Transforming treatments for rare neurological disorders

Through an innovative approach to both science and business, Ovid Therapeutics is developing impactful medicines for people with rare neurological disorders.

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There are over 100 different rare brain disorders for which there are few effective medicines. It’s an area of unmet need, and one in which Ovid Therapeutics sees itself as a catalyst for transformation. 

“Over a million people in the US are affected by rare brain disorders, which have been largely ignored until now,” said Ovid CMO Amit Rakhit, a pediatric cardi­ologist who, when at Biogen, developed Spinraza (nusinersen) for a rare neuromuscular disorder. “Previously, there was little focus or understanding of rare diseases, particularly in pediatrics, and neu­rologists didn’t have the tools to make meaningful interventions. Now we’re experiencing a knowledge explosion—neurology today is becoming the new immuno-oncology.”

Over the past ten years there has been a sea change in the scientific understanding of many of these rare disorders, explained Ovid CEO Jeremy Levin, former CEO of Teva Pharmaceuticals. Additionally, tools for unravelling and influencing the molecular pathways and causes of these diseases have blossomed, regula­tory agencies attitudes to rare disorders are maturing, and patient advocacy bodies use social media to call attention to these disorders and disseminate research findings. “Consequently, neurological diseases that were previously considered intractable are now potentially treatable,” he said.

The Ovid approach

Established in 2014, Ovid was built in a very specific and strategic fashion to address a particular oppor­tunity, and its founders hired a highly experienced management team with deep expertise in transla­tional science, drug evaluation, orphan clinical drug development and commercialization.

What further sets the company apart is the targeted approach it takes to select compounds for develop­ment. Ovid seeks and secures novel molecules with excellent safety profiles for which new scientific understanding suggests a mechanism of action bet­ter suited to treating a rare neurological disorder. The team also goes out of its way to cultivate a full appre­ciation of the impact of a condition on patients, their families, support organizations, doctors, regulators and payers. 

This deep understanding enables them to construct a working hypothesis of how the candidate medicine should work, as well as the endpoints that will lead to meaningful and measurable evidence of its impact, thereby driving new therapeutic options for these devastating disorders.

Ovid’s lead candidate OV101, for instance, was originally under development by Lundbeck for insomnia but was never brought to market. The actual mode of action, identified after the drug was put aside, speaks to the presumed underlying causes of Fragile X and Angelman syndromes, said Rakhit. Recognizing this, Ovid licensed exclusive rights to the compound in 2015.

Ovid’s focus on related neurologic disorders allows for a scalable clinical and business development model.

Both Angelman and Fragile X syndrome cause a range of physical, intellectual and psychological dis­abilities. It is believed that in these disorders reduced levels of the neurological transmitter GABA result in neurons that are not properly modulated by the extrasynaptic GABA receptor. OV101 is a potent ago­nist that selectively targets this receptor and thereby restores neuron function. Its safety profile has been assessed in clinical data from over 4,000 adults, and it is now in phase 2 trials in adults with Angelman syndrome and in phase 1 trials in adolescents with Angelman or Fragile X syndrome.

Building on its experience with OV101 and by ‘cloning’ its scientific and medical capability, Ovid was able to strike a unique 50:50 partnership in January 2017 to codevelop and commercialize OV935, a compound discovered by Takeda. OV935 had been considered for a number of conditions, but Ovid and Takeda scientists realized that using OV935 to modulate its target, cholesterol 24 hydroxylase (CH24H), an enzyme expressed predominantly in the brain with a central role in neuronal cholesterol homeostasis, might be of great value in helping to alleviate epileptic encephalopathies, such as Dravet and Lennox–Gastaut syndromes and tuberous scle­rosis complex.

It is thought that increased CH24H levels in these disorders lead to the activation of NMDA receptors and high glutamatergic signaling implicated in seizures and cognitive and behavioural deficits. OV935, a CH24H inhibitor, reduces glutama­tergic signaling via modulation of the NMDA recep­tor. The candidate, which has been tested in over 80 adults, is currently in phase 1b/2a trials in adults with developmental and/or epileptic encephalopathies.

Looking forward and partnering

With two potential first-in-class assets and a proven scalable model allowing expansion into additional patient populations and with novel molecules, Ovid is on the way to becoming a leading neurological disorder company. “Diseases of the brain previously thought to be rare are actually very common in total, representing a compelling medical opportunity,” said Levin. “We are on the cusp of a transformation in treating these disorders.”

Over time, Ovid plans to in-license other compounds that address rare neuronal disorders. Through each collaboration it aims to build on existing strengths to expand the diseases it can treat, and it is looking for partners with the right scientific, medical, technical and financial fit. “Our programs meet very high stan­dards of science and our investment in patients doesn’t rest on only one compound,” said Levin. “For each dis­order, we are looking to deepen our pipeline and seek partnerships that can bolster that commitment.”


Jeremy M. Levin, CEO
Ovid Therapeutics Inc.
New York, New York, USA
Tel: +1-646-661-7661

Go to the profile of Ovid Therapeutics

Ovid Therapeutics

Ovid Therapeutics is a New York-based biopharmaceutical company using its BoldMedicine™ approach to focus exclusively on developing impactful medicines for patients and families living with rare neurological disorders. Ovid’s drug candidate OV101 is currently in development for the treatment of Angelman syndrome and Fragile X syndrome. Ovid has initiated the Phase 2 STARS trial of OV101 in adults with Angelman syndrome and a Phase 1 trial of OV101 in adolescents with Angelman syndrome or Fragile X syndrome. Ovid is also developing OV935 as part of a global collaboration with Takeda Pharmaceutical Company Limited for the treatment of certain types of rare epilepsies. A Phase 1b/2a trial is currently studying OV935 in adult patients with developmental and/or epileptic encephalopathy. Ovid is led by Jeremy M. Levin, who serves as the company’s chief executive offer and chairman of the board of directors.

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