Invivyd, Inc. recently announced the US FDA has cleared the company’s Investigational New Drug (IND) application and provided feedback to advance the company’s REVOLUTION clinical program, Invivyd’s development program for VYD2311, a vaccine alternative monoclonal antibody candidate for the prevention of COVID.

The DECLARATION clinical trial is the company’s Biologics License Application (BLA)-enabling, Phase 3 pivotal clinical trial evaluating VYD2311 safety and prevention of COVID versus placebo. The LIBERTY clinical trial will assess the safety and tolerability of VYD2311 in a head-to-head clinical trial against mRNA-based COVID vaccine, as well as evaluate co-administration of VYD2311 with vaccination, subject to final alignment with the FDA. Together, these two clinical trials are designed to provide robust, medical practice-changing information to regulators, populations at risk for COVID, and policy makers seeking high-quality, safe, non-vaccine protection from COVID. Invivyd intends to initiate these clinical trials as soon as practicable, with the goal of year-end 2025 trial start and top-line data mid-2026. Additional studies in the REVOLUTION program may be contemplated for conduct post-approval of VYD2311, if a BLA is granted by the FDA, to further elaborate the profile of antibody prevention of COVID.

The DECLARATION Phase 3 clinical trial will evaluate prevention of symptomatic COVID at three months, with either a single dose or monthly doses of VYD2311, each administered via intramuscular (IM) injection, compared to placebo. A single IM dose of VYD2311 is expected to confer strong protection from COVID across the three-month measured dosing interval and beyond, with further clinical demonstration of long-term protection possible post-approval. By including a monthly dosing arm, the DECLARATION trial could also provide safety and efficacy data that support a VYD2311 indication and administration paradigm that enables individual choice and flexibility for extra periodic protection from COVID if desired, as opposed to a single centrally defined or mandated protection regimen. If approved, access to baseline and periodic extra protection via VYD2311 could, for example, support long interval protection such as annual or semi-annual dosing, as well as provide a mechanism for increased protection through additional doses for at-risk populations seeking extra protection or for individuals facing periods of enhanced risk of COVID.

The LIBERTY clinical trial is anticipated to demonstrate the meaningful safety and tolerability advantage expected for antibody-based prophylaxis versus mRNA-based vaccine-induced inflammatory mechanisms, and to provide safety and immunologic data regarding any interaction between the mRNA-based vaccine and VYD2311 for people who may receive both, if approved. Invivyd expects that its broader REVOLUTION clinical program may also include pediatric and other post-approval Phase 4 studies designed to establish VYD2311 and potential future Invivyd antibodies as the preferred option for protection from COVID over mRNA-based vaccination going forward.

“We are moving as fast as possible to bring Americans a new choice in protection from COVID,” said Marc Elia, Chairman of Invivyd’s Board of Directors. “We have designed the DECLARATION and LIBERTY clinical trials towards providing Americans with a convenient, safe, high-quality protective option to avoid COVID harm and burden without repeated use of inflammatory COVID vaccines. These trials and the broader REVOLUTION program will aim to generate clinical data that support a new approach to COVID prevention: one that enables at-risk Americans to exercise their individual freedom of choice to select the timing and quantity of safe, high-quality protection both annually and during periods of heightened risk such as medical vulnerability or major COVID waves, as well as during life’s important moments, such as family gatherings, holidays, and travel. COVID antibody medicines build on the science of natural, human immunity that begins at birth with maternal antibody transfer, and could serve as a critical, first-line option for protection for millions of Americans.”

Invivyd has produced commercial launch quantities of VYD2311 and has secured capital to support clinical trial execution through pivotal data readouts.

More details about the REVOLUTION clinical program for VYD2311, including the scientific basis for trial design, dose selection, endpoints, populations, and potential commercial implications will be shared in a public investor event later this month.

VYD2311 is a novel monoclonal antibody (mAb) candidate being developed for COVID-19 to continue to address the urgent need for new prophylactic and therapeutic options. The pharmacokinetic profile and antiviral potency of VYD2311 may offer the ability to deliver clinically meaningful titer levels through more patient-friendly means such as an intramuscular route of administration.

VYD2311 was engineered using Invivyd’s proprietary integrated technology platform and is the product of serial molecular evolution designed to generate an antibody optimized for neutralizing contemporary virus lineages. VYD2311 leverages the same antibody backbone as pemivibart, Invivyd’s investigational mAb granted emergency use authorization in the U.S. for the pre-exposure prophylaxis (PrEP) of symptomatic COVID-19 in certain immunocompromised patients, and adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and demonstrated clinically meaningful results in global Phase 2/3 clinical trials for the prevention and treatment of COVID-19.

Invivyd, Inc. (Nasdaq: IVVD) is a biopharmaceutical company devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2. Invivyd deploys a proprietary integrated technology platform unique in the industry designed to assess, monitor, develop, and adapt to create best in class antibodies. In March 2024, Invivyd received emergency use authorization (EUA) from the U.S. FDA for a monoclonal antibody (mAb) in its pipeline of innovative antibody candidates. Visit https://invivyd.com/ to learn more.