An Exclusive Interview with Jacob Jacobsen
Chief Executive Officer, Evecxia Therapeutics
Building on the momentum from Cobenfy’s success, how has the psychiatric drug development landscape evolved over the past 6 to 12 months, and what is the current state of play?
Commercially and from an M&A standpoint, recent successes include Cobenfy, Auvelity, Caplyta, and even Spravato. Those successes demonstrate the massive commercial potential in psychiatry. Cobenfy, Auvelity, and particularly Caplyta win on safety. Safety = scalability. Scalability = large markets. Large markets = blockbuster potential. All four drugs are based on clinical evidence. Cobenfy and Spravato use novel mechanisms of action, while Auvelity and Caplyta optimize on validated pharmacologies of yore. Unfortunately, in depression, there have been regrettable—yet no unexpected—trial failures.
- The kappa opioid antagonists (Navacaprant, Aticaprant) were always long shots, as (i) this is not a potent pharmacology and (ii) the therapeutic range is very narrow. But kudos to Neumora and J&J for taking the risk for patients.
- Non-hallucinogenic NMDA antagonists, e.g., REL1017, Arketamine. Over the last two decades, all non-hallucinogenic NMDA antagonists failed. This, interestingly, raises the question whether NMDA antagonism is even antidepressant...? Ketamine has numerous other pharmacologies than NMDA antagonism.
- ALTO-100 failed once in Phase 2 and is based on the BDNF hypothesis of antidepressant action, which is, in turn, based on 30 years of animal, rather varied, animal data.
From new targets to emerging technologies, where are the most exciting areas of innovation?
To me, “exciting” are options that make a difference to patients. I can only speak to drugs.
- Cobenfy, and other muscarinergics for schizophrenia: New safer option.
- Neurocrine’s AMPA positive allosteric modulator osavampator for depression: Novel option.
- Psychedelics: Although psychedelics are likely to be less effective in Phase 3 trials, high cost will likely reserve psychedelics for the sickest and best insured patients.
- Evecxia’s EVX-101 (our company’s lead candidate), as safety, scalability, and a robust clinical evidence rationale support widespread implementation across multiple psychiatric disorders.
Which specific challenges are you looking forward to addressing with colleagues at the Neuropsychiatric Drug Development Summit in order to collaboratively propel advancements?
- Abandoning animal psychiatric disease models so we can concentrate on what is meaningful and fruitful, namely, human research.
- Clinical trial integrity, e.g., avoidin inappropriat and/or professional patients.
- Realism. Let’s not get our excitement too far in front
of the data.
Which sessions in the agenda are you most looking forward to at the 8th Neuropsychiatric Drug Development Summit?
- Panel Discussion: Overcoming the Phase II/III Roadblock: Reflecting on Lessons Learned to Drive Novel Mechanisms of Action Through Clinical Trials & Beyond
- Rethinking Neuropsychiatry: Moving from Symptomatic Frameworks to a Biology-Led Discipline
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