ROCK

Scholar Rock contends its experimental drug for spinal muscular atrophy can achieve what none of the currently available therapies can do to treat this rare disease. After positive data from a pivotal study sent the biotech’s shares skyward, Scholar Rock has raised $300 million from a stock offering that will be applied toward regulatory submissions and launch preparation of what could become its first commercialized product. The stock sale follows the company’s Phase 3 data readout earlier this week showing its drug, apitegromab, met the goal of showing muscle function improvement in spinal muscular atrophy (SMA). The Cambridge, Massachusetts-based biotech is planning regulatory submissions to the FDA and the European Medicines Agency early next year. SMA stems from mutations to the gene that codes for survival motor neuron (SMN), a protein key to keeping motor neurons healthy. Patients who have the rare inherited disease develop progressively worsening muscle weakness. Few therapies are available for SMA. Biogen was first with Spinraza, an antisense oligonucleotide intended to increase production of functional SMN protein. Novartis offers a one-time treatment with Zolgensma, a gene therapy that replaces the defective gene with a functioning one. Evrysdi, a drug developed by PTC Therapeutics and commercialized by Roche, offers another approach. This oral small molecule is designed to get the SMN2 gene to produce more SMN protein. sponsored content Upcoming Webinar: Battle of the Budget: Employers vs. Rising Healthcare Costs Gain valuable knowledge and practical insights on how employers are addressing an increasingly complex healthcare budget landscape. By Personify Health Scholar Rock takes a different and perhaps complementary approach to available SMA therapies. Treatments that target SMN prevent further degeneration of motor neurons, but they do not directly affect muscle atrophy, the company said in an investor presentation. Apitegromab is a monoclonal antibody designed to block activation of myostatin, a protein in skeletal muscle that inhibits muscle growth. It’s administered as an intravenous infusion every four weeks. The placebo-controlled Phase 3 test evaluated the study drug in patients who were already taking the standard chronic SMA therapies Spinraza or Evrysdi. This trial enrolled 188 SMA patients ages 2 to 21. In preliminary results reported Monday, Scholar Rock said the drug achieved statistically significant and clinically meaningful improvement at 12 months, measured according to a scale used to assess muscle function in SMA patients (a higher score indicates better muscle function). The company added that 30% of patients who received the study drug showed a 3 point or greater improvement in score compared to 12.5% of patients in the placebo group. Early motor function improvement was observed at eight weeks and that benefit expanded at week 52, as measured according to the rating scale. The drug was well tolerated and no serious adverse events were reported. “The results clearly demonstrate robust and clinically meaningful improvement in motor function in patients with SMA,” Scholar Rock CEO Jay Backstrom said in a prepared statement. “At Scholar Rock, we are working with urgency to deliver the potentially transformative benefits of apitegromab to children and adults with SMA in the U.S., Europe, and around the world.” The apitegromab results will be presented on Friday during the Annual Congress of the World Muscle Society meeting in Prague. In the investor presentation, Scholar Rock claimed its drug is the first and only muscle-targeted therapy to show both clinically meaningful and statistically significant functional improvement in SMA. The company added that apitegromab is the first and only anti-myostatin therapy to show muscle improvement in a Phase 3 study. Biohaven might have something to say about that soon. That company’s experimental SMA therapy taldefgrobep alfa, an inhibitor of both myostatin and the activin A pathway, is expected to post Phase 3 data by the end of this year. Sponsored Post Get Ready for HLTH 2024: A Preview Guide HLTH 2024, scheduled for October 20-23 at the Venetian Expo Center in Las Vegas, will highlight new programming, a physicians roundtable, generative AI, the shifting landscapes of telemedicine, retail health, women's health, and lots more. By Stephanie Baum Shares of Scholar Rock soared more than 300% after the biotech’s data release, and the company seized on the opportunity to raise money. Late Tuesday, Scholar Rock priced an offering of more than 10.2 million shares at $28.25 each. The offering includes pre-funded warrants to purchase 353,983 shares at the public offering price. Scholar Rock has also granted underwriters a 30-day option to purchase up to 1.5 million shares of stock at the public offering price, which could raise $42 million more. Scholar Rock said regulatory submissions for apitegromab in the U.S. and Europe are planned for the first quarter of next year, setting the stage for a potential fourth quarter 2025 commercial launch. Scholar Rock sees additional potential applications for apitegromab. The company is evaluating the drug as a way to help preserve muscle in patients taking a GLP-1 drug for weight loss. Muscle loss is a known side effect of the GLP-1 drug class, leading a growing number of companies to try and address the complication. Late last month, BioAge Labs’ IPO raised more than $200 million to continue clinical development of an oral small molecule intended to preserve muscle mass. A Phase 2 study is underway evaluating the BioAge drug in combination with Eli Lilly obesity drug Zepbound; preliminary results are expected in the third quarter of 2025. By then, Scholar Rock should already have topline results for the obesity study, which on track to post data in the second quarter of 2025. In the prospectus, Scholar Rock said proceeds from the offering combined with its existing capital will be used to support commercialization of apitegromab and to advance other programs. The company estimates that the stock offering provides enough capital to fund operations into the fourth quarter of 2026. Image: koto_feja, Getty Images

Study found OV329 cleared and remained undetectable in the retina, eye, and brain tissues of mice, unlike vigabatrin which has repeatedly shown to preferentially accumulate in mouse retinas, eyes, and other tissues OV329’s potency, mechanism of inhibition, short half-life, rapid tissue elimination and prolonged pharmacodynamic effect suggests it delivers a differentiated ocular safety and efficacy profile from vigabatrin A Phase 1 trial evaluating OV329 in healthy volunteers is on-track for completion in late 2024 and will evaluate safety and two biomarkers for target engagement and evidence of clinical effect NEW YORK, Sept. 26, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company dedicated to improving the lives of people affected by rare epilepsies and brain conditions presented the results of a head-to-head animal study evaluating whether OV329 could be found to accumulate in mouse retinas and brains, as has been previously shown to occur with vigabatrin (VGB) the only FDA-approved GABA-aminotransferase (GABA-AT) inhibitor. The findings, which were presented via a poster at the Epilepsy Pipeline Conference, found that OV329 cleared and remained undetectable in the retinas, eyes, and brains of mice after 48 hours of continuous exposure via a sub-cutaneous osmotic pump, suggesting a lack of accumulation. In contrast, ocular accumulation of VGB was confirmed within this period. Full results from the head-to-head animal study will be presented at the 2024 American Epilepsy Society conference in December. These results replicate previously published findings that indicate VGB preferentially and rapidly accumulates within mouse tissue and plasma, including retina, visual cortex, and brain at subtherapeutic doses (70 mg/kg).1,2 In contrast, a therapeutic dose of OV329 in animals (5 mg/kg) did not show signs of ocular accumulation in the same study design. These results complement previously presented studies which showed that therapeutic doses of OV329 (3 mg/kg) did not result in retinal tissue pathology at 45 days in Sprague Dawley rats, an animal model that investigates structural and functional ocular toxicity.3 In contrast, VGB did show retinal cell degradation at the therapeutic dose in animals of 300 mg/kg at 45 days. “Today’s findings suggest a compelling and potentially differentiated profile for OV329. A combination of attributes potentially enables OV329 to deliver an anti-convulsant effect at lower, safer, and non-sedative doses without the same ocular changes seen with vigabatrin,” stated Zhong Zhong, Ph.D. and Chief Scientific Officer of Ovid Therapeutics. “Specifically, OV329’s potency, tissue-clearance, mechanism of inhibition, pharmacokinetic and pharmacodynamic profile suggest it is highly efficient at binding to, and inhibiting the GABA-AT enzyme, and then, rapidly clearing the tissue. We believe this unique combination of drug characteristics may have application in a variety of conditions characterized by hyperexcitation,” he added. STUDY METHODS AND RESULTS At the Epilepsy Pipeline Conference, Ovid presented results from a preclinical head-to-head study intended to evaluate the tissue distribution of OV329 and VGB following continuous infusion via a subcutaneous osmotic pump in mice for two days. This study replicates and builds upon published research examining how VGB preferentially accumulates in the retina, eye, and visual cortex.1,2 The presented study tested OV329 at 5 mg/kg/day, compared to 80 mg/kg/day of VGB. Notably, the dose studied for OV329 led to exposures above those expected to be reached in humans, while VGB was tested at the established therapeutic exposure level in humans. OV329 was not observed to accumulate in the retina, eye, or brain. The concentrations of OV329 in target tissues were below the lower limit of quantification, or undetectable, indicating that OV329 clears and does not accumulate in the retina, eye, or brain. It is thought that OV329’s short-half-life of 1.5 hours, quick tissue elimination properties, and prolonged pharmacodynamic effect may reduce the risk of ocular accumulation to occur. VGB has been shown to accumulate in the eye at sub-therapeutic doses in animals and was associated with ocular toxicity at therapeutic doses in humans. Previous animal studies have demonstrated VGB’s tendency to accumulate preferentially in the retina, eye, visual cortex and brain with significantly higher retina/plasma ratios observed (6.1 ± 0.29).1 VGB also demonstrated a higher preference of the biological active S- (+) enantiomer to accumulate in tissues suggesting the potential for more prominent off target effects.4 OV329 PHASE 1 TRIAL Ovid anticipates the completion of a Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study of OV329 in healthy volunteers in late 2024. This safety and tolerability study is additionally applying magnetic resonance spectrometry and transcranial magnetic stimulation, respectively, as biomarkers of target engagement and potential clinical effect. The poster presented at the Epilepsy Pipeline Conference can be found under the Posters and Publications section of Ovid’s website at investors.ovidrx.com ABOUT OV329 OV329 is a next-generation anti-seizure medicine being developed for the potential treatment of rare and treatment-resistant forms of epilepsy and seizures, such as seizures associated with tuberous sclerosis complex, infantile spasms and conditions with focal onset seizures. OV329 inhibits GABA-AT, which is an enzyme in the brain that catabolizes GABA and thereby increases endogenous levels of GABA, the brain’s inhibitory neurotransmitter. By increasing GABA, OV329 is thought to reduce neuronal hyperexcitability and suppress seizures. OV329 was rationally designed to improve upon and potentially supplant VGB, the only FDA-approved GABA-AT inhibitor. VGB is an approved anti-convulsant for the treatment of infantile spasms and refractory complex partial seizures. Use of VGB has been limited by its Black Box warning for permanent bilateral peripheral visual field constriction, a form of irreversible blindness that occurs in some patients taking the drug. Prior studies have shown OV329 to be 200-to-1,000-fold more potent than VGB. OV329 has been shown to possess favorable tissue clearance characteristics, while delivering prolonged PD effect through both phasic (synaptic) and tonic (extrasynaptically) inhibition, thereby strengthening inhibitory neurotransmission in the neuronal milieu. About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company that is dedicated to improving the lives of people affected by rare epilepsies and brain conditions with seizure symptoms. Ovid is advancing a pipeline of novel, targeted small molecule candidates that modulate the intrinsic and extrinsic factors involved in neuronal hyperexcitability causative of seizures and other neurological symptoms. Ovid is developing: OV888/GV101 capsule, a potent and highly selective rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor, for the potential treatment of cerebral cavernous malformations and other rare central nervous system diseases; OV329, a GABA-AT inhibitor, a potential therapy for treatment-resistant seizures; and OV350, a direct activator of the potassium-chloride co-transporter 2 (KCC2), for the potential treatment of epilepsies and other psychiatric conditions. For more information about these and other Ovid research programs, please visit www.ovidrx.com. Forward Looking Statements This press release includes certain disclosures by Ovid that contain “forward-looking statements” including, without limitation: statements regarding the potentially differentiated ocular safety and efficacy profile of OV329; the expected timing of completion of Ovid’s Phase 1 SAD and MAD trial evaluating OV329 in healthy volunteers; the therapeutic potential of OV329, including potential anti-convulsant effect, tolerability and non-sedative dosing; the potential application of OV329 to a variety of conditions characterized by hyperexcitation; OV329’s potential as a treatment of rare and treatment-resistant epilepsy and seizures; the potential therapeutic opportunity of OV888/GV101 capsule, OV329 and OV350; and other statements that are not historical fact. You can identify forward-looking statements because they contain words such as “anticipates,” “believes,” “expects,” “intends,” “may,” “plan,” “potentially,” and “will,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, the risk that results of preclinical studies or earlier clinical trials are not necessarily predictive of future results, our drug candidates may not have favorable results in planned or future preclinical studies or clinical trials, or may not receive regulatory approval. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”) on August 13, 2024, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Ovid assumes no obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Investor Relations:Garret Bonney617-735-6093gbonney@ovidrx.com Media:Raquel Caborcabo@ovidrx.com ________________________1 Walters DC, et al. Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects. Pharmacol Res Perspect. 2019 Jan 72 Colmers PLW, et al. Sustained Inhibition of GABA-AT by OV329 Enhances Neuronal Inhibition and Prevents Development of Benzodiazepine Refractory Seizures. eNeuro. 2024 Jul 3 Bailer, et al. Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): I. Drugs in preclinical and early clinical development. Epilepsia. 2022 Aug.4 Walters DC, et al. Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity. Epilepsy Res. 2021 Feb.

Valo Health, the well-funded computational drug discovery and development startup launched by Flagship Pioneering, lost its interim CEO less than a year after he took the role, Endpoints News has learned. Graeme Bell is no longer steering the startup, according to a Flagship spokesperson. He vacated the position this month, according to his LinkedIn profile, after stepping up from CFO duties at the beginning of this year when founding CEO David Berry departed. Berry is now running a $300 million health tech and longevity VC firm with his brother. Bell did not immediately respond to inquiries from Endpoints. The startup also made changes to its board. Pioneering Medicines President Paul Biondi is now executive chair of Valo and its acting CEO “until a new leader is appointed,” according to the Flagship spokesperson. Earlier this year, Flagship’s growth partner Chris Schade was named executive chair. “We remain excited about the company’s strong momentum as we continue on our mission to harness high-quality patient data and powerful AI-driven technology” to create medicines, Biondi said in an emailed statement. Bell’s departure comes as Valo’s biggest clinical readout to date looms. The startup anticipates data from its Phase 2 Spectra trial in diabetic retinopathy by year’s end, the spokesperson confirmed Thursday. The placebo-controlled trial is testing OPL-0401, an oral small molecule that inhibits Rho kinase (ROCK) 1 and 2. It abandoned plans for a mid-stage trial of another drug candidate last year. Valo, which launched out of Flagship in 2019, is one of multiple computational and AI-driven biotech startups in a class that has started to present key mid-stage clinical tests . The Moderna incubator has been placing increasing emphasis on AI in drug discovery and development. The startup almost went public. In 2021, Valo attempted to ride the blank-check wave but didn’t follow through on the proposed combination with a Khosla Ventures special purpose acquisition company, which was set to value it at $2.8 billion . It’s raised more than $450 million from Flagship, Koch Disruptive Technologies and other investors. Valo has made a few acquisitions and last year inked a cardiometabolic deal with Novo Nordisk that could provide billions of dollars in downstream payments. Editor’s note: This story was updated to include comment from acting CEO Paul Biondi.