Nordisk

David Grayzel, MD

Partner, Atlas Venture

Christoph Westphal, MD, PhD

General Partner, Longwood Fund

Deborah Wexler, MD

Chief, Diabetes Unit, Massachusetts General Hospital;

Associate Professor of Medicine, Harvard Medical School

12:45 PM – 1:00 PM

Break and Transition to Plenary Session

1:00 PM – 1:20 PM

Picasso Ballroom

Opening Remarks

Introducer

Miceal Chamberlain

President of Massachusetts, Bank of America

Opening Remarks

Maura Healey

Governor of the Commonwealth of Massachusetts

1:20 PM – 2:00 PM

Picasso Ballroom

Healthcare Innovation and Regional Competitiveness

Panelists

John Fish

Chairman & CEO, Suffolk

Reshma Kewalramani, MD

CEO & President, Vertex Pharmaceuticals

Jonathan Kraft

President, The Kraft Group;

Board Chair, Massachusetts General Hospital

2:05 PM – 2:30 PM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

Tazeen Ahmad

SMid-Cap Biotech Analyst, BofA Global Research

Roger Hajjar, MD

Director, Gene & Cell Therapy Institute, Mass General Brigham

Panelist

Reshma Kewalramani, MD

CEO & President, Vertex Pharmaceuticals

2:35 PM – 3:10 PM

Picasso Ballroom

Delivering Care: New Tools, Evolving Challenges, Bold Aspirations

Moderator

Andrew Bressler

Washington Healthcare Policy Analyst, BofA Global Research

Panelists

Rod Hochman, MD

President & CEO, Providence

Anne Klibanski, MD

President & CEO, Mass General Brigham;

Laurie Carrol Guthart Professor of Medicine, Harvard Medical School

Kevin Mahoney

CEO, University of Pennsylvania Health System

3:10 PM – 3:35 PM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

Caroline Sokol, MD, PhD

Assistant Physician, Massachusetts General Hospital;

Assistant Professor, Harvard Medical School

Charlie Yang, PhD

Large/SMid-Cap Biotech and Major Pharma Analyst, BofA Global Research

Panelist

Mark McKenna

Chairman & CEO, Mirador Therapeutics

3:40 PM – 4:05 PM

Picasso Ballroom

RECORDING OF SPEAKERS’ QUOTES ON WordPress.com

STARTS HERE

Fireside

Fireside Chat

Moderators

Jason Gerberry

Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research

Allan Goldstein, MD

Chief of Pediatric Surgery, Massachusetts General Hospital;

Surgeon-in-Chief, Mass General for Children;

Marshall K. Bartlett Professor of Surgery, Harvard Medical School

Panelist

Christophe Weber, President & CEO, Takeda

pipeline is very diverse at the R&D center in Boston

Phase III:

TAK-279 Psorisis

Neurocrine’s Takeda-Partnered Drug Candidate Aces Phase II Depression Study

The Markets for Takeda

US market is 40% of revenue, It is a difficult market but still the most important for Phama in the World

Japan is 8%

Growth by acquisitions and internal development like above, two Phase III drugs

Price control and policies:

negotiation

price war create tension

Team:

Public company traded in NYSE

Management team has 10 nationalities – Global company

AI is adopted as a digital companion

Recruiting Patients for Clinical Trial:

Very difficult

M&A

After acquisition of Shire – not many other opportunities are left

4:05 PM – 4:40 PM

Picasso Ballroom

The Innovation Gap: A Review of the Future of Viral Vector Manufacturing and the Delivery of Genetic Medicines

Moderators

Elizabeth Henske, MD, Director, Center for LAM Research and Clinical Care, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Alec Stranahan, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Peter Anastasiou, CEO, Capsida Biotherapeutics

Capsid technology for Liver disease, Parkinson’s

AV and CNS crossing BBB

One capsid for one disease

manufacture caspids

Challenges: manufacturable after screening

IV delivery – brain disorder, blood flow would bring therapeutics to all brain tissue consistently vs localized

Partnership with Eli Lilly and with Crisper technologies with Abbvie

Steve Favaloro, Chairman & CEO, Genezen

200 persons Team manufacture

Partnerships: synthetic plasma

Alexandria Forbes, PhD, CEO, MeiraGTx

Optimize promoters, control transcription expression by injection or by pill, control translation

improving potency of gene therapies capsule technology

cost hundred of $ not thousand of $

ALL manufacturing in house

9 years of data can help to narrow down the parameters

time frame is shortened

company established 9 years ago

apply DNA expression – invented a technology

splicing control mRNA

control cell lines

give an injection or a pill and control antibodies, glucagon

control dosing for efficatious therapeutics

Potency

Ribozon is a delivery system

Partnership with J&J –

Fraser Wright, PhD, Chief Gene Therapy Officer, Kriya Therapeutics

manufacturing – changing in capsule design

manufacture viruses

cost of manufacturing – efficiency matters a lot

delivery of the gene in the tissue

Partnerships: basic vs applied Quality from research to manufacturing

4:45 PM – 5:20 PM

Picasso Ballroom

A Deep Dive on Genetic Modalities for Rare Disease: Genetic Medicines Are Here

Moderator

Tazeen Ahmad, SMid-Cap Biotech Analyst, BofA Global Research

Treat once or repeat therapy?

Patricia Musolino, MD, PhD, MGH

Panelists

Faraz Ali, Tenaya Therpeutics

genetic therapy for a genetic mutation – NOVEL approach

400 mutation related to cardiomyopathy

2018 – gene therapy was an innovation

genetic medicine Cardiology introducing opportunities wiht validation that did not exist

find novel targets Partnerships are a must to have

Viral therapies vs gene therapy

Lucas Harrington, PhD, Co-Founder & CSO, Mammoth Biosciences

How to turm Genome 2012 to therapy?

targeting: Taking risk Patient interaction with treatment

variation between Rare diseases some are very small some are not small – incentive to investors

The field will grow fast

Raju Prasad, PhD, Chief Financial Officer, CRISPR Therapeutics

various indications

FDA Approval

Gene editing technology for rare diseases

LPA for RNA therapy

incentive to investors

Important for investor to understand the siize of the market, CRISPR can be a technology for a large market size

Sickle cell disease – market is large and therapy can be made affordable

Sandi See Tai, MD, Chief Development Officer, Lexeo Therapeutics

cardiomyopathy

protective gene

Early genetic testing

Educating patients

5:20 PM – 6:30 PM

Picasso Terrace and Harborside Lawns 1 & 2

Opening Reception

Tuesday, September 24, 2024

7:00 AM – 5:00 PM

Rotunda

Registration

8:00 AM – 8:55 AM

Picasso Ballroom

The Transforming World

Introducer

Liz Everett Krisberg, Head of Bank of America Institute

Record attendance this year

Introduction to Haim

Panelist

Haim Israel

Head of Global Thematic Investing Research, BofA Global Research

Concept of the Future and for the Future: Short-term and long-term

Humanity achievements in Ten Year: Data, Processing power and BRAIN – Long-term becomes Short-term – Last 10 years: 2012, 2014 solar system, 2015 medicine, 2019 blackhole, 2023 core of sun – star was created hotter than core sun

2022, 2024 – galaxy picture of the universe

Volume of data created every month in terrabyts every 18 month data is duplicating itself.

Olny 1% is used – imagine 2% or 3%

Processing power since Apollo 11 [one trillion] – getting cheaper – cost for calculation went down 16,000 fold since 1995

AMMOUNT of DATA goes up and Cost of COMPUTATION goes down – price per giga byte

Projections for the next 100 years

Negative for people and Negative for Companies who are concerned with quarterly financial data

Companies: Walmart, Alphabet, Home Depot – DATA larger that COuntries

Living in defining moment: started by iPhone revolution and 2023 by AI revolution – 6x outpaced Moore’s Law by GPT by 3000x

18 months into AI revolution – GPT in use

The next 10 years:

Aging population

2024 – birth rate low in US, Japan, CHina, S. Korea – Pension system will decline in size

2.2 millions new material were created by DeepMind at Alphabet by simulation of AI on molecule

Microsoft in 80 hours identified 18 materials winners for Batteries using AI from 32 million material candidates

AI- weather calculations in minutes 1,000x faster, cheaper and more accurate

2025 – GPT-6 AI surpass Human Brain

China is a big player in AI

Cyber CRIME is the 3rd largest economy in the World. Hackers are using ChatGPT to create fake pictures leading to ZERO privacy

PRIVACY: Deepfakes up 62x, social media

2024 – Global Grid – needs much more energy because AI consumes so much energy

Metals shortages: Nickel, Copper,

Scarcity of water for 2/3 of the planet

data centers consume water more than Japan

2025 – Genomics Data sequencing bigger that X.com or Youtube

2027 – Peak oil demand: needed to be scalable, cheaper 25%

2028 – 5G networks reaches full capacity, 6G will be needed

2029 – 25x more satellites in Orbit than today

2029 – Personalized AI medicines and treatments will manipulate death and revive LONGEVITY – AI will generate drugs and all treatments

2030 – Generative AI: re-skill 1 Billion people

2035 – Fusion energy, known technology since the atomic bomb, how to keep it stable in plasma state of material – not yet achieved, it is clean, cheap: to Power the World – equivalent of 11 barrels of oil

Large cities: Cable diameter 17cm wide to power a large city

AI will change scarcity into abundance

2037 – Artifitial SUPER Intelligence – AI to outsmart Life

Quantum computer – Consortium of NASA and other governmental agencies and Google on quantum computer design

2024 the most interesting year in human history

9:00 AM – 9:45 AM

Medicine’s Hottest Topics – Block III of IV

Concurrent Events

9:00 AM – 9:45 AM

Current and Future States of Immunology

Moderators

Caroline Sokol, MD, PhD, Assistant Physician, Massachusetts General Hospital;, Assistant Professor, Harvard Medical School

Alec Stranahan, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Dong Feng Chen, MD, PhD, Associate Scientist, Massachusetts Eye and Ear;, Associate Professor, Harvard Medical School

Steven Grinspoon, MD, Chief, Metabolism Unit, Massachusetts General Hospital; Professor of Medicine, Harvard Medical School

Alexandra-Chloé Villani, PhD, Investigator, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

9:00 AM – 9:45 AM

Therapeutic Psychedelics – Opportunities and Impact

Moderators

Maurizio Fava, MD

Chair, Department of Psychiatry, Massachusetts General Hospital;

Slater Family Professor of Psychiatry, Harvard Medical School

Jason Gerberry

Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research

Kerry Ressler, MD, PhD

Chief Scientific Officer, McLean Hospital;

Professor of Psychiatry, Harvard Medical School

Panelists

Cristina Cusin, MD

Director, MGH Ketamine Clinic and Psychiatrist, Depression Clinical and Research Program, Massachusetts General Hospital;

Associate Professor in Psychiatry, Harvard Medical School

Daniel Karlin, MD

Chief Medical Officer, MindMed

John Krystal, MD

Chair, Department of Psychiatry, Yale School of Medicine

Jennifer Warner-Schmidt, PhD

Vice President, Scientific Affairs, Transcend Therapeutics

9:00 AM – 9:45 AM

Innovations Advancing Community Health Equity

Moderators

Allen Lutz

Health Care Services Analyst, BofA Global Research

Elsie Taveras, MD

Chief Community Health & Health Equity Officer, Mass General Brigham;

Conrad Taff Endowed Chair and Professor of Pediatrics, Harvard Medical School

Panelists

Rebecca Mishuris, MD

Chief Medical Information Officer, Mass General Brigham;

Member of the Faculty, Harvard Medical School

Claire-Cecile Pierre, MD

Vice President, Community Health Programs, Mass General Brigham;

Instructor in Medicine, Harvard Medical School

Jorge Rodriguez, MD

Clinician-investigator, Brigham and Women’s Hospital;

Assistant Professor, Harvard Medical School

Prabhjot Singh, MD, PhD

Senior Advisor, Strategic Initiatives Peterson Health Technology Institute

9:00 AM – 9:45 AM

Earliest Detection

Moderators

James Brink, MD

Enterprise Chief, Radiology, Mass General Brigham;

Juan M. Taveras Professor of Radiology, Harvard Medical School

David Louis, MD

Enterprise Chief, Pathology, Mass General Brigham

Benjamin Castleman Professor of Pathology, Harvard Medical School

Jason Zemansky, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Panelists

Jasmeer Chhatwal, MD, PhD

Associate Neurologist, Massachusetts General Hospital;

Associate Professor of Neurology, Harvard Medical School

Pradeep Natarajan, MD

Director of Preventive Cardiology, Paul & Phyllis Fireman Endowed Chair in Vascular Medicine, Massachusetts General Hospital;

Associate Professor of Medicine, Harvard Medical School

Yakeel Quiroz, PhD

Director, Familial Dementia Neuroimaging Lab and Director, Multicultural Alzheimer’s Prevention Program, Massachusetts General Hospital;

Paul B. and Sandra M. Edgerley MGH Research Scholar;

Associate Professor, Harvard Medical School

Heidi Rehm, PhD

Chief Genomics Officer, Massachusetts General Hospital;

Professor of Pathology, Harvard Medical School

9:00 AM – 9:45 AM

Women’s Health Technology Revolution

Moderators

Tazeen Ahmad

SMid-Cap Biotech Analyst, BofA Global Research

Hadine Joffe, MD

Executive Director of the Connors Center for Women’s Health and Gender Biology;

Interim Chair, Department of Psychiatry, Brigham and Women’s Hospital;

Paula A. Johnson Professor of Psychiatry in the Field of Women’s Health, Harvard Medical School

Panelists

Keith Isaacson, MD

Director of Minimally Invasive Gynecologic Surgery and Infertility, Newton Wellesley Hospital;

Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Nawal Nour, MD

Chair, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital;

Associate Professor, Kate Macy Ladd Professorship, Harvard Medical School

Kaveeta Vasisht, MD, PharmD

Associate Commissioner, Women’s Health, U.S. Food and Drug Administration

Alice Zheng, MD

Principal, RH Capital

9:50 AM – 10:15 AM

Picasso Ballroom

Fireside

Fireside Chat

Moderator

David Brown, MD, President, Academic Medical Centers, Mass General Brigham; Mass General Trustees Professor of Emergency Medicine, Harvard Medical School

Hoe do you balance Private medicine with Public not for profit HealthCare

Healthcare delivery system can achieve that much in Human health

Resources for Equity: housing and services: Capacity and COst

Evolution of care close to home catalyst of the Pandemic – How government think about the right patient for the right care level

MGB 40-60 In-patients at Home – Largest Program in the State – product needs to scale across all population though some do not have food security at home

Panelist

Kate Walsh, Secretary of Health and Human Services, State of Massachusetts

Stuart Bankrupcy – pstioents and providers involvement – structure challenges

Race and ethnicity – disparities, access and equity

Identify the challenge for Race and ethnicity

Focus to identify resources

Medicare & Medicaid – Human needs equity involve housing, food and home care – Public and Private sector cooperation

Pay for Performance

MA vs NYC – resources for welcoming new populations to the State of MA

Help finding Housing vs Shelter people

MA is the only State in the Union that is a Shelter State

People in our COuntry LEGALLY are in and out of shelters, new arrivals of skilled labor – temporary assistance to get jobs that we can’t find people to fill: CNA as example

MA has a community of shelters and medical center in the communities

Services for people that are at risk due to past life in home countries

Support for kids that do not speak English

Care and location: Keep care at home or SNF at home or in the community

Low income person at Home Hospital vs at MGB ?

Autist kids becoming Adult – how to care for ?

10:15 AM – 10:40 AM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

Alec Stranahan, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Teresa Gomez-Isla, MD, PhD, MGH, Neurology, Memory division

Altzheimer’s biomarkers

Clinical trials lessons on drug benefits

Panelist

David Hyman, MD, Chief Medical Officer, Eli Lilly and Company

Cardio-metabolic – medicines redefining disease by medicines benefit to patients

Investment in manufacturing medicines for Obesity, demand continue to expand

Oral small molecule and scaling focus on Sleep apnea, half of the population have metabolic disease and heart failure

Extension Program with sustained weigh loss in pre-diabetes progressing into maintained weigh loss

Invest in R&D in the cardio-metabolic

Listed to community feedback on experience how the drugs in AD affected patients in the Community – learning about challenges in delivery innovation in AD – irreversible neurodegenerative diseases – prevent not to loose the patients entirely – brain function

Targeted therapies, genetic therapies

Past life Oncologist – delivered innovations into Cancer patients – genetic medicines

AD medicines are not accessible even to people of means, Drug delivery using PET spinal injections

Ten years horizons at Eli Lilly is common

Obligation to provide scientific evidence from clinical trials

Inventory of patients qualification to participate in Clinical trials

Oncology: Interactions in biologics, cell therapies, conjucate compounds

Renewal of Targeting antigens

In Oncology: Proportions of patients get long term disease control by molecules developed in Academic Centers.

Eli Lilly acquired a BioPharma with manufacturing capabilities

Innovations are core vs discount cash-flow, strategy is to look at the science due to capacity to develop innovations

10:40 AM – 11:20 AM

Picasso Ballroom

Disruptors

The Disruptors: Metabolic Power…Need It…Want it

Moderator

Alec Stranahan, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Caroline Apovian, MD, MGH, HMS

Last ten years, from metabolic lessons of Bariatric patients

Treat obesity before surgery

product composition

multidisciplinary approach to obesity needs to be like in Oncology – multiple dsciplines

Bariatric and weigh regain like stent stenosis after surgery

Obesity dysfunction inflammation Gut-Brain transfer of hormones from the gut do not reach the brain to carb hunger socieaty is not signaled in the Brain and eating continued to mitigate hunger

Insurance must cover

Obesity Medicine – training 25 new practitioners to treat Obesity – Standards of Care, life style change

Primary care providers do not have resources to treat Life style component of

To reduce mortality by 20% by Bariatric surgery – No reduce of mortality by stenting – THAT I DISAGREE with

Panelists

David Hyman, MD, Chief Medical Officer, Eli Lilly and Company

non-peptide agonist, bariatric level for obesity

peptide injecting device

hormones and peptids activan inhibitor

hundred of million of people – scaling up

Adolescence with obesity will develop CVD, NASH

Epidemic of obesity the medicines are combating the epidemic

Vials, differential pricing, orals vs injectables

Productivity of work force, coverage by employers health insurance vs Government to handle coverage

10 additional drug

Xiayang Qiu, PhD, CEO, Regor Therapeutics

six years ago, great opportunity peptide and biologics for lifetime disease of obesity

cardiovascular favorably = affected by reduction in weigh

Medicines that works start early at age 35

Harith Rajagopalan, MD, PhD, CEO & Co-Founder, Fractyl Health

Diet & Life Style

Eli Lilly and Novo Nordik – have great drugs

Patients stop using them before they see the benefit

durable long term of mentainance long-tern to stay on the drug

Past life coronary cardiologist: PCI vs surgery choice of care angioplasty vs open heart surgery

Bariatric surgery vs great medicines

may be angioplasty for Bariatric patients

Obesity is different than CVD

BC-BS coverage of obesity drugs because weight is gained back vs Statins – continual use control cholestrol

maintenance drugs in the field of Obesity are needed

cost of drugs will come down

more evidence on obesity drugs will affect Formulary

11:20 AM – 12:00 PM

Picasso Ballroom

The Innovation Gap: The Broader Impact of Metabolic Drugs on Related Diseases

Moderator

Jason Zemansky, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Patrick Ellinor, MD, PhD, MGH, HMS

Panelists

Craig Basson, MD, PhD, Chief Medical Officer, Bitterroot Bio

17,000 patients obese no DM

prior CVD followed 3 yrs of treatment 6% mortality during the Trial

Death from CVD endpoint

weight at joining the trial, loss during the trial, benefir from the drug’

improve CVD not weigh loss

mechanism of Inflammation – drug, reduced atherosclerosis and reduced plaque and cytokins and inflammation improve CVD status

combination of life style and drugs GI axis systemic

cardiac artery disease: cholesterol, inhibit inflammatory signals plaque build on top of itself – approaches to remove debris macrophages in the plaque for artherosclerosis mechanism as CVD risk

Joshua Cohen, Co-CEO, Amylyx Pharmaceuticals

Bariatric surgery lower obesity

genetics, eating habits,

GLP-1 agonist developed

Punit Dhillon, CEO, Skye Bioscience

Phase II study combination therapy CVD and Obesity

optimize body composition – more productive on the body periphery

subtypes metabolic gains

Pharmacotherapy for obesity: mechanisms complementary life style change is a must have for long-term benefits

weight loss as a start before obesity treatment

co-morbidities of obesity

Justin Klee, Co-CEO, Amylyx Pharmaceuticals

Parkinson’s CNS peripheral Brain access therapies

revolution in metabolic disease treatment options, more studies for pathways to target the right patients for the right treatment

GLP-1 is energy regulator, Hypoglycemia is very dangerous

Rohan Palekar, CEO, 89bio

applications to obesity – data support

bariatric surgery intervention is not enough, NASH will not be impacted only by the surgery

NASH is a disease taking 25 years to develop

risk of fibrosis to set in Cirrhosis which is not curable

12:00 PM – 12:15 PM

Break

12:15 PM – 1:00 PM

Lunch and Medicine’s Hottest Topics – Block IV of IV

Concurrent Events

12:15 PM – 1:00 PM

ARPA-H: Opening New Frontiers in Health Innovations

Panel of 5

Glioblastoma Treatment Reinvented

Moderators

E. Antonio Chiocca, MD, PhD

Chair, Department of Neurosurgery, Brigham and Women’s Hospital;

Harvey W. Cushing Professor of Neurosurgery, Harvard Medical School

Charlie Yang, PhD

Large/SMid-Cap Biotech and Major Pharma Analyst, BofA Global Research

Panelists

Natalie Artzi, PhD

Associate Professor of Medicine, Brigham and Women’s Hospital & Harvard Medical School

Bryan Choi, MD, PhD

Associate Director, Center for Brain Tumor Immunology and Immunotherapy, Massachusetts General Hospital;

Assistant Professor of Neurosurgery, Harvard Medical School

Alexandra Golby, MD

Neurosurgeon;

Director of Image-guided Neurosurgery, Brigham and Women’s Hospital;

Professor of Neurosurgery, Professor of Radiology, Harvard Medical School

12:15 PM – 1:00 PM

Healthcare Corporate Venture

Moderator

Roger Kitterman

Senior Vice President, Ventures and Business Development & Licensing, Mass General Brigham

Managing Partner, Mass General Brigham Ventures

Panelists

Rahul Ballal, PhD

CEO, Mediar Therapeutics

Tim Luker, PhD

VP, Ventures & West Coast Head, Eli Lilly

James Mawson

CEO, Global Corporate Venturing

12:15 PM – 1:00 PM

Inflammation Pathways

Moderators

Tazeen Ahmad

SMid-Cap Biotech Analyst, BofA Global Research

Katherine Liao, MD

Associate Physician, Department of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital;

Associate Professor of Medicine and Biomedical Informatics, Harvard Medical School

Panelists

Jessica Allegretti, MD

Director, Crohn’s and Colitis Center, Brigham and Women’s Hospital;

Associate Professor of Medicine, Harvard Medical School

Andrew Luster, MD, PhD

Chief, Division of Rheumatology, Allergy and Immunology;

Director, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital;

Persis, Cyrus and Marlow B. Harrison Professor of Medicine, Harvard Medical School

Thorsten Mempel, MD, PhD

Associate Director, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital;

Professor of Medicine, Harvard Medical School

12:15 PM – 1:00 PM

Hospital at Home

Moderators

Joanna Gajuk

Health Care Facilities and Managed Care Analyst, BofA Global Research

Heather O’Sullivan, MS, RN, AGNP

President, Mass General Brigham Healthcare at Home

Panelists

O’Neil Britton, MD

Chief Integration Officer & Executive Vice President, Mass General Brigham

Jatin Dave, MD

Chief Medical Officer, MassHealth;

Director of Clinical Affairs, UMass Chan Medical School

Chemu Lang’at

Chief Operating Officer, Best Buy Health

1:05 PM – 1:45 PM

Picasso Ballroom

Pioneering Digital Transformation

Moderator

Liz Kwo, MD, Chief Commercial Officer, Everly Health

Infrastructure

AI used for

Panelists

Anna Åsberg, Vice President, AstraZeneca Pharmaceuticals

Massive data bases organize

AI to augment intelligence inside the data

Tyler Bryson, Corporate Vice President, US Health & Public Sector Industries, Microsoft Corporation

Do we have platforms to serve new problem

Regulatory changes require visiting use cases

Pharma has the research data, providers have EMR – Microsoft builds new models using that data

Tumor imaging data was processed and new pattern recognition done on data of these tumors. New patterns are now a subject for research, just identified inside the data

Trust in Healthcare

NYC and Microsoft developed a System for small businesses to access city resources

Works with Academic institutions: Programs at Harvard and Princeton to train students by Microsoft employees on MIcrosoft AI technologies that as they graduate there will be trained new AI-trained employees

collaborations

Aditya Bhasin, BofA

AI in Banking: Bias, security

AI virtual system analytics to provide insight for scaling

Jane Moran, MGH

Network, Data structure needs updates

technology to help clinicians

care team to work with Generative AI to assist in e-mail reading and problem solving

Healthcare equity – avoid Bias

AI is not an answer to every problem

innovate at scale: using Epic and Microsoft

Clinical data structure for LLM, AI to renovate administrative processes inside MGH

Data structure for transperancy

Digital Rounds like Medical ROunds audit problems

equity in data

1:45 PM – 2:25 PM

Picasso Ballroom

Capital Formation: Putting Money to Work – State of Affairs in Capital Markets

Moderators

John Bishai, PhD, BofA

valuations went down

Brendan Singleton, Healthcare Equity Capital Markets, BofA Securities

what impact Capital flow

Emma Somers-Roy, Chief Investment Officer, Mass General Brigham

Panelists

Chris Garabedian, Chairman & CEO, Xontogeny; Venture Portfolio Manager, Perceptive Advisors

Valuations done with comparables for IPO

Not quick to invest in companies, responsible behavior

Private rounds, Biotech and Pharma strategic partners

M&A stable requires are exciting valuation

foundations, institutional investors – level of interest is related to valuations number of years to exit

Peak sale, Public markets different than Private markets

Obesity is a crowd space, diferentiation is important

Exit tow ways: year for IPO natural acquirer – Who is he??

Cancer was a dominant now CNS, Cardio-metabolic, ophthalmology

size of market – Cancer was attractive, less in 2024

Early venture investor: 50-100MM valuation to 2Bil

CMS has discounting since profits are been realize at present time

Patents`

Presidential election

investors scarce pushed fewer mega rounds 100MM financing requires early clinical data

Hedge fund very conservative with valuations

Downsize in Biotech is over

Arjun Goyal, MD, Vida Ventures

Investment in private markets

2019-2021 – IPOs on narratives and proof of concept, only only, no financials

M&A or Partnering – financial risk clinical data point

validation of team success

size of market is very important

Innovation matters always in Pharma, prospects for Biotech very bright

what is HOT in a moment

combination therapies

Life cycle: compound right gene, financing history, fundamentals

calibration of market valuations

2:25 PM – 2:50 PM

Picasso Ballroom

Fireside

Lessons Learned Shaping New Horizons: Visionary Change Agent Perspectives

Moderator

Yvonne Hao, Secretary of Economic Development, Commonwealth of Massachusetts

accelerate AI adoption by nurses, How do you do that??

Public private partnerships

If you have a blank slate – do it differently

Great impact of Cleveland Clinic

Panelists

Delos “Toby” Cosgrove, MD, Executive Advisor; former CEO & President, Cleveland Clinic

Housing, education, research beyond healthcare

Reduce cost in healthcare, call centers by AI: equipment to measure BP every 4 hours

Technology is approved 13 years to become standard of care

COST in healthcare requires SALVATION

mistakes by leadership

Regulators have their share in current situation of Healthcare

Leadership in Health care must change

Marc Harrison, MD, Co-founder & CEO, Health Assurance Transformation Corp. (HATCo)

collaborate with competitors

AI is a tool not a solution

Streamline processes to reduce costs

Government should not solve the Healthcare problem

Residents are victims of leaders mistakes

Only healthcare industry sees the medical records of all the population

gene therapy, innovations to change healthcare and get financial solvency

2:50 PM – 3:15 PM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

Andrew Bressler, Washington Healthcare Policy Analyst, BofA Global Research

What is coming up in the next two years

Are you growing and Hiring?

Yvonne Hao, Secretary of Economic Development, Commonwealth of Massachusetts

AI – what is the potential for Healthcare

MA to work with ARPA-H

Panelist

Renee Wegrzyn, PhD, Director, Advanced Research Projects Agency for Health – A Federal Governmental Agency

ARPA-H Model was introduce under the Advanced Research Projects Agency for Health

Hired 21 Program Managers to manage Health initiatives in research

Health is not a partizan affair

Bring young innovators, mantored by experiences healthcare professionals

cellular therapeutics is an example selected to advanced the field

Data driven – looking at +100 project approved by government agency

Governtment, Academia, Private sector – SOLICITATIONS for solving a research problem

Technical merit in judging applications

Value-baced pricing – data to influence policy FDA, NIH collaboration

FDA to finance projects spending

Pediatrics

President announced a program for ARPA-H to work on

Investors are welcome to review proof of concepts of ARPA-H

Return on Investment for all Americans’ Tax payers money

Yes, growing and hiring. $1.5 milion budget

3:15 PM – 3:20 PM

First Look

First Look Award Presentation

3:20 PM – 3:35 PM

Selector of Winner: Doug Marshall & Paul Anderson, MD, PhD

Leigh Hochberg, MD, PhD @harvardmed

John Hanna, MD, PhD @harvardmed

Afternoon Break

3:35 PM – 4:15 PM

Picasso Ballroom

Disruptors

The Disruptors: The Biologic Revolution in Radiotherapies

Moderator

John Bishai, PhD, Global Healthcare Investment Banking, BofA Securities

Umar Mahmood, MD, PhD, MGH, HMS

Panelists

Amos Hedt, Chief Business Strategy Officer, Perspective Therapeutics

imaging used to deliver the therapeutics before the drug touch the patient to calculate toxicity

PL-1 combined with radiotherapy synergistics results

immunogenic combination therapy, in presence of these agents, immune response reaction in the immune cells

Matthew Roden, PhD, President & CEO, Aktis Oncology

Conjugates – delivery direct to tumors

Opportunity two targets: (1) SSTA2 marker (2) xx

WHen agent inside the tumor, shrinkage and no emergence of cell nascent

optimization design

Treatment break for patients and families

Philip Kantoff, MD, Co-Founder & CEO, Convergent Therapeutics

Radio-pharmeceutics : 10 days half-life carrier not a target for small molecules Data on 120 patient, namo robust response synergy of antibody and molecule

image alphas

durable responses

Matt Vincent, PhD, AdvanCell Isotopes

ROS species generated in the tumor

peptides, protein binders

paradigm shift in delivery of oncology therapeutics directly to tumors

Lena Janes, PhD, Abdera Therapeutics

isotope will deliver the payload without damaging the DNA and healthy tissue

target different types of tumors, different half-life

Radiation therapy using isotopes id one of two modalities: tumor in and tumor out approach

screen for patient for the translational therapy

Next generation of products will come, now it is the beginning of these agents

4:20 PM – 4:45 PM

Picasso Ballroom

Fireside

Fireside Chat

Moderator

Michael Ryskin, Life Science Tools & Diagnostics Analyst, BofA Global Research

Precision Medicine was it a paradigm shift??

Acquisition of manufacturing capabilities

research, manufacturinf line blurred

WHat excites you the most

Panelist

Marc Casper, Chairman, President & CEO, Thermo Fisher Scientific

Enabling Life sceinces, Pharmaceutical industries $1.5Billion internal investment annually

AI increasing knowledge

How is Precision Medicine applied? Sequencing in Cancer accelerated the Genomics information in use for 24 hours response of the sequence – adopted around the World.

at MGH lung cancers are treated with genomic sequencing

identification of the patients suitability for a targeted treatment

treatment during pregnacy at home vs hospitalization

History of company: Tools first: Mass spectrometry, one year for one sequence, protein identification and carrying to Mass spectrometry

Interactions need understanding acquiring electro spectrometry allowing analytical chemistry on proteins

Broad range of products: Clinical research to meet regulatory requirements entry into Reagents products.

Clinical Trials made effective by Thermo Scientific Products

Capabilities in registries, patient safety in psoriasis

Large role in experimental medicine drives efficiency in LABS

SIze of customers: small Biotech and large Pharma

Manufacture medicines: work with partnersbuilt by acquisitions small molecules,

100 engagements research, supply chain making medicines available at sites

Role for AI at Thermo Scientific:

Productivity – Cost effective for processes in use by 120,000 employees

Super customer interaction perfected by interogations with internal manuals to provide answers quickly

Improvement of products

Excitement Points: Responsiveness to COVID pandemic

New medicine development

4:50 PM – 5:30 PM

Picasso Ballroom

The Reemergence of ADCs, Precision Medicine, T-cell engagers, and Bispecifics: Oncology at Its Finest

Moderators

John Bishai, PhD, BofA

Approach to AI

Strategy regarding clinical trial design, vs molecule design

Justin Gainor, MD, MGH, HMS

How strategies are developed and then modified?

immune therapies work better open new paradeigm

Panelists

Moitreyee Chatterjee-Kishore, PhD, Head of Development, Immuno-Oncology and Cancer Cell Therapy, Astellas Pharma Inc.

cancer – first line of treatment vs 2nd and 3rd

Precision medicine more precise

mix and match immunotherapy and other modalities

small molecule early on

molecule formulation is science and art

Stratify the patient population early on

Help needed to design better trials

Research is key for molecule design

Niall Martin, PhD, CEO, Artios Pharma

peptide chemistry

molecule design had options several are applied

biomarker driven event in development cycle

strategy of biomarkers – lack structure

effect of combination therapy on survival?

Chris Varma, PhD, Co-founder, Chairman & CEO, Frontier Medicines

5:30 PM – 8:30 PM

South Lawn Tent

Attendee Reception and Dinner

Moderator

Anne Oxrider

Senior Vice President, Benefits Executive, Bank of America

Panelist

Deepak Chopra, MD

Founder, The Chopra Foundation

Wednesday, September 25, 2024

7:30 AM – 11:00 AM

Rotunda

Registration

7:30 AM – 8:30 AM

Picasso Foyer

Continental Breakfast

8:30 AM – 8:55 AM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

David Ting, MD, Associate Clinical Director for Innovation, Mass General Cancer Center; Associate Professor of Medicine, Harvard Medical School

Innovation is the foundation of the future

Creative thinking vs one agent and one target

Openness is much appreciated

Jason Zemansky, PhD, SMid-Cap Biotech Analyst, BofA Global Research

On WSJ article on M&A in Biotech attributing decline in M&A of Biotech companies due to LACK of Innovations

Q from audience: organizational structure and innovation

Vision on leveraging Partnerships

Panelist

Tadaaki Taniguchi, MD, PhD, Chief Medical Officer, Astellas Pharma

Pharma and Biotech heavy betting on new medicines in Oncology

Astellas Pharma is different than other Pharma companies

We focus on Oncology and in combination therapies as a priority

Investment pay attention to Leadership priorities

One product vs BEST combination therapy for best treatment and outcomes

Innovations come from anywhere

ADCs: Target, payload emerged recently by a partnership

Collaborations: several pathways, several modalities, several combinations therapies

Partnership requires greater flexibility

Created Small flexible Labs to enable to innovate with Partners, “we can’t innovate alone”

9:00 AM – 9:40 AM

Picasso Ballroom

Disruptors

The Disruptors: The Role of Pathway Inhibition in Inflammation and Inflammatory Diseases

Moderators

Tazeen Ahmad, SMid-Cap Biotech Analyst, BofA Global Research

Are you using AI

Neuroinflammation

Cynthia Lemere, PhD, BWH, HMS

What systems are primarily impacted by the Immunes system

Drug delivery for inflammation huge area

Getting antibodies to the Brain

Precision medicine, genetics,specific person with specific immune disease

Panelists

Jo Viney, PhD, Cofounder, President & CEO, Seismic Therapeutic

Pandemics highlighted the impact of the immune system

Targeting cytokines in specific locations – hew approach

Modalities on hand: protein degradation mediation by bringing two cells together

AI is used for Patient stratification

AI to be used in Pathways involved in disease process to identify Biologics, PROTAC,

AI and ML for training models from interaction between proteins

ChatGPT to predict interactions among proteins

Immune disease and remission bust the immune system to improve quality of life of patient undergoing interventions

T-cell engaggers – in cases of refractory – great approach for boosting the immune system: removal of antibidies, recycling antibodies,

Two ends: Cell depletion vs Early detection

Therapy is every 6 months, cell depletion takes 3 months to come back.

Target immune system in the periphery,

Immune system in neurodegenerative diseases: Parkinson’s local modulation to penetrate neurological system

Markers to cross the BBB or not cross in neurological diseases

Immune disease is POLYGENIC multiple o=etiologies, mutation, genetics, which cell and which pathway to target a therapeutics: Biologics

Patient stratification is key for Precision Medicine at the cell level

T-cell, B-cell, Cytokines and antibodies mediated disease

ADGs degradation

9:45 AM – 10:10 AM

Picasso Ballroom

H. Jeffrey Wilkins, MD, Abcuro

Inflammation play a role in activating the immune system

zin the days of Medical School: inhibition of cytokines

Today: specificity to target cells for depletion

Specific biomarkers for response to therapies

cell types by mutations and physiology and causality in the inflammation area: we know why they have inflammation we need to learn interventions for inflammation

Asthma in the 40s as an inflammatory disease

assess treatment of inflammation

Neuro-inflammation – not well understood

What is the cause that drive the disease: understanding encephalitis?

NiranJana Nagarajan, PhD, MGB Ventures

Biology is the driver not AI

depletion of cells in a certain stage

Translation from disease to other diseases in the case of cell therapy potential – active area companies are trying solutions

Inflammation is a huge challenge to treat

Fireside

Fireside Chat

Moderators

Daniel Kuritzkes, MD, Chief, Division of Infectious Diseases, Brigham and Women’s Hospital; Harriet Ryan Albee Professor of Medicine, Harvard Medical School

Pathways in vaccine design

How to educate population on Vaccines

other approaches than vaccines

Alec Stranahan, PhD, SMid-Cap Biotech Analyst, BofA Global Research

Vaccine approval

Next generation vaccines

Panelist

Stéphane Bancel, CEO, Moderna

Vaccine design: long term vaccines weakens in aged population

data on role of AVV in Multiple Sclerosis

working on in the US vs France, Netherland in Europe different approaches

Vaccine for HIV

Vaccine was approved last year for children, pharmacies shortage

Season of FLu three times more vaccines in use

Employees run vaccine clinics on site

Vaccines not related to COVID

Misinformation from COVID vaccine

5% of COVID hospitalized were on the booster

Combination vaccines for high risk populations

Healthcare providers need to be involved in Education, many do not have an interest in the education on vaccines

Local stories from Vaccine manufectures and developer to be used in education in the communities

Individual DNA cancer celll signature of the cancer – data over time for development of vaccine to cancer many more tumor types are needed

Checkpoints in early disease

biopsy are too expensive

Side effect studies going on

mono-therapy vs immunotherapy costs involved

Naive virus to get into the Liver two diseases – cassets for sose management

Recombinant antibodies technology from the 70s

PD-1

COVID – was nto in the plan for development – design in silicon in two weeks – no change after this design

10:10 AM – 10:20 AM

Break

10:20 AM – 11:00 AM

Picasso Ballroom

The Innovation Gap: Understanding the Role of Cell Therapies in Autoimmune Disease

Moderator

Charlie Yang, PhD

Large/SMid-Cap Biotech and Major Pharma Analyst, BofA Global Research

TCM

CAR-T

advantages of each cell type

Angele Shen, MGB Innovations

CAR-T

What would be a quick breakthrough?

Panelists

Jeff Bluestone, PhD, CEO & President, Sonoma Biotherapeutics

Cell therapy for cell depletion elimination of B-cells like its role in Multiple Sclerosis

Working with regulatory T-cells

Population of cells to study: T-cells master regulator in multiple ways – produce metabolic factors, infection tone in activation of other cells

Biology of cell: RNA, DNA

TCR – target antigens in tissues they are in in immune suppression

FInding the right peptide bindes to a certain MAC

CAR-T – recornize the cells in the local milieu like in patients with RA as an autoimmune disease

Clinical models ascertain cell types involvement leading to clinical trial insights then to therapies on a decision tree

recent data on CAR-T immune response in allogeneic for potential use in neurodegenerative diseases

patients and companies over react on immune therapy: Patients and Science vs hype

next generation: POC,

Gene therapy specificities vs Cell therapies – each approach will develop a different drug

FDA and NIH has in 11/2023 a meeting on Regulation of Cell therapy on stability and their approach to immune disease where there are already several drugs

approvals challenges companies

Price, too expensive a treatment is cell therapy

Chad Cowan, PhD, Executive Advisor, Century Therapeutics

use Natural Killer cells to elicit long-term immune response, T-cells,

active Beta cells]Regulatory monitoring use

DM – regulatory cells made from Stem cells

mission durable response

Clinical issues – not easy way for treatment wiht a cell line and bioreactors and modalities less similar to autologoous celles

CAR-T in oncology lessons now are transferred to Immune disease

Cell therapy requires technologies to mature multiple modalities and multiple drugs not one cell therapy for all immune diseases

Stability of the therapy vs rejection by immune system

FDA making cells is not as making drugs – higher level of scrutiny for cell therapy

SYNTHETIC BIOLOGY on B-cells for future breakthrough

Samantha Singer, President & CEO, Abata Therapeutics

Immune response involve many cell types in many diseases

Oncology the use of T-cells as tissue residents staying in tissue long time

Specific biology of the disease and regulatory cells receptors optimizing TCR presentation in pathology of tissue residents phyno types

activate in nervous system or in pancreas – intersection of cell biology with disease biology

Market feasibility – scaling, biology, pathology for reimbursement

antibody therapy may be appropriate than cell therapy is only a novel option

Cell manufacturing requires optimization of process, companies commercializing across all cell types

comprehensive approach for systemic immune suppression

: healthy tissue vs diseased tissue with cell theray implanted cells as residents in tissue

clinical data on product performance and on the biology reactions

11:00 AM – 11:40 AM

Picasso Ballroom

Unmet Clinical Needs: 100 Harvard KOLs Weigh In

Moderators

Jose Florez, MD, PhD, Physician-in-Chief and Chair, Department of Medicine, Massachusetts General Hospital; Professor, Harvard Medical School

40 minutes to deal with big needs collected from 100 faculties at Harvard Medical School

The ten issues on one slide

How could we use compute to distill data

Bruce Levy, MD, Physician-In-Chief and Co-Chair, Department of Medicine, Brigham and Women’s Hospital; Parker B. Francis Professor of Medicine, Harvard Medical School

Transformation from the Present to the Future

identifying the needs

Infectious diseases: Rapid diagnostics need

resistance to antibiotics and metabolic reactions endogenous

Pandemics globally of diseases erradicated in the past: Pox, polio

Improving health in Geriatrics, not population growing but geriatric population growing. Beyong age 60 a citizen will use 1 or 2 physicians each

7,000 diseases, Genetic diseases requires integration and innovations in therapy

Innovations in Home devices

Panelists

Rox Anderson, MD, Lancer Endowed Chair of Dermatology;, Director, Wellman Center for Photomedicine, MGH; Professor of Dermatology, HMS

Access to data across institutions

Nicole Davis, PhD, Biomedical Communications

We asked 104 expert practitioners, content collected was analyzed

detection early

keeping the Human brain healthy

geriatrics Medicine, aging and compound effects on health system with aging and Health equity

Bias in Data

Jean-François Formela, MD, Partner, Atlas Venture

genetic information used in therapeutics design

Steven Greenberg, MD, Neurologist, Brigham and Women’s Hospital; Professor of Neurology, Harvard Medical School

Human genome completed in 1999, human genetic diseases were discovered learn about the disease at the tissue level with genomics and a system approach

Pathogenic drivers, systme integration by therapeutics approaches to pathways multiple cytokines in allergic reactions Pfizer had two biomarkers and therapies for systemic biology of disease

Pediatrics has its own challenges

Imaging medicine

Living longer at a lower cost – HOW TO ACHIEVE THAT?

growth abnormality in children: Body growth and Skull shrink

John Lepore, MD, CEO, ProFound Therapeutics;, CEO-Partner, Flagship Pioneering

Pathway, targeting therapy to patients in a System biological approach

Database of systme biology has missing components not included in the Human genome project – completion of the Data

Definition of End points needs revisiting

Identifying specific populations vs getting quickly to market

Diseases of aging: Muscles diseases – how to promote improvement in muscle mass

CONCLUSIONS

Gray Tsunami

Brain health

Cancer treatment paradigm shift

Fibrosis in many diseases

infectious disease in changing World

Equity in HC

Clinical Data is VAST

Systemic view of Human disease

New approaches to Psychaitry

Rare disease treatment needs a charter

In addition,

new generation of pain treatment

skin treatment new drugs

Chronic disease: improve treatment and prevention.

Obesity medicine – new discipline in a new Era

11:45 AM – 12:30 PM

Picasso Ballroom

Fireside

Fireside Chat

Moderators

Tazeen Ahmad, SMid-Cap Biotech Analyst, BofA Global Research

FDA sets criteria – How is that done?

Autoimmune disease therapies – What is in the horizon?

Paul Anderson, MD, PhD, Chief Academic Officer, Mass General Brigham;

drug development

drug pricing in Europe

New book

RA needs more medicines

UNCONTROLLED SPREAD

In Uncontrolled Spread, a New York Times Best Seller, Dr. Scott Gottlieb identifies the reasons why the US was caught unprepared for the pandemic and how the country can improve its strategic planning to prepare for future viral threats.

Panelist

Scott Gottlieb, MD, Physician; Former Commissioner, Food and Drug Administration (2017-2019)

FDA approval 1st gene therapy in his tenure

Price of drugs: efficatious vs time to deveop

competitors in the marketplace are there for market share

New Book: Episodes in the FDA, appproval process at FDA, Gene therapy 1st in class approved – a special moment. Back in 1980s era translated to antibodies, to T-cell pioneering work.

Publisher worried it will not sell very well

FDA had concerns about manufacturing aspects

In 2024 we understand Biologics on novel platforms

Worries that Medicare will not reimbursement and cover the new therapies: Cell therapy

Statins approval had a known very large market vs Cell therapy not known which Cancer patients will benefit???

Black box involved in Autoimmune, studies bring exciting results

In 2018 – needs arise for early approved of drugs in AD, amyloid plaque – change in thinking and is controversial

In early 2020, change in settings of clinical trials, placido no more the only way for Randomized trials

Approval for AD drug vs othe indication – the process is difference (DMD a case to think about)

AI & NLP: Train on data of 10,000 lesions

FDA choose not to regulate AI the physician is in the Middle

Who is wrong: CHatGPT or the clinician ?

Data set on gene may represents NEW biologies that Physicians had not seen before

Data validation on medical devices and their approval after regulating them

Diagnostics tests: Validation Panels are involved

Regulated on input data vs Output data and validate the input data

Platforms are needed for regulation of AI involvement in the drug discovery and the drug approval process

investment in this platforms will be done by Whom?? It will come

Framework for AI at FDA: Regulatory gray data for applications and standards for output – not a novel regulatory concept

If AI will be applied widely, I/O accuracy is a must have

may be achievable soon?

FDA is evolutionary organization in its decision process NOT a REVOLUTIONARY organization. Simulation work started in 2003, 40 people doing that then.

Recently, new team in Agency working of Safety with tools and technologies that are common in Science – Approvals to drug labels and off labels that 20 years ago would not have happened

Tolerance for higher prices is to support Private sector that brings the innovating drugs to market

12:30 PM – 12:35 PM

Picasso Ballroom

Closing Remarks

SPEAKERS

C-Suite Speakers

Faraz Ali

CEO, Tenaya Therapeutics

Peter Anastasiou

CEO, Capsida Biotherapeutics

Paul Anderson, MD, PhD

Chief Academic Officer, Mass General Brigham; K. Frank Austen Professor of Medicine, Harvard Medical School

Rahul Ballal, PhD

CEO, Mediar Therapeutics

Stéphane Bancel

CEO, Moderna

Craig Basson MD, PhD

Chief Medical Officer, Bitterroot Bio

Jeff Bluestone, PhD

CEO & President, Sonoma Biotherapeutics

Albert Bourla, PhD

Chairman & CEO, Pfizer

O’Neil Britton, MD

Chief Integration Officer & Executive Vice President, Mass General Brigham

Marc Casper

Chairman, President & CEO, Thermo Fisher Scientific

Joshua Cohen

Co-CEO, Amylyx Pharmaceuticals

Delos “Toby” Cosgrove, MD

Executive Advisor; former CEO & President, Cleveland Clinic

Jatin Dave, MD

Chief Medical Officer, MassHealth; Director of Clinical Affairs, UMass Chan Medical School

Punit Dhillon

CEO, Skye Bioscience

Steve Favaloro

Chairman & CEO, Genezen

John Fish

Chairman & CEO, Suffolk

Alexandria Forbes, PhD

CEO, MeiraGTx

Niyum Gandhi

CFO & Treasurer, Mass General Brigham

Chris Garabedian

Chairman & CEO, Xontogeny; Venture Portfolio Manager, Perceptive Advisors

Lucas Harrington, PhD

Co-Founder & CSO, Mammoth Biosciences

Marc Harrison, MD

Co-founder & CEO, Health Assurance Transformation Corp. (HATCo)

Amos Hedt

Chief Business Strategy Officer, Perspective Therapeutics

Rod Hochman, MD

President & CEO, Providence

David Hyman, MD

Chief Medical Officer, Eli Lilly and Company

Philip Kantoff, MD

Co-Founder & CEO, Convergent Therapeutics

Daniel Karlin, MD

Chief Medical Officer, MindMed

Reshma Kewalramani, MD

CEO & President, Vertex Pharmaceuticals

Justin Klee

Co-CEO, Amylyx Pharmaceuticals

Anne Klibanski, MD

President & CEO, Mass General Brigham; Laurie Carrol Guthart Professor of Medicine, Harvard Medical School

Samarth Kulkarni, PhD

CEO, CRISPR Therapeutics

Liz Kwo, MD

Chief Commercial Officer, Everly Health

Adam Landman, MD

Chief Information Officer & SVP, Digital, Mass General Brigham; Associate Professor of Emergency Medicine, Harvard Medical School

Chemu Lang’at

Chief Operating Officer, Best Buy Health

Paul LaViolette

Managing Partner & COO, SV Health Investors

John Lepore, MD

CEO, ProFound Therapeutics; CEO-Partner, Flagship Pioneering

Christopher Longhurst, MD

Chief Medical & Digital Officer, UC San Diego Health

Kevin Mahoney

CEO, University of Pennsylvania Health System

Niall Martin, PhD

CEO, Artios Pharma

James Mawson

CEO, Global Corporate Venturing

Mark McKenna

Chairman & CEO, Mirador Therapeutics

Jane Moran

Chief Information and Digital Officer, Mass General Brigham

William Morris, MD

Chief Medical Information Officer, Google Cloud

Rohan Palekar

CEO, 89bio

Raju Prasad, PhD

Chief Financial Officer, CRISPR Therapeutics

Xiayang Qiu, PhD

CEO, Regor Therapeutics

Harith Rajagopalan MD, PhD

CEO & Co-Founder, Fractyl Health

Shiv Rao, MD

CEO & Founder, Abridge

Kerry Ressler, MD, PhD

Chief Scientific Officer, McLean Hospital; Professor of Psychiatry, Harvard Medical School

Matthew Roden, PhD

President & CEO, Aktis Oncology

Sandi See Tai, MD

Chief Development Officer, Lexeo Therapeutics

Samantha Singer

President & CEO, Abata Therapeutics

Joanne Smith-Farrell, PhD

CEO & Director, Be Biopharma

Emma Somers-Roy

Chief Investment Officer, Mass General Brigham

Adam Steensberg, MD

President & CEO, Zealand Pharma

Tadaaki Taniguchi, MD, PhD

Chief Medical Officer, Astellas Pharma

Elsie Taveras, MD

Chief Community Health & Health Equity Officer, Mass General Brigham; Conrad Taff Endowed Chair and Professor of Pediatrics, Harvard Medical School

Jo Viney, PhD

Cofounder, President & CEO, Seismic Therapeutic

Ron Walls, MD

Chief Operating Officer, Mass General Brigham; Neskey Family Professor of Emergency Medicine, Harvard Medical School

Christophe Weber

President & CEO, Takeda

Fraser Wright, PhD

Chief Gene Therapy Officer, Kriya Therapeutics

Speakers

Anna Åsberg

Vice President, AstraZeneca Pharmaceuticals

Tazeen Ahmad

SMid-Cap Biotech Analyst, BofA Global Research

Jessica Allegretti, MD

Director, Crohn’s and Colitis Center, Brigham and Women’s Hospital; Associate Professor of Medicine, Harvard Medical School

Rox Anderson, MD

Lancer Endowed Chair of Dermatology; Director, Wellman Center for Photomedicine, MGH; Professor of Dermatology, HMS

Katherine Andriole, PhD

Director of Academic Research and Education, Mass General Brigham Data Science Office; Associate Professor, Harvard Medical School

Caroline Apovian, MD

Co-Director, Center for Weight Management and Wellness, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Vanita Aroda, MD

Director, Diabetes Clinical Research, Brigham and Women’s Hospital; Associate Professor, Harvard Medical School

Natalie Artzi, PhD

Associate Professor of Medicine, Brigham and Women’s Hospital & Harvard Medical School

John Bishai, PhD

Global Healthcare Investment Banking, BofA Securities

David Blumenthal, MD

Professor of Practice of Public Health and Health Policy, Harvard TH Chan School of Public Health; Research Fellow, Harvard Kennedy School of Government; Samuel O. Thier Professor of Medicine, Emeritus, Harvard Medical School

Giles Boland, MD

President, Brigham and Women’s Hospital and Brigham and Women’s Physicians Organization; Philip H. Cook Distinguished Professor of Radiology, Harvard Medical School

Andrew Bressler

Washington Healthcare Policy Analyst, BofA Global Research

James Brink, MD

Enterprise Chief, Radiology, Mass General Brigham; Juan M. Taveras Professor of Radiology, Harvard Medical School

David Brown, MD

President, Academic Medical Centers, Mass General Brigham; Mass General Trustees Professor of Emergency Medicine, Harvard Medical School

Tyler Bryson

Corporate Vice President, US Health & Public Sector Industries, Microsoft Corporation

Jonathan Carlson, MD, PhD

Director of Chemistry, Center for Systems Biology, Massachusetts General Hospital; Assistant Professor of Medicine, Harvard Medical School

Miceal Chamberlain

President of Massachusetts, Bank of America

Moitreyee Chatterjee-Kishore, PhD

Head of Development, Immuno-Oncology and Cancer Cell Therapy, Astellas Pharma Inc.

Dong Feng Chen, MD, PhD

Associate Scientist, Massachusetts Eye and Ear; Associate Professor, Harvard Medical School

Jasmeer Chhatwal, MD, PhD

Associate Neurologist, Massachusetts General Hospital; Associate Professor of Neurology, Harvard Medical School

E. Antonio Chiocca, MD, PhD

Chair, Department of Neurosurgery, Brigham and Women’s Hospital; Harvey W. Cushing Professor of Neurosurgery, Harvard Medical School

Bryan Choi, MD, PhD

Associate Director, Center for Brain Tumor Immunology and Immunotherapy, Massachusetts General Hospital; Assistant Professor of Neurosurgery, Harvard Medical School

Deepak Chopra, MD

Founder, The Chopra Foundation

Yolonda Colson, MD, PhD

Chief, Division of Thoracic Surgery, Massachusetts General Hospital; Hermes C. Grillo Professor of Surgery, Harvard Medical School

Chad Cowan, PhD

Executive Advisor, Century Therapeutics

Cristina Cusin, MD

Director, MGH Ketamine Clinic and Psychiatrist, Depression Clinical and Research Program, Massachusetts General Hospital; Associate Professor in Psychiatry, Harvard Medical School

Nicole Davis, PhD

Biomedical Communications

Marcela del Carmen, MD

President, Massachusetts General Hospital and Massachusetts General Physicians Organization (MGPO); Executive Vice President, Mass General Brigham; Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Gerard Doherty, MD

Surgeon-in-Chief, Mass General Brigham Cancer; Surgeon-in-Chief, Brigham and Women’s Hospital; Moseley Professor of Surgery, Harvard Medical School

Liz Everett Krisberg

Head of Bank of America Institute

Maurizio Fava, MD

Chair, Department of Psychiatry, Massachusetts General Hospital; Slater Family Professor of Psychiatry, Harvard Medical School

Keith Flaherty, MD

Director of Clinical Research, Mass General Cancer Center; Professor of Medicine, Harvard Medical School

Jose Florez, MD, PhD

Physician-in-Chief and Chair, Department of Medicine, Massachusetts General Hospital; Professor, Harvard Medical School

Jean-François Formela, MD

Partner, Atlas Venture

Fritz François, MD

Executive Vice President and Vice Dean, Chief of Hospital Operations, NYU Langone Health

Joanna Gajuk

Health Care Facilities and Managed Care Analyst, BofA Global Research

Jason Gerberry

Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research

Gad Getz, PhD

Director of Bioinformatics, Krantz Center for Cancer Research and Department of Pathology; Paul C. Zamecnik Chair in Cancer Research, Mass General Cancer Center; Professor of Pathology, Harvard Medical School

Alexandra Golby, MD

Neurosurgeon; Director of Image-guided Neurosurgery, Brigham and Women’s Hospital; Professor of Neurosurgery, Professor of Radiology, Harvard Medical School

Allan Goldstein, MD

Chief of Pediatric Surgery, Massachusetts General Hospital; Surgeon-in-Chief, Mass General for Children; Marshall K. Bartlett Professor of Surgery, Harvard Medical School

Scott Gottlieb, MD

Physician; Former Commissioner, Food and Drug Administration (2017-2019)

David Grayzel, MD

Partner, Atlas Venture

Steven Greenberg, MD

Neurologist, Brigham and Women’s Hospital; Professor of Neurology, Harvard Medical School

Steven Grinspoon, MD

Chief, Metabolism Unit, Massachusetts General Hospital; Professor of Medicine, Harvard Medical School

Daphne Haas-Kogan, MD

Chief, Enterprise Radiation Oncology, Mass General Brigham; Professor, Harvard Medical School

Roger Hajjar, MD

Director, Gene & Cell Therapy Institute, Mass General Brigham

John Hanna, MD, PhD

Associate Professor, Brigham and Women’s Hospital & Harvard Medical School

Yvonne Hao

Secretary of Economic Development, Commonwealth of Massachusetts

Nobuhiko Hata PhD

Director, Surgical Navigation and Robotics Laboratory, Brigham and Women’s Hospital; Professor of Radiology, Harvard Medical School

Maura Healey

Governor of the Commonwealth of Massachusetts

Elizabeth Henske, MD

Director, Center for LAM Research and Clinical Care, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Leigh Hochberg MD, PhD

Director of Neurotechnology and Neurorecovery, Massachusetts General Hospital; Senior Lecturer on Neurology, Harvard Medical School

Daphne Holt, MD, PhD

Director of the Resilience and Prevention Program, Massachusetts General Hospital; Associate Professor of Psychiatry, Harvard Medical School

Susan Huang, MD

EVP, Chief Executive, Providence Clinical Network, Providence Southern CA

Keith Isaacson, MD

Director of Minimally Invasive Gynecologic Surgery and Infertility, Newton Wellesley Hospital; Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Ole Isacson, MD-PhD

Founding Director, Neuroregeneration Research Institute, McLean Hospital; Professor of Neurology and Neuroscience, Harvard Medical School

Haim Israel

Head of Global Thematic Investing Research, BofA Global Research

Farouc Jaffer, MD, PhD

Director, Coronary Intervention, Massachusetts General Hospital; Associate Professor of Medicine, Harvard Medical School

Russell Jenkins, MD, PhD

Krantz Family Center for Cancer Research, Massachusetts General Hospital; Mass General Cancer Center, Center for Melanoma; Assistant Professor of Medicine, Harvard Medical School

Hadine Joffe, MD

Executive Director of the Connors Center for Women’s Health and Gender Biology; Interim Chair, Department of Psychiatry, Brigham and Women’s Hospital; Paula A. Johnson Professor of Psychiatry in the Field of Women’s Health, Harvard Medical School

Benjamin Kann, MD

Assistant Professor, Brigham and Women’s Hospital & Harvard Medical School

Tatsuo Kawai, MD, PhD

Director of the Legorreta Center for Clinical Transplantation Tolerance, A.Benedict Cosimi Chair in Transplant Surgery, Massachusetts General Hospital; Professor of Surgery, Harvard Medical School

Albert Kim, MD

Assistant Physician, Mass General Cancer Center; Assistant Professor, Harvard Medical School

Roger Kitterman

Senior Vice President, Ventures and Business Development & Licensing, Mass General Brigham Managing Partner, Mass General Brigham Ventures

Lotte Bjerre Knudsen, DMSc

Chief Scientific Advisor, Novo Nordisk

Vesela Kovacheva, MD, PhD

Director of Translational and Clinical Research, Mass General Brigham; Assistant Professor of Anesthesia, Harvard Medical School

Jonathan Kraft

President, The Kraft Group; Board Chair, Massachusetts General Hospital

John Krystal, MD

Chair, Department of Psychiatry, Yale School of Medicine

Daniel Kuritzkes, MD

Chief, Division of Infectious Diseases, Brigham and Women’s Hospital; Harriet Ryan Albee Professor of Medicine, Harvard Medical School

Bruce Levy, MD

Physician-In-Chief and Co-Chair, Department of Medicine, Brigham and Women’s Hospital; Parker B. Francis Professor of Medicine, Harvard Medical School

Katherine Liao, MD

Associate Physician, Department of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital; Associate Professor of Medicine and Biomedical Informatics, Harvard Medical School

David Louis, MD

Enterprise Chief, Pathology, Mass General Brigham Benjamin Castleman Professor of Pathology, Harvard Medical School

Tim Luker, PhD

VP, Ventures & West Coast Head, Eli Lilly

Andrew Luster, MD, PhD

Chief, Division of Rheumatology, Allergy and Immunology; Director, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital; Persis, Cyrus and Marlow B. Harrison Professor of Medicine, Harvard Medical School

Allen Lutz

Health Care Services Analyst, BofA Global Research

Calum MacRae MD, PhD

Vice Chair for Scientific Innovation, Department of Medicine, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Joren Madsen, MD, PhD

Director, MGH Transplant Center; Paul S. Russell/Warner-Lambert Professor of Surgery, Harvard Medical School

Faisal Mahmood, PhD

Associate Professor, Brigham and Women’s Hospital & Harvard Medical School

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research, FDA

Marcela Maus, MD, PhD

Director of Cellular Therapy and Paula O’Keeffe Chair in Cancer Research, Krantz Family Center for Cancer Research and Mass General Cancer Center; Associate Director, Gene and Cell Therapy Institute, Mass General Brigham; Associate Professor, Harvard Medical School

Thorsten Mempel, MD, PhD

Associate Director, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital; Professor of Medicine, Harvard Medical School

Rebecca Mishuris, MD

Chief Medical Information Officer, Mass General Brigham; Member of the Faculty, Harvard Medical School

Pradeep Natarajan, MD

Director of Preventive Cardiology, Paul & Phyllis Fireman Endowed Chair in Vascular Medicine, Massachusetts General Hospital; Associate Professor of Medicine, Harvard Medical School

Nawal Nour, MD

Chair, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital; Associate Professor, Kate Macy Ladd Professorship, Harvard Medical School

Heather O’Sullivan, MS, RN, AGNP

President, Mass General Brigham Healthcare at Home

Anne Oxrider

Senior Vice President, Benefits Executive, Bank of America

Claire-Cecile Pierre, MD

Vice President, Community Health Programs, Mass General Brigham; Instructor in Medicine, Harvard Medical School

Richard Pierson III, MD

Scientific Director, Center for Transplantation Sciences, Massachusetts General Hospital; Professor of Surgery, Harvard Medical School

Mark Poznansky, MD, PhD

Director, Vaccine and Immunotherapy Center, Massachusetts General Hospital; Steve and Deborah Gorlin MGH Research Scholar; Professor of Medicine, Harvard Medical School

Yakeel Quiroz, PhD

Director, Familial Dementia Neuroimaging Lab and Director, Multicultural Alzheimer’s Prevention Program, Massachusetts General Hospital; Paul B. and Sandra M. Edgerley MGH Research Scholar; Associate Professor, Harvard Medical School

Heidi Rehm, PhD

Chief Genomics Officer, Massachusetts General Hospital; Professor of Pathology, Harvard Medical School

Leonardo Riella, MD, PhD

Medical Director of Kidney Transplantation, Massachusetts General Hospital; Harold and Ellen Danser Endowed Chair in Transplantation, Harvard Medical School

Jorge Rodriguez, MD

Clinician-investigator, Brigham and Women’s Hospital; Assistant Professor, Harvard Medical School

Adam Ron

Health Care Facilities and Managed Care Analyst, BofA Global Research

David Ryan, MD

Physician-in-Chief, Mass General Brigham Cancer; Professor of Medicine, Harvard Medical School

Michael Ryskin

Life Science Tools & Diagnostics Analyst, BofA Global Research

Alkesh Shah

Head of US Equity Software Research, BofA Global Research

Angela Shen, MD

Vice President, Strategic Innovation Leaders, Mass General Brigham Innovation

Gregory Simon

President, Simonovation

Prabhjot Singh, MD, PhD

Senior Advisor, Strategic Initiatives Peterson Health Technology Institute

Brendan Singleton

Healthcare Equity Capital Markets, BofA Securities

Caroline Sokol, MD, PhD

Assistant Physician, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

Daniel Solomon, MD

Matthew H. Liang Distinguished Chair in Arthritis and Population Health, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Scott Solomon, MD

Director, Clinical Trials Outcomes Center; Edward D. Frohlich Distinguished Chair in Cardiovascular Pathophysiology, Brigham and Women’s Hospital; Professor of Medicine, Harvard Medical School

Fatima Cody Stanford, MD

Obesity Medicine Physician Scientist, Massachusetts General Hospital; Associate Professor of Medicine and Pediatrics, Harvard Medical School

Shannon Stott, PhD

Associate Investigator, Krantz Family Center for Cancer Research and Mass General Cancer Center; d’Arbeloff Research Scholar, Massachusetts General Hospital; Associate Investigator, Krantz Family Center for Cancer Research Harvard Medical School

Alec Stranahan, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Marc Succi, MD

Executive Director, Mass General Brigham MESH Incubator; Associate Chair of Innovation & Commercialization, Mass General Brigham Radiology; Assistant Professor, Harvard Medical School

Guillermo Tearney, MD, PhD

Principal Investigator, Wellman Center for Photomedicine, Massachusetts General Hospital; Remondi Family Endowed MGH Research Institute Chair; Professor of Pathology, Harvard Medical School

David Ting, MD

Associate Clinical Director for Innovation, Mass General Cancer Center; Associate Professor of Medicine, Harvard Medical School

Raul Uppot, MD

Interventional Radiologist, Massachusetts General Hospital; Associate Professor, Harvard Medical School

Chris Varma, PhD

Co-founder, Chairman & CEO, Frontier Medicines

Kaveeta Vasisht, MD, PharmD

Associate Commissioner, Women’s Health, U.S. Food and Drug Administration

Alexandra-Chloé Villani PhD

Investigator, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

Kate Walsh

Secretary of Health and Human Services, State of Massachusetts

David Walt, PhD

Professor of Pathology, Brigham and Women’s Hospital; Hansjörg Wyss Professor of Biologically Inspired Engineering, Harvard Medical School

Jennifer Warner-Schmidt, PhD

Vice President, Scientific Affairs, Transcend Therapeutics

Renee Wegrzyn, PhD

Director, Advanced Research Projects Agency for Health

Christoph Westphal, MD, PhD

General Partner, Longwood Fund

Deborah Wexler, MD

Chief, Diabetes Unit, Massachusetts General Hospital; Associate Professor of Medicine, Harvard Medical School

Charlie Yang, PhD

Large/SMid-Cap Biotech and Major Pharma Analyst, BofA Global Research

Nathan Yozwiak, PhD

Head of Research, Gene and Cell Therapy Institute, Mass General Brigham

Jason Zemansky, PhD

SMid-Cap Biotech Analyst, BofA Global Research

Alice Zheng, MD

Principal, RH Capital

We continue to confirm more speakers. Please check back regularly for updates.

SOURCE

https://2024.worldmedicalinnovation.org/speakers/

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Regulatory T cells (Tregs) are important for sperm tolerance and male fertility

Posted in Autoimmune Inflammatory DIseases, Developmental biology, Diagnostic Immunology, Human Antibody Response, Human Immune System in Health and in Disease, Immunodiagnostics, Immunology, Immunotherapy, Innovation in Immunology Diagnostics, Personal Health Applications: Tech Innovations serves HealhCare, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Preimplantation Genetic Diagnosis and Reproductive Genomics, Protection Against Autoimmune Disease, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Tolerance-inducing Autoimmune Disease Therapeutics, tagged autoimmune disease, autoimmunity, fertility, immune cells, infertility, Regulatory T cell, sperm tolerence, Tregs on September 11, 2023| Leave a Comment »

Regulatory T cells (Tregs) are important for sperm tolerance and male fertility

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Regulatory T cells (Tregs) are specialized immune cells that modulate tissue homeostasis. They are a specialized subset of T lymphocytes that function as suppressive immune cells and inhibit various elements of immune response in vitro and in vivo. While there are constraints on the number or function of Tregs which can be exploited to evoke an effective anti-tumor response, sufficient expansion of Tregs is essential for successful organ transplantation and for promoting tolerance of self and foreign antigens. Current studies have provided evidence that a defect in the number or function of Tregs contributes to the etiology of several reproductive diseases.

In the male reproductive tract, prevention of autoimmune responses against antigenic spermatozoa, while ensuring protection against stressors, is a key determinant of fertility. Using an autoimmunity-induced model, it was uncovered that the role of Tregs in maintaining the tolerogenic state of the testis and epididymis. The loss of tolerance induced an exacerbated immune cell infiltration and the development of anti-sperm antibodies, which caused severe male subfertility. By identifying immunoregulatory mechanisms in the testis and epididymis.

Tregs modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, it was reported that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature. It was found that Treg depletion induces severe autoimmune orchitis and epididymitis, manifested by an exacerbated immune cell infiltration [CD4 T cells, monocytes, and mononuclear phagocytes (MPs)] and the development of anti-sperm antibodies (ASA).

In Treg-depleted mice, MPs increased projections toward the epididymal lumen as well as invading the lumen. ASA-bound sperm enhance sperm agglutination and might facilitate sperm phagocytosis. Tolerance breakdown impaired epididymal epithelial function and altered extracellular vesicle cargo, both of which play crucial roles in the acquisition of sperm fertilizing ability and subsequent embryo development. The affected mice had reduced sperm number and motility and severe fertility defects.

Deciphering these immunoregulatory mechanisms may lead to the development of therapies for infertility and identifying potential targets for immuno-contraception. Ultimately, such knowledge fills gaps related to reproductive mucosa, which is an understudied facet of human male health.

References:

https://www.pnas.org/doi/10.1073/pnas.2306797120

https://pubmed.ncbi.nlm.nih.gov/24048122/

https://pubmed.ncbi.nlm.nih.gov/34845322/

https://pubmed.ncbi.nlm.nih.gov/29648649/

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Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Posted in Acute Myocardial Infarction, Adaptive Immune Response to Biomaterials and Tissue Repair, Advanced Drug Manufacturing Technology, Amino acids, Apoptosis, Apoptosis, Artificial intelligence applications for cardiology, Artificial Intelligence in Medicine - Application for Diagnosis, Artificial Intelligence in Medicine - Applications in Therapeutics, Atherogenic Processes & Pathology, Autoimmune Inflammatory DIseases, Autologous Cell Therapy, Automated Cell Processing, Autophagosome, Autophagy, Autophagy-Modulating Proteins, “Antibody–enzyme conjugates”, Bio Instrumentation in Experimental Life Sciences Research, Biochemical pathways, Bioengineering & reverse engineering design, Biological Engineering, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Ca2+ triggered activation, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cancer - General, Cardiac muscle regeneration, Cardiovascular Pharmacogenomics, Cell Biology, Signaling & Cell Circuits, 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Genomics, Genomic Endocrinology, Genomics Pharmacy, Glycobiology: Biopharmaceutical Production, Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics, Gut Microbiome and Obesity, HTN, HTN in Youth, Human Antibody Response, Human Circulating Antibody Repertoire, Human Immune System in Health and in Disease, Human Sensation and Cellular Transduction: Physiology and Therapeutics, Immuno-Oncology & Genomics, Immunodiagnostics, Immunology, Immunotherapy, Indigent Nutrition, inflammation independent of lipid levels, Inflammatory Pathophysiology, Innovation in Immunology Diagnostics, Inosine nucleotides, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Interviews with Scientific Leaders, Investment in Technological Breakthrough, ion-transporting enzyme, IP Development by LPBI Group Team, Kinase, Lipid metabolism, Lipidomics, Lipids, Liposome, Liver & Digestive Diseases Research, Machine learning in predicting type 2 diabetes, Materials Science & Engineering, Medical and Population Genetics, Meta-analysis of transcriptome data, Metabolism, Metabolomics, Methylation, Microbiologial genetics, microbiome, Microfuidics, Micronutrients, Microvesicle, Molecular Genetics & Pharmaceutical, Mutant Gene Expression, Myocardial adenine nucleotide metabolism, Myocardial Ischemia, Myocardial Metabolism, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Nanotechnology for Drug Delivery, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Nitric Oxide in Health and Disease, Nutrigenomics, Nutrition, Nutrition and Phytochemistry, Nutrition Disorders, Nutritional Supplements: Atherogenesis, Nutritional Supplements: Atherogenesis, lipid metabolism, Obesity, Organic BioElectronics, Origins of Cardiovascular Disease, Pancreatic adenocarcinoma classifier, Patient-centered Medicine, Perioperative Statins at Noncardiac Surgery, Personalized and Precision Medicine & Genomic Research, Phagophore, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmacodynamics and Pharmacokinetics, Pharmacogenomics, Pharmacotherapy and Cell Activity, Pharmacotherapy of Cardiovascular Disease, Phosphatase, Phosphorylase, Phosphorylation, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Precision Cancer Medicine, Protection Against Autoimmune Disease, Protein-energy malnutrition, Proteins, Proteomics, Rare heart rhythm disorders and Long QT syndrome (LQTS), Regenerative Biology and Medicine, RNA Biology, S-nitrosylation, Sensors & Analytics, Signaling, Signaling & Cell Circuits, single cell sequencing, Skeletal muscle regeneration, Small Molecules in Development of Therapeutic Drugs, Statistical Methods for Research Evaluation, Stress Disorders, Stroke, Stroke, Systemic Inflammatory Diseases as CVD Risk, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, therapeutics, Tissue Engineering and Regenerative Medicine, Tissue Microenvironment, Tolerance-inducing Autoimmune Disease Therapeutics, Transcriptomics, Transformative Technologies in Healthcare, Translational Research, tyrosine decarboxylases, Ubiquitin, Ubiquitinylation, Unfolded Protein Response (UPR), Universal Immune Cell Therapies (uICT), Variation in human protein-coding regions, Vascular Diseases, Water Transporters on August 19, 2023| Leave a Comment »

Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Curators:

Cardiovascular Expertise – Dr. Justin D. Pearlman, MD, PhD, FACC
Pharmacology and Oncology Expertise – Dr. Stephen J. Williams, PhD
Principal Investigator, initiator of the project – Aviva Lev-Ari, PhD, RN

THE VOICE of Aviva Lev-Ari, PhD, RN

In this curation we wish to present two breaking through goals:

Goal 1:

Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer

Goal 2:

Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.

According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.

These eight subcellular pathologies can’t be measured at present time.

In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.

Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases

Glycation
Oxidative Stress
Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
Membrane instability
Inflammation in the gut [mucin layer and tight junctions]
Epigenetics/Methylation
Autophagy [AMPKbeta1 improvement in health span]

Diseases that are not Diseases: no drugs for them, only diet modification will help

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

Exercise will not undo Unhealthy Diet

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:

Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL

In the Bioelecronics domain we are inspired by the work of the following three research sources:

Biological and Biomedical Electrical Engineering (B2E2) at Cornell University, School of Engineering https://www.engineering.cornell.edu/bio-electrical-engineering-0
Bioelectronics Group at MIT https://bioelectronics.mit.edu/
The work of Michael Levin @Tufts, The Levin Lab

Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia

Born: 1969 (age 54 years), Moscow, Russia

Education: Harvard University (1992–1996), Tufts University (1988–1992)

Affiliation: University of Cape Town

Research interests: Allergy, Immunology, Cross Cultural Communication

Awards: Cozzarelli prize (2020)

Doctoral advisor: Clifford Tabin

Fields: Developmental biology, synthetic biology

SOURCE

https://www.google.com/search?q=Michael+Levin+%40Tufts&oq=Michael+Levin+%40Tufts&aqs=chrome..69i57j69i58.894128314j0j15&sourceid=chrome&ie=UTF-8

Most recent 20 Publications by Michael Levin, PhD

SOURCE

https://facultyprofiles.tufts.edu/michael-levin-1/publications

SCHOLARLY ARTICLE

The nonlinearity of regulation in biological networks

1 Dec 2023npj Systems Biology and Applications9(1)

Co-authorsManicka S, Johnson K, Levin M…

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10.1038/S41540-023-00273-W

SCHOLARLY ARTICLE

Toward an ethics of autopoietic technology: Stress, care, and intelligence

1 Sep 2023BioSystems231

Co-authorsWitkowski O, Doctor T, Solomonova E…

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10.1016/J.BIOSYSTEMS.2023.104964

SCHOLARLY ARTICLE

Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion

14 Aug 2023Frontiers in Cell and Developmental Biology11:1087650

Co-authorsGrodstein J, McMillen P, Levin M

VIEW PDF

10.3389/FCELL.2023.1087650

SCHOLARLY ARTICLE

Correcting instructive electric potential patterns in multicellular systems: External actions and endogenous processes.

30 Jul 2023Biochim Biophys Acta Gen Subj1867(10):130440

Co-authorsCervera J, Levin M, Mafe S

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10.1016/J.BBAGEN.2023.130440

SCHOLARLY ARTICLE

Regulative development as a model for origin of life and artificial life studies

1 Jul 2023BioSystems229

Co-authorsFields C, Levin M

10.1016/J.BIOSYSTEMS.2023.104927

SCHOLARLY ARTICLE

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences

1 Jul 2023International Journal of Molecular Sciences24(13)

Co-authorsMasuelli S, Real S, McMillen P…

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10.3390/IJMS241311121

SCHOLARLY ARTICLE

Bioelectricidad en agregados multicelulares de células no excitables- modelos biofísicos

Jun 2023Revista Española de Física32(2)

Co-authorsCervera J, Levin M, Mafé S

SCHOLARLY ARTICLE

Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!

1 Jun 2023Bioelectricity5(2):75

Co-authorsDjamgoz MBA, Levin M

10.1089/BIOE.2023.0022.EDITORIAL

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part I: Classical and Quantum Formulations of Active Inference

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):235-245

Co-authorsFields C, Fabrocini F, Friston K…

10.1109/TMBMC.2023.3272150

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part II: Tensor Networks as General Models of Control Flow

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):246-256

Co-authorsFields C, Fabrocini F, Friston K…

10.1109/TMBMC.2023.3272158

SCHOLARLY ARTICLE

Darwin’s agential materials: evolutionary implications of multiscale competency in developmental biology

1 Jun 2023Cellular and Molecular Life Sciences80(6)

Co-authorsLevin M

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10.1007/S00018-023-04790-Z

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

1 Jun 2023Drug Discovery Today28(6)

Co-authorsPio-Lopez L, Levin M

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10.1016/J.DRUDIS.2023.103585

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

Jun 2023DRUG DISCOVERY TODAY28(6):1-13

Co-authorsPio-Lopez L, Levin M

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10.1016/J.DRUDIS.2023.103585THIS

SCHOLARLY ARTICLE

Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine

12 May 2023Patterns4(5)

Co-authorsMathews J, Chang A, Devlin L…

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10.1016/J.PATTER.2023.100737

SCHOLARLY ARTICLE

Making and breaking symmetries in mind and life

14 Apr 2023Interface Focus13(3)

Co-authorsSafron A, Sakthivadivel DAR, Sheikhbahaee Z…

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10.1098/RSFS.2023.0015

SCHOLARLY ARTICLE

The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis

14 Apr 2023Interface Focus13(3)

Co-authorsPio-Lopez L, Bischof J, LaPalme JV…

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10.1098/RSFS.2022.0072

SCHOLARLY ARTICLE

The collective intelligence of evolution and development

Apr 2023Collective Intelligence2(2):263391372311683SAGE Publications

Co-authorsWatson R, Levin M

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10.1177/26339137231168355

SCHOLARLY ARTICLE

Bioelectricity of non-excitable cells and multicellular pattern memories: Biophysical modeling

13 Mar 2023Physics Reports1004:1-31

Co-authorsCervera J, Levin M, Mafe S

10.1016/J.PHYSREP.2022.12.003

SCHOLARLY ARTICLE

There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines

1 Mar 2023Biomimetics8(1)

Co-authorsBongard J, Levin M

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10.3390/BIOMIMETICS8010110

SCHOLARLY ARTICLE

Transplantation of fragments from different planaria: A bioelectrical model for head regeneration

7 Feb 2023Journal of Theoretical Biology558

Co-authorsCervera J, Manzanares JA, Levin M…

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10.1016/J.JTBI.2022.111356

SCHOLARLY ARTICLE

Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind

1 Jan 2023Animal Cognition

Co-authorsLevin M

VIEW PDF

10.1007/S10071-023-01780-3

SCHOLARLY ARTICLE

Biological Robots: Perspectives on an Emerging Interdisciplinary Field

1 Jan 2023Soft Robotics

Co-authorsBlackiston D, Kriegman S, Bongard J…

10.1089/SORO.2022.0142

SCHOLARLY ARTICLE

Cellular Competency during Development Alters Evolutionary Dynamics in an Artificial Embryogeny Model

1 Jan 2023Entropy25(1)

Co-authorsShreesha L, Levin M

VIEW PDF

10.3390/E25010131

SCHOLARLY ARTICLE

Endless forms most beautiful 2.0: teleonomy and the bioengineering of chimaeric and synthetic organisms (July, blac073, 2022)

1 Jan 2023BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY138(1):141

Co-authorsClawson WP, Levin M

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VIEW MORE INFO

10.1093/BIOLINNEAN/BLAC116

SCHOLARLY ARTICLE

Future medicine: from molecular pathways to the collective intelligence of the body

1 Jan 2023Trends in Molecular Medicine

Co-authorsLagasse E, Levin M

10.1016/J.MOLMED.2023.06.007

THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC

PENDING

THE VOICE of Stephen J. Williams, PhD

Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes

25% of US children have fatty liver
Type II diabetes can be manifested from fatty live with 151 million people worldwide affected moving up to 568 million in 7 years
A common myth is diabetes due to overweight condition driving the metabolic disease
There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
Thirty percent of ‘obese’ people just have high subcutaneous fat. the visceral fat is more problematic
there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects. Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
At any BMI some patients are insulin sensitive while some resistant
Visceral fat accumulation may be more due to chronic stress condition
Fructose can decrease liver mitochondrial function
A methionine and choline deficient diet can lead to rapid NASH development

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New studies link cell cycle proteins to immunosurveillance of premalignant cells

Posted in Apoptosis, Biological Networks, Biological Networks, Gene Regulation and Evolution, Cancer - General, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer-Immune Interactions, Cell Biology, Signaling & Cell Circuits, Circulating Tumor Cells (CTC), Disease Biology, DNA repair, Efficacy of Anti-Tumor T Cells, Exosomes, Exosomes: Natural Carriers for siRNA Delivery, Immune Modulatory, Immuno-Oncology & Genomics, Immunology, KRAS Mutation, Modulating Macrophages in Cancer Immunotherapy, NK Cell-Based Cancer Immunotherapy, TP53 - Germline mutations, tagged CDKI, cell cycle, cell cycle arrest, cell cycle protein, cellular senescence, DNA repair or transcription factor genes, Immunology, immunosuppression, immunosurveillance, NF-kB, p21, p53, premalignant, transcriptional, transcriptional regulation, tumor suppressors on December 16, 2021| Leave a Comment »

New studies link cell cycle proteins to immunosurveillance of premalignant cells

Curator: Stephen J. Williams, Ph.D.

The following is from a Perspectives article in the journal Science by Virinder Reen and Jesus Gil called “Clearing Stressed Cells: Cell cycle arrest produces a p21-dependent secretome that initaites immunosurveillance of premalignant cells”. This is a synopsis of the Sturmlechener et al. research article in the same issue (2).

Complex organisms repair stress-induced damage to limit the replication of faulty cells that could drive cancer. When repair is not possible, tissue homeostasis is maintained by the activation of stress response programs such as apoptosis, which eliminates the cells, or senescence, which arrests them (1). Cellular senescence causes the arrest of damaged cells through the induction of cyclin-dependent kinase inhibitors (CDKIs) such as p16 and p21 (2). Senescent cells also produce a bioactive secretome (the senescence-associated secretory phenotype, SASP) that places cells under immunosurveillance, which is key to avoiding the detrimental inflammatory effects caused by lingering senescent cells on surrounding tissues. On page 577 of this issue, Sturmlechner et al. (3) report that induction of p21 not only contributes to the arrest of senescent cells, but is also an early signal that primes stressed cells for immunosurveillance.Senescence is a complex program that is tightly regulated at the epigenetic and transcriptional levels. For example, exit from the cell cycle is controlled by the induction of p16 and p21, which inhibit phosphorylation of the retinoblastoma protein (RB), a transcriptional regulator and tumor suppressor. Hypophosphorylated RB represses transcription of E2F target genes, which are necessary for cell cycle progression. Conversely, production of the SASP is regulated by a complex program that involves super-enhancer (SE) remodeling and activation of transcriptional regulators such as nuclear factor κB (NF-κB) or CCAAT enhancer binding protein–β (C/EBPβ) (4).

Senescence is a complex program that is tightly regulated at the epigenetic and transcriptional levels. For example, exit from the cell cycle is controlled by the induction of p16 and p21, which inhibit phosphorylation of the retinoblastoma protein (RB), a transcriptional regulator and tumor suppressor. Hypophosphorylated RB represses transcription of E2F target genes, which are necessary for cell cycle progression. Conversely, production of the SASP is regulated by a complex program that involves super-enhancer (SE) remodeling and activation of transcriptional regulators such as nuclear factor κB (NF-κB) or CCAAT enhancer binding protein–β (C/EBPβ) (4).

Sturmlechner et al. found that activation of p21 following stress rapidly halted cell cycle progression and triggered an internal biological timer (of ∼4 days in hepatocytes), allowing time to repair and resolve damage (see the figure). In parallel, C-X-C motif chemokine 14 (CXCL14), a component of the PASP, attracted macrophages to surround and closely surveil these damaged cells. Stressed cells that recovered and normalized p21 expression suspended PASP production and circumvented immunosurveillance. However, if the p21-induced stress was unmanageable, the repair timer expired, and the immune cells transitioned from surveillance to clearance mode. Adjacent macrophages mounted a cytotoxic T lymphocyte response that destroyed damaged cells. Notably, the overexpression of p21 alone was sufficient to orchestrate immune killing of stressed cells, without the need of a senescence phenotype. Overexpression of other CDKIs, such as p16 and p27, did not trigger immunosurveillance, likely because they do not induce CXCL14 expression.In the context of cancer, senescent cell clearance was first observed following reactivation of the tumor suppressor p53 in liver cancer cells. Restoring p53 signaling induced senescence and triggered the elimination of senescent cells by the innate immune system, prompting tumor regression (5). Subsequent work has revealed that the SASP alerts the immune system to target preneoplastic senescent cells. Hepatocytes expressing the oncogenic mutant NRAS^G12V (Gly¹²→Val) become senescent and secrete chemokines and cytokines that trigger CD4⁺ T cell–mediated clearance (6). Despite the relevance for tumor suppression, relatively little is known about how immunosurveillance of oncogene-induced senescent cells is initiated and controlled.

Source of image: Reen, V. and Gil, J. Clearing Stressed Cells. Science Perspectives 2021;Vol 374(6567) p 534-535.

References

2. Sturmlechner I, Zhang C, Sine CC, van Deursen EJ, Jeganathan KB, Hamada N, Grasic J, Friedman D, Stutchman JT, Can I, Hamada M, Lim DY, Lee JH, Ordog T, Laberge RM, Shapiro V, Baker DJ, Li H, van Deursen JM. p21 produces a bioactive secretome that places stressed cells under immunosurveillance. Science. 2021 Oct 29;374(6567):eabb3420. doi: 10.1126/science.abb3420. Epub 2021 Oct 29. PMID: 34709885.

Yet another Success Story: Machine Learning to predict immunotherapy response

Posted in Artificial Intelligence - General, Artificial Intelligence Applications in Health Care, Artificial Intelligence in CANCER, Biomarkers & Medical Diagnostics, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer-Immune Interactions, Glioblastoma, Immuno-Oncology & Genomics, Immunology, Immunotherapy, Machine Learning, RNA Biology, Cancer and Therapeutics, tumor microenvironment, tagged biomarkers, Cancer immunotherapy, cell-cell interactions, computational algorithms, immune inhibitory checkpoints, immuno-oncology therapeutics, Machine Learning models, mathematical model, PDL1/PD1 pathway, RNA sequencing, transcription factors, tumor microenvironment on July 6, 2021| Leave a Comment »

Yet another Success Story: Machine Learning to predict immunotherapy response

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Immune-checkpoint blockers (ICBs) immunotherapy appears promising for various cancer types, offering a durable therapeutic advantage. Only a number of cases with cancer respond to this therapy. Biomarkers are required to adequately predict the responses of patients. This article evaluates this issue utilizing a system method to characterize the immune response of the anti-tumor based on the entire tumor environment. Researchers build mechanical biomarkers and cancer-specific response models using interpretable machine learning that predict the response of patients to ICB.

The lymphatic and immunological systems help the body defend itself by combating. The immune system functions as the body’s own personal police force, hunting down and eliminating pathogenic baddies.

Image Source: https://www.genengnews.com/wp-content/uploads/2021/03/Getty_1185598172-T-celFfightingCancerCell.jpg

According to Federica Eduati, Department of Biomedical Engineering at TU/e, “The immune system of the body is quite adept at detecting abnormally behaving cells. Cells that potentially grow into tumors or cancer in the future are included in this category. Once identified, the immune system attacks and destroys the cells.”

Immunotherapy and machine learning are combining to assist the immune system solve one of its most vexing problems: detecting hidden tumorous cells in the human body.

It is the fundamental responsibility of our immune system to identify and remove alien invaders like bacteria or viruses, but also to identify risks within the body, such as cancer. However, cancer cells have sophisticated ways of escaping death by shutting off immune cells. Immunotherapy can reverse the process, but not for all patients and types of cancer. To unravel the mystery, Eindhoven University of Technology researchers used machine learning. They developed a model to predict whether immunotherapy will be effective for a patient using a simple trick. Even better, the model outperforms conventional clinical approaches.

The outcomes of this research are published on 30th June, 2021 in the journal Patterns in an article entitled “Interpretable systems biomarkers predict response to immune-checkpoint inhibitors”.

The Study

Characterization of the tumor microenvironment from RNAseq and prior knowledge
Multi-task machine-learning models for predicting antitumor immune responses
Identification of cancer-type-specific, interpretable biomarkers of immune responses
EaSIeR is a tool to predict biomarker-based immunotherapy response from RNA-seq

**Experimental Strategy (Lapuente-Santana et al., 2021)**
**Image Source:** https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/attachment/815c5676-4343-4b3e-a8db-92ceecf7a464/fx1_lrg.jpg

“Tumor also contains multiple types of immune and fibroblast cells which can play a role in favor of or anti-tumor, and communicates among themselves,” said Oscar Lapuente-Santana, a researcher doctoral student in the computational biology group. “We had to learn how complicated regulatory mechanisms in the micro-environment of the tumor affect the ICB response. We have used RNA sequencing datasets to depict numerous components of the Tumor Microenvironment (TME) in a high-level illustration.”

Using computational algorithms and datasets from previous clinical patient care, the researchers investigated the TME.

Eduati explained

While RNA-sequencing databases are publically available, information on which patients responded to ICB therapy is only available for a limited group of patients and cancer types. So, to tackle the data problem, we used a trick.

All 100 models learned in the randomized cross-validation were included in the EaSIeR tool. For each validation dataset, we used the corresponding cancer-type-specific model: SKCM for the melanoma Gide, Auslander, Riaz, and Liu cohorts; STAD for the gastric cancer Kim cohort; BLCA for the bladder cancer Mariathasan cohort; and GBM for the glioblastoma Cloughesy cohort. To make predictions for each job, the average of the 100 cancer-type-specific models was employed. The predictions of each dataset’s cancer-type-specific models were also compared to models generated for the remaining 17 cancer types.

From the same datasets, the researchers selected several surrogate immunological responses to be used as a measure of ICB effectiveness.

Lapuente-Santana stated

One of the most difficult aspects of our job was properly training the machine learning models. We were able to fix this by looking at alternative immune responses during the training process.

Some of the researchers employed the machine learning approach given in the paper to participate in the “Anti-PD1 Response Prediction DREAM Challenge.”

DREAM is an organization that carries out crowd-based tasks with biomedical algorithms. “We were the first to compete in one of the sub-challenges under the name cSysImmunoOnco team,” Eduati remarks.

The researchers noted,

We applied machine learning to seek for connections between the obtained system-based attributes and the immune response, estimated using 14 predictors (proxies) derived from previous publications. We treated these proxies as individual tasks to be predicted by our machine learning models, and we employed multi-task learning algorithms to jointly learn all tasks.

The researchers discovered that their machine learning model surpasses biomarkers that are already utilized in clinical settings to evaluate ICB therapies.

But why are Eduati, Lapuente-Santana, and their colleagues using mathematical models to tackle a medical treatment problem? Is this going to take the place of the doctor?

Eduati explains

Mathematical models can provide an overview of the interconnection between individual molecules and cells and at the same time predicting a particular patient’s tumor behavior. This implies that immunotherapy with ICB can be personalized in a patient’s clinical setting. The models can aid physicians with their decisions about optimum therapy, it is vital to note that they will not replace them.

Furthermore, the model aids in determining which biological mechanisms are relevant for the biological response.

The researchers noted

Another advantage of our concept is that it does not need a dataset with known patient responses to immunotherapy for model training.

Further testing is required before these findings may be implemented in clinical settings.

Main Source:

Lapuente-Santana, Ó., van Genderen, M., Hilbers, P. A., Finotello, F., & Eduati, F. (2021). Interpretable systems biomarkers predict response to immune-checkpoint inhibitors. Patterns, 100293. https://www.cell.com/patterns/pdfExtended/S2666-3899(21)00126-4

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Inhibitory CD161 receptor recognized as a potential immunotherapy target in glioma-infiltrating T cells by single-cell analysis

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/02/20/inhibitory-cd161-receptor-identified-in-glioma-infiltrating-t-cells-by-single-cell-analysis-2/

Immunotherapy may help in glioblastoma survival

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

https://pharmaceuticalintelligence.com/2019/03/16/immunotherapy-may-help-in-glioblastoma-survival/

Deep Learning for In-silico Drug Discovery and Drug Repurposing: Artificial Intelligence to search for molecules boosting response rates in Cancer Immunotherapy: Insilico Medicine @John Hopkins University

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/17/deep-learning-for-in-silico-drug-discovery-and-drug-repurposing-artificial-intelligence-to-search-for-molecules-boosting-response-rates-in-cancer-immunotherapy-insilico-medicine-john-hopkins-univer/

Machine Learning (ML) in cancer prognosis prediction helps the researcher to identify multiple known as well as candidate cancer diver genes

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/05/04/machine-learning-ml-in-cancer-prognosis-prediction-helps-the-researcher-to-identify-multiple-known-as-well-as-candidate-cancer-diver-genes/

AI System Used to Detect Lung Cancer

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2019/06/28/ai-system-used-to-detect-lung-cancer/

Cancer detection and therapeutics

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/05/02/cancer-detection-and-therapeutics/

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Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM

Reporter: Stephen J. Williams, PhD

New Drugs on the Horizon: Part 3
Introduction

Andrew J. Phillips, C4 Therapeutics

symposium brought by AACR CICR and had about 30 proposals for talks and chose three talks
unfortunately the networking event is not possible but hope to see you soon in good health

ABBV-184: A novel survivin specific T cell receptor/CD3 bispecific therapeutic that targets both solid tumor and hematological malignancies

Edward B Reilly
AbbVie Inc. @abbvie

T-cell receptors (TCR) can recognize the intracellular targets whereas antibodies only recognize the 25% of potential extracellular targets
survivin is expressed in multiple cancers and correlates with poor survival and prognosis
CD3 bispecific TCR to survivn (Ab to CD3 on T- cells and TCR to survivin on cancer cells presented in MHC Class A3)
ABBV184 effective in vivo in lung cancer models as single agent;
in humanized mouse tumor models CD3/survivin bispecific can recruit T cells into solid tumors; multiple immune cells CD4 and CD8 positive T cells were found to infiltrate into tumor
therapeutic window as measured by cytokine release assays in tumor vs. normal cells very wide (>25 fold)
ABBV184 does not bind platelets and has good in vivo safety profile
First- in human dose determination trial: used in vitro cancer cell assays to determine 1st human dose
looking at AML and lung cancer indications
phase 1 trial is underway for safety and efficacy and determine phase 2 dose
survivin has very few mutations so they are not worried about a changing epitope of their target TCR peptide of choice

The discovery of TNO155: A first in class SHP2 inhibitor

Matthew J. LaMarche
Novartis @Novartis

SHP2 is an intracellular phosphatase that is upstream of MEK ERK pathway; has an SH2 domain and PTP domain
knockdown of SHP2 inhibits tumor growth and colony formation in soft agar
55 TKIs there are very little phosphatase inhibitors; difficult to target the active catalytic site; inhibitors can be oxidized at the active site; so they tried to target the two domains and developed an allosteric inhibitor at binding site where three domains come together and stabilize it
they produced a number of chemical scaffolds that would bind and stabilize this allosteric site
block the redox reaction by blocking the cysteine in the binding site
lead compound had phototoxicity; used SAR analysis to improve affinity and reduce phototox effects
was very difficult to balance efficacy, binding properties, and tox by adjusting stuctures
TNO155 is their lead into trials
SHP2 expressed in T cells and they find good combo with I/O with uptick of CD8 cells
TNO155 is very selective no SHP1 inhibition; SHP2 can autoinhibit itself when three domains come together and stabilize; no cross reactivity with other phosphatases
they screened 1.5 million compounds and got low hit rate so that is why they needed to chemically engineer and improve on the classes they found as near hits

Closing Remarks

Xiaojing Wang
Genentech, Inc. @genentech

Follow on Twitter at:

Actemra, immunosuppressive which was designed to treat rheumatoid arthritis but also approved in 2017 to treat cytokine storms in cancer patients SAVED the sickest of all COVID-19 patients

Posted in Antibody Responses Predict Antigen Exposure, COVID-19, Cytokine Receptor Structure, Human Antibody Response, Human Circulating Antibody Repertoire, Human Naive B Cell Repertoire, Immunodiagnostics, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Inflammasome, Innovation in Immunology Diagnostics, MHC Repertoires for Antigen Prediction, Population Health Management, Genetics & Pharmaceutical, Protection Against Autoimmune Disease, SARS-CoV-2, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged Actemra, cytokine storms, immunosuppressive on April 14, 2020| Leave a Comment »

Actemra, immunosuppressive which was designed to treat rheumatoid arthritis but also approved in 2017 to treat cytokine storms in cancer patients SAVED the sickest of all COVID-19 patients

Reporter: Aviva Lev-Ari, PhD, RN

Emergency room doctor, near death with coronavirus, saved with experimental treatment

By RICHARD READ SEATTLE BUREAU CHIEF

APRIL 13, 2020

10:48 PM

Soon after being admitted to his own hospital with a fever, cough and difficulty breathing, he was placed on a ventilator. Five days after that, his lungs and kidneys were failing, his heart was in trouble, and doctors figured he had a day or so to live.

He owes his survival to an elite team of doctors who tried an experimental treatment pioneered in China and used on the sickest of all COVID-19 patients.

Lessons from his dramatic recovery could help doctors worldwide treat other extremely ill COVID-19 patients.

Based on the astronomical level of inflammation in his body and reports written by Chinese and Italian physicians who had treated the sickest COVID-19 patients, the doctors came to believe that it was not the disease itself killing him but his own immune system.

It had gone haywire and began to attack itself — a syndrome known as a “cytokine storm.”

The immune system normally uses proteins called cytokines as weapons in fighting a disease. For unknown reasons in some COVID-19 patients, the immune system first fails to respond quickly enough and then floods the body with cytokines, destroying blood vessels and filling the lungs with fluid.

Dr. Matt Hartman, a cardiologist, said that after four days on the immunosuppressive drug, supplemented by high-dose vitamin C and other therapies, the level of oxygen in Padgett’s blood improved dramatically. On March 23, doctors were able to take him off life support.

Four days later, they removed his breathing tube. He slowly came out of his sedated coma, at first imagining that he was in the top floor of the Space Needle converted to a COVID ward.

https://www.latimes.com/world-nation/story/2020-04-13/coworkers-save-coronavirus-doctor?utm_source=nl&utm_brand=wired&utm_mailing=WIR_Science_041420&utm_campaign=aud-dev&utm_medium=email&utm_term=WIR_Science&bxid=5be9cb353f92a40469de971e&cndid=22119822&esrc=ArticleLinkBottom&source=EDT_WIR_NEWSLETTER_0_SCIENCE_ZZ

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Responses to the COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients

Posted in Cancer - General, Cancer and Current Therapeutics, Cancer Prevention: Research & Programs, Cancer Screening, Cancer-Immune Interactions, COVID-19, Immunotherapy, Infectious Disease & New Antibiotic Targets, interventional oncology, Lung and pulmonology, Neutropenia, Neutrophilia, Patient Experience, Patient Experience: Personal Memories of Invasive Medical Intervantion, Patient Outlook, Population Health Management, Nutrition and Phytochemistry, Pulmonary diseases, Pulmonary pathology, SARS-CoV-2, Support Staff, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV, Voices of Patients and Healthcare Providers, Women Health, tagged cancer adverse event, Cancer Centers of America, cancer chemotherapy, cancer patient advocacy, cancer patient management, covid, COVID-19, hospital and patient, immunosuppression, national cancer institute, National Comprehensive Cancer Network, NCI comprehensive cancer center, patient education, physician and patient, physician-patient relationship, SARS-CoV-2, Virus Infective Acute Respiratory Syndrome: SARS-CoV | Tagged COVID-19 on March 19, 2020| Leave a Comment »

Responses to the #COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients

Curator: Stephen J. Williams, Ph.D.

UPDATED 3/20/2020

Among the people who are identified at risk of coronovirus 2019 infection and complications of the virus include cancer patients undergoing chemotherapy, who in general, can be immunosuppressed, especially while patients are undergoing their treatment. This has created anxiety among many cancer patients as well as their care givers and prompted many oncologist professional groups, cancer societies, and cancer centers to formulate some sort of guidelines for both the cancer patients and the oncology professional with respect to limiting the risk of infection to coronavirus (COVID19).

This information will be periodically updated and we are working to get a Live Twitter Feed to bring oncologist and cancer patient advocacy groups together so up to date information can be communicated rapidly. Please see this page regularly for updates as new information is curated.

IN ADDITION, I will curate a listing of drugs with adverse events of immunosuppression for people who might wonder if the medications they are taking are raising their risk of infections.

Please also see @pharma_BI for updates as well.

Please also see our Coronavirus Portal at https://pharmaceuticalintelligence.com/coronavirus-portal/

For ease of reading information for patients are BOLDED and in RED

ASCO’s Response to COVID-19

From the Cancer Letter: The following is a guest editorial by American Society of Clinical Oncology (ASCO) Executive Vice President and Chief Medical Officer Richard L. Schilsky MD, FACP, FSCT, FASCO. This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.

The worldwide spread of the coronavirus (COVID-19) presents unprecedented challenges to the cancer care delivery system.

Our patients are already dealing with a life-threatening illness and are particularly vulnerable to this viral infection, which can be even more deadly for them. Further, as restrictions in daily movement and social distancing take hold, vulnerable patients may be disconnected from friends, family or other support they need as they manage their cancer.

As providers, we rely on evidence and experience when treating patients but now we face uncertainty. There are limited data to guide us in the specific management of cancer patients confronting COVID-19 and, at present, we have no population-level guidance regarding acceptable or appropriate adjustments of treatment and practice operations that both ensure the best outcome for our patients and protect the safety of our colleagues and staff.

As normal life is dramatically changed, we are all feeling anxious about the extreme economic challenges we face, but these issues are perhaps even more difficult for our patients, many of whom are now facing interruption

As we confront this extraordinary situation, the health and safety of members, staff, and individuals with cancer—in fact, the entire cancer community—is ASCO’s highest priority.

ASCO has been actively monitoring and responding to the pandemic to ensure that accurate information is readily available to clinicians and their patients. Recognizing that this is a rapidly evolving situation and that limited oncology-specific, evidence-based information is available, we are committed to sharing what is known and acknowledging what is unknown so that the most informed decisions can be made.

To help guide oncology professionals as they deal with the impact of coronavirus on both their patients and staff, ASCO has collated questions from its members, posted responses at asco.org and assembled a compendium of additional resources we hope will be helpful as the virus spreads and the disease unfolds. We continue to receive additional questions regarding clinical care and we are updating our FAQs on a regular basis.

We hope this information is helpful even when it merely confirms that there are no certain answers to many questions. Our answers are based on the best available information we identify in the literature, guidance from public health authorities, and input received from oncology and infectious disease experts.

For patients, we have posted a blog by Dr. Merry Jennifer Markham, chair of ASCO’s Cancer Communications Committee. This can be found on Cancer.Net, ASCO’s patient information website, and it provides practical guidance to help patients reduce their risk of exposure, better understand COVID-19 symptoms, and locate additional information.

This blog is available both in English and Spanish. Additional blog posts addressing patient questions will be posted as new questions are received and new information becomes available.

Find below a Tweet from Dr.Markham which includes links to her article on COVID-19 for cancer patients

What do patients with cancer need to know about COVID-19? I've written this piece for @CancerDotNet that might be helpful. In English: https://t.co/UILTXbb1SD In Spanish: https://t.co/gNt4MXHkvC pic.twitter.com/TwRKxpT9zK

— Merry-Jennifer Markham, MD, FACP, FASCO (@DrMarkham) March 11, 2020

https://twitter.com/DrMarkham/status/1237797251038220289?s=20

NCCN’s Response to COVID-19 and COVID-19 Resources

JNCCN: How to Manage Cancer Care during COVID-19 Pandemic

Experts from the Seattle Cancer Care Alliance (SCCA)—a Member Institution of the National Comprehensive Cancer Network® (NCCN®)—are sharing insights and advice on how to continue providing optimal cancer care during the novel coronavirus (COVID-19) pandemic. SCCA includes the Fred Hutchinson Cancer Research Center and the University of Washington, which are located in the epicenter of the COVID-19 outbreak in the United States. The peer-reviewed article sharing best practices is available for free online-ahead-of-print via open access at JNCCN.org.

Coronavirus disease 2019 (COVID-19) Resources for the Cancer Care Community

NCCN recognizes the rapidly changing medical information relating to COVID-19 in the oncology ecosystem, but understands that a forum for sharing best practices and specific institutional responses may be helpful to others. Therefore, we are expeditiously providing documents and recommendations developed by NCCN Member Institutions or Guideline Panels as resources for oncology care providers. These resources have not been developed or reviewed by the standard NCCN processes, and are provided for information purposes only. We will post more resources as they become available so check back for additional updates.

Documents

National Cancer Institute Response to COVID-19

More information at https://www.cancer.gov/contact/emergency-preparedness/coronavirus

What people with cancer should know: https://www.cancer.gov/coronavirus

Get the latest public health information from CDC: https://www.coronavirus.gov

Get the latest research information from NIH: https://www.nih.gov/coronavirus

Coronavirus: What People with Cancer Should Know

ON THIS PAGE

Both the resources at cancer.gov (NCI) as well as the resources from ASCO are updated as new information is evaluated and more guidelines are formulated by members of the oncologist and cancer care community and are excellent resources for those living with cancer, and also those who either care for cancer patients or their family and relatives.

Related Resources for Patients (please click on links)

Children with Cancer: A Guide for Parents

3 Steps Toward Preventing Infections During Cancer Treatment – CDC

Some resources and information for cancer patients from Twitter

Twitter feeds which may be useful sources of discussion and for cancer patients include:

@OncLive OncLive.com includes healthcare information for patients and includes videos and newsletters

Oncology-Based Organizations Take Action to Prevent Spread of Coronavirus #COVID19 #COVID2019 #oncology https://t.co/EDTX3eLaMI

— OncLive.com (@OncLive) March 17, 2020

@DrMarkham Dr. Markham is Chief of Heme-Onc & gyn med onc @UF | AD Med Affairs @UFHealthCancer and has collected very good information for patients concerning #Covid19

What do patients with cancer need to know about COVID-19? I've written this piece for @CancerDotNet that might be helpful. In English: https://t.co/UILTXbb1SD In Spanish: https://t.co/gNt4MXHkvC pic.twitter.com/TwRKxpT9zK

— Merry-Jennifer Markham, MD, FACP, FASCO (@DrMarkham) March 11, 2020

@DrMaurieMarkman Dr. Maurie Markman is President of Medicine and Science (Cancer Centers of America, Philadelphia) @CancerCenter #TreatThePerson #Oncology #Genomics #PrecisionMedicine and hosts a great online live Tweet feed discussing current topics in cancer treatment and care for patients called #TreatThePerson Chat

Cancer patients on chemotherapy concerned about traveling for treatment during the #COVID19 crisis may have another option. Find out about the pros and cons of taking an oral medication. https://t.co/4djwfji5WR #CTCABlog

— CTCA, part of City of Hope (@CancerCenter) March 19, 2020

UPDATED 3/20/2020 INFORMATION FROM NCI DESIGNATED CANCER CENTERS FOR PATIENTS/PROVIDERS

The following is a listing with links of NCI Designated Comprehensive Cancer Centers and some select designated Cancer Centers* which have information on infectious risk guidance for cancer patients as well as their physicians and caregivers. There are 51 NCI Comprehensive Cancer Centers and as more cancer centers formulate guidance this list will be updated.

Cancer Center	State	Link to COVID19 guidance
City of Hope	CA	Advice for cancer patients, survivors and caregivers
Jonsson Cancer Center at UCLA	CA	Cancer and COVID19
UCSF Hellen Diller Family Comprehensive Cancer	CA	COVID-19 Links for Patients and Providers
Lee Moffit	FL	Protecting against Coronavirus 19
University of Kansas Cancer Center*	KS	COVID19 Info for patients
Barbara & Karmanos Cancer Institute (Wayne State)	MI	COVID19 Resources
Rogel Cancer Center (Univ of Michigan)	MI	COVID19 Patient Specific Guidelines
Alvin J. Siteman Cancer Center	(MO)	Coronavirus
Fred & Pamela Buffet CC*	NE	Resources for Patients and Providers
Rutgers Cancer Institute of NJ	NJ	What patients should know about COVID19
Memorial Sloan Kettering	NY	What COVID19 means for cancer patients
Herbert Irving CC (Columbia University)	NY	Coronavirus Resource Center
MD Anderson Cancer	TX	Planning for Patients, Providers
Hunstman Cancer Center	UT	COVID19 What you need to know
Fred Hutchinson	WA	COVID19 What patients need to know

Please also see related information on Coronavirus 2019 and Cancer and Immunotherapy at the following links on the Open Access Online Journal:

Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery

https://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/volume-two-immunotherapy-in-cancer-radiation-oncology/

AND

Coronavirus Portal

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Structure-guided Drug Discovery: (1) The Coronavirus 3CL hydrolase (Mpro) enzyme (main protease) essential for proteolytic maturation of the virus and (2) viral protease, the RNA polymerase, the viral spike protein, a viral RNA as promising two targets for discovery of cleavage inhibitors of the viral spike polyprotein preventing the Coronavirus Virion the spread of infection

Posted in Antibody Responses Predict Antigen Exposure, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, COVID-19, Immunodiagnostics, Immunology, Innovation in Immunology Diagnostics, MHC Repertoires for Antigen Prediction, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Viral diseases, Virology - Vector-borne DIsease, tagged BioIT: BioInformatics, Biological Engineering, Biological Networks, Biomarkers & Medical Diagnostics, Cancer Informatics, Clinical & Translational, clinical genomics, Commercialization, COVID-19, Gene Regulation and Evolution, Genetics & Pharmaceutical, Immunotherapy, Innovation in Immunology Diagnostics, Innovations, Intellectual property, Investment in Technological Breakthrough, NGS, Pharmaceutical R&D Informatics, Population Health Management, Proteomics, SARS-CoV, SARS-CoV-2, Universal Immune Cell Therapies (uICT), Virus Infective Acute Respiratory Syndrome: SARS-CoV | Tagged COVID-19 on March 12, 2020| Leave a Comment »

Structure-guided Drug Discovery: (1) The Coronavirus 3CL hydrolase (Mpro) enzyme (main protease) essential for proteolytic maturation of the virus and (2) viral protease, the RNA polymerase, the viral spike protein, a viral RNA as promising two targets for discovery of cleavage inhibitors of the viral spike polyprotein preventing the Coronavirus Virion the spread of infection

Curators and Reporters: Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN

Therapeutical options to coronavirus (2019-nCoV) include consideration of the following:

(a) Monoclonal and polyclonal antibodies

(b) Vaccines

(c) Small molecule treatments (e.g., chloroquinolone and derivatives), including compounds already approved for other indications

(d) Immuno-therapies derived from human or other sources

Structure of the nCoV trimeric spike

The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. [Bold Face Added by ALA]

Science, this issue p. 1260

Abstract

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp¹,*,
Nianshuang Wang¹,*,
Kizzmekia S. Corbett²,
Jory A. Goldsmith¹,
Ching-Lin Hsieh¹,
Olubukola Abiona²,
Barney S. Graham²,
Jason S. McLellan ¹,†

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
²Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

↵†Corresponding author. Email: jmclellan@austin.utexas.edu

↵* These authors contributed equally to this work.

Science 13 Mar 2020:
Vol. 367, Issue 6483, pp. 1260-1263
DOI: 10.1126/science.abb2507

02/04/2020

New Coronavirus Protease Structure Available

PDB data provide a starting point for structure-guided drug discovery

A high-resolution crystal structure of COVID-19 (2019-nCoV) coronavirus 3CL hydrolase (Mpro) has been determined by Zihe Rao and Haitao Yang’s research team at ShanghaiTech University. Rapid public release of this structure of the main protease of the virus (PDB 6lu7) will enable research on this newly-recognized human pathogen.

Recent emergence of the COVID-19 coronavirus has resulted in a WHO-declared public health emergency of international concern. Research efforts around the world are working towards establishing a greater understanding of this particular virus and developing treatments and vaccines to prevent further spread.

https://doi.org/10.2210/pdb6lu7/pdb

While PDB entry 6lu7 is currently the only public-domain 3D structure from this specific coronavirus, the PDB contains structures of the corresponding enzyme from other coronaviruses. The 2003 outbreak of the closely-related Severe Acute Respiratory Syndrome-related coronavirus (SARS) led to the first 3D structures, and today there are more than 200 PDB structures of SARS proteins. Structural information from these related proteins could be vital in furthering our understanding of coronaviruses and in discovery and development of new treatments and vaccines to contain the current outbreak.

The coronavirus 3CL hydrolase (Mpro) enzyme, also known as the main protease, is essential for proteolytic maturation of the virus. It is thought to be a promising target for discovery of small-molecule drugs that would inhibit cleavage of the viral polyprotein and prevent spread of the infection.

Comparison of the protein sequence of the COVID-19 coronavirus 3CL hydrolase (Mpro) against the PDB archive identified 95 PDB proteins with at least 90% sequence identity. Furthermore, these related protein structures contain approximately 30 distinct small molecule inhibitors, which could guide discovery of new drugs. Of particular significance for drug discovery is the very high amino acid sequence identity (96%) between the COVID-19 coronavirus 3CL hydrolase (Mpro) and the SARS virus main protease (PDB 1q2w). Summary data about these closely-related PDB structures are available (CSV) to help researchers more easily find this information. In addition, the PDB houses 3D structure data for more than 20 unique SARS proteins represented in more than 200 PDB structures, including a second viral protease, the RNA polymerase, the viral spike protein, a viral RNA, and other proteins (CSV).

Public release of the COVID-19 coronavirus 3CL hydrolase (Mpro), at a time when this information can prove most vital and valuable, highlights the importance of open and timely availability of scientific data. The wwPDB strives to ensure that 3D biological structure data remain freely accessible for all, while maintaining as comprehensive and accurate an archive as possible. We hope that this new structure, and those from related viruses, will help researchers and clinicians address the COVID-19 coronavirus global public health emergency.

Update: Released COVID-19-related PDB structures include

PDB structure 6lu7 (X. Liu, B. Zhang, Z. Jin, H. Yang, Z. Rao Crystal structure of COVID-19 main protease in complex with an inhibitor N3 doi: 10.2210/pdb6lu7/pdb) Released 2020-02-05

PDB structure 6vsb (D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.-L. Hsieh, O. Abiona, B.S. Graham, J.S. McLellan (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Science doi: 10.1126/science.abb2507) Released 2020-02-26

PDB structure 6lxt (Y. Zhu, F. Sun Structure of post fusion core of 2019-nCoV S2 subunit doi: 10.2210/pdb6lxt/pdb) Released 2020-02-26

PDB structure 6lvn (Y. Zhu, F. Sun Structure of the 2019-nCoV HR2 Domain doi: 10.2210/pdb6lvn/pdb) Released 2020-02-26

PDB structure 6vw1
J. Shang, G. Ye, K. Shi, Y.S. Wan, H. Aihara, F. Li Structural basis for receptor recognition by the novel coronavirus from Wuhan doi: 10.2210/pdb6vw1/pdb
Released 2020-03-04

PDB structure 6vww
Y. Kim, R. Jedrzejczak, N. Maltseva, M. Endres, A. Godzik, K. Michalska, A. Joachimiak, Center for Structural Genomics of Infectious Diseases Crystal Structure of NSP15 Endoribonuclease from SARS CoV-2 doi: 10.2210/pdb6vww/pdb
Released 2020-03-04

PDB structure 6y2e
L. Zhang, X. Sun, R. Hilgenfeld Crystal structure of the free enzyme of the SARS-CoV-2 (2019-nCoV) main protease doi: 10.2210/pdb6y2e/pdb
Released 2020-03-04

PDB structure 6y2f
L. Zhang, X. Sun, R. Hilgenfeld Crystal structure (monoclinic form) of the complex resulting from the reaction between SARS-CoV-2 (2019-nCoV) main protease and tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate (alpha-ketoamide 13b) doi: 10.2210/pdb6y2f/pdb
Released 2020-03-04

PDB structure 6y2g
L. Zhang, X. Sun, R. Hilgenfeld Crystal structure (orthorhombic form) of the complex resulting from the reaction between SARS-CoV-2 (2019-nCoV) main protease and tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate (alpha-ketoamide 13b) doi: 10.2210/pdb6y2g/pdb
Released 2020-03-04

SOURCE – 02/04/2020

https://www.wwpdb.org/news/news?year=2020&fbclid=IwAR0mFKQD7KX29hkJcnV0MxeAe_1themx7KuBDo8txaMiYHJ08JvNN0cisug#5e39e03fa5007a04a313edc3

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease

Kevin J. Clerkin , Justin A. Fried, Jayant Raikhelkar, Gabriel Sayer, Jan M. Griffin, Amirali Masoumi, Sneha S. Jain, Daniel Burkhoff, Deepa Kumaraiah, LeRoy Rabbani, Allan Schwartz

and

Nir Uriel

Originally published 21 Mar 2020 https://doi.org/10.1161/CIRCULATIONAHA.120.046941 Circulation. ;0:null

Abstract

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting nearly 170 countries/regions and more than 285,000 patients worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which invades cells through the angiotensin converting enzyme 2 (ACE2) receptor. Among those with COVID-19, there is a higher prevalence of cardiovascular disease and more than 7% of patients suffer myocardial injury from the infection (22% of the critically ill). Despite ACE2 serving as the portal for infection, the role of ACE inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, impacting donor selection, immunosuppression, and post-transplant management. Thankfully there are a number of promising therapies under active investigation to both treat and prevent COVID-19. Key Words: COVID-19; myocardial injury; pandemic; heart transplant

SOURCE

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.046941

ACE2

Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW (Apr 2004). “ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis”. The Journal of Biological Chemistry. 279 (17): 17996–8007. doi:10.1074/jbc.M311191200. PMID 14754895.

Turner AJ, Tipnis SR, Guy JL, Rice G, Hooper NM (Apr 2002). “ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors”. Canadian Journal of Physiology and Pharmacology. 80 (4): 346–53. doi:10.1139/y02-021. PMID 12025971.

Zhang, Haibo; Penninger, Josef M.; Li, Yimin; Zhong, Nanshan; Slutsky, Arthur S. (3 March 2020). “Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target”. Intensive Care Medicine. Springer Science and Business Media LLC. doi:10.1007/s00134-020-05985-9. ISSN 0342-4642. PMID 32125455.

^ Gurwitz, David (2020). “Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics”. Drug Development Research. doi:10.1002/ddr.21656. PMID 32129518.

Angiotensin converting enzyme 2 (ACE2)

is an exopeptidase that catalyses the conversion of angiotensin I to the nonapeptide angiotensin[1-9]^[5] or the conversion of angiotensin II to angiotensin 1-7.^[6]^[7] ACE2 has direct effects on cardiac function^a and is expressed predominantly in vascular endothelial cells of the heart and the kidneys.^[8] ACE2 is not sensitive to the ACE inhibitor drugs used to treat hypertension.^[9]

ACE2 receptors have been shown to be the entry point into human cells for some coronaviruses, including the SARS virus.^[10] A number of studies have identified that the entry point is the same for SARS-CoV-2,^[11] the virus that causes COVID-19.^[12]^[13]^[14]^[15]

Some have suggested that a decrease in ACE2 could be protective against Covid-19 disease^[16], but others have suggested the opposite, that Angiotensin II receptor blocker drugs could be protective against Covid-19 disease via increasing ACE2, and that these hypotheses need to be tested by datamining of clinical patient records.^[17]

REFERENCES

https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2

FOLDING@HOME TAKES UP THE FIGHT AGAINST COVID-19 / 2019-NCOV

February 27, 2020

by Greg Bowman

We need your help! Folding@home is joining researchers around the world working to better understand the 2019 Coronavirus (2019-nCoV) to accelerate the open science effort to develop new life-saving therapies. By downloading Folding@Home, you can donate your unused computational resources to the Folding@home Consortium, where researchers working to advance our understanding of the structures of potential drug targets for 2019-nCoV that could aid in the design of new therapies. The data you help us generate will be quickly and openly disseminated as part of an open science collaboration of multiple laboratories around the world, giving researchers new tools that may unlock new opportunities for developing lifesaving drugs.

2019-nCoV is a close cousin to SARS coronavirus (SARS-CoV), and acts in a similar way. For both coronaviruses, the first step of infection occurs in the lungs, when a protein on the surface of the virus binds to a receptor protein on a lung cell. This viral protein is called the spike protein, depicted in red in the image below, and the receptor is known as ACE2. A therapeutic antibody is a type of protein that can block the viral protein from binding to its receptor, therefore preventing the virus from infecting the lung cell. A therapeutic antibody has already been developed for SARS-CoV, but to develop therapeutic antibodies or small molecules for 2019-nCoV, scientists need to better understand the structure of the viral spike protein and how it binds to the human ACE2 receptor required for viral entry into human cells.

Proteins are not stagnant—they wiggle and fold and unfold to take on numerous shapes. We need to study not only one shape of the viral spike protein, but all the ways the protein wiggles and folds into alternative shapes in order to best understand how it interacts with the ACE2 receptor, so that an antibody can be designed. Low-resolution structures of the SARS-CoV spike protein exist and we know the mutations that differ between SARS-CoV and 2019-nCoV. Given this information, we are uniquely positioned to help model the structure of the 2019-nCoV spike protein and identify sites that can be targeted by a therapeutic antibody. We can build computational models that accomplish this goal, but it takes a lot of computing power.

This is where you come in! With many computers working towards the same goal, we aim to help develop a therapeutic remedy as quickly as possible. By downloading Folding@home here [LINK] and selecting to contribute to “Any Disease”, you can help provide us with the computational power required to tackle this problem. One protein from 2019-nCoV, a protease encoded by the viral RNA, has already been crystallized. Although the 2019-nCoV spike protein of interest has not yet been resolved bound to ACE2, our objective is to use the homologous structure of the SARS-CoV spike protein to identify therapeutic antibody targets.

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus virus was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019.

Image and Caption Credit: Alissa Eckert, MS; Dan Higgins, MAM available at https://phil.cdc.gov/Details.aspx?pid=23311

Structures of the closely related SARS-CoV spike protein bound by therapeutic antibodies may help rapidly design better therapies. The three monomers of the SARS-CoV spike protein are shown in different shades of red; the antibody is depicted in green. [PDB: 6NB7 https://www.rcsb.org/structure/6nb7]

(post authored by Ariana Brenner Clerkin)

References:

PDB 6lu7 structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI https://www.ebi.ac.uk/pdbe/entry/pdb/6lu7 (accessed Feb 5, 2020).

Tian, X.; Li, C.; Huang, A.; Xia, S.; Lu, S.; Shi, Z.; Lu, L.; Jiang, S.; Yang, Z.; Wu, Y.; et al. Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody; preprint; Microbiology, 2020. https://doi.org/10.1101/2020.01.28.923011.

Walls, A. C.; Xiong, X.; Park, Y. J.; Tortorici, M. A.; Snijder, J.; Quispe, J.; Cameroni, E.; Gopal, R.; Dai, M.; Lanzavecchia, A.; et al. Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. Cell 2019, 176, 1026-1039.e15. https://doi.org/10.2210/pdb6nb7/pdb.

SOURCE

https://foldingathome.org/2020/02/27/foldinghome-takes-up-the-fight-against-covid-19-2019-ncov/

UPDATED 3/13/2020

I am reposting the following Science blog post from Derrick Lowe as is and ask people go browse through the comments on his Science blog In the Pipeline because, as Dr. Lowe states that in this current crisis it is important to disseminate good information as quickly as possible so wanted the readers here to have the ability to read his great posting on this matter of Covid-19. Also i would like to direct readers to the journal Science opinion letter concerning how important it is to rebuild the trust in good science and the scientific process. The full link for the following In the Pipeline post is: https://blogs.sciencemag.org/pipeline/archives/2020/03/06/covid-19-small-molecule-therapies-reviewed

A Summary of current potential repurposed therapeutics for COVID-19 Infection from In The Pipeline: A Science blog from Derick Lowe

Covid-19 Small Molecule Therapies Reviewed

By Derek Lowe 6 March, 2020

Let’s take inventory on the therapies that are being developed for the coronavirus epidemic. Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they’re making all their Covid-19 content free to all readers during this crisis. I’d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world.

The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons. The Biocentury list doesn’t cover these, but here’s an article at Nature Biotechnology that goes into detail. Clinical trials are a huge time sink – they sort of have to be, in most cases, if they’re going to be any good – and if you’ve already done all that stuff it’s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease. So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right. This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses. That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit.

The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524. It mechanism of action is to get incorporated into viral RNA, since it’s taken up by RNA polymerase and it largely seems to evade proofreading. This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited.

There are five clinical trials underway (here’s an overview at Biocentury). The NIH has an adaptive-design Phase II trial that has already started in Nebraska, with doses to be changed according to Bayesian readouts along the way. There are two Phase III trials underway at China-Japan Friendship Hospital in Hubei, double-blinded and placebo-controlled (since placebo is, as far as drug therapy goes, the current standard of care). And Gilead themselves are starting two open-label trials, one with no control arm and one with an (unblinded) standard-of-care comparison arm. Those might read out first, depending on when they get off the ground, but will be only rough readouts due to the fast-and-loose trial design. The two Hubei trials and the NIH one will add some rigor to the process, but I’m not sure when they’re going to report. My personal opinion is that I like the chances of this drug more than anything else on this list, but it’s still unlikely to be a game-changer.

There’s an RNA polymerase inhibitor (favipiravir) from Toyama, at right, that’s in a trial in China. It’s a thought – a broad-spectrum agent of this sort would be the sort of thing to try. But unfortunately, from what I can see, it has already turned up as ineffective in in vitro tests. The human trial that’s underway is honestly the sort of thing that would only happen under circumstances like the present: a developing epidemic with a new pathogen and no real standard of care. I hold out little hope for this one, but given that there’s nothing else at present, it probably should be tried. As you’ll see, this is far from the only situation like this.

One of the screens of known drugs in China that also flagged remdesivir noted that the old antimalarial drug chloroquine seemed to be effective in vitro. It had been reported some years back as a possible antiviral, working through more than one mechanism, probably both at viral entry and intracellularly thereafter. That part shouldn’t be surprising – chloroquine’s actual mode(s) of action against malaria parasites are still not completely worked out, either, and some of what people thought they knew about it has turned out to be wrong. There are several trials underway with it at Chinese facilities, some in combination with other agents like remdesivir. Chloroquine has of course been taken for many decades as an antimalarial, but it has a number of liabilities, including seizures, hearing damage, retinopathy and sudden effects on blood glucose. So it’s going to be important to establish just how effective it is and what doses will be needed. Just as with vaccine candidates, it’s possible to do more harm with a rushed treatment than the disease is doing itself

There are several other known antiviral drugs are being tried in China, but I don’t have too much hope for those, either. The neuraminidase inhibitors such as oseltamivir (better known as Tamiflu) were tried against SARS and were ineffective; there is no reason to expect anything versus Covid-19 although these drugs are a component of some drug cocktail trials. The HIV protease therapies such as darunavir and the combination therapy Kaletra are in trials, but that’s also a rather desperate long shot, since there’s no particular reason to think that they will have any such protease inhibition against what this new virus has to offer (and indeed, such agents weren’t much help against SARS in the end, either). The classic interferon/ribavirin combination seems to have had some activity against SARS and MERS, and is in two trials from what I can see. That’s not an awful idea by any means, but it’s not a great one, either: if your viral disease has interferon/ribavirin as a front line therapy, it generally means that there’s nothing really good available. No, unless we get really lucky none of these ideas are going to slow the disease down much.

There are a few other repurposed-protease-inhibitors ideas out there, such as this one. (Edit: I had seen this paper but couldn’t track it down, so thanks to those who sent it along). This paper suggests that the TMPRSS2 protease is important for viral entry on the human-cell-side of the process, a pathway that has been noted for other coronaviruses. And it points out that there is a an approved inhibitor (in Japan) for this enzyme (camostat), so that would definitely seem to be worth a trial, probably in combination with remdesivir.

That’s about it for the existing small molecules, from what I can see. What about new ones? Don’t hold your breath, is all I can say. A drug discovery program from scratch against a new pathogen is, as many readers here well know, not a trivial exercise. As this Bloomberg article details, many such efforts in the past (small molecules and vaccines alike) have come to grief because by the time they had anything to deliver the epidemic itself had passed. Indeed, Gilead’s remdesivir had already been dropped as a potential Ebola therapy.

You will either need to have a target in mind up front or go phenotypic. For the former, what you’d see are better characterizations of the viral protease and more extensive screens against it. Two other big target areas are viral entry (which involves the “spike” proteins on the virus surface and the ACE2 protein on human cells) and viral replication. To the former, it’s worth quickly noting that ACE2 is so much unlike the more familiar ACE protein that none of the cardiovascular ACE inhibitors do anything to it at all. And targeting the latter mechanisms is how remdesivir was developed as a possible Ebola agent, but as you can see, that took time, too. Phenotypic screens are perfectly reasonable against viral pathogens as well, but you’ll need to put time and effort into that assay up front, just as with any phenotypic effort, because as anyone who does that sort of work will tell you, a bad phenotypic screen is a complete waste of everyone’s time.

One of the key steps for either route is identifying an animal model. While animal models of infectious disease can be extremely well translated to human therapy, that doesn’t happen by accident: you need to choose the right animal. Viruses in general (and coronaviruses are no exception) vary widely in their effects in different species, and not just across the gaps of bird/reptile/human and the like. No, you’ll run into things where even the usual set of small mammals are acting differently from each other, with some of them not even getting sick at all. This current virus may well have gone through a couple of other mammalian species before landing on us, but you’ll note that dogs (to pick one) don’t seem to have any problem with it.

All this means that any new-target new-chemical-matter effort against Covid-19 (or any new pathogen) is going to take years, and there is just no way around that. Update: see here for just such an effort to start finding fragment hits for the viral protease. This puts small molecules in a very bimodal distribution: you have the existing drugs that might be repurposed, and are presumably available right now. Nothing else is! At the other end, for completely new therapies you have the usual prospects of drug discovery: years from now, lots of money, low success rate, good luck to all of us. The gap between these two could in theory be filled by vaccines and antibody therapies (if everything goes really, really well) but those are very much their own area and will be dealt with in a separate post.

Either way, the odds are that we (and I mean “we as a species” here) are going to be fighting this epidemic without any particularly amazing pharmacological weapons. Eventually we’ll have some, but I would advise people, pundits, and politicians not to get all excited about the prospects for some new therapies to come riding up over the hill to help us out. The odds of that happening in time to do anything about the current outbreak are very small. We will be going for months, years, with the therapeutic options we have right now. Look around you: what we have today is what we have to work with.

19th Annual Koch Institute Summer Symposium on Cancer Immunotherapy, June 12, 2020 at MIT’s Kresge Auditorium

Posted in Cancer-Immune Interactions, Conference Coverage with Social Media, Immuno-Oncology & Genomics on February 16, 2020| Leave a Comment »

19th Annual Koch Institute Summer Symposium on Cancer Immunotherapy, June 12, 2020 at MIT’s Kresge Auditorium

Reporter: Aviva Lev-Ari, PhD, RN

Summer Symposium 2020

Engineering the Next Wave of Immunotherapy

The 19th Annual Koch Institute Summer Symposium on June 12, 2020 at MIT’s Kresge Auditorium will focus on cancer immunotherapy.

Cancer immunotherapy has revolutionized the landscape of cancer treatment, our thinking of tumor biology and clinical practice. Following the groundbreaking successes of checkpoint blockade therapy and CAR T cell therapy, culminating in multiple FDA-approved treatments and the awarding of the 2018 Nobel Prize in Medicine to Jim Allison and Tasuku Honjo, the field is currently at a critical juncture.

While checkpoint blockade therapy has demonstrated that the immune system can be harnessed to fight cancer, the next generation of treatments will require us to understand what causes resistance in non-responders, how this can be overcome, and how these issues are best addressed clinically. Discussing these questions will be at the core of this symposium as we move towards our ultimate goal to increase the number of patients benefiting from immunotherapy.

Session Speakers

Targeting T Cells
Rafi Ahmed, Michael Dougan, Chris Love

Thinking Beyond T Cells
Angelika Amon, Yasemine Belkaid, Stefani Spranger

Engineering Clinical Translation
Nina Bhardwaj, Chris Garcia

Panel Discussion: Clinical Translation: A Real Life Perspective

Daniel Chen, Howard Kaufman, Kimberly Schaefer-Weaver
Moderator: Steven Silverstein

SOURCE

https://ki.mit.edu/news/events/symposium/2020

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