How did your professional journey lead you to Arialys Therapeutics?
At the outset of the Human Genome Project, I found myself at Yale University getting a deep understanding of classical human genetics and moved to an industrial post doc at DuPont Merck, where I engaged in the crucial task of collecting DNA samples from clinical trials. This work was pivotal in beginning to uncover the genetic factors influencing individual responses to drugs.
My path took an unexpected turn when a venture capitalist, who remains my partner after three decades, presented me with an opportunity to cofound a company in the early 90s. This venture, Sequana Therapeutics, was one of the pioneering four in genomics. Then I navigated through various roles in other genomics companies and spent a year at Pfizer, which enriched my experience further.
Since 2007, I have been at Avalon Ventures, now known as Avalon BioVentures, co-founding around 30 companies, with Arialys being my latest venture. In our unique approach at Avalon, we actively take management roles in our startups, guiding them through critical early stages to either significant funding rounds, full-time management transitions, or other pivotal milestones. My career has been a blend of entrepreneurship, venture capitalism, and scientific inquiry.
Arialys Therapeutics is delving into groundbreaking areas in psychiatry and immunology. Can you elaborate on the connection between the immune system and psychiatric disorders?
The connection between the immune system and psychiatric disorders is a relatively new and exciting area of research. For many years, the prevailing belief in CNS research was that the brain was immune privileged, much like the eye. However, recent data has begun to challenge this long-standing dogma.
Looking back, indications of an immune system connection were present in diseases like multiple sclerosis (MS) and myasthenia gravis, which have neurological components. A key breakthrough in our understanding came with the identification of pathogenic autoantibodies in cerebrospinal fluid (CSF) of patients with MS. We are developing a therapeutic for anti-NMDA receptor encephalitis (ANRE), a rare, potentially lethal, and poorly managed neurological disease, where NMDA receptor autoantibodies lead to psychosis and severe neurological challenges. These discoveries have led to a shift in perceptions and a surge in interest and research in this field.
For instance,
Our research was recognized as a top presentation among hundreds at a major neuropsychopharmacology conference.
This shift marks a turning point in acknowledging the impact of the immune system on psychiatric conditions, setting the stage for innovative treatment approaches.
How do you view the trend of investment in neurosciences, having in mind the little traditional appetite that investors have had for the field?
There is also a notable shift in the investment landscape for neuroscience. Historically, this field has faced skepticism due to the lack of significant innovations over the past few decades, resulting in a lack of investments. However, companies like Denali and Karuna have demonstrated success, renewing interest in the field. Denali's approach bypasses unreliable animal models, favoring direct clinical trials based on strong biological conviction. Karuna, albeit following a more conventional path, achieved a staggering $14 billion valuation. These examples underscore a new optimism in neuroscience investments.
What are the principal challenges you anticipate at Arialys?
Our primary challenge is navigating the regulatory landscape, as there is no FDA approved treatment for ANRE. We are working closely with the FDA, hoping to secure Fast Track designation for our lead drug candidate, ART5803. Fast Track supports more frequent communication and collaboration with the FDA, which is vital for addressing their concerns and accelerating the development of new treatments.
Patient recruitment poses another hurdle, especially given the rarity and severity of the diseases we target. Recruiting patients early in their disease progression is crucial, as delayed treatment can lead to irreversible neuronal damage. This necessitates a broad, international network of clinical sites.
Additionally, for broader indications like schizophrenia, where about 5% of patients have autoantibodies against NMDA receptors, we face a high screen failure rate. So we’ve developed a diagnostic assay to measure CSF for the pathogenic autoantibodies as well as markers of immune responses.
When will your therapeutic be available on the market?
We are currently progressing through significant stages of development for our lead therapeutic candidate. We have seen promising and rapid efficacy results in marmoset models and are conducting a toxicology study in higher animal models, which is yielding promising results without any observable adverse events. This will pave the way for trials with healthy volunteers later this year.
Following this, we aim to commence trials with ANRE patients around the middle of 2025, assuming all progresses well. In terms of timeline, we are engaging with the FDA to define the registration process. Optimistically, our therapeutic could hit the market by 2027, but a more realistic projection would be around 2028 or 2029. This timeline is contingent upon the performance of our drug candidate and the responses we observe in patients.
A key factor that could accelerate our progress would be if we observed in our clinical trials a rapid and remarkable recovery in patients akin to what we have seen in marmosets. If we see this, it could significantly expedite patient recruitment and overall development speed.
