Ventus Therapeutics Announces Successful Completion of Phase 1 Clinical Trial of VENT-03, a First-in-Class, Orally Administered cGAS Inhibitor

VENT-03 was safe and well-tolerated at all tested dose levels

Favorable pharmacokinetic profile enables once-daily dosing

Demonstrated full target inhibition

Initiation of a Phase 2 trial with VENT-03 in patients with systemic lupus erythematosus (SLE) expected in 2025

Ventus Therapeutics, a clinical-stage biopharmaceutical company utilizing its proprietary ReSOLVE™ platform to discover and develop differentiated small-molecule therapeutics, today announced results from its Phase 1 clinical trial of VENT-03, the first cyclic GMP-AMP synthase (cGAS) inhibitor to successfully complete a first-in-human study. The Phase 1 trial evaluated the pharmacokinetics (PK), target engagement, safety, and tolerability of VENT-03 across a broad range of single and multiple ascending doses in 72 healthy adult volunteers.

“The extraordinary profile demonstrated by this trial qualifies VENT-03 as a first- and best-in-class anti-cGAS medication and underscores the power of our ReSOLVE™ platform to develop high-quality small molecules for targets that have historically been undruggable,” said Marcelo Bigal, M.D., Ph.D., President and CEO of Ventus. “These results unlock the path to exploring the broad potential of cGAS inhibition across a wide range of autoimmune disorders and cardiometabolic diseases, beginning with lupus. We’re excited to continue leading the way in cGAS development and look forward to initiating a Phase 2 trial with VENT-03 in SLE in 2025.”

In the Phase 1 trial, VENT-03 was safe and well-tolerated at doses far exceeding those planned for use in Phase 2 trials. There were no dose-limiting or dose-related toxicities, serious adverse events, or changes in clinical laboratory parameters, electrocardiogram (ECG), or vital signs. All treatment-related adverse events were mild, transient, and easily managed.

VENT-03 demonstrated a favorable PK profile that supports once-daily dosing. In addition, VENT-03 reached plasma concentrations required for full target inhibition and demonstrated robust pharmacodynamics. Ventus plans to present full data from the Phase 1 trial at a future medical conference.

“Available treatments for lupus today include injectable medicines for the type I interferon or BAFF pathways that address only limited aspects of patients’ symptoms and disease course,” said Xavier Valencia, M.D., Head of Clinical Development at Ventus. “A once-daily oral cGAS inhibitor has the potential to modulate both pathways validated by biologics, impact multiple facets of SLE, and provide superior efficacy compared to existing treatments and therapies in development.”

About cGAS

cGAS is an intracellular pattern recognition receptor that is activated after binding to double-stranded DNA (dsDNA) in the cytoplasm. The presence of dsDNA in the cytoplasm is often the result of cellular dysfunction, which is a hallmark of many autoimmune and inflammatory diseases. Activation of cGAS leads to cGAMP formation, activation of STING, pronounced inflammation, and tissue damage. In both patients and preclinical models of disease, the cGAS pathway has been shown to be a key driver of lupus and other inflammatory diseases, such as systemic sclerosis, dermatomyositis, and Sjögren's disease.

About Ventus Therapeutics

Ventus Therapeutics is a clinical-stage biopharmaceutical company deploying deep protein science expertise and a proprietary computational chemistry platform to develop novel small molecule therapeutics for immunology, inflammation, and neurology disorders. Ventus’ ReSOLVE™ platform combines the latest advances in artificial intelligence/machine learning (AI/ML), structural biology, and biophysics to model the full spectrum of protein dynamics at an unparalleled resolution. Using ReSOLVE™, the company screened its first target in 2020, selected three development candidates in 2022, advanced its two wholly-owned product candidates into the clinic in 2023, and completed Phase 1 trials for both programs in 2024: VENT-03, a potent, selective, oral cGAS inhibitor, and VENT-02, a potent, brain-penetrant, oral NLRP3 inhibitor. In addition, Ventus has out-licensed VENT-01, a peripherally-restricted NLRP3 inhibitor in Phase 1, to Novo Nordisk A/S. For more information, please visit www.ventustx.com and engage with Ventus on LinkedIn.

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