Advertisements
Feeds:
Posts
Comments

Archive for the ‘Pharmaceutical Drug Discovery’ Category


Real Time Coverage @BIOConvention #BIO2019: Gene Therapy 2.0: No Longer Science Fiction 1:00-2:15 pm June 3 Philadelphia PA

Reporter: Stephen J. Williams Ph.D. @StephenJWillia2

kkjk

Other Articles on Gene Therapy on this Open Access Journal Include:

Advertisements

Read Full Post »


eProceedings – Day 1: Charles River Laboratories – 3rd World Congress, Delivering Therapies to the Clinic Faster, September 23 – 24, 2019, 25 Edwin H. Land Boulevard, Cambridge, MA

 

https://events.criver.com/event/9eab0ee1-982e-42c6-a4cd-fb43f9f2f1d0/confirmation:7c68cf9b-c599-469e-b602-42178c77e4f9

 

ANNOUNCEMENT

 

Leaders in Pharmaceutical Business Intelligence (LPBI) Group will cover this event in Real Time for pharmaceuticalintelligence.com 

Confirmation Number: 8ZNCBYNGHCK

In attendance generating in realtime event’s eProceeding and social media coverage by

 

Aviva Lev-Ari, PhD, RN

Director & Founder

Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

Editor-in-Chief

http://pharmaceuticalintelligence.com 

e-Mail: avivalev-ari@alum.berkeley.edu

(M) 617-775-0451

https://cal.berkeley.edu/AvivaLev-Ari,PhD,RN

SkypeID: HarpPlayer83          LinkedIn Profile        Twitter Profile

#crlworldcon

@CRiverLabs

@pharma_BI

@AVIVA1950

 

 

Join us this year as we explore novel approaches to drug development that effectively reduce program timelines and accelerate delivery to the clinic. Using a variety of case studies, our speakers will illustrate methods that successfully cut time to market and highlight how artificial intelligence and genomics are expediting target discovery and drug development. In an agenda that includes presentations, panel discussions, and short technology demonstrations, you will learn how the latest science and regulatory strategies are helping us get drugs to patients faster than ever.

AGENDA

Day One, September 23, 2019

  • Novel approaches to silence disease drivers
  • The role of AI in expediting drug discovery

Monday, September 23

8:30 – 9:00 a.m. Introduction and Welcome Remarks James C. Foster, Chairman of the Board, President, and Chief Executive Officer, Charles River
9:00 – 9:30 a.m. 2019 Award Winner: A Silicon Valley Approach to Understanding and Treating Disease Matt Wilsey, Chairman, President, and Co-Founder, Grace Science Foundation
9:30 – 10:15 a.m. Keynote Session Brian Hubbard, PhD, Chief Executive Officer, Dogma Therapeutics
10:15 – 10:30 a.m. Break
10:30 – 11:15 a.m. Novel Approaches to Silence Disease Drivers Systemic Delivery of Investigational RNAi Therapeutics: Safety Considerations and Clinical Outcomes Peter Smith, PhD, Senior Vice President, Early Development, Alnylam Pharmaceuticals
11:15 a.m. – 12:00 p.m. Novel Approaches to Silence Disease Drivers: Considerations for Viral Vector Manufacturing to Support Product Commercialization Richard Snyder, PhD, Chief Scientific Officer and Founder, Brammer Bio
12:00 – 1:00 p.m. Lunch
1:00 – 1:45 p.m. Accelerating Drug Discovery Through the Power of Microscopy Images Anne E. Carpenter, Ph.D., Institute Scientist, Sr. Director, Imaging Platform, Merkin Institute Fellow, Broad Institute of Harvard and MIT
1:45 – 2:30 p.m. The Role of AI in Expediting Drug Discovery Target Identification for Nonalcoholic Steatohepatitis Using Machine Learning: The Case for nference Tyler Wagner PhD, Head of Cardiovascular Research, nference
2:30 – 2:45 p.m. Break
2:45 – 3:30 p.m. Technobite Sessions with Emulate Bio and University of Pittsburgh Drug Discovery Institute

Kyung Jin H Jang, VP of Bio Product development, Emulate, Inc.

Albert Gough, PhD, U Pittsburg School of Medicine

3:30 – 4:15 p.m. Artificial Intelligence Panel Discussion: Real World Applications from Discovery to Clinic Moderated by Carey Goldberg, WBUR
4:15 – 4:45 p.m. Jack’s Journey Jake and Elizabeth Burke, Cure NF with Jack
4:45 – 5:00 p.m. Closing Remarks
5:00 – 6:00 p.m. Networking Reception

 

 

Day Two – September 24, 2019

  • How genomics is expediting drug discovery
  • Accelerating therapies through the regulatory process

Tuesday, September 24

8:45 – 9:00 a.m. Opening Remarks and Recap James C. Foster, Chairman of the Board, President, and Chief Executive Officer, Charles River
9:00 – 9:30 a.m. 2018 Award Winner Update David Hysong, Patient Founder and Chief Executive Officer, Shepherd Therapeutics William Siders, CDO, Shepherd Therapeutics
9:30 – 10:15 a.m. Advances in Human Genetics and Therapeutic Modalities Enable Novel Therapies Eric Green, Vice President of Research and Development, Maze Therapeutics
10:15 – 11:00 a.m. How Genomics is Expediting Drug Discovery Manuel Rivas, Assistant Professor, Department of Biomedical Data Science, Stanford University
11:00 – 11:15 a.m. Break
11:15 a.m. – 12:00 p.m. Genomics Panel Discussion: Signposting Targets That Will Speed the Path to Market Moderated by Martin Mackay, Co-Founder, RallyBio
12:00 – 1:00 p.m. Lunch
1:00 – 1:45 p.m Truly Personalized Medicines for Ultra-rare Diseases: New Opportunities in Genomic Medicine Timothy Yu, Attending Physician, Division of Genetics and Genomics and Assistant Professor in Pediatrics, Boston Children’s Hospital
1:45 – 2:30 p.m. Application of Machine Learning Technology for the Assessment of Bulbar Symptoms in ALS Fernando Vieira, Chief Scientific Officer, ALS Therapy Development Institute
2:30 – 2:45 p.m. Break
2:45 – 3:30 p.m. Accelerating Rare Disease Therapies Through the Regulatory Process Martine Zimmermann, Senior Vice President and Head of Global Regulatory Affairs, Alexion Pharmaceuticals, Inc.
3:30 – 4:00 p.m. Wearing ALL the Hats: From Impossible to Possible Allyson Berent, Chief Operating Officer, GeneTx Biotherapeutics
4:00 – 4:15 p.m. Closing Remarks

 

jim.jpg
Matt_Wilsey.jpg
  • Find a cause and work with passion
  • CVD increased 53% from 2005 to 2016
  • Cholesterol, LDL receptor and CV disease
  • Genetics  evolution and discovery of PCSK9
  1. A PCSK9 Variant lowers CV risk
  2. complete lack of PCSK9 is safe – protects from CVD
  • LDL receptor
  • Statins do not work on LDL receptor if the mutation exists
  • Antibody and antisense for the PCSK9 mutation – Inexpensive Oral Medications can change Global Diseases
  • Dogma of Drug DIscovery: Approach a Patent vs Approach a Disease
  • Ligands bind within a cryptic binding pocket adjacent to a novel PCSK9 polymorphism

12 years of drug discovery

  1. 2003: PCSK9 mutation discovered
  2. 2005:
  3. 2006:
  4. 2012;
  5. 2012: Dogma Scientists begin
  6. compound found binds to primates
  7. 2015:
  8. 2018: Efficiency DGM-4403 lowers LDL-c by 55% 0ver 14 days
peter smith.jpg
  • 2014 – @Moderna, mRNA
  • 2017 – Alnylam

RNAi – delivery is the most difficult

  • gene silencing changes medicine and diseases
  • Small Interfeering RNA (siRNA) Therapeutics
  • Delivery challenges – stability and targeting
  • RNA Interference (RNAi) – Onpattro (patisiran)
  • GalNAc-siRNA Conjugates – delivery to the hepatocytes
  • N-Acetyl Galactosamine (GalNACc-siRNA conjugates
  • Hepatocyte specific : Liver across species: ASGPR expression
  • Metabolic Stability: Chemistry to Improve siRNA
  • Platform for genetic diseases
  • Evolution of COnjugate Design: GalNAc-siRNA – enhanced stabilization chemistry
  • ALN-TTRSC02 compared to Revusiran
  • ALN-TTRsc02 (advanced) –  – tetrameric protein binds transports serum retinol binding
  • AL Amyloidosis
  • ApoA1 Amyloidosis
  • ATTR Amyloidosis – manufacture in the Liver: Hereditery vs non-hereditary – Wild-Type
  • Patisiran Therapeutic Hypothesis – siRNA targeting TTR formulated
  • Pharmacology of TTR siRNA in Animal Model
  • V30M TTR Transgenic Mouse Model: Patisiran Phase 1 Study to Phase 3 APOLLA Study Design for any TTR mutation – Prior tetramer stabilizer used permitted
  • hATTR Amyloidosis and APOLLO Assessment: Phase 3 is Global – Cardiomyopathy – potential,
  • Patisiran met all secondary Endpoints: Canadian, Japanese approval – US approved indication, European approved
  • Alnylam Investigational RNAi Therapeutics:
  • Pipeline: Genetic medicines
  • Hepatic Infectious diseases
  • CNS & Ocular
  • Cardiovascular
11:15 AM-12:00 PM
richard snyder.jpg
  • Viral-Vector-mediated in vivo Gene Therapy
  • VVS Viral Vector Platforms:
  1. Adenovirus immunogenicity
  2. Lentivirus
  3. Retrovirus
  4. Herpes
  5. Recombinant Adeno-Associated Viral Vectors: Glybera, Luxturna
  6. Zolgenzma
  • Establish the product specifications based on data (CQAs)
  • Is the vector product: parenteral or anciliary material

Considerations:

  • Large scall vs small
  • lot demand vs platform choice
  • Proof of concept
  • Own/License the manufacturing reagents (portability) vs reliance on providers
  • Process and Analytical Design & Development: Cell line: Mamalian, others
  • Raw materials: Viral clearance steps – cell banks generation
  • impurity profiles
  • Cell Substrates
  • Cell clone screening
  • Preclinical/Clinical, Alachua, FL; Phase III/Commercial: Cambridge & Lexington
  • Biologics Upstream Process Flow: Master cell banks
  • Transient Transfection Process (Lenti and AAV)
  • rAAV Proviral cell line
  • Production Vector-based Process (Baculo or HSV)
  • Product purification: Filtration methods, Chromatography, centrifugal separation: Concentration/filtration
  • Formulation
  • Compatibility wiht vial: Glass, CZ, COP: absorption vs Inactivation
  • Single use
  • Frozen storage
  • Storage, Packing and Distribution
  • Technology Transfer: Research vs Mature Process (Qualified cell bank)
  • Plasmids: E.coli MCB backbone
  • Analytics Design & Development: Testing: Nucleic-acid based, protein-based
  1. AAV Vector Lot Release Assays
  2. Lentivirus
  • QA: QA Management System –
  • Analytical Assays
  • FDA Issues SIX New Draft Guidance Documents in 7/2018
  • Process Validation: Life cycle approach: Process caracterizationProcess performance qualification
Anne_Carpenter photo (003).jpg
  • assayGene clusterbased on morphological similarity: Express each gene, gene painting Image analysis, cluster morphological profiles
  • identification of allelle that are not constitutively activating mutants.
  • weakly supervised deep learning to extract features
  • identify similarities and differences among treatments at the same population level
  • Predict many distinct expensive assays on a huge compound library using a single cell painting
  1. Test 5,000 compounds in the assay of interest as well as cell painting
  2. Find combination of iamge-based features that predict in the assay of interest
  3. Predict “hit” from existing 1Million compound cell paining data set
The Role of AI in Expediting Drug Discovery Target Identification for Nonalcoholic Steatohepatitis Using Machine Learning: The Case for nference
Tyler Wagner PhD, Head of Cardiovascular Research, nference
KJ.jpg
DT.jpg
  • Lung-Chip Applications
  • Pulmonary inflammation
  • Intestine-chip Applications
  • Liver-Chip: Building Tissue Complexity: Co-culture, tri-culture, quatro-culture, Transcriptomic Analysis
  • Liver-Chip: Kupffer cells Characterization
  • Stellate Cells
  • parenchymal channel, non-parenchymal channel
  • Liver Chip: Predicting species differences in liver toxicity: Effects of Bosentan on Albumin secretion
  • Acetaminophen Toxicity in Liver-Chip: APAP Metabolism: detected changes in morphology, ATP, GSH – Dosepdependent increase of ROS
  • Steatosis and Stellate Cell Activation: and Species difference in Toxicity Liver chip data correlates with in vivo data
  • Predict Human safety risks with liver chip
Albert Gough, PhD, U Pittsburg School of Medicine
  • Approaches for repurposing drugs:
  1. Integrated, fluidic organ MPD,
  2. cells, 3D structures,
  3. O2 Modulation & Sensing
  4. Biosensors
  5. secretome
  • Higher Biomimetic content Higher throughput
  • regulatory liver-pancreas axis in Type 2 Diabetes model
  • Estradiol-Induced proliferation of mutants in Breast Cancer varies from 2D monoculture to 3D LAMP
  • MPS Models:
  1. celle and organ Structure in MPS
  2. Single organ MPS & Coupled organ
Carey Goldberg.PNG
Carey Goldberg, WBUR
burke family.jpg

September 24, 2019

jim.jpg
david hysong.png
bill siders.png
eric green.jpg
MacArthurD.jpg
mackay_1644931c.jpg
timothy yu.jpg
fernando-vieira.jpg
crop-VOISCHTS-Presenter-ZimmermannM.png
Allyson-Berent.jpg

Read Full Post »


Pfizer buys out Array BioPharma for $11.4 Billion to beef up its oncology offerings

Reporter: Stephen J. Williams, PhD

As reported in FiercePharma.com:

by Angus Liu |

Three years after purchasing Medivation for $14.3 billion, Pfizer is back with another hefty M&A deal. And once again, it’s betting on oncology.

In the first big M&A deal under new CEO Albert Bourla, Pfizer has agreed to buy oncology specialist Array BioPharma for a total value of about $11.4 billion, the two companies unveiled Monday. The $48-per-share offer represents a premium of about 62% to Array stock’s closing price on Friday.

With the acquisition, Pfizer will beef up its oncology offerings with two marketed drugs, MEK inhibitor Mektovi and BRAF inhibitor Braftovi, which are approved as a combo treatment for melanoma and recently turned up positive results in colon cancer.

The buy will enhance the Pfizer innovative drug business’ “long-term growth trajectory,” Bourla said in a Monday statement, dubbing Mektovi-Braftovi “a potentially industry-leading franchise for colorectal cancer.”

RELATED: Array’s ‘extremely compelling’ new colon cancer data spark blockbuster talk

In a recent interim analysis of a trial in BRAF-mutant metastatic colorectal cancer, the pair, used in tandem with Eli Lilly and Merck KGaA’s Erbitux, produced a benefit in 26% of patients, versus the 2% that chemotherapy helped. The combo also showed it could reduce the risk of death by 48%. SVB Leerink analysts at that time called the data “extremely compelling.”

Right now, one in every three new patients with mutated metastatic melanoma is getting the combo, despite its third-to-market behind combos from Roche and Novartis, Andy Schmeltz, Pfizer’s oncology global president, said during an investor briefing on Monday.

It is being studied in more than 30 clinical studies across several solid tumor indications. Moving forward, Pfizer believes the combo could potentially be used in the adjuvant setting to prevent tumor recurrence after surgery, Pfizer’s chief scientific officer, Mikael Dolsten, said on the call. The company is also keen to know how it could be paired up with Pfizer’s own investigational PD-1, he said, as the combo is already in studies with other PD-1/L1s.

But as Pfizer execs have previously said, the company’s current business development strategy no longer centers on adding revenues “now or soon,” but rather on strengthening Pfizer’s pipeline with earlier-stage assets. And Array can help there, too.

“We are very excited by Array’s impressive track record of successfully discovering and developing innovative small-molecules and targeted cancer therapies,” Dolsten said in a statement.

On top of Mektovi and Braftovi, Array has a long list of out-licensed drugs that could generate big royalties over time. For example, Vitrakvi, the first drug to get an initial FDA approval in tumors with a particular molecular feature regardless of their location, was initially licensed to Loxo Oncology—which was itself snapped up by Eli Lilly for $8 billion—but was taken over by pipeline-hungry Bayer. There are other drugs licensed to the likes of AstraZeneca, Roche, Celgene, Ono Pharmaceutical and Seattle Genetics, among others.

Those drugs are also a manifestation of Array’s strong research capabilities. To keep those Array scientists doing what they do best, Pfizer is keeping a 100-person team in Colorado as a standalone research unit alongside Pfizer’s existing hubs, Schmeltz said.

Pfizer is counting on Array to augment its leadership in breast cancer, an area championed by Ibrance, and prostate cancer, the pharma giant markets Astellas-partnered Xtandi. For 2018, revenues from the Pfizer oncology portfolio jumped to $7.20 billion—up from $6.06 billion in 2017—mainly thanks to those two drugs.

Source: https://www.fiercepharma.com/pharma/pfizer-never-say-never-m-a-buys-oncology-innovator-array-for-11-4b

 

About Array BioPharma

Array markets BRAFTOVI® (encorafenib) capsules in combination with MEKTOVI® (binimetinib)  tablets for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K  mutation in the United States and with partners in other major worldwide markets.* Array’s lead clinical programs, encorafenib and binimetinib, are being investigated in over 30 clinical trials across a number of solid tumor indications, including a Phase 3 trial in BRAF-mutant metastatic colorectal cancer. Array’s pipeline includes several additional programs being advanced by Array or current license-holders, including the following programs currently in registration trials: selumetinib (partnered with AstraZeneca), LOXO-292 (partnered with Eli Lilly), ipatasertib (partnered with Genentech), tucatinib (partnered with Seattle Genetics) and ARRY-797. Vitrakvi® (larotrectinib, partnered with Bayer AG) is approved in the United States and Ganovo® (danoprevir, partnered with Roche) is approved in China.

 

Other Articles of Note of Pfizer Merger and Acquisition deals on this Open Access Journal Include:

From Thalidomide to Revlimid: Celgene to Bristol Myers to possibly Pfizer; A Curation of Deals, Discovery and the State of Pharma

Pfizer Near Allergan Buyout Deal But Will Fed Allow It?

Pfizer offers legal guarantees over AstraZeneca bid

Re-Creation of the Big Pharma Model via Transformational Deals for Accelerating Innovations: Licensing vs In-house inventions

Read Full Post »


Real Time Coverage @BIOConvention #BIO2019: June 4 Morning Sessions; Global Biotech Investment & Public-Private Partnerships

Reporter: Stephen J Williams PhD @StephenJWillia2

Each country have their own needs and most important drug cost structure. Must involve patients and providers.
BCI survey: countries output different, who improved who didnt
Is industry having collaboration with government? hardly ten percent by survey and worse vice versa
Transparancy and holistic view important for collaboration
Korea: lack of communication need input from government on pricing; wants global open innovation and enhance RD investments
Tawain: price, price but based on efficacy; pharma needs to talk with doctors hospital patients, find balance
Pitts: we need trust; staff that country offices with people who know that country. Price not defining value
Columbia:  need to attract investors

Please follow LIVE on TWITTER using the following @ handles and # hashtags:

@Handles

@pharma_BI

@AVIVA1950

@BIOConvention

# Hashtags

#BIO2019 (official meeting hashtag)

Read Full Post »


Real Time Coverage @BIOConvention #BIO2019:  Issues of Risk and Reproduceability in Translational and Academic Collaboration; 2:30-4:00 June 3 Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

Derisking Academic Science: The Unmet Need  

Translating academic research into products and new therapies is a very risky venture as only 1% of academic research has been successfully translated into successful products.

Speakers
Collaboration from Chicago area universities like U of Chicago, Northwestern, etc.  First phase was enhance collaboration between universities by funding faculty recruitment and basic research.  Access to core facilities across universities.  Have expanded to give alternatives to company formation.
Half of the partnerships from Harvard and companies have been able to spin out viable startups.
Most academic PI are not as savvy to start a biotech so they bring in biotechs and build project teams as well as developing a team of ex pharma and biotech experts.  Derisk as running as one asset project.  Partner as early as possible.  A third of their pipeline have been successfully partnered.  Work with investors and patent attorneys.
Focused on getting PIs to get to startup.  Focused on oncology and vaccines and I/O.  The result can be liscensing or partnership. Running around 50 to 60 projects. Creating a new company from these US PI partnerships.
Most projects from Harvard have been therapeutics-based.  At Harvard they have a network of investors ($50 million).   They screen PI proposals based on translateability and what investors are interested in.
In Chicago they solicit multiple projects but are agnostic on area but as they are limited they are focused on projects that will assist in developing a stronger proposal to investor/funding mechanism.
NYU goes around university doing due diligence reaching out to investigators. They shop around their projects to wet their investors, pharma appetite future funding.  At Takeda they have five centers around US.  They want to have more input so go into the university with their scientists and discuss ideas.
Challenges:

Takeda: Data Validation very important. Second there may be disconnect with the amount of equity the PI wants in the new company as well as management.  Third PIs not aware of all steps in drug development.

Harvard:  Pharma and biotech have robust research and academic does not have the size or scope of pharma.  PIs must be more diligent on e.g. the compounds they get from a screen… they only focus narrowly

NYU:  bring in consultants as PIs don’t understand all the management issues.  Need to understand development so they bring in the experts to help them.  Pharma he feels have to much risk aversion and none of their PIs want 100% equity.

Chicago:  they like to publish at early stage so publication freedom is a challenge

Dr. Freedman: Most scientists responding to Nature survey said yes a reproduceability crisis.  The reasons: experimental bias, lack of validation techniques, reagents, and protocols etc.
And as he says there is a great ECONOMIC IMPACT of preclinical reproducability issues: to the tune of $56 billion of irreproducable results (paper published in PLOS Biology).  If can find the core drivers of this issue they can solve the problem.  STANDARDS are constantly used in various industries however academic research are lagging in developing such standards.  Just the problem of cell line authentication is costing $4 billion.
Dr. Cousins:  There are multiple high throughput screening (HTS) academic centers around the world (150 in US).  So where does the industry go for best practices in assays?  Eli Lilly had developed a manual for HTS best practices and in 1984 made publicly available (Assay Guidance Manual).  To date there have been constant updates to this manual to incorporate new assays.  Workshops have been developed to train scientists in these best practices.
NIH has been developing new programs to address these reproducability issues.  Developed a method called
Ring Testing Initiative” where multiple centers involved in sharing reagents as well as assays and allowing scientists to test at multiple facilities.
Dr.Tong: Reproduceability of Microarrays:  As microarrays were the only methodology to do high through put genomics in the early 2000s, and although much research had been performed to standardize and achieve best reproduceability of the microarray technology (determining best practices in spotting RNA on glass slides, hybridization protocols, image analysis) little had been done on evaluating the reproducibility of results obtained from microarray experiments involving biological samples.  The advent of Artificial Intelligence and Machine Learning though can be used to help validate microarray results.  This was done in a Nature Biotechnology paper (Nature Biotechnology volume28pages827–838 (2010)) by an international consortium, the International MAQC (Microarray Quality Control) Society and can be found here
However Dr. Tong feels there is much confusion in how we define reproduceability.  Dr. Tong identified a few key points of data reproduceability:
  1. Traceability: what are the practices and procedures from going from point A to point B (steps in a protocol or experimental design)
  2. Repeatability:  ability to repeat results within the same laboratory
  3. Replicatablilty:  ability to repeat results cross laboratory
  4. Transferability:  are the results validated across multiple platforms?

The panel then discussed the role of journals and funders to drive reproduceability in research.  They felt that editors have been doing as much as they can do as they receive an end product (the paper) but all agreed funders need to do more to promote data validity, especially in requiring that systematic evaluation and validation of each step in protocols are performed..  There could be more training of PIs with respect to protocol and data validation.

Other Articles on Industry/Academic Research Partnerships and Translational Research on this Open Access Online Journal Include

Envisage-Wistar Partnership and Immunacel LLC Presents at PCCI

BIO Partnering: Intersection of Academic and Industry: BIO INTERNATIONAL CONVENTION June 23-26, 2014 | San Diego, CA

R&D Alliances between Big Pharma and Academic Research Centers: Pharma’s Realization that Internal R&D Groups alone aren’t enough

Read Full Post »


Real Time Coverage @BIOConvention #BIO2019: What’s Next: The Landscape of Innovation in 2019 and Beyond. 3-4 PM June 3 Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

 

Results from Clarivate
In 2018 most of deals were in CART area but now we are seeing more series A rounds that are on novel mechanisms as well as rare diseases.  US is still highest in venture capital series A but next is China. 10 of top ex US VC are from China, a whole lot of money.
Preclinical is very strong for US VC but China VC is focused on clinical.  First time this year we see US series A break above 100.  But ex US the series A is going down.  Although preclinical deals in US is coming back not like as good as in 2006.  But alot of > 1 billion $ deals.  Most of money into mAbs and protein therapy;  antisense is big and cell therapy is big too; small molecule not as much
ClearView Healthcare
Which innovation classes attracted VC in 2018?
  • Oncology drives a disproportionate focus could be driven by pharma focus on oncology; however there is some focus on neuro and infectious disease
  • therapeutic classes: shift to differentiated technology…. companies want technologic platforms not just drugs.  Nucleic Acid tech and antibody tech is high need platforms.  Startups can win by developing a strong platform not just a drug
There are pros and cons of developing a platform company versus a focused company.  Many VCs have a portfolio and want something to fit in so look for a focused company and may not want a platform company.  Pfizer feels that when alot of money is available (like now) platform investing is fine but when money becomes limited they will focus on those are what will be needed to fill therapy gaps.  They believe buy the therapy and only rent the platform.
Merck does feel the way Pfizer does but they have separate ventures so they can look and license platforms.  they are active in looking at companies with new modalities but they are focused on the money so they feel best kept in hands of biotech not pharma.
At Celgene they were solely focused on approvals not platforms.  Alot of money is required to get these platforms to market.  Concentration for platform companies should be the VCs not partnering or getting bought out by pharma.  it seems from panel speakers from pharma that they are waiting for science to prove itself and waiting for favorable monetary environments (easy money).  However it seems they (big pharma) are indicating that money is drying up or at least expect it too.
At Axial and with VCs they feel it is important to paint a picture or a vision at the early stage.
At Ontogeny, they focus on evaluating assets especially and most important, ThE MANAGEMENT TEAM.  There are not that many great talented drug development management teams he feels out there even though great science out there.

Read Full Post »


LIVE 13th Annual BioPharma and Healthcare Summit, Thursday, May 9, 2019, Marriott Hotel, Cambridge, MA

 

http://www.usaindiachamber.org

8:40 AM – 9:10 AM Registration and Networking
9:10 AM – 9:20 AM Welcome addressKarun Rishi, President, USAIC

Opening comments: Dr Andrew Plump, President R&D and Director, Takeda Pharmaceuticals

9:20 AM – 9:40 AM Fireside Chat

  • Mark Abdoo, Acting Deputy Commissioner, U.S. Food and Drug Administration
  • Dr Eswara Reddy, Drug Controller General of India, Central Drug Control Organization

Moderator: Sanat Chattopadhyay, President, Merck Manufacturing Division; Merck & Co.

9:40 AM – 10:00 AM Presentation on CAR (chimeric antigen receptor) T-cell Therapies
Dr. Carl June, Director of Translational Research, Abramson Cancer Center University of Pennsylvania Moderator: Dr. Raju Kucherlapati, Professor of Genetics, Harvard Medical School
10:00 AM – 10:50 AM Panel Discussion: Oncology – The Emperor of BioPharma Development

Panelists:

Moderator: Dr. Christiana Bardon, Managing Director, MPM Capital

10:50 AM – 11:20 AM Networking Break
11:20 AM – 12:10 PM Panel Discussion: Future of Clinical Trials and Drug Development

Panelists:

Moderator: Dr. William Chin, Professor of Medicine, Emeritus, Harvard Medical School

12:10 PM – 1:00 PM Panel Discussion: Manufacturing in the Future

Panelists:

  • Hari Bhartia, Founder and Co-Chairman, Jubilant Bhartia Group
  • Mark Abdoo, Acting Deputy Commissioner, U.S. Food and Drug Administration
  • Dr. Paul McKenzie, Executive Vice President, Pharma Operations & Technology, Biogen
  • Sanat Chattopadhyay, President, Merck Manufacturing Division; Merck & Co.
  • Vinay Ranade, Chief Executive Officer, Reliance Life Sciences

Moderator: Professor N. Venkat Venkatraman, Boston University Questrom School of Business

1:00 PM – 1:50 PM Lunch
1:50 PM – 1:55 PM Video message from Suresh Prabhu, Hon’ble Minister of Commerce & Industry, Gov. of India
1:55 PM – 2:45 PM Panel Discussion: One in a million – Emerging trends in Rare Diseases

Panelists:

Moderator: Dr. Samarth Kulkarni, Chief Executive Officer, CRISPR Therapeutics

2:45 PM – 3:20 PM Networking & Tea Break
3:20 PM – 3:50 PM Fireside Chat: Value and Access – The ongoing debate

Moderator: Dr Andrew Plump, President R&D, Takeda Pharmaceuticals

3:50 PM – 4:10 PM India update on Clinical Trial Regulations

  • Arun Singhal, Additional Secretary, Ministry of Health & Family Welfare, India
  • Dr Eswara Reddy, Drug Controller General of India, Central Drug Control Organization
4:10 PM – 5:00 PM Panel Discussion: Research and Development Strategies and Trends

Panelists:

Moderator: Dr. Martin Mackay, Co-Founde, Rallybio

5:00 PM – 5:05 PM Closing Remarks
5:05 PM – 6:15 PM Cocktails & Networking Reception

Aviva Lev-Ari, PhD, RN & Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

REAL TIME COVERAGE USING SOCIAL MEDIA

 

LIVE Images taken by @AVIVA1950

 

 

 

9:10 AM – 9:20 AM

Welcome addressKarun Rishi, President, USAIC

Opening comments: Dr Andrew Plump, President R&D and Director, Takeda Pharmaceuticals

  • tomorrow announcement @Shire
  • India 1.3Billion in India, each person is a potential patient in the largest democracy in the World
  • China – transformation takes place every day
  • The Patient and the Pricing of Drugs the biggest issue missing the ball dialoguing on Panel today

9:20 AM – 9:40 AM

Fireside Chat

  • Mark Abdoo, Acting Deputy Commissioner, U.S. Food and Drug Administration (FDA)
  • Dr Eswara Reddy, Drug Controller General of India (DCGI), Central Drug Control Organization

Moderator: Sanat Chattopadhyay, President, Merck Manufacturing Division; Merck & Co.

9:40 AM – 10:00 AM Presentation on CAR (chimeric antigen receptor) T-cell Therapies
Dr. Carl June, Director of Translational Research, Abramson Cancer Center University of Pennsylvania Moderator: Dr. Raju Kucherlapati, Professor of Genetics, Harvard Medical School

  • Video on child with recurrent twice of leukhimia
  • T-cell HIV Virus infect

 

10:00 AM – 10:50 AM

Panel Discussion: Oncology – The Emperor of BioPharma Development

Panelists:

  1. solid vs blood tumors
  2. T-Cells amplification microenvironment and biology
  3. PD-1 in combination therapies thousand Trials
  4. Biomarker allows to check response in conjunction with genomics data brings insights
  5. Tumors World, Biomarkers in Immuno oncology respond to PD-1 no response to other drug
  6. stratify patients
  1. Protein experimental data compound design from simulations of VIRTUAL compounds,
  2. how to incentivise to take on new innovations
  1. more that one single administration by injection
  2. response rates different even in one patient let alone among patients
  3. detection gene
  4. CAR-T glioblastoma
  5. pancreatic cancer good responses in combination therapies
  6. immunr repertoire biology so complex that biomarkers are limited

Moderator: Dr. Christiana Bardon, Managing Director, MPM Capital

  • 30% patinets with complete cure

10:50 AM – 11:20 AM Networking Break11:20 AM – 12:10 PM

Panel Discussion: Future of Clinical Trials and Drug Development

Panelists:

  1. endpoints need to be redefined it effect price of drug development
  2. in Oncology – Basket and Umbrellas Trial – two stufies approval for melanoma, biomarker
  3. Is response rate is 30% va 50% and Phase 3 is negative Kertuda when worked at Merck dose ranging last phase when response dropped from 60% to 30% in the case of Study C3
  4. 30% of the cost of the study – 30% was translational
  5. CRO model appropriate oversite vs douplication of tasks
  • Dr. Bruce Chabner, Director of Clinical Research, Mass General Hospital Cancer Center
  1. Old paradigm Phase 1,2,3 – off the board now, New drugs do not need the old paradigm
  2. Phase i1 changed if genomics is involved multiple cohorts at same time
  3. FDA play amazing role
  4. patient selection is key
  5. mutations in rare disease vs mutations in cancer
  6. immunotherapy and endogenic drugs with chemo in RENAL cancer
  7. check-points – lung cancer understood money spent to find responders
  8. HOW to select which cheno therapy — no improvement today vs past
  9. 40 drugs approved by accelerated approval one came back on the market
  10. Financial burden of being in a clinical trial
  11. Foundation gives money to Institutions to reimburse patients for flights, meals, acommodation, Pharma are reluctant to participants due to potential accusation of bias id Pharma pays Patients that participate in Clinical Trials
  1. FDA recognizes approval process – systems involved AFTER approval for reimbursement and monitoring after market
  2. regulatory by countires are different
  3. which factors are sacrifiable in the long tern in clinical trial design
  1. Safety – benefit risk is what physicians work with every day
  2. Drugs paradign of small molecules does not hold is you have a drug that deliver entire organelle – how you dose for half life how you prive the rate of replication in the body
  3. Surrogate markers
  4. Taking a drug off the market ->>  conditional approvals [approval can be taken back or require additional studies] not a favorable view of Pharma in the present to support Conditional approval vs accelerated approval

 

  1. speed
  2. differentiation from competition
  3. drug development in crisis is CVD not cancer, US and the rest of the world – lowest investment in drugs is CVD
  4. Studies designed by Physicians using SAME design
  5. need to create experts to use ML in the course of clinical trial design
  6. regulators as Partners not as Barriers
  7. Proof of efficacy is a burden on the developers of the drug not on the Regulatory
  8. Increase use of advertising to recruit
  9. 70% OF PATIENTS WILLING TO PARTICIPATE  lives to far from site of trials
  10. Telecommunication between administrators of study ans clinical Trials participants
  11. Back when I was at Pfizer, designing study – patients burden relieved more willingness to participate
  12. Preferrs to run studies in house vs use CRO they are not effective in monitoring like study run in house

Moderator: Dr. William Chin, Professor of Medicine, Emeritus, Harvard Medical School

  • Probability of success to clinic has not changed
  • challenge is design and execution in clinical trials
  • changes in drug modalities: RNA, DNA,
  • which combination to use
  • how to find the many patients needed
  • Basket and Umbrellas Trial

12:10 PM – 1:00 PM

Panel Discussion: Manufacturing in the Future

Panelists:

  • Hari Bhartia, Founder and Co-Chairman, Jubilant Bhartia Group
  1. supply change
  2. blockchain
  3. quality by design
  4. CPK
  5. productivity will go up variability will decrease
  6. manufacturng must happen in India
  7. Genetics price selection
  8. Secure system, data quality the data logic and the analytics
  9. infrastructure in manufacturing is not completed yet
  10. Training by augmented reality Turnover high in India
  11. cyber security – digitization and central control
  12. demonstration data offense
  • Mark Abdoo, Acting Deputy Commissioner, U.S. Food and Drug Administration
  1. next 10 years India and China will improve regulatory activities and match better the US requirements
  2. review foreign hosts
  3. skills and location of hosts:
  4. India: Standards and unannounced inspections and
  5. China: same
  6. Blockchain is experienced as experimentation at FDA across each all parts of the Agency
  • Dr. Paul McKenzie, Executive Vice President, Pharma Operations & Technology, Biogen
  1. raw material to patients: Pharma very slow than other industries Reliable needs be very high, relationships
  2. Hurrican in PortoRIco affected supply chain
  3. Reality, every one HAVE to be in China
  4. Platforming for each modality for Scaling out vs Scaling up
  5. diversify vs modality x
  6. build capacity and capabilities customization of ultra filtration different in two plants lowers standardizations
  7. Training on Demand, Virtually, documnetation needs to change to electronic
  8. Continueous manufacturing Academic contribution
  • Vinay Ranade, Chief Executive Officer, Reliance Life Sciences
  1. Pharma was slow in India the manufacturing
  2. infantile diarreha vaccine 70,000 in 4 years needs that drug,
  3. massive intellectual capital in India
  4. How to implement and make best use of data to improve processes
  5. cyber security was not experiences
  1. Phase 1 scaling out vs up – it is different in vaccine field
  2. ML, Block chain, supply chain and manufacturing will be adapted in supply chain
  3. Apply analytics and relationships in manufacturing
  4. obsolescence and upgrades
  5. capture data electronically
  6. cyber security can be a hazard hard to mitigate when all systems are down
  7. significant challenges in manufacturing and data security

Moderator: Professor N. Venkat Venkatraman, Boston University Questrom School of Business

  • How can Pharma become leaner
  • heterogenuious environment for production
  • cyber security

1:00 PM – 1:50 PMLunch1:50 PM – 1:55 PM Video message from Suresh Prabhu, Hon’ble Minister of Commerce & Industry, Gov. of India1:55 PM – 2:45 PM

Panel Discussion: One in a million – Emerging trends in Rare Diseases

Panelists:

  1. worked with Academic community on how to treat rare disease in the future
  1. Show clinical benefit and impact multiplemyeloma
  2. patients becoming activists
  3. access
  4. foundation by patients
  5. Patient to get cloud
  • Dr. Dhaval Patel, Executive Vice President  and Chief Scientific Officer, UCB
  1. if a modality will cure a disease justify innovation Model for payment: Mortgage Model
  2. Access INDEX pricing – US will benchmark the price in other parts of the world
  3. Gene therapy is not only got monognenic diseases but for
  4. decrease work involved in development of drugs
  • Dr. James Wilson, Director – Gene Therapy Program, University of Pennsylvania
  1. tension between physicians and development of the perfect drug.
  2. AV
  3. Protein replacement therapy repeated infusion gene therapy infrastructure develop in China for China, Develop in India for India vs develop in US for India or China
  4. Cost of manufacturing to decrease
  • Dr. Timothy Yu, Assistant Professor in Pediatrics, Harvard Medical School
  1. Scalability beyond the one case: the mechanism for the drug has generability for other aptients iwth same mutation the method has no limit
  2. Molecular type of mutation Spice Switching strategy, just-in-time manufacturing

Moderator: Dr. Samarth Kulkarni, Chief Executive Officer, CRISPR Therapeutics

  1. Rare diseases, potential for cure
  2. Academia, Hospitals, biotech
  3. commercial model of the disease

2:45 PM – 3:20 PMNetworking & Tea Break3:20 PM – 3:50 PM

Fireside Chat: Value and Access – The ongoing debate

  1. since 2003 testify in the House, against Canadian  David Brenner was asked about importation from Canada of breast cancer tamoxiphen at a lower price than in the US.
  2. From importation crisis to Obama Care – stable system Medicare Part D – drug coverage for Olderly
  3. After Obama – Price is part of doing business REBATES $100Billion the valur of REBATES
  4. Co-Insurance
  1. right for innovation will be preserved
  2. price increase
  3. give and take
  4. Co-pay – We need lower co-pay
  5. with current administration, sink finding the Well instead of Well funding the sick
  6. CHange is coming, co-pay will change
  1. Genzyme days vs 2019
  2. changes how drugs are priced?
  3. Flaws of the system:Gevernment induce prices that will change
  4. $800,000 drug is now $80 [ala Regeneron] – R&D was $2Billion
  5. CO-pay for hospital stay is lower than co-pay on drugs – 10% twice a year

Moderator: Dr Andrew Plump, President R&D, Takeda Pharmaceuticals

3:50 PM – 4:10 PM

India update on Clinical Trial Regulations

  • Arun Singhal, Additional Secretary, Ministry of Health & Family Welfare, India
  1. Each patient deserve access to healthcare in India
  2. experimenting
  • Dr Eswara Reddy, Drug Controller General of India, Central Drug Control Organization
  1. Time line for Application approval for drugs, if approved in another country 60 days
  2. Gov’t hospitals can import New drugs which have not been permitted in India

4:10 PM – 5:00 PM

Panel Discussion: Research and Development Strategies and Trends

Panelists:

  1. Neuroscience – Pharma understand biomarkers and now genetics
  2. Vaccines – across species in the animal WORLD
  1. Attempt not to tweak the PIPELINE: CVD, NEUROSCIENCE AND CANCER
  2. 485 Teams doing R&D convluence of interests to develop cure
  3. Modularity – BioMolecule — multimodality biophysical biochemical protein degradation – rewire disease cells with biomolecules combing propertitie of permiability of small molecules
  4. PHARMACOLOGICAL PREVENTION – biotech is inspiring only Pharma can solve
  1. immunooncology – mutation signature – marker protein signature — that group of diseases respond to
  2. colon cancer and multiple myeloma — understanding of the biology was deep

Moderator: Dr. Martin Mackay, Co-Founder, Rallybio

5:00 PM – 5:05 PM Closing Remarks

5:05 PM – 6:15 PM Cocktails & Networking Reception

Read Full Post »

Older Posts »