ASGCT 2024 highlights: will the new modalities reignite interest in a sector hit by brutal economic realities?
By Simon Goldman
Posted
The wheels have just touched the ground back here in the UK from ASGCT 2024 in Baltimore, and the zeitgeist was definitively more positive and forward-looking than in either of the previous two years. Of course, the markedly more benign funding environment was at least part of that, but some good clinical progress and a shiny new collection of advanced therapy modalities supported a lot of productive interactions. Here are some key themes we took away from a full-on week of presentations, posters, and discussions in the queue for the barista team at the Regeneron stand:
The brutal reality of adoption dynamics in cell and gene therapy.
Though there was still a big focus at the conference on rare disease and autologous CAR-T (and rightfully so given the enormous unmet need in these areas), it’s abundantly clear that therapeutic programs are going to need to generate a profit if their impact is to be felt by patients globally. Many of the academics and companies presenting in Baltimore seemed driven not only by getting to clinical proof-of-concept and then FDA approval, but also increasingly by the potential for reimbursement and in making these therapies easy/cheap for patients to access. Predictably, there was also a much bigger focus on more common diseases (yet more shifting from oncology to autoimmune), in vivo applications and COGS reduction. If the cost of a therapy halves, then does the incident patient population required for IC approval halve as well?
Shiny will have its reckoning with reality, too.
Cell & Gene Therapy v1.0 approaches (such as your favourite AAV 2/5/8 or 9) are only just getting through pivotal trials and into their first taste of market reality. Yet it was clear at ASGCT that the ‘hype cycle’ has already lapped them twice, with precision approaches such as base and prime editing getting relatively little attention this year compared to epigenetic modulation and novel targeting approaches. Indeed the gene editing space seemed to be making slower progress towards clinic that we think many expected even one or two years ago, with regulatory authorities placing a much higher burden on developers to demonstrate a lack of off-target effects ahead of going into man – we think there’s still some life yet in the more clinically proven modalities. Tissue targeting and appropriate cellular delivery remain big challenges, and there’s a scramble for IP in the LNP and VLP space.
Platforms are great – but biology is better:
AAV approaches continued to dominate the 2024 conference overall (as they have for some years now), and yet again there was a plethora of next-generation capsids targeting a wide variety of different tissue types. While better tropism and better targeting is vital in enabling AAVs to effectively treat previously undruggable tissues, we’d argue that we need to complement these efforts with just as much work on new disease-relevant targets with clear mechanisms of action. Our assumption is that even when combined with these superior capsids, the vast majority of existing targets we’re going after will not lead to viable gene therapies. However, we’re also conscious that these next-generation capsids will provide talented R&D groups across the world with new tools that will enable them to push the boundaries of what we can do therapeutically. Our hope is that next year’s conference is dominated by academic and industry groups demonstrating the therapeutic potential of these new capsids in meaningful ways.
Oncology will have to wait for ASCO.
In comparison to previous years, the 2024 conference featured noticeably less overall focus on immunotherapies within oncology. This was irrespective of your preferred cell type or tumour target, and is reflective of the wider challenging biotech market that is no longer as forgiving on costly R&D immunotherapy pipelines or lukewarm clinical updates. While a number of these groups have quickly pivoted to using the same tools and chasses in immunology, our hope is that R&D groups and biotech don’t wholly abandon the impressive advancements we’ve made to date within oncology. We’re still very far from overcoming the formidable hurdles in creating viable treatments for solid tumours, but the high-unmet need and (eventual) size of the prize should justify the continued effort. It was at conferences like ASGCT that you saw the rapid understanding that a platform approach will be needed for effective immunotherapies – but you need revenue-generating products in the nearer term too. Perhaps next year we will see a return to this tinkering and even some cross-over learnings from immunology.
