Adam Stoten PhD RTTP

Immunogenicity assessments - why do we bother? As an industry we spend millions of $ measuring the pre-clinical immunogenicity of our biologics. We do this because none of us want our project stopped in the clinic due to a high anti-drug antibody (ADA) response. But to deimmunize or triage those with high immunogenicity you need to be able to reliably predict ADA in an in vitro or in silico assay. Andrew Buchanan, FRSC recently made an excellent post on this topic. For most late stage clinical antibodies the ADA data is publicly available but it is buried in datasheets and reports. There is no single freely available source of the truth when it comes to ADA. I can well imagine the countless days it took Andrew to gather this data because Geoff Hale and I went through a similar exercise years ago. We extracted ADA data for 80 mAbs and hoped to show some correlation between in silico prediction and clinical ADA. We had seen others report impressive results on much smaller datasets. We were sorely disappointed with the random scatter plot we obtained. There was no correlation between prediction and reality. But is this a surprise? At times immunogenicity feels like a biological random number generator. It's dependent on sequence, structure, aggregation, dose, route of injection, health of the patient and many other factors. Most people go off the ADA value stated in the info sheet provided with a drug. But dig deeper and for something like adalimumab (Humira) you find hundreds of clinical ADA readouts with values ranging from 0 to 100%. And then we have golimumab, another anti-TNF mAb but it stands out as the only one with low immunogenicity, reported at 2.8%. But years after this measurement the scientists at Janssen decided to re-run the samples in an updated assay. The ADA response jumped 8-fold. Good on them for doing this, many others wouldn't have! For clinical ADA measurements there is no consistency in the assay setup, sensitivity or reporting. The more of this data you look at the more you question why you are even bothering! The assumption is also that ADA is a project killer, but that's not always the case. Humira is the poster child for ADA but has total sales of +$230B. People are hyping up AI as the solution to immunogenicity prediction. Surely this is a nonsense? AI needs accurate, complete and consistent data. Real world ADA data is far from this! Almost everyone I speak to treats pre-clinical immunogenicity predictions with a pinch of salt but we all continue to do them to give management, investors or advisors a warm fuzzy feeling inside that their asset is squeaky clean. Problem is, the first real experiment isn't until phase 1. ----- I'm Ian, I post about antibody engineering, recombinant proteins and my journey to bootstrap Gamma Proteins into a leading supplier of Fc receptors. If you like my content please reshare with your network and follow me to see more.

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𝗧𝗮𝗸𝗲𝗱𝗮 𝗲𝘅𝗶𝘁𝘀 𝗰𝗲𝗹𝗹 𝘁𝗵𝗲𝗿𝗮𝗽𝘆—𝗯𝘂𝘁 𝘁𝗵𝗶𝘀 𝗶𝘀𝗻’𝘁 𝘁𝗵𝗲 𝗲𝗻𝗱 𝗼𝗳 𝘁𝗵𝗲 𝘀𝘁𝗼𝗿𝘆 Takeda just announced they’re ending all ex vivo cell therapy work as part of a strategic portfolio shift. It’s easy to read this as a death knell for the modality. But history tells a different story. Promising modalities don’t die—they hibernate. Builders keep iterating through the quiet periods. Then, when the science catches up, pharma rushes back in. We’ve seen this pattern before:  • 𝗔𝗗𝗖𝘀 — Largely abandoned after early toxicity failures. Revived through better linkers, novel payloads, and smarter patient selection. Now a cornerstone of oncology.  • 𝗥𝗡𝗔 𝘁𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 — Stalled for years due to delivery challenges. Rescued by breakthroughs in siRNA and antisense chemistry. Now foundational to drug discovery.  • 𝗺𝗥𝗡𝗔 — Dismissed as too unstable and impractical. COVID vaccines changed everything overnight. Now every major pharma has an mRNA program. Ex vivo cell therapies might be in their “winter” phase. The challenges—complex manufacturing, hostile tumor microenvironments, limited persistence—are real but not insurmountable. The next wave is already forming: automated manufacturing platforms, multiplex genome editing, novel conditioning regimens, off-the-shelf products, and TME-resistant designs. If you’re building in cell therapy right now, you’re exactly where the winners were during past troughs. When the breakthrough arrives—and it will—pharma will flood back in, just like they always do. The question isn’t 𝘸𝘩𝘦𝘵𝘩𝘦𝘳 cell therapy will rebound. It’s 𝘸𝘩𝘰 𝘸𝘪𝘭𝘭 𝘴𝘵𝘪𝘭𝘭 𝘣𝘦 𝘣𝘶𝘪𝘭𝘥𝘪𝘯𝘨 when it does. https://lnkd.in/eKy6hMpx

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The Double Click: New Episode Now Live!    Here is our second episode of #TheDoubleClick, where we explore "change leadership" in large companies. When disruptive technologies emerge, it's important to strategically invest in disruptive innovation for the tectonic industry shifts as well as sustaining innovation for competitive improvements in current trajectory. Both strategies are valuable and necessary. In this episode, I chat with Luis Arosemena, GSK’s Senior Vice President of Global Commercial Strategy. We discuss what endurance sports teach us about leadership, balancing global strategy with local empowerment, the importance of reimagining healthcare in the age of AI, and what Peruvian ceviche can teach us about leadership. It's a thoughtful discussion with practical takeaways for leaders navigating complexity and change. Watch the full conversation here: https://lnkd.in/e24gb6bN #TheDoubleClick #AheadTogether #Innovation #Healthcare #Technology  

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Regenerative Medicines are starting to work, and now it’s time to make them scalable! I’m super excited to launch Mytos CDMO: our automated CDMO for manufacturing Regenerative Medicines! 🚀🚀 Site 1 launches today housed in the Cell and Gene Therapy Catapult's building, and we have a network of global sites planned. Our aim is to scale to 100,000 patient doses/year within a decade. Over the past 18 months, Regenerative Medicines have shown incredible results from reversing Parkinson’s symptoms, to restoring lost vision. But today these therapies are produced by hand, making them extremely hard and expensive to scale. Mytos CDMO industrialises these therapies, enabling scalable production at low cost - to get these therapies to the patients that need them. And because Mytos CDMO leverages our automated iDEM technology, most manual processes can be transitioned to automated in as little as 3 runs. Reach out to find out how we can make your therapies scalable today! Read more in the Press Release here: https://lnkd.in/eGs3mquw Matthew Durdy, David DiGiusto, Barry J. Oliver

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Fantastic to see Trogenix close one of Europe’s largest early-stage biotech rounds this year—a £70M Series A to advance potentially curative therapies for aggressive cancers. This milestone highlights the transformative potential of their Odysseus® platform and Scotland’s growing leadership in cell and gene therapy.   Scottish Enterprise supports Trogenix through strategic account management, and long-term investment in the Edinburgh BioQuarter —home to the CGT Catapult and the world’s largest academic grouping in cell and gene therapy and tissue engineering. Following initial support through our High Growth Spin Out Programme, Trogenix has benefited from assistance with investment readiness, intellectual property and ongoing guidance and scaling support from our High Growth Companies Team.    From exciting spinouts like RoslinCT, Resolution Therapeutics and Trogenix to cutting-edge facilities and funding, Scotland provides a world-class environment for companies tackling global health challenges.   We’ll continue to back ambition in this vital sector.   #WeBackAmbition #LifeSciences #CGTCatapult #Trogenix

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A key lesson from mAbs in the 90's was not to build too much capacity. Did we learn our lesson for CGT? Andy Lewin joined us recently on our new podcast 𝗟𝗲𝗻𝘁𝗶 𝘄𝗶𝘁𝗵 𝗙𝗿𝗶𝗲𝗻𝗱𝘀 where he recalls a lot of discussion in the late 90's about the demand for manufacturing capacity in mAb bioproduction. At that time there was a lot of demand for the production of clinical material, with the expectation that mAb candidates would flourish. Developers built a lot of manufacturing capacity to meet this demand. While many mAbs did become highly successful and could fill this capacity. Many others did not. This led a lot of developers to either just shut down this additional capacity, or sell off whole sites to CDMO's. 𝗗𝗶𝗱 𝘁𝗵𝗶𝘀 𝗲𝘅𝗽𝗲𝗿𝗶𝗲𝗻𝗰𝗲 𝘁𝗲𝗮𝗰𝗵 𝘂𝘀 𝗮𝗻𝘆𝘁𝗵𝗶𝗻𝗴 𝗳𝗼𝗿 𝘃𝗶𝗿𝗮𝗹 𝘃𝗲𝗰𝘁𝗼𝗿 𝗺𝗮𝗻𝗳𝘂𝗮𝗰𝘁𝘂𝗿𝗶𝗻𝗴? Fast forward circa 2018 and the dilemma is the same. Huge demand for viral vector manufacturing, and not enough capacity. Many developers were wary, and rather than build they relied on CDMOs. 𝗦𝗼 𝘆𝗲𝘀, 𝗱𝗲𝘃𝗲𝗹𝗼𝗽𝗲𝗿𝘀 𝗱𝗶𝗱 𝗹𝗲𝗮𝗿𝗻 𝘁𝗵𝗲 𝗹𝗲𝘀𝘀𝗼𝗻 (𝗺𝗼𝘀𝘁𝗹𝘆𝗅). Unfortunately, the CDMOs didn't... they built a lot of manufacturing capability modeled on highly optimistic demand assumptions. That CDMOs like Exothera are closing up shop should not surprise us - we have seen it before. 25 years ago! Last time around CDMOs picked up the pieces of developers unwanted mAb capacity. Do you think anyone will pick up unwanted vector capacity now? Let me know in the comments below. P.S. if you want to see the full podcast, I will put the links in the comments.

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It’s great to see LinkGevity featured in the Financial Times as part of their five-part series on companies focused on #ageing science & #longevity - and to be featured alongside some of the biggest names in the field. The timing has been interesting. Just a week ago, Calico Life Sciences (set up as Google’s aging and longevity division) announced they’re targeting the #kidney in their latest programme. It’s encouraging to see this focus - their work reinforces how central kidney health is. At LinkGevity, our #Anti-Necrotic™ therapeutic is designed to prevent the cascade of cell death that drives tissue decline - bringing longevity science closer to the clinic. The FT story highlights how this work is helping translate cutting-edge science into medical applications, and bridging a gap that has held the field back for decades. A huge thank you to everyone who made this possible - our team: Serena Kern-Libera, Greg J., Lukasz Rzeczkowski, Nikodem Grzesiak, Bill Davis; our partners and advisors: Justin Stebbing, Annalisa Jenkins, Joseph Bonventre, @Richard Faragher; and the brilliant community at Babraham Research Campus including Louise Jopling, Jenny Hirst, Ruth Campbell and Rachel Williams (McMenamin). Also grateful for the continued support from Barbara Domayne-Hayman, Beth Massam, Emma Fox, KQ Labs The Francis Crick Institute And all the hard work from Domainex including Jesse Peterson, Carlos Turrado García, Nima Abbasian, Roland Schindler, Poppy Wood, Chloe Eeles, Barbara Vaccari Cardoso It’s inspiring to see how far the field has come, with groups like Altos Labs and others pushing boundaries alongside us. Together, we’re proving that tackling ageing isn’t science fiction - it’s an emerging therapeutic frontier. https://lnkd.in/eYX9Z85i

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Met up yesterday at our office with an exciting UK company that has leveraged research and AI tools to offer novel solutions for cancer treatment, and particularly colorectal cancer. It was great to learn from and exchange ideas with the innovative and passionate team at Vivan Therapeutics, led by Laura Towart and Nahuel Villegas. Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10% of all cancer cases and is the second leading cause of cancer-related deaths. It predominantly affects older individuals, with the majority of cases incurring in people aged 50 and above. Sadly we will all know someone in our lifetimes who will be impacted by this aggressive cancer. Treatment options are most effective if colorectal cancer is detected in the early stages, and treatments for more advanced stage cancers aim to slow down its spread and extend patient life. Survival rates are high if detected at Stage 1. but fighting this cancer is more challenging if it is detected only in the later Stages. Vivan's TuMatch service was developed in partnership with the prestigious Mt Sinai Medical Center, and uses groundbreaking software to build on years of Mt Sinai's research to suggest new possible personalised drug combinations based on the genetic profile of a patient's tumour. The Vivan team likes to work closely with patients and their oncologists who are already undergoing conventional treatments for colorectal cancer, or who face delays in receiving surgery or radiation treatment. What underpins TuMatch? The personalised treatment recommendation for a colorectal cancer is created using a novel combination of already individually approved drugs. This combination is established for a particular patient based on Vivan's unique database , ongoing continuous lab testing, and proprietary software and tools. Vivan has historically focused its efforts in the US, China, UK, and UAE, but CEO Laura says her team is ready to work with patients and their oncologists anywhere in the world. I asked her if she was willing to hear directly from people who might want to learn more and she replied, "of course". She said either DM her directly at Laura Towart or contact her team via the Vivan website at https://lnkd.in/eTW4S4cR

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