Ovid Therapeutics Reports Phase 1 Results for the First-Ever Direct Activator of Potassium-Chloride Cotransporter 2 (KCC2), OV350 Intravenous (IV)

Rhea-AI Summary

Ovid Therapeutics (NASDAQ: OVID) reported Phase 1 results for OV350, the first-ever KCC2 direct activator dosed in humans. The randomized, placebo-controlled single-ascending dose study in 16 healthy participants met primary objectives for safety, tolerability, and pharmacokinetics. No treatment-related serious adverse events were reported and pharmacokinetics matched predictions. Exploratory qEEG showed central activity consistent with expected KCC2 modulation and brain exposure. The IV program will not advance further; Ovid is prioritizing oral KCC2 activators, including OV4071 (20-fold more potent than OV350) with a regulatory filing targeted in Q1 2026 and clinical start planned for Q2 2026.

Positive

• Phase 1 met safety, tolerability, and PK objectives
• qEEG showed central activity aligned with brain exposure
• OV4071 is twenty-fold more potent than OV350
• Regulatory submission for OV4071 targeted in Q1 2026
• Planned Phase 1/1b initiation for OV4071 in Q2 2026

Negative

• Most frequent treatment-emergent adverse event was headache
• Nausea and vomiting occurred in a subset of participants
• OV350 IV will not be advanced further in the clinic
• Phase 1 sample size was small (16 healthy participants)

Key Figures

Phase 1 participants 16 healthy participants Randomized, placebo-controlled, single-ascending dose OV350 study

OV350 dose levels 50 mg and 100 mg IV infusion doses over ten minutes in Phase 1

PK sampling window Up to 48 hours Post-dosing pharmacokinetic assessments for OV350

OV4071 potency Twenty-fold greater potency OV4071 vs OV350 in pharmacodynamic disease models

OV4071 regulatory timing Q1 2026 Planned regulatory submission for Phase 1/1b trial

OV4071 Phase 1/1b start Q2 2026 Planned initiation of safety and proof-of-concept study

Infusion duration Ten minutes OV350 IV infusion period per dose

KCC2 activator class First-ever direct activator OV350 as first direct KCC2 activator dosed in humans

Market Reality Check

$1.47 Last Close

Volume Volume 836,600 is below the 20-day average of 1,660,574, suggesting muted trading interest ahead of this update. low

Technical Shares at $1.48 are trading above the $0.83 200-day MA, but still 26.37% below the $2.01 52-week high.

Peers on Argus

OVID fell 4.52% while several biotech peers like ENTX (-4.37%), IRD (-6.91%) and ATRA (-2.94%) were also down, but no broad sector momentum signal was flagged.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 02	Executive appointment	Neutral	-13.3%	New Chief Medical Officer appointed to lead clinical and regulatory strategy.
Nov 12	Earnings and updates	Positive	-2.2%	Q3 results plus OV329 and KCC2 updates alongside CEO succession plan.
Oct 03	Private placement	Neutral	+12.2%	PIPE financing up to $175M in gross proceeds with preferred and warrants.
Oct 03	Clinical trial data	Positive	+12.2%	Positive Phase 1 OV329 biomarker data with strong GABA-AT inhibition.
Aug 13	Earnings and updates	Positive	+56.9%	Q2 2025 results, OV329 timeline, KCC2 plans, and royalty monetization.

Pattern Detected

News flow has often driven sharp moves, but reactions are mixed: some positive clinical and financing updates aligned with strong gains, while leadership and earnings news occasionally saw selling pressure.

Recent Company History

Over the last six months, Ovid combined pipeline, financing, and governance milestones. On Aug 13, Q2 2025 results and KCC2/OV329 updates coincided with a 56.86% gain. Positive OV329 Phase 1 data on Oct 03 and a sizeable private placement the same day both saw 12.2% moves higher. Subsequent Q3 earnings and leadership succession on Nov 12 produced a modest -2.22% reaction, while appointing a new CMO on Dec 02 preceded a larger -13.33% drop. Today’s OV350 Phase 1 results extend this clinical trial narrative within the KCC2 portfolio.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-12-15

An effective Form S-3 filed on Dec 15, 2025 registers up to 125,064,325 existing-investor shares for resale. The company is not selling shares or receiving proceeds; the registration mainly enables PIPE investors from October 2025 to gradually resell holdings, potentially increasing tradable supply over time.

Market Pulse Summary

The stock moved -9.5% in the session following this news. A negative reaction despite favorable OV350 safety and central activity data would fit prior divergence episodes, such as the stock’s declines of -13.33% after a CMO appointment and -2.22% on Q3 results. Selling pressure could reflect concerns about long development timelines or overhang from the registration of up to 125,064,325 resale shares. Past patterns show that while strong data and financings sometimes drove large gains, governance and capital-structure developments have also coincided with drawdowns.

Key Terms

potassium-chloride cotransporter 2 medical

"First-Ever Direct Activator of Potassium-Chloride Cotransporter 2 (KCC2), OV350"

Potassium-chloride cotransporter 2 is a protein embedded in nerve cell membranes that moves potassium and chloride ions together to help control the cell’s electrical balance, like a gatekeeper regulating the flow of charged particles. Investors care because modulating this transporter is a proven strategy for developing drugs that affect brain excitability (for disorders such as epilepsy, pain, or mood conditions), so success or failure in related clinical programs can strongly influence a company’s value.

pharmacokinetics medical

"The study met its primary objectives to evaluate safety, tolerability and pharmacokinetics."

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

electrophysiology medical

"Exploratory quantitative electrophysiology results suggest OV350 had central activity"

The study and measurement of the electrical signals that control cells and tissues, most commonly used to diagnose and treat heart rhythm problems and to test how nerves and muscles communicate. Investors care because electrophysiology drives products, procedures and drugs—like monitoring systems, catheter tools and implants—that can alter a medical device or drug maker’s sales, regulatory approvals and clinical trial outcomes; think of it as checking and fixing the wiring that makes the body run.

qEEG medical

"exploratory quantitative electroencephalography (qEEG) endpoints were collected."

Quantitative electroencephalography (qEEG) is a medical technique that records the brain’s electrical signals with sensors and uses computer analysis to convert those signals into visual maps and numeric patterns—like turning the brain’s radio waves into a visual equalizer. For investors, qEEG matters because its accuracy, clinical acceptance and regulatory or insurance support can drive demand for related diagnostic devices, therapies and services, affecting revenue potential and regulatory risk.

pharmacodynamic medical

"OV4071, which performs with twenty-fold greater potency than OV350 in pharmacodynamic models."

Pharmacodynamic describes how a drug acts on the body — the biological effects it produces, how strong those effects are, and how long they last. For investors, pharmacodynamic data show whether a treatment actually works and at what dose, shaping expectations about a drug’s safety, effectiveness, regulatory success and market potential; think of it like testing how well a key turns a lock and whether it reliably opens the door.

AI-generated analysis. Not financial advice.

• OV350 showed a good safety profile, supporting the advancement of the Company’s KCC2 portfolio, including the first oral direct activator, OV4071
• There were no treatment-related laboratory findings, no safety findings, and no treatment-related serious adverse events (SAEs)
• Exploratory quantitative electrophysiology results suggest OV350 had central activity and spectral power consistent with expected physiological effects of KCC2 modulation; aligned with expected drug exposure in the brain
• Pharmacokinetics for OV350 were as predicted, and will inform dosing strategies for future KCC2 development programs
• OV4071 (oral) is on track for regulatory submission for a Phase 1/1b clinical trial in Q1 2026
  
  

NEW YORK, Dec. 18, 2025 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (Nasdaq: OVID), a biopharmaceutical company developing small molecule medicines to treat brain disorders and symptoms caused by excess neural excitability, today announced results from its Phase 1 study of OV350, the first-ever KCC2 direct activator known to be dosed in humans. The study met its primary objectives to evaluate safety, tolerability and pharmacokinetics. Results from this intravenous program support the advancement of the Company’s portfolio of oral KCC2 direct activators into the clinic.

“OV350 is a valuable tool program that supported human safety for drugging KCC2, an entirely new therapeutic target in the brain, which could be a master switch to curb neural hyperexcitability,” said Meg Alexander, President and Chief Operating Officer of Ovid Therapeutics. “The results from this study give us confidence that this new mechanistic class is amenable for further development and reinforces our decision earlier this year to invest in the development of additional direct activator molecules and formulations for chronic use, including OV4071, the first oral KCC2 direct activator. We expect to submit our regulatory application for a Phase 1/1b study of OV4071 in Q1 2026 and plan to initiate clinical studies in Q2 2026.”

Study Design and Key Results

OV350 was evaluated in an exploratory randomized, placebo-controlled, single-ascending dose study in 16 healthy participants (six active, two placebo per cohort). Doses of 50 mg and 100 mg were administered by IV infusion over ten minutes, with pharmacokinetic sampling conducted up to 48 hours post-dosing. In addition to laboratory and clinical results, exploratory quantitative electroencephalography (qEEG) endpoints were collected.

Key findings include:

• At 50 mg and 100 mg doses of OV350, exposure levels achieved expected pharmacologically active concentrations reinforcing the potential for further clinical development of KCC2 direct activators, including OV4071, which performs with twenty-fold greater potency than OV350 in pharmacodynamic models.
• The most frequent treatment-emergent adverse event (AE) associated with OV350 was headache.
• Nausea and vomiting occurred in a subset of participants who experienced headache. These AEs coincided with the timing of food intake and are believed to be caused by secondary off-target pharmacology unique to OV350.
• There were no treatment-emergent SAEs associated with OV350 and stopping criteria were not met in the study.
• The pharmacokinetics were as predicted for all doses.
• qEEG findings supportive of central activity and spectral power relevant for the expected pharmacologic impact of KCC2 modulation were observed. These effects were contemporaneous with the expected exposure of OV350 in the brain.

Results from the study will be submitted for a future congress.

Earlier this year, Ovid prioritized and directed its capital resources to accelerate chronic (oral) formulations of its oral direct activator programs, including OV4071 and OV4041. Accordingly, the Company does not intend to advance OV350 IV further in the clinic.

Advancing a First-in-Class Portfolio of Oral KCC2 Direct Activators

Ovid believes the results from OV350 support the advancement of Ovid’s portfolio of KCC2 direct activators, which contains multiple unique molecules. Most advanced in the portfolio is development candidate OV4071, an oral direct activator that is twenty-fold more potent than OV350 in pharmacodynamic disease models. Ovid expects to initiate a Phase 1/1b safety and proof-of-concept clinical study in Q2 2026 for the treatment of psychosis associated with Parkinson’s disease and Lewy body dementia. These conditions have high unmet need, validated endpoints, an established regulatory pathway, and traditional atypical antipsychotics are typically contraindicated. Additionally, the Company is planning to characterize the pharmacodynamic effects of OV4071 and relevant mechanisms in additional neuropsychiatric conditions, such as schizophrenia and psychoses or agitation associated with other neurodegenerative conditions including Alzheimer’s disease.

Concurrent to the clinical translation of OV4071, Ovid is advancing next-generation KCC2 activators from its proprietary library of compounds. These molecules are designed for oral and injectable formulations.

About KCC2

KCC2 is a neuron-specific chloride transporter that maintains inhibitory balance in the brain. The cotransporter plays a central role in regulating neuronal excitability by enabling gamma-aminobutyric acid (GABA) to exert its inhibitory effect. Direct activation of KCC2 represents a differentiated, mechanism-based approach to treating serious neurological and neuropsychiatric conditions in which neuronal hyperexcitability is central to disease and symptom manifestation. Ovid’s KCC2 programs are designed to build a first-in-class franchise targeting restoration of excitatory/inhibitory balance in the brain, which may offer therapeutic benefit across multiple neurological and neuropsychiatric disorders.

About OV350

OV350 is a first-in-class, investigational direct activator of KCC2, the neuron-specific chloride transporter that restores inhibitory signaling and helps rebalance hyperexcitable neural circuits. Data from this tool program is informative in establishing safety, tolerability, pharmacokinetics and pharmacodynamic properties of this new mechanism of action for the brain.

About Ovid Therapeutics

Ovid Therapeutics Inc. is a New York-based biopharmaceutical company dedicated to developing small molecule medicines for brain conditions and symptoms caused by excess neural excitability. Ovid is advancing a pipeline of novel targeted small molecule candidates that modulate the intrinsic and extrinsic factors involved in neuronal hyperexcitability causative of multiple neurological and neuropsychiatric disorders. Ovid is developing: OV329, a next-generation GABA-aminotransferase inhibitor, as a potential therapy for treatment-resistant seizures and other undisclosed indications; and is developing OV4071 and other candidates within a library of compounds that directly activate the KCC2 transporter for multiple CNS disorders. 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 expected timing of initiation, completion, and results and data of Ovid’s ongoing and planned clinical studies; the potential use and development of OV329, OV4071 and other compounds from Ovid’s library of direct activators of KCC2; the potential therapeutic opportunity of OV329, OV4071 and other compounds from Ovid’s library of direct activators of KCC2; Ovid’s clinical pipeline strategy and plans for future clinical studies; the expected timing of IND-enabling and formulation efforts for molecules from its KCC2 direct activator library and related regulatory submissions; 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, uncertainties inherent in the preclinical and clinical development and regulatory approval processes, impediments to Ovid’s ability to achieve expected benefits of cost-savings efforts, risks related to Ovid’s ability to achieve its financial objectives, the risk that Ovid may not be able to realize the intended benefits of its business strategy, or risks related to Ovid’s ability to identify business development targets or strategic partners, to enter into strategic transactions on favorable terms, or to consummate and realize the benefits of any business development transactions or unanticipated or greater than anticipated impacts or delays due to macroeconomic and geopolitical conditions. 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 most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”), and in subsequent and 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.

Contact

Investor Relations & Media
Victoria Fort
VFort@ovidrx.com
202.361.0445

FAQ

What were the primary outcomes of OVID's OV350 Phase 1 study dated Dec 18, 2025?

The study met its primary objectives for safety, tolerability, and pharmacokinetics in 16 healthy participants.

Did OV350 cause serious adverse events in the Phase 1 study (OVID)?

No treatment-related serious adverse events were reported and stopping criteria were not met.

What central nervous system activity did OV350 show in OVID's trial?

Exploratory qEEG showed central activity and spectral power consistent with expected KCC2 modulation and brain exposure.

Why is OVID prioritizing OV4071 over OV350 and when will OV4071 enter trials?

OV350 IV will not be advanced; OV4071 (oral, 20-fold more potent) targets regulatory submission in Q1 2026 and trial start in Q2 2026.

What adverse events were most common with OV350 in OVID's Phase 1?

The most frequent treatment-emergent adverse event was headache; some participants also had nausea and vomiting.

How many participants received OV350 in the Phase 1 study by OVID?

The single-ascending dose study enrolled 16 healthy participants with six active and two placebo per cohort.