Invivyd Announces Full Phase 1/2 Clinical Data For VYD2311, Next-Gen Monoclonal Antibody Candidate Designed To Prevent And Treat COVID-19

• Attractive safety profile demonstrated across all dosing cohorts and routes of administration (IV, SC, and IM); all reported adverse events (AEs) deemed unrelated or classified as mild to moderate and largely related to injection site and infusion reactions with no serious or severe adverse events observed
• Following a single dose, serum concentrations of VYD2311 remained high at six months with an observed half-life of the IM dose route having the longest duration at 76.0 (CI: 68.5 – 90.7) days
• Comprehensive dose modeling of VYD2311 sVNA titers (submitted to FDA and under preparation for publication) indicates possible strong protection from symptomatic COVID-19 achievable via IM dosing on a long interval (months to quarters and beyond)
• Type C meeting scheduled with FDA for early Q3 to discuss registration-directed next steps for the VYD2311 program and overall approval pathway for Invivyd COVID-19 monoclonal antibodies

WALTHAM, Mass., June 26, 2025 (GLOBE NEWSWIRE) -- Invivyd, Inc. (NASDAQ:IVVD), today announced full Phase 1/2 clinical data for VYD2311, a next-generation monoclonal antibody (mAb) candidate designed to prevent and treat COVID-19.

VYD2311 builds on the success of Invivyd's first-generation mAb, pemivibart, which received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and adolescents (12 years of age and older weighing at least 40 kg) who have moderate to-severe immune compromise. VYD2311 is 99%+ structurally identical to predicate antibodies adintrevimab and pemivibart, and represents the result of a technologically enabled, directed change in antibody sequence and spike protein target engagement uniquely accessible via Invivyd's technology platform. These subtle but critical molecular changes for VYD2311 confer an increase in in vitro potency and a differentiated resistance profile compared to pemivibart, with corresponding potential improvements in clinical profile and accessibility, if approved. VYD2311 is now the third mAb from Invivyd to undergo randomized clinical trial evaluation while retaining a near-identical molecular structure and target binding site on the SARS-CoV-2 spike protein, a feature of Invivyd's platform designed to provide vulnerable populations, healthcare professionals (HCPs), and regulatory authorities with a steady stream of high-assurance, minimally altered mAbs sufficient to navigate natural SARS-CoV-2 evolution rapidly with a non-vaccine approach.

The Phase 1/2 study of VYD2311 was a randomized, double-blind, first-in-human clinical trial evaluating the safety and clinical pharmacokinetic (PK) profile of VYD2311 in 40 subjects across multiple routes of administration (ROAs) and dose levels for a single dose, and includes VYD2311 dosed intravenously (IV), intramuscularly (IM), and subcutaneously (SC) in four cohorts of 10 participants each, randomized 8:2 to receive drug or placebo. This range of ROAs and doses was tested to provide maximum flexibility in designing registrational pathways for both COVID-19 prophylaxis and treatment, while retaining a high barrier to resistance in the form of doses expected to accommodate significant evolutionary changes in SARS-CoV-2 viruses.

VYD2311 was well tolerated with all adverse events (AEs) considered mild to moderate in severity with no serious or severe AEs reported. All AEs were deemed unrelated to study drug, or as expected and largely related to injection site erythema, injection site pain, injection site swelling, headache, dizziness, and infusion-related reactions, one of which (Grade 2) required an infusion interruption and was later restarted without any further reaction.

A formal estimate of in vivo half-life based on full Phase 1/2 clinical trial data confirmed the long half-life of VYD2311. At six months (end of study follow-up), serum concentrations of VYD2311 remained high and were observed to be substantially greater than that of pemivibart. Specifically, half-life estimates by cohort ranged from 61 days (high dose IV) to 76 days (IM) as compared to pemivibart estimated half-life of 49 days. VYD2311's long half-life could allow meaningful, long-term protection from symptomatic disease, potentially over multiple quarters, which is expected to be more durable than a COVID-19 vaccine, given rapid waning of protective benefit. High dose IV administration could similarly provide very long-term follow-up viral suppression in a COVID-19 treatment use case.

In addition to assessing safety and tolerability of VYD2311 across the various ROAs, a comprehensive dose modeling analysis was conducted to support development discussions with FDA and other global regulators about a rational dosing paradigm for VYD2311 and follow-on COVID-19 mAbs. A Cox model analysis was employed using data from Invivyd's recent CANOPY Phase 3 clinical trial for pemivibart, incorporating both serum virus neutralizing antibody (sVNA) titers and long-term clinical efficacy data to provide a robust foundation on which to reevaluate titer thresholds used to define efficacy for immunobridging purposes for both immunocompetent and immunocompromised (IC) individuals.

The VYD2311 dose modeling strategy contemplated a range of doses for IV up to 4500 mg, doses for IM up to 1000 mg, and doses for SC up to 750 mg. The results of this most recent analysis align well with prior published estimates of relationships between sVNA titers and observed clinical efficacy across multiple COVID-19 mAbs. Key findings of Invivyd's updated dose modeling analysis include:

• Robust Modeled Protective Efficacy: All dosing routes and doses assessed yielded modeled efficacy rates that appear to eclipse estimated contemporary rates of COVID-19 vaccine protection for both IC and non-IC individuals. Notably, IM and SC dosing every three months reflected robust efficacy for both IC and non-IC individuals and such routes could simplify and scale administration, improving convenience.
• IM Dosing Comparable Performance to IV for Prevention: Modeling data indicate that IM administration can offer efficacy comparable to high dose IV dosing. Critically, the IM route could eliminate the need for IV infrastructure - enhancing tolerability, accessibility, and convenience.
• Very High Antiviral Titers Available via IV for Treatment of Active Infection: Antiviral titers conferred by VYD2311 via IV to treat active infection are expected to substantially exceed the titers conferred by pemivibart and provide longer suppression of virus compared to pemivibart, and would seem to meet the criteria previously suggested by the FDA as persuasive of expected treatment effect in prior correspondence to Invivyd.

Invivyd plans to discuss approval pathways for VYD2311 and follow-on COVID-19 mAbs with the FDA early in the third quarter of 2025, and expects to announce additional information about the VYD2311 program throughout 2025. Invivyd expects those discussions will include approval pathways for treatment of active COVID-19 and prophylaxis for vulnerable populations including the elderly, the immunocompromised, and pediatric populations including neonates and infants.