Leverage AI to Lower Cost, Barriers to Cell Therapies

Noam Solomon, CEO, Immunai

Cell therapy is advancing to a future where treatments are ready-made and accessible, bypassing the limitations of current personalized medicine. In recent years, cell therapy has evolved from autologous (using one’s own cells) to allogeneic (using cells from donors), also known as off-the-shelf therapies.

The biggest challenge with off-the-shelf cell therapies is the risk of the immune system rejecting them entirely. Because we don’t fully understand how the chain reactions — akin to dominos falling in a network — in the immune system work, we are at a crossroads.

Right now, we’re only able to look at the first one-three dominos that fall (aka immune responses), leaving us guessing whether a drug will trigger the right domino effect. This is what leads to expensive clinical trial failures.

It’s why I’ve focused my career and research on mapping the human immune system in order to predict how all the dominos will fall so we can find a clinical cure.

One key to unlocking the potential of off-the-shelf cell therapies lies in our ability to engineer immune-evasive cells. If we’re successful in this, these therapies will be one of the biggest breakthroughs in precision medicine, akin to the current hype around GLP-1s. In fact, there are already companies like Allogene¹ that are in early clinical trials hoping to make this a reality for patients suffering from lymphoma.

Personalized cell therapies often exceed millions of dollars, creating a significant barrier to access, which is why there is so much hope in off-the-shelf therapies, which can easily be administered to anyone when needed. But even off-the-shelf therapies are not without challenges. The human body's immune system can recognize and reject the donor cells in the therapy before they can take effect (a key indicator of efficacy) or cause adverse reactions.

This won’t lead us to the end of personalized medicine, it will be a shift toward more effective, affordable, and accessible personalized medicine. Cells from certain donors can be more adequate for certain patients and being able to identify this is a different path to personalized medicine. But the important advantage of this over autologous cells is that this should bypass the long wait for custom-made therapies, potentially saving lives in time-sensitive cases. Accessibility and affordability also become crucial factors. Additionally, these therapies can be made from healthy donor cells as opposed to cells of patients who have been exposed to multiple rounds of chemo, older patients, etc. Imagine life-saving treatments available to all, not just those who can afford the wait and cost of personalized options.

But how do we overcome the rejection barrier? With the adequate high throughput and high-resolution molecular profiling of big data of cells, AI frameworks may provide the ability to analyze vast datasets and predict optimal cell combinations. By identifying features that minimize rejection and maximize efficacy, AI can become the “brain” for designing or for screening off-the-shelf cells, predicting which combination of features will be most effective and safe, and then performing high-throughput functional screens to validate these predictions. AI will also predict optimal combinations of these cell therapies with other treatments for even better results.

While the potential of AI-powered off-the-shelf cell therapies for precision medicine is undeniable, a significant obstacle stands in the way: the current FDA clinical trial and approval process. Recent FDA approvals and early phase 3 trial data have drawn attention to profoundly exciting new drugs and therapies like Iptacopan for rare autoimmune diseases or Tiragolumab for cancer immunotherapy, but these new drugs and therapies highlight the costs of precision medicine: billions of dollars and decades of time. This process, designed for highly individualized treatments with limited patient groups, risks hindering the advancement of these broader-reaching therapies that will be necessary for treating all patients including those without access to precision medicine.

The undeniably high cost of medication in the US stems from various factors, including lengthy and expensive clinical trials, intellectual property protections, and market dynamics. While it's true that investors expect a decent return on investment, a system solely driven by ROI can leave essential treatments out of reach for many — and in the hands of the wealthy or those who are fortunate to be covered by insurance.

Several factors contribute to the FDA roadblock. Firstly, traditional clinical trials, geared towards small, specific populations, may not be suitable for evaluating the wider applicability of off-the-shelf therapies. New models accommodating larger and more diverse patient groups are crucial.

Secondly, the multi-phase approval pathway, known for its extended timelines and substantial costs, creates a significant hurdle for smaller companies developing these next-generation therapies. Streamlining the process through innovative approaches like adaptive trials and incorporating real-world data could expedite approvals and encourage vital investment from pharmaceutical companies.

Finally, the payer paradigm is designed for lower cost per dose for ongoing and chronic treatment, but we are learning that a higher cost upfront for a single dose treatment might achieve better clinical outcomes.

Perhaps the key lies in exploring alternative and collaborative approaches within the existing framework. Could the FDA, in partnership with startups, explore streamlining clinical trials through their cutting-edge platforms, focusing on earlier lines of treatment? This could expedite approval while providing valuable data for further development. Alternatively, biopharma companies can leverage cutting-edge platforms to improve drug development.

Modernizing the FDA's approach doesn't equate to neglecting safety; it signifies adapting to scientific advancements and ensuring innovative, life-saving treatments reach patients more readily. By embracing flexibility, inclusivity, and collaboration, the FDA can bridge the gap between regulation and innovation, unlocking the full potential of off-the-shelf cell therapies and propelling precision medicine forward.

This isn't blind optimism — it's the potential of technology harnessed responsibly. Off-the-shelf cell therapies could unlock a future where treatments are readily available, personalized medicine evolves further, and healthcare equity is front and center.

Noam Solomon, CEO, Immunai

References

1. https://www.statnews.com/2024/01/04/cancer-allogene-car-t-strategy/