In the middle of November, Editas Medicine (NASDAQ:EDIT) and Celgene (NASDAQ:CELG) announced changes to a development pact originally formed in 2015 with Juno Therapeutics, which is now part of Celgene. The agreement was amended in 2018, too, so the fact that changes were made wasn't necessarily big news. Editas received a $70 million upfront payment for executing the amended agreement, which was interpreted as the main takeaway from the announcement.
The announcement barely registered with investors and few gave it much thought for too long, especially after promising early results from the first clinical trials using a CRISPR-based medicine were announced by CRISPR Therapeutics days later.
But revisiting the amended collaboration agreement, and specifically what changes were made, hints at the long-term development plans of Editas Medicine. In short, it now has full control over an important class of immune cells. Whether that means the gene-editing pioneer lands another major development partner or goes full-steam ahead alone, investors can't overlook the significance.
Image source: Getty Images.
The basic scientific goal of the collaboration hasn't changed. Editas Medicine will use its gene-editing technology platform to engineer T cell receptors (TCR), while Juno Therapeutics will leverage its immunotherapy leadership to develop the engineered cellular medicines in clinical trials.
Why engineer TCRs? Immune cells rely on their receptors to identify targets, such as pathogenic bacteria and cancer cells. But immune cell receptors can be confused by molecules secreted within the tumor microenvironment, forcing them to halt their attack. They can also incorrectly attack an individual's own cells to trigger an autoimmune disease. A more recent concern stems from cellular medicines derived from a donor. Since the donor cells present different receptors compared to what the recipient's native T cells carry, the recipient's immune system (correctly) identifies the immunotherapy as a foreign substance, attacks it, and renders it less effective and less safe.
Therefore, it makes sense to engineer TCRs to create more potent and stealthier immunotherapies that are less likely to be tricked. Editas Medicine and Celgene still intend to do just that, albeit with subtle, yet important, differences to their development agreement.
Consideration
Previous Agreement (2015, 2018)
Amended Agreement (2019)
Focus
Cancer
Cancer and autoimmune diseases
Types of cells
CAR-T cells, alpha-beta T cells, gamma-delta T cells
Alpha-beta T cells
Juno Therapeutics exclusivity
Editas Medicine prohibited from all other work with CAR-T and TCRs in oncology
Editas Medicine prohibited from all other work on alpha-beta T cells and T cells derived from pluripotent stem cells
Upfront payment
$57.7 million (includes milestones collected under agreement)
$70 million
Milestone potential
$920 million plus tiered royalties
$195 million plus tiered royalties
Data source: SEC filings.
Essentially, Editas Medicine and Celgene have scaled back their original agreement in cancer and expanded their work to include autoimmune diseases. The most important detail is that the amended agreement allows the gene-editing pioneer to pursue the development of gamma-delta T cells, which were previously under the exclusive control of Juno Therapeutics. What does that mean?
Image source: Getty Images.
Without getting too far into the weeds, there are two main types of TCRs: alpha-beta and gamma-delta. The name refers to the molecular structure of the receptor, but that's not the important part.
Gamma-delta T cells, which comprise only about 5% of the T cells in your body, are thought to be one of the missing links in our understanding of the immune system. They're a mysterious bunch, but there could be significant value residing in the knowledge gaps.
These unique immune cells are governed by their own unique set of rules (relative to their alpha-beta peers) and straddle the innate immune system (what we're programmed with at birth) and adaptive immune systems (what's programmed as we encounter new environments throughout life). Gamma-delta T cells could be tinkered with in gut microbiome applications, to treat cardiovascular diseases, and to neutralize antibiotic-resistant infections. But the nearest commercial target of the mysterious immune cells is likely to be treating solid tumor cancers.
They possess potent anti-tumor activity where current immunotherapies fail, such as attacking cancer cells that lack tumor-specific antigens to target or that have become immune to checkpoint inhibitors. In fact, there's a link between certain cancer outcomes and the activity of specific gamma-delta T cells.
Given that, why would Celgene amend the agreement to ditch the rare subset of immune cells? Well, in August 2019, Celgene inked with a start-up called Immatics to develop engineered TCRs. The start-up's platform is based on gamma-delta tech.
Don't feel too bad for Editas Medicine, though. SEC filings reveal that the gene-editing pioneer didn't receive any money from the original collaboration deal with Celgene in the first nine months of 2019. That suggests the work had stalled or that the amendment was being hammered out for some time. The gene-editing pioneer wrestled back control of the tech and took a $70 million upfront payment to boot. While the potential milestone payments in the amended agreement are significantly lower than the originally promised bounty, Editas Medicine can offset that by signing a lucrative collaboration deal with a new partner.
There should be plenty of interest. Fellow gamma-delta T cell developer Adicet Bio recently landed an $80 million series B round funded in part by Johnson & Johnson, Regeneron,Samsung Biologics(not the same company as the electronics powerhouse), and Novartis. There's also Immatics, GammaDelta Therapeutics, and a handful of other start-ups making noise in the space.
Some competitors are directly engineering gamma-delta cells, and others are developing molecules to trigger the immune cells into action. Editas Medicine believes it has the edge, as it has a relatively precise and efficient method for engineering immune cells: gene editing.
The amended collaboration deal between Editas Medicine and Celgene received relatively little attention from investors. Perhaps that was a good thing, as Wall Street likely would have overreacted to the reduced scope of development and milestones. But investors that take the time to understand the details might be intrigued by the new research avenue for the gene-editing stock.
Can Editas Medicine become a leading force in gamma-delta T cell development? Perhaps. While it isn't the only company wielding a gene-editing platform, and CRISPR gene editing isn't the only type of gene editing, the company is well-positioned to take advantage of the opportunity. Investors will have to wait to see how (or if) the development strategy evolves around the new tech.
Originally posted here:
Celgene Gave This Tech Back to Editas Medicine, but It Could Prove Valuable - The Motley Fool
- Technion team discovers important adaptive strategy of the microbiome, impacting immune system - The Jerusalem Post - April 16th, 2024
- Targeting aging and age-related diseases with vaccines - Nature.com - April 16th, 2024
- Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic ... - Nature.com - April 16th, 2024
- After the Smoke Clears: Scars on the Immune System - The Scientist - April 16th, 2024
- Exercise and the Immune System: What's the Latest Research? - Technology Networks - April 16th, 2024
- Analysis of immune cell infiltration characteristics in severe acute pancreatitis through integrated bioinformatics ... - Nature.com - April 16th, 2024
- Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original ... - Nature.com - April 16th, 2024
- Harnessing the power of the body's own cells to defeat cancer - Press Publications Inc. - April 16th, 2024
- Best Life: Immunotherapy targets brain cancer - Action News 5 - April 16th, 2024
- Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review | Cell Death ... - Nature.com - April 16th, 2024
- New insights on B cells: Researchers explore building better antibodies and curbing autoimmune diseases - Medical Xpress - April 16th, 2024
- Immune cells' intense reaction to the coronavirus may lead to pneumonia - Science News Magazine - April 16th, 2024
- The telltale traces long Covid leaves in the blood - healthcare-in-europe.com - April 16th, 2024
- Overview of the Immune System - The Merck Manuals - March 18th, 2024
- SUNDAY Unraveling The Gut-Brain Connection: How Infant Gut Bacteria Shape Immune Resilience | TheHealthSit - TheHealthSite - March 18th, 2024
- Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics | npj Systems Biology and ... - Nature.com - March 18th, 2024
- Study unlocks the mystery of neonatal neutropenia in newborns - News-Medical.Net - March 18th, 2024
- Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic ... - Cureus - March 18th, 2024
- A new strategy to attack aggressive brain cancer shrank tumors in two early tests - ABC News - March 18th, 2024
- Turning on the Bat Signal - The Scientist - March 18th, 2024
- Power Foods That Can Support Your Immune System - Videos from The Weather Channel - The Weather Channel - March 18th, 2024
- Report: Aggressive brain tumors respond to new, immune-focused therapy - UPI News - March 18th, 2024
- Designer immune-cell therapy could shrink deadly brain tumors, early trials show - Livescience.com - March 18th, 2024
- 20.2: Introduction to the Immune System - Biology LibreTexts - February 27th, 2024
- Can one shot of yoghurt really boost your immunity and gut health? - Daily Mail - February 27th, 2024
- New cancer therapy approved by FDA supercharges bodys immune system - The Washington Post - February 27th, 2024
- How bubonic plague rewired the human immune system - BBC.com - February 27th, 2024
- Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net - February 27th, 2024
- Participate in Our Study for $100; Open Slots This Week - University of Arkansas Newswire - February 27th, 2024
- Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice | Scientific Reports - Nature.com - February 27th, 2024
- Comprehensive pan-cancer analysis identifies the RNA-binding protein LRPPRC as a novel prognostic and immune ... - ScienceDirect.com - February 27th, 2024
- YOUR HEALTH: The HAMR fights cancer - WAFB - February 27th, 2024
- Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat - News-Medical.Net - February 27th, 2024
- How the powerhouse of the cell could be cancers Achilles heel - Freethink - February 27th, 2024
- Food is medicine: The science behind zinc and other supplements for immune health - Healio - February 27th, 2024
- Unleashing Our Immune Response to Quash Cancer - Medscape - February 27th, 2024
- Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 ... - Nature.com - February 27th, 2024
- Converging and evolving immuno-genomic routes toward immune escape in breast cancer - Nature.com - February 27th, 2024
- Sanjula Jain Urges a Comprehensive Approach in Address Alarming Rise in Cancer Cases Among Younger Populations - Managed Healthcare Executive - February 27th, 2024
- Cystic fibrosis breakthrough points to zinc as infection buster - New Atlas - February 27th, 2024
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIVworkshop ... - Nature.com - February 27th, 2024
- Is the 100-year old TB vaccine a new weapon against Alzheimers? - The Guardian - February 27th, 2024
- Immune system in the blood of Alzheimer's patients found to be epigenetically altered - News-Medical.Net - February 10th, 2024
- What impact does exercise have on your immune system? And how to stay well while cycling - BikeRadar - February 10th, 2024
- Had COVID recently? Here's what to know about how long immunity lasts, long COVID, and more - AAMC - February 10th, 2024
- Noor Momin harnesses the immune system to treat heart disease | Penn Today - Penn Today - February 10th, 2024
- Research reveals a process tumors use to induce immune suppressor cells and evade immunotherapy - Medical Xpress - February 10th, 2024
- Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure - Nature.com - February 10th, 2024
- Preventing severe allergic reactions with nanoparticles - National Institutes of Health (NIH) (.gov) - February 10th, 2024
- Sugary handshakes are how cells talk to each other understanding these name tags can clarify how the immune ... - The Conversation Indonesia - February 10th, 2024
- Scientists have identified an immune cell that can cause allergies - EL PAS USA - February 10th, 2024
- Sickle cell and the importance of the immune system - Punch Newspapers - February 10th, 2024
- Which cancers can be treated with immune checkpoint inhibitors? - MD Anderson Cancer Center - February 10th, 2024
- How does waste leave the brain? Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis - February 10th, 2024
- Healthy Kids: Give your immune system a boost to stay healthy this winter - nbc16.com - February 10th, 2024
- The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode ... - Cardiovascular Diabetology - February 10th, 2024
- Impact of Chronic Stress on Immune System and Depression | Health News - Medriva - February 10th, 2024
- I tried 'swamp soup,' the viral recipe that promises to boost your immune system - Yahoo News - February 10th, 2024
- Understanding Immune Checkpoint Inhibition Therapy: Challenges and Strategies - Medriva - February 10th, 2024
- One Simple Change May Dramatically Boost The Effect of COVID-19 Vaccines - ScienceAlert - February 10th, 2024
- The gut virome is associated with stress-induced changes in behaviour and immune responses in mice - Nature.com - February 10th, 2024
- Cancer vaccines are in the works to fight BRCA-linked gene mutations - The Philadelphia Inquirer - February 10th, 2024
- What are the organs of the immune system? - InformedHealth.org - NCBI ... - January 17th, 2024
- Novel insights into the immune response to bacterial T cell superantigens - Nature.com - January 17th, 2024
- FDA signs off on Takeda's HyQvia as maintenance therapy for CIDP - FiercePharma - January 17th, 2024
- CBDs Pobezinsky and Pobezinskaya Use Flow Cytometry to Determine How Tumor Cells Outwit the Bodys Immune ... - UMass News and Media Relations - January 17th, 2024
- Boosting. What To Do. - Science Based Medicine - January 17th, 2024
- Axelia Oncology takes its TLR2/6 agonist into the clinic to harness the innate immune system - BioWorld Online - January 17th, 2024
- Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to ... - Nature.com - January 17th, 2024
- Opinion | Thanks to mRNA, Future Drugs Will Be Easier and Faster to Make - Mississippi Free Press - January 17th, 2024
- Elon research team models the COVID immune response, one equation at a time - Today at Elon - January 17th, 2024
- Are plant-based meals good for your immune system? 4 things to know about improving your health this week. - Yahoo Life - January 17th, 2024
- Scientists Find Key To Potential Breast Cancer Prevention, Treatment | Newsroom - UNC Health and UNC School of Medicine - January 17th, 2024
- What if every germ hit you at the exact same time? An immunologist explains - The Conversation - January 17th, 2024
- Why Don't We Have a Staph Vaccine? - Healthnews.com - January 17th, 2024
- Best ways to improve your immune system - The Business Standard - January 17th, 2024
- Stanford University researchers think future pandemics could be prevented with universal vaccines - KGO-TV - January 17th, 2024
- Why you may feel depressed and anxious when you're ill and how to cope with it - The Conversation - January 17th, 2024
- New mechanism with potential to boost checkpoint-blocking cancer immunotherapies identified - Medical Xpress - January 17th, 2024
- Battling Bugs and Blues: The Interplay of Infection and Emotion - News-Medical.Net - January 17th, 2024