Setbacks can lurk round any nook in neuroscience R&D — even when the trail forward seems to be clear. Ovid Therapeutics just lately encountered a harsh reminder of that truth.
About three years in the past, Ovid bought growth and commercialization rights for an experimental drug soticlestat to Takeda after scoring optimistic mid-stage readouts for 2 uncommon types of epilepsy. And if section 3 research confirmed the outcomes, soticlestat was poised to turn out to be a “blockbuster of main proportions” for the advanced situation with scores of ineffective or facet effect-laden remedies, Ovid’s CEO, Jeremy Levin, advised PharmaVoice final spring.
But it surely wasn’t fairly meant to be.
In June, Takeda introduced soticlestat missed major endpoints in late-stage trials concentrating on Dravet syndrome and Lennox-Gastaut syndrome. Now the drug’s future, and Ovid’s potential $660 million in milestone funds, cling within the steadiness as Takeda works with regulators to find out if optimistic outcomes on secondary endpoints for sure sufferers is sufficient to transfer ahead.
Dr. Amanda Banks, CDO, Ovid Therapeutics
Permission granted by Ovid
Regardless of the outcomes and the layoffs it triggered, Ovid is charging confidently forward with new management on the helm. Dr. Amanda Banks got here on board as the brand new chief growth officer in August, bringing a deep background in biotech drug growth and neuroscience. And earlier this month, Meg Alexander was promoted to president and chief working officer after serving in different government positions since 2020.
The C-suite shakeup comes as Ovid embarks on a metamorphosis from a core give attention to epilepsy to restoring “steadiness and homeostasis within the mind,” Alexander mentioned.
“Underneath the hood of our firm we’ve thrilling applications,” Alexandra mentioned.
Pipeline hopefuls
The corporate’s lead asset is a novel ROCK2 inhibitor in early-stage trials for brainstem cavernous malformations. However as a result of the ROCK2 signaling pathway “could also be hyperactive in a number of neurological illnesses,” the corporate sees broader potential.
Alexander mentioned Ovid may even have a “potential franchise” on its fingers with a preclinical KCC2 platform that would ship a number of first-in-class compounds for epilepsy and different CNS issues.
“Every program is permitting us to broaden into extra therapeutic areas by addressing the reason for pathology of illness,” Alexander mentioned.
Ovid isn’t abandoning its roots, nonetheless, and can be advancing a GABA-AT inhibitor that would ship higher efficacy and security for uncommon and treatment-resistant types of epilepsy.
Regardless of latest obstacles, Financial institution mentioned classes from soticlestat’s shortcomings together with bigger-picture advances in neuroscience have turn out to be “fertile floor” for an eventual win.
Classes discovered
When requested what went flawed with the section 3 trials for soticlestat, Alexander pointed to the inherent complexities of the illness.
“Lennox-Gastaut specifically is an extremely tough indication to discover a therapeutic for,” she mentioned. “As we study extra about it, my robust suspicion is that we’ll really not name it Lennox-Gastaut — it is going to possible be generally known as 10 to twenty totally different circumstances.”
Trial design may have additionally come into play.
“Endpoints are usually exquisitely depending on the sufferers,” Banks mentioned.
“That is the one firm I do know that has these applications and mechanisms.”
Meg Alexander
President, COO, Ovid Therapeutics
Going ahead, specialised drug growth and staffing experience may assist Ovid design fit-for-purpose trials concentrating on the suitable affected person inhabitants, Banks mentioned.
“In neurodegenerative illnesses, there are a few areas of variability we are able to management,” Banks mentioned. “We have now to work with individuals who have deep expertise working with these circumstances.”
Ovid can be banking on an elevated use of biomarkers, which Banks mentioned may decrease the variability that “plagues” the trade in neuroscience. For instance, Ovid can use transcranial magnetic stimulation to measure ranges of GABA within the mind whereas testing its GABA-AT inhibitor, OV329.
“That offers us a superb sense of [whether] we see indicators of that mechanism of motion within the works,” Alexander mentioned. “These are extremely delicate instruments that don’t require taking spinal fluid from a affected person or different invasive procedures … and it helps give us conviction that we’ve a drugs that works, which de-risks the trials.”
Whereas the pursuit of experimental medication could seem dicier, Alexander mentioned it’s a lane Ovid is snug occupying.
“We’re doubling down on novel mechanisms,” she mentioned, stating that if Ovid follows present developments in neurodegenerative drug growth, it gained’t be as effectively positioned in 5 to 10 years.
“Yet one more small firm going after the identical goal, and you then’re attempting to win in the marketplace with barely higher pharmacology or efficacy — that’s not good for sufferers or the corporate,” she mentioned.
Within the coming months, Alexander mentioned among the playing cards from its medical applications can be “beginning to flip over.”
Ovid plans to ship new preclinical animal knowledge on its GABA-AT program inside the subsequent few weeks together with a section 1 readout earlier than the yr’s out. And whereas Ovid prepares for a section 2 of its ROCK2 program, Banks is on the brink of file the primary regulatory submission for its KCC2 platform. After that, Alexander predicts Ovid can be submitting an IND leveraging KCC2 yearly for the following 5 years.
However Alexander admitted that “none of that is going to work” if Ovid goes it alone.
“We’re centered on the precise partnerships to convey all of it ahead,” she mentioned. “That is the one firm I do know that has these applications and mechanisms, so it’s very thrilling, and hopefully we’ll make an amazing impression for affected person communities.”
