Feeds:
Posts
Comments

Posts Tagged ‘antibody-drug conjugate’

Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024

Reporter: Stephen J. Williams, Ph.D.

Endpoints at #JPM24 | Primed to unlock biopharma’s next dealmaking wave
Endpoints at JP Morgan Healthcare Conference
January 8-9 | San Francisco, CA80 Mission St, San Francisco, CA

An oasis has emerged in the biopharma money desert as backers look to replenish capital — still, uncertainty remains on whether it’s a mirage or the much needed dealmaking bump the industry needs. Yet spirits run high as JPM24 marks the triumphant return of inking strategic alliances and peering into the industry crystal ball — while keeping an eye out for some major M&A.

We’re back live from San Francisco for JPM Monday and Tuesday — our calendar of can’t-miss panels and fireside chats will feature prominent biopharma leaders to watch. The Endpoints Hub provides the ultimate coworking space with everything you need — 1:1 and group meeting spots plus guest pass capabilities and more. Join us in-person at the Endpoints Hub or watch online to stay plugged into all the action.

8 JAN
Welcome remarks
8:05 AM – 8:25 AM PST
Pfizer vet Mikael Dolsten has some thoughts on Big Pharma R&D

Endpoints News founding editor John Carroll will sit down with longtime Pfizer CSO Mikael Dolsten to talk about Pfizer’s pipeline, what he’s learned on the job about preclinical research and development and what’s ahead for the pharma giant in drug development and deals.

Mikael Dolsten

Chief Scientific Officer, President, Pfizer Research & Development

Pfizer

Pfizer Mikael Dolsten: Pfizer produced a series of AI generated molecules with new properties. Sees rapid adoption of AI in the area of drug discovery and molecular design.

 
 
8:25 AM – 9:05 AM PST
What pharma wants: The industry’s dealmakers look ahead at 2024

The drug industry’s appetite for new assets hasn’t slowed down. Top business development execs will give their outlook on the year, what they’re looking for and how they see the market.

Glenn Hunzinger

Pharmaceutical & Life Sciences Consulting Solutions Leader

PwC US

Rachna Khosla

SVP, Head of Business Development

Amgen

James Sabry

Global Head of Pharma Partnering

Roche

Devang Bhuva

SVP, Corporate Development

Gilead Sciences, Inc.

Endpoints News

Dealmaking panel

Glenn Hunzinger: if you do not have a GLP1 will have a tough time getting a good market price for your company; capital markets are not where they want to be; sees a tough deal making climate like last year.  The problem with many biotech companies are they are coming earlier to the venture capital because of greater funding needs and so it is imperative that they articulate the potential of their company in scientific detail

Rachna Khosla:  Make sure your investors are not just CAPITAL PARTNERS but use their expertise and involve them in development issues you may have, especially ones that a young firm will face.  The problem is most investments assume what the future looks like (for example how antibody drug conjugates, once a field left for dead, has been rejuvenated because of advances in chemistry). 

James Sabry: noted that cardiac and metabolic drugs are now at the focus of many investors, especially with the new anti-obesity drugs on market

Devang Bhuva: Most deals we see start as collaborations or partnerships.  You want to involve an alliance management team early in the deal making process.  This process could take years.

 
9:05 AM – 9:20 AM PST
The IPO: How Apogee Therapeutics went public in the most challenging market in years

Not many biotechs went public in 2023. And of those that did, not many have had a great time of it. Apogee is the exception and our panel will offer a behind-the-scenes look at their decision to enter the market and what life is like as a young public company.

Michael Henderson

CEO

Apogee Therapeutics

Kyle LaHucik

MODERATOR

Senior Reporter

Endpoints News

Michael Henderson:  Not many biotech IPOs deals happened in 2023.  Michael feels it is because too many biotechs focused on building platforms, which was a hard sell in 2023.  He felt not many biotechs had clear milestones and investors wanted a clear primary validated target.  He said many biotech startups are in a funding crunch and most need at least $440M on their balance sheet to get to 2026.

9:50 AM – 10:10 AM PST
Top predictions for biotech in 2024

Catalent CEO Alessandro Maselli will be back at the big JPM healthcare confab to talk with Endpoints News founder John Carroll about their top predictions of what’s coming up for the biotech industry in 2024. The stakes couldn’t be higher as the industry grapples with headwinds and new opportunities in a gale of market forces. Two top observers share their thoughts on the year ahead.

Alessandro Maselli

President & CEO

Catalent

10:15 AM – 10:35 AM PST
Innovation at a crossroads: Keys to unlocking the value of science and technology

The industry has long discussed the promise of technology and the acceleration it provides in scientific advancement and across the industry value chain. However, the promise of its impact has yet to fully be realized. This discussion will outline the keys to unleashing this promise and the implications and actions to be taken by the biopharmaceutical companies across the industry.

Ray Pressburger

North America Life Sciences Industry Lead & Global Life Sciences Strategy Lead

Accenture

SPONSORED BY

10:35 AM – 11:05 AM PST
Activism and Investing: In conversation with Elliott Investment Management’s Marc Steinberg

Elliott has been behind many of 2023’s highest-profile healthcare investments, including multiple activist engagements and taking Syneos Health private. What has made large healthcare companies such interesting investment opportunities for firms like Elliott? What’s Elliott’s investing strategy in healthcare? And what should companies expect when an activist calls?

Marc Steinberg

Senior Portfolio Manager

Elliott Investment Management

Andrew Dunn

MODERATOR

Biopharma Correspondent

Endpoints News

11:05 AM – 11:35 AM PST
Creating ROI from AI

AI is predicted to transform the way drugs are made, from discovery to clinical trials to market. But beyond the initial hype and early adoption, where has AI made meaningful contributions to R&D? How does it help drug developers advance science? Endpoints publisher Arsalan Arif is convening a panel of leading experts to discuss the state of AI in the pharmaceutical landscape and the outlook for 2024. How does AI impact the drug pipeline, from the early steps of discovery to reducing trial failure rate?

Thomas Clozel

Co-Founder & CEO

Owkin

Venkat Sethuraman

SVP, Global Biometrics & Data Sciences

Bristol Myers Squibb

Frank O. Nestle

Global Head of Research & Chief Scientific Officer

Sanofi

Matthias Evers

Chief Business Officer

Evotec

Arsalan Arif

MODERATOR

Founder & Publisher

Endpoints News

SPONSORED BY

11:35 AM – 12:00 PM PST
Biopharma’s dealmaker: Behind the scenes with Centerview Partners co-president Eric Tokat

Almost every major biopharma deal in 2023 had Centerview’s name attached to it. And much of the time, Eric Tokat was the banker making those deals happen. Hear his outlook for 2024, how transactions are getting done and what’s placed his firm at the center of so much action.

E. Eric Tokat

Co-President, Investment Banking

Centerview Partners

CenterView Partners Eric Tokat feels dealmaking will improve in 2024, given the recent flurry of dealmaking at end of last year and right before main JPM Healthcare Conference.  He says Centerview wants to help the biotechs they invest in on their strategic path.  This may translate into buyers more actively involved (more than startups want) and buyers now are in the drivers seat as far as the timeline of deals and development.

Is the megamerger dead for this year?  He says it is very hard to see two major mergers happening but there will be many smaller and mid size biotech deals happening, but these deals will be more speculative in nature..  The focus for large pharma is top line growth.  Most of the buyers have an infrastructure and value is more of buying and dropping it in their business so there is now a huge emphasis on due diligence on whether synergies exist or not

 
12:00 PM – 12:30 PM PST
Founder, legend, leader: In conversation with Nobel laureate Carolyn Bertozzi

Carolyn Bertozzi’s discoveries around bioorthogonal chemistry won the Nobel Prize in Chemistry in 2022 and are at the heart of new therapies being tested in patients. Join us as we discuss what inspires her and where she sees the next big advances.

Carolyn Bertozzi

Prof. of Chemistry, Stanford University and Baker Family Director of Sarafan ChEM-H

Stanford University

Nicole DeFeudis

MODERATOR

Editor

Endpoints News

Bioorthogonal chemistry: class of high yielding chemical reactions that proceed rapidly and selectively in biological environments without side reactions toward endogenous functions.  This is also a type of ‘click chemistry’ in biological system where only specifically alter the biomolecule of interest.

Orthogonal: two chemicals not interacting with each other

Dr. Bertozzi noted she has started a new Antibody-Drug-Conjugate (ADC) company which involves designing with biorthogonal chemistry to make new functional molecules with varying properties

She noted hardly any biologists knew anything about glycobiology when she first started.  However now she feels pharma and academia are working very well with each other

Bioorthogonal and Click Chemistry
Curated by Prof. Carolyn R. Bertozzi, 2022 winner of the Nobel Prize in Chemistry

Source: https://pubs.acs.org/page/vi/bioorthogonal-click-chemistry

The 2022 Nobel Prize in Chemistry has been awarded jointly to ACS Central Science Editor-in-Chief, Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research, for the development of click chemistry and bioorthogonal chemistry.

To celebrate this remarkable achievement, 2022 Nobel Prize winner Professor Carolyn R. Bertozzi has curated this Bioorthogonal and Click Chemistry Virtual Issue, highlighting papers published across ACS journals that have built upon the foundational work in this exciting area of chemistry.

From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions

Ellen M. Sletten and Carolyn R. Bertozzi* Acc. Chem. Res. 2011, 44, 9, 666-676 August 15, 2011

Abstract

Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Examples from the past decade suggest that a promising strategy for bioorthogonal reaction development begins with an analysis of functional group and reactivity space outside those defined by nature. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. Finally, the reaction must be tested in a variety of environments, escalating from aqueous media to biomolecule solutions to cultured cells and, for the most optimized transformations, to live organisms.

9 JAN

9:40 AM – 10:10 AM PST

Biotech downturn survival school

Our panelists have seen the worst, and made it through to the other side. Join us for downturn survival school as our panelists talk about what sets apart the ones who make it through tough times.

These panalists think it will be specialist capital year to shine while the general capital is still sitting on the sidelines

JJ Kang

CEO

Appia Bio

“2023 was a tough year while 2020 was a boon year to start a company.  We will continue to see these cycles; many of these new CEOs have never seen a biotech downturn yet and may not know how to preserve capital for the downturn”.

“Doing a partnership with Kite Pharmaceuticals early in our startp allowed us to get work done without risking a lot of capital, even if it means equity and asset dilution.  That makes sense. However even if you are small insist on being an equal partner.”

“There are many investors we talk to who do not want to invest in cell therapy.  Too risky now”

Carl Gordon

Managing Partner

OrbiMed Advisors

There are many macroeconomic factors affecting investment and capital today which will carry on through 2024.   Not raising money when you do not need money is a bad philosophy.  Always bbe raising captial.  This is especially true when you have to rely on hedge funds.  Parnerships howeve are sometimes the only way for small biotechs to leverage their strengths.

Joshua Boger

Executive Chair

Alkeus Pharmaceuticals, Inc.

Boger: Expect volatility for 2024.  This environment feels very different than past downturns.

Even in downturns there is still lots of capital; remember access to human capital is better in a downturn and is easier to access;  however it has become harder to get drug approvals

The panelists agree that access to capital and funding will be as tricky in 2024 than 2023.  They did

suggest that a new funding avenue, private credit, may be a source of capital.  This is discussed below:

When thinking about a private alternative investment asset class, the first thing that springs to mind is private equity. But there’s one more asset class with the word private in its name that has recently gained much attention. We’re talking about private credit

Indeed, this once little-known investment strategy is now growing rapidly in popularity, offering private investors worldwide an exciting opportunity to diversify their portfolio with, in theory, less risky investments that yield significant returns. 

  • Private credit investments refer to investors lending money to companies who then repay the loan at a given interest rate within the predetermined period.
  • The private credit market has grown significantly over the past years, rising from $875 million in 2020 to $1.4 trillion at the beginning of 2023. 

Please WATCH VIDEO BY GOLDMAN SACHS ON PRIVATE CREDIT

 

 

 

 

10:50 AM – 11:20 AM PST

The New Molecule: How breakthrough technologies are actually changing pharma R&D

Join us for a look at how AI, machine learning and generative technologies are actually being applied inside drugmakers’ labs. We’ll explore how new technologies are being used, their implications, how they intersect with regulatory and IP issues and how this fast-changing field is likely to evolve.

Kailash Swarna

Managing Director & Global Life Sciences Clinical Development Lead

Accenture

Artificial Intelligence is making impact in a grand way on biology in three aspects:

  1. Speeding up target validation: now we can get through 300 molecules a day
  2. Predicition like AlphaFold is doing; molecular simulations
  3. Document submission especially with regulatory and IND submissions

Pamela Carroll

COO

Isomorphic Labs formerly of AlphaFold

We were first with Novartis at last year JPM and was one year old but parnering with them in that initial year was very important for sealing the deal.

They are looking now at neurologic diseases like ALS.  She wondered whether ALS is actually multiple diseases and we need to stratify patients like we do in oncology trials.  Their main competion is the whole tech world like Amazon, Google and other Machine Learning companies so being a tech player in the biotech world means you are not just competing with other biotechs but large tech companies as well.

Jorge Conde

General Partner

Andreessen Horowitz

Need is still great for drug discovery; early adopters show AI tools can be used in big pharma. There are lots of applications of AI in managing care; a lot of back office applications including patient triaging.  He does not see big AI mergers with pharma companies –  this will be mainly partnerships not M&A deals

Alicyn Campbell

Chief Scientific Officer

Evinova, a Healthtech Subsidiary of the AstraZeneca Group

There is a need to turn AI for real world example.  For example AI tools were used in clinical trials to determine patient cohorts with pneumonitis.  At Evinova they are determining how AI can hel[p show clinical benefit with respect to efficacy and safety

Joshua Boger at #JPM24 (Brian Benton Photography)

  January 12, 2024 09:06 AM ESTUpdated 10:00 AM PeopleStartups

Vertex founder Joshua Boger on surviving downturns, ‘painful’ partnerships, and the importance of culture: #JPM24

Andrew Dunn

Biopharma Correspondent

Source: https://endpts.com/jpm24-vertex-founder-joshua-boger-on-surviving-downturns-painful-partnerships-and-the-importance-of-culture/

While the JP Morgan Healthcare Conference was full of voices of measured optimism, rooting for the market to bounce back in 2024, one longtime biotech leader warned against setting any firm expectations.

Instead of predicting when the downturn may end, Vertex Pharmaceuticals founder Joshua Boger said he advises biotech leaders to expect — and plan for — volatility. Speaking Tuesday on an Endpoints News panel alongside OrbiMed’s Carl Gordon and Appia Bio CEO JJ Kang, Boger shared lessons learned on surviving downturns, striking pharma deals, and the importance of keeping a company’s culture based on his two decades of founding and leading Vertex as CEO from 1989 to 2009. The 72-year-old is now serving as executive chairman of Alkeus Pharmaceuticals, a startup developing a rare disease drug.

“I never experienced a straight line up,” Boger said. “Everything had its cycles, and it was how you respond to the cycle, not by predicting when the end is going to be, but just by responding to the present situation.”

At Boger’s first appearance at the JP Morgan conference in 1991, he said the conference’s theme was the end of biotech financing. Just a few months later, Regeneron successfully went public, rapidly changing the outlook for the whole field.

“We had no idea we were ever going to take public money,” he said. “When Regeneron did their IPO, we went, ‘Whoa, there’s something happening here,’ and we pivoted quickly.”

Vertex went public later that year. Throughout his 20-year tenure, Boger said no pharma company ever made an acquisition offer for Vertex, which now commands a market value of $110 billion and recently won the first FDA approval for a CRISPR gene editing therapy.

“We had an uber corporate policy to always make ourselves more expensive than anyone would stomach,” Boger said.

However, Vertex did strike a range of partnerships with Big Pharmas, which Boger described as a painful but necessary part of running a biotech startup.

“It’s impossible for a partnership not to slow you down,” he said. “You can and should try as hard as you can not to do that, but just count on it. They’ll slow you down.”

Boger said startups should insist on being equal partners in pharma deals, at least making sure they have a seat at a partner’s development meetings.

“Realize they’re going to be painful, it’s going to be horrible, and you need to do it,” Boger said.

While Vertex suffered through layoffs, stock price plunges, and trial failures, Boger credited a focus on culture as key to its long-term success.

“It’s the most important ingredient for a successful company,” he said. “Technology is acquirable. Culture is not acquirable. There are 10 companies that will fail because of culture for every one that succeeds, and the successful companies in retrospect will almost always have special cultural aspects that kept them through those downtimes.”

JPM24 opens with ADCs the hottest ticket in San Francisco

By Annalee ArmstrongJan 8, 2024 6:30am

Source: https://www.fiercebiotech.com/biotech/jpm24-opens-adcs-hottest-ticket-san-francisco

The overall deal flow in biopharma tapered off in 2023 but the big companies sure know what they want (what they really, really want), according to a new report from J.P. Morgan.

And that’s antibody-drug conjugates, which drove a fourth-quarter spike in licensing deal proceeds and provided a glimmer of hope to an industry battered by outside forces and grim financing prospects.

J.P. Morgan’s annual 2023 Biopharma Licensing and Venture Report arrived on the eve of the firm’s famous conference, which is set to welcome thousands of attendees in San Francisco today—East Coast weather permitting.

2023 was tough, but clinical biotechs still had a lot of opportunities to wheel and deal, according to J.P. Morgan. While licensing deals, venture investments, M&A and IPOs were down overall in the fourth quarter, deal values stayed fairly high thanks to a flurry of late-stage tie ups.

Follow the Fierce team’s coverage of the 2024 J.P. Morgan Healthcare Conference here

Biopharma licensing partnerships accounted for $63 billion in total value during the fourth quarter from 108 deals. Just one deal—Merck’s ADC partnership with Daiichi Sankyo—accounted for $22 billion of that. Another huge one was another ADC bet, with Bristol Myers Squibb signing on to work with SystImmune for a total value of $8.4 billion. If you exclude the Merck deal, the total value of these partnerships is still higher than the previous quarter, which ended with $32.1 billion.

The total number of licensing deals compares to 149 in the same quarter a year earlier, 195 for Q4 2021 and 223 for Q4 2022.

As for venture investments, the year closed out with $17 billion total across 250 rounds, thanks to $3.5 billion earned through 79 rounds in the last quarter. Aiolos Bio snagged the title of largest venture round of the quarter with $245 million, which also proved to be the largest series A, too.

There was just one IPO in all of the fourth quarter—Cargo Therapeutics making the plunge for $300 million—and 13 overall for the year. It’s a far cry from the heyday of 2021 and experts are still unsure what 2024 will hold. J.P. Morgan reported $2.5 billion raised from 12 completed biopharma IPOs for the year on Nasdaq and NYSE. Nine out of the 12 companies had clinical programs when they took the leap to the public markets. As of December 13, five of the companies were trading above their IPO price.

As for M&A, December saw a rush of Big Pharmas snapping up companies around Christmas. J.P. Morgan tallied the fourth quarter at $37.6 billion and $128.8 billion across 112 total acquisitions for all of 2023.

AbbVie was the top buyer of the quarter with the two largest acquisitions thanks to the $10 billion outlay for ImmunoGen and $8.7 billion buy of Cerevel Therapeutics.

All of this adds up to 270 total deals in the fourth quarter total, which is lower than the third quarter which exceeded 300.

J.P. Morgan sees some big potential for smaller biopharmas looking for licensing partners, as Big Pharmas have been handing out larger upfront payments for the deals they really want.

Cancer was once again the most in-demand therapeutic areas, reaching a new height of $86.1 billion in 2023. Followed by $21.1 billion for neurological disorders.

For More Articles on Real Time Conference Coverage in this Open Access Scientific Journal see:

Part One: The Process of Real Time Coverage using Social Media

Part Two: List of BioTech Conferences 2013 to Present

https://worldmedicalinnovation.org/

https://pharmaceuticalintelligence.com/2022/05/01/2022-world-medical-innovation-forum-gene-cell-therapy-may-2-4-2022-boston-in-person/

 

https://event.technologyreview.com/emtech-digital-2022/agenda-overview

 

Read Full Post »

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

 

Brain tumors, especially the diffused Gliomas are of the most devastating forms of cancer and have so-far been resistant to immunotherapy. It is comprehended that T cells can penetrate the glioma cells, but it still remains unknown why infiltrating cells miscarry to mount a resistant reaction or stop the tumor development.

Gliomas are brain tumors that begin from neuroglial begetter cells. The conventional therapeutic methods including, surgery, chemotherapy, and radiotherapy, have accomplished restricted changes inside glioma patients. Immunotherapy, a compliance in cancer treatment, has introduced a promising strategy with the capacity to penetrate the blood-brain barrier. This has been recognized since the spearheading revelation of lymphatics within the central nervous system. Glioma is not generally carcinogenic. As observed in a number of cases, the tumor cells viably reproduce and assault the adjoining tissues, by and large, gliomas are malignant in nature and tend to metastasize. There are four grades in glioma, and each grade has distinctive cell features and different treatment strategies. Glioblastoma is a grade IV glioma, which is the crucial aggravated form. This infers that all glioblastomas are gliomas, however, not all gliomas are glioblastomas.

Decades of investigations on infiltrating gliomas still take off vital questions with respect to the etiology, cellular lineage, and function of various cell types inside glial malignancies. In spite of the available treatment options such as surgical resection, radiotherapy, and chemotherapy, the average survival rate for high-grade glioma patients remains 1–3 years (1).

A recent in vitro study performed by the researchers of Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard, USA, has recognized that CD161 is identified as a potential new target for immunotherapy of malignant brain tumors. The scientific team depicted their work in the Cell Journal, in a paper entitled, “Inhibitory CD161 receptor recognized in glioma-infiltrating T cells by single-cell analysis.” on 15th February 2021.

To further expand their research and findings, Dr. Kai Wucherpfennig, MD, PhD, Chief of the Center for Cancer Immunotherapy, at Dana-Farber stated that their research is additionally important in a number of other major human cancer types such as 

  • melanoma,
  • lung,
  • colon, and
  • liver cancer.

Dr. Wucherpfennig has praised the other authors of the report Mario Suva, MD, PhD, of Massachusetts Common Clinic; Aviv Regev, PhD, of the Klarman Cell Observatory at Broad Institute of MIT and Harvard, and David Reardon, MD, clinical executive of the Center for Neuro-Oncology at Dana-Farber.

Hence, this new study elaborates the effectiveness of the potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes.

The Study-

IMAGE SOURCE: Experimental Strategy (Mathewson et al., 2021)

 

The group utilized single-cell RNA sequencing (RNA-seq) to mull over gene expression and the clonal picture of tumor-infiltrating T cells. It involved the participation of 31 patients suffering from diffused gliomas and glioblastoma. Their work illustrated that the ligand molecule CLEC2D activates CD161, which is an immune cell surface receptor that restrains the development of cancer combating activity of immune T cells and tumor cells in the brain. The study reveals that the activation of CD161 weakens the T cell response against tumor cells.

Based on the study, the facts suggest that the analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 that codes for CD161 as a candidate inhibitory receptor. This was followed by the use of 

  • CRISPR/Cas9 gene-editing technology to inactivate the KLRB1 gene in T cells and showed that CD161 inhibits the tumor cell-killing function of T cells. Accordingly,
  • genetic inactivation of KLRB1 or
  • antibody-mediated CD161 blockade

enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other forms of human cancers. The work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immune checkpoint targets.

Further, it has been identified that many cancer patients are being treated with immunotherapy drugs that disable their “immune checkpoints” and their molecular brakes are exploited by the cancer cells to suppress the body’s defensive response induced by T cells against tumors. Disabling these checkpoints lead the immune system to attack the cancer cells. One of the most frequently targeted checkpoints is PD-1. However, recent trials of drugs that target PD-1 in glioblastomas have failed to benefit the patients.

In the current study, the researchers found that fewer T cells from gliomas contained PD-1 than CD161. As a result, they said, “CD161 may represent an attractive target, as it is a cell surface molecule expressed by both CD8 and CD4 T cell subsets [the two types of T cells engaged in response against tumor cells] and a larger fraction of T cells express CD161 than the PD-1 protein.”

However, potential side effects of antibody-mediated blockade of the CLEC2D-CD161 pathway remain unknown and will need to be examined in a non-human primate model. The group hopes to use this finding in their future work by

utilizing their outline by expression of KLRB1 gene in tumor-infiltrating T cells in diffuse gliomas to make a remarkable contribution in therapeutics related to immunosuppression in brain tumors along with four other common human cancers ( Viz. melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma, and colorectal cancer) and how this may be manipulated for prevalent survival of the patients.

References

(1) Anders I. Persson, QiWen Fan, Joanna J. Phillips, William A. Weiss, 39 – Glioma, Editor(s): Sid Gilman, Neurobiology of Disease, Academic Press, 2007, Pages 433-444, ISBN 9780120885923, https://doi.org/10.1016/B978-012088592-3/50041-4.

Main Source

Mathewson ND, Ashenberg O, Tirosh I, Gritsch S, Perez EM, Marx S, et al. 2021. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell.https://www.cell.com/cell/fulltext/S0092-8674(21)00065-9?elqTrackId=c3dd8ff1d51f4aea87edd0153b4f2dc7

Related Articles

VIDEOS on Cancer Biology, Cancer Genetics, Cancer Immunotherapy

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

 

Other related articles published in this Open Access Online Scientific Journal include the following:

 

Single Cell Sequencing:

Part 4.1 in Genomics Volume 2

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology 

On Amazon.com since 12/28/2019

https://www.amazon.com/dp/B08385KF87

 

4.1.3   Single-cell Genomics: Directions in Computational and Systems Biology – Contributions of Prof. Aviv Regev @Broad Institute of MIT and Harvard, Cochair, the Human Cell Atlas Organizing Committee with Sarah Teichmann of the Wellcome Trust Sanger Institute

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/09/03/single-cell-genomics-directions-in-computational-and-systems-biology-contributions-of-ms-aviv-regev-phd-broad-institute-of-mit-and-harvard-cochair-the-human-cell-atlas-organizing-committee-wit/

 

4.1.4   Cellular Genetics

https://www.sanger.ac.uk/science/programmes/cellular-genetics

 

4.1.5   Cellular Genomics

https://www.garvan.org.au/research/cellular-genomics

 

4.1.6   SINGLE CELL GENOMICS 2019 – sometimes the sum of the parts is greater than the whole, September 24-26, 2019, Djurönäset, Stockholm, Sweden http://www.weizmann.ac.il/conferences/SCG2019/single-cell-genomics-2019

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/05/29/single-cell-genomics-2019-september-24-26-2019-djuronaset-stockholm-sweden/

 

4.1.7   Norwich Single-Cell Symposium 2019, Earlham Institute, single-cell genomics technologies and their application in microbial, plant, animal and human health and disease, October 16-17, 2019, 10AM-5PM

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/06/04/norwich-single-cell-symposium-2019-earlham-institute-single-cell-genomics-technologies-and-their-application-in-microbial-plant-animal-and-human-health-and-disease-october-16-17-2019-10am-5pm/

 

4.1.8   Newly Found Functions of B Cell

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

https://pharmaceuticalintelligence.com/2019/05/23/newly-found-functions-of-b-cell/

 

4.1.9 RESEARCH HIGHLIGHTS: HUMAN CELL ATLAS

https://www.broadinstitute.org/research-highlights-human-cell-atlas

 

CRISPR – 200 articles in the Journal

 

Chapter 21 in Genomics Volume 1

Genomics Orientations for Personalized Medicine. On Amazon.com since 11/23/2015

http://www.amazon.com/dp/B018DHBUO6

 

Glioblastoma – 150 articles in the Journal

Most recent

 

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/

 

New Treatment in Development for Glioblastoma: Hopes for Sen. John McCain

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/25/new-treatment-in-development-for-glioblastoma-hopes-for-sen-john-mccain/

 

Funding Oncorus’s Immunotherapy Platform: Next-generation Oncolytic Herpes Simplex Virus (oHSV) for Brain Cancer, Glioblastoma Multiforme (GBM)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/funding-oncoruss-immunotherapy-platform-next-generation-oncolytic-herpes-simplex-virus-ohsv-for-brain-cancer-glioblastoma-multiforme-gbm/

 

Glioma, Glioblastoma and Neurooncology

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/10/19/glioma-glioblastoma-and-neurooncology/

 

Positron Emission Tomography (PET) and Near-Infrared Fluorescence Imaging:  Noninvasive Imaging of Cancer Stem Cells (CSCs)  monitoring of AC133+ glioblastoma in subcutaneous and intracerebral xenograft tumors

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/29/positron-emission-tomography-pet-and-near-infrared-fluorescence-imaging-noninvasive-imaging-of-cancer-stem-cells-cscs-monitoring-of-ac133-glioblastoma-in-subcutaneous-and-intracerebral-xenogra/

 

Gamma Linolenic Acid (GLA) as a Therapeutic tool in the Management of Glioblastoma

Eric Fine* (1), Mike Briggs* (1,2), Raphael Nir# (1,2,3)

https://pharmaceuticalintelligence.com/2013/07/15/gamma-linolenic-acid-gla-as-a-therapeutic-tool-in-the-management-of-glioblastoma/

 

 

Read Full Post »

Spirogen’s Cytotoxic Warheads IP Taken over for $400 Million by AstraZeneca PLC (AZN)’s MedImmune (AZN) for Avoidance Capabilities of Emergent Drug Resistance

Reporter: Aviva Lev-Ari, PhD, RN

AstraZeneca PLC (AZN)’s MedImmune (AZN) Takes OverSpirogen Ltd. for Up to $400 Million to Bolster Oncolology Portfolio

10/15/2013 7:54:15 AM

 

AstraZeneca PLC Oncology Portfolio Strengthened as MedImmune Acquisition of Spirogen Ltd. Boosts Antibody-Drug Conjugate Capability 

AstraZeneca PLC Oncology Portfolio Strengthened as MedImmune Acquisition of Spirogen Ltd. Boosts Antibody-Drug Conjugate Capability 

Tuesday, 15 October 2013 — AstraZeneca today announced that MedImmune, its global biologics research and development arm, has acquired Spirogen, a privately-held biotech company focused on antibody-drug conjugate technology for use in oncology.

MedImmune has also entered into a collaboration agreement with ADC Therapeutics to jointly develop two of ADC Therapeutics’ antibody-drug conjugate programmes in preclinical development. MedImmune will also make an equity investment in ADC Therapeutics, which has an existing licensing agreement with Spirogen.

MedImmune will acquire 100 per cent of Spirogen’s shares for an initial consideration of $200 million and deferred consideration of up to $240 million based on reaching predetermined development milestones. Existing out-licensing agreements and associated revenue streams are excluded from this acquisition.

MedImmune will also pay $20 million for an equity investment in ADC Therapeutics, which will be matched by Auven Therapeutics, the majority shareholder in both ADC Therapeutics and Spirogen. The collaboration agreement will include an upfront payment with predetermined development milestones for two programmes from a defined list and a cost- and profit-sharing arrangement with MedImmune representing the majority share. ADC Therapeutics will also have the option to co-promote one of the products in the US.

Antibody-drug conjugates are a clinically-validated cancer drug technology that offers both high potency and selective targeting of cancer cells. Spirogen’s proprietary pyrrolobenzodiazepine (PBD) technology attaches highly potent cytotoxic agents, or ‘warheads’ to specific cancer-targeting antibodies using biodegradable ‘linkers’. This targeting optimises the delivery of the cancer drug to the tumour cells only and provides the greatest degree of tumour killing while minimising the toxicity to the patient.

“Antibody-drug conjugates are ground-breaking technologies with the potential for directly targeting many types of cancer tumours while safeguarding healthy cells. The cutting-edge technologies developed by Spirogen and ADC Therapeutics complement MedImmune’s innovative antibody engineering capabilities, enabling us to accelerate antibody-drug conjugates into the clinic,” said Dr. Bahija Jallal, Executive Vice President, MedImmune.

Oncology is a core therapy area for AstraZeneca spanning both small molecule and biologics research and development. MedImmune is developing a comprehensive portfolio with an emphasis on two key areas in oncology development: antibody-drug conjugates and immune-mediated cancer therapy, which aims to harness the power of the patient’s own immune system to fight cancer. Together, immune-mediated cancer therapies and antibody-drug conjugates have the potential to treat cancer in a way that current therapies are unable to do.

“This deal reflects the very significant progress made by our scientists, most notably over the last two years, as we have applied our warhead and linker technologies to the development of highly potent and specific antibody-drug conjugates,” said Dr. Chris Martin, Chief Executive Officer, Spirogen. “We believe that pyrrolobenzodiazepine-armed antibody-drug conjugates will emerge as a critical component in the next generation of cancer biologics with the potential to make a difference for oncologists and their patients. We look forward to combining our world-class capabilities in this area with MedImmune’s ability to develop this exciting class of oncology drugs.”

About Antibody-Drug Conjugates

An antibody-drug conjugate is a three-component system consisting of a potent cytotoxic agent, or ‘warhead’, a biodegradable linker and a monoclonal antibody. The antibody binds to specific markers at the surface of the cancer cell. The whole antibody-drug conjugate is then internalised within the cancer cell where the active drug is released. Antibody-drug conjugates have extensive potential therapeutic applications in several disease areas, particularly in cancer. The principle can also be applied beyond antibodies, with the possibility of linking warheads to antibody fragments, peptides, vitamins and hormones.

About Spirogen

The Spirogen group was founded in 2001 as a spin-out from several institutions including University College London and with partial funding by Cancer Research UK. It is majority owned by Auven Therapeutics. It has developed a novel class of highly potent cytotoxic warheads based on its proprietary pyrrolobenzodiazepines (PBDs), DNA minor groove binding agents, which bind and cross-link specific sites of DNA of the cancer cell. This blocks the cancer cells’ division without distorting its DNA helix, thus potentially avoiding the common phenomenon of emergent drug resistance. Spirogen has been developing its PBD technology for more than ten years, including a standalone PBD agent in a Phase II study in acute myeloid leukemia. Its business model has been to partner its technology with pharma and biotech for use in the development of novel drugs. It has a number of industry collaborations, including collaborations with Genentech announced in 2011 and with ADC Therapeutics announced in 2012. For further information, please visit: http://www.spirogen.com.

About ADC Therapeutics

ADC Therapeutics (ADCT) is a Swiss-based oncology drug development company that specialises in the development of proprietary antibody-drug conjugates (ADCs) targeting major cancers such as breast, lung, prostate, renal and blood. The company’s ADCs are highly targeted drug constructs which combine monoclonal antibodies specific to particular types of tumour cells with a novel class of highly potent PBD-based warheads. The company was launched in 2012 with a $50m commitment from private equity firm Auven Therapeutics. ADCT has access to warhead and linker chemistries via existing agreements with Spirogen. It operates a virtual business model based in Lausanne, Switzerland. For further information, please visit: http://www.adctherapeutics.com.

About Auven Therapeutics

Auven Therapeutics was founded by Stephen Evans-Freke and Dr. Peter B Corr in 2007 with an innovative investment strategy that enables it to operate as a drug development company while remaining structured as a private equity fund. Auven Therapeutics has a portfolio of biologic and small molecule drug candidates for a range of therapeutic indications including cancer, ophthalmic conditions, women’s health and orphan diseases. Auven manages its drug development activities from its bases in Lausanne, Switzerland, New York, USA and Hamilton, Bermuda. Auven Therapeutics Management LLLP, based in the US Virgin Islands, serves as its Investment Advisor. For further information, please visit: http://www.auventx.com.

About MedImmune

MedImmune is the worldwide biologics research and development arm of AstraZeneca. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience, and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, MD, one of AstraZeneca’s three global R&D centres. For more information, please visit http://www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: http://www.astrazeneca.com

SOURCE

http://www.biospace.com/news_story.aspx?NewsEntityId=311765&type=email&source=DD_101513

 

Read Full Post »

Treatment for Metastatic HER2 Breast Cancer

Screen Shot 2021-07-19 at 7.34.43 PM

Word Cloud By Danielle Smolyar

Reporter: Larry H Bernstein, MD, FCAP
Leaders in Pharmaceutical Innovation
http://pharmaceuticalintelligence.com/2013/03/03/9680/Treatment for Metastatic HER2 Breast Cancer 

FDA Approves New Treatment for Metastatic HER2 Breast Cancer (antibody-drug conjugate)
T-DM1 is indicated for patients who were previously treated with the anti-HER2 therapy trastuzumab (Herceptin, Genentech) and a taxane chemotherapy.

The US Food and Drug Administration (FDA) today approved ado-trastuzumab emtansine (Kadcyla, Genentech), also known as T-DM1, for the treatment of patients with HER2-positive metastatic breast cancer.
T-DM1 is indicated for patients who were previously treated with

  • the anti-HER2 therapy trastuzumab (Herceptin, Genentech) and a taxane chemotherapy.

This product offers a new twist on an older product; it is an antibody–drug conjugate in which the

  • HER2-targeted antibody trastuzumab
  • is chemically linked to the cytotoxin mertansine (DM1).

The antibody homes in on HER2 breast cancer cells, delivering the chemotherapy directly to the tumor, which reduces the risk for toxicity.  According to Richard Pazdur, MD, at the FDA Center for Drug Evaluation and Research, T-DM1 carries the drug-conjugate

  • directly to the cancer site
  • to shrink the tumor,
  • slow disease progression, and
  • prolong survival .

It is the fourth drug approved that targets the HER2 protein. Apart from lapatinib, which is marketed by GlaxoSmithKline, all the other HER2-targeted products have been developed and are marketed by Genentech/Roche. For T-DM1, the proprietary technology involved in the DM1 portion of the product was developed by ImmunoGen, working in collaboration with Genentech/Roche.

In the pivotal phase 3 EMILIA study, patients receiving T-DM1 survived nearly 6 months longer than patients receiving the standard therapy of

  • lapatinib (Tykerb) plus capecitabine (Xeloda) (median overall survival, 30.9 vs 25.1 months).

There were fewer grade 3 or higher (severe) adverse events with TDM-1 than with standard therapy

  • 43.1% vs. 59.2%)

The approval represents a “momentous” day in breast cancer, said Kathy Miller, MD, from Indiana University in Indianapolis, in her Miller on Oncology Medscape blog.

  • HER2-positive patients with metastatic disease have a therapy that offers prolonged disease control with less toxicity

 T-DM1 was more effective in EMILIA than standard therapy on every outcome:

  • overall response rate,
  • disease-free survival,
  • progression-free survival, and
  • overall survival.

Herceptin Fab (antibody) - light and heavy chains

Herceptin Fab (antibody) – light and heavy chains (Photo credit: Wikipedia)

Ribbon diagram of the Fab fragment of , a , bo...

Ribbon diagram of the Fab fragment of , a , bound to the extracellular domain of HER2. Created using Accelrys DS Visualizer Pro 1.6 and . ; Legend Trastuzumab Fab fragment, Trastuzumab Fab fragment, HER2, extracellular domain (Photo credit: Wikipedia)

Breast cancer (Infiltrating ductal carcinoma o...

Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody. (Photo credit: Wikipedia)

English: Breast cancer incidence by age in wom...

English: Breast cancer incidence by age in women in the United Kingdom 2006-2008. Reference: Excel chart for Figure 1.1: Breast Cancer (C50), Average Number of New Cases per Year and Age-Specific Incidence Rates, UK, 2006-2008 at Breast cancer – UK incidence statistics at Cancer Research UK. Section updated 18/07/11. (Photo credit: Wikipedia)

Read Full Post »