Invivyd doses first participants in phase 3 COVID-19 trial of VYD2311

According to a new announcement from Invivyd, the company has dosed the first participants in LIBERTY, a phase 3 clinical trial evaluating the safety and tolerability of VYD2311, its investigational monoclonal antibody candidate for COVID-19 prevention, compared with an mRNA COVID vaccine and in combination with coadministration of both.¹ The milestone advances Invivyd’s REVOLUTION clinical program, which is designed to generate contemporary comparative safety data for antibody-based COVID-19 prevention as an alternative to traditional vaccination.

“We are pleased to have dosed the first participants in LIBERTY, a trial we believe can better characterize the favorable tolerability profile of a mAb and highlight the benefits of our expected new standard of care in COVID-19 prevention if VYD2311 is approved,” Marc Elia, the chairman of Invivyd’s Board of Directors, said in a statement.¹ “In light of Sanofi’s recent findings in the COMPARE study that greater than 80% of patients who received a COVID-19 vaccine experienced at least one systemic side effect, we are moving with urgency to provide Americans with a COVID prevention option that does not require the repeated inflammation of COVID-19 vaccination. CDC data have shown that concern about serious or unknown [adverse] effects [has] been a leading [reason] adults have elected not to receive a COVID-19 vaccine booster, which is why Invivyd is focused on developing a potential prevention option that is more tolerable.”

LIBERTY represents a distinct trial concept in the COVID-19 prevention landscape, directly comparing a monoclonal antibody prophylaxis candidate against an mRNA vaccine rather than a placebo, with a third arm evaluating the safety and immunologic profile of simultaneous coadministration.¹ Concerns about serious or unknown adverse effects have remained a primary reason some Americans have declined COVID-19 booster doses, and Invivyd has positioned LIBERTY as a source of rigorous, head-to-head tolerability data for clinicians and patients weighing prevention options.²

Phase 3 LIBERTY Trial Design, VYD2311’s Mechanism

The trial is a phase 3, randomized, double-blind study with an expected enrollment of approximately 210 participants.¹ The 3 arms compare VYD2311 administered as a single intramuscular (IM) injection, an mRNA COVID vaccine, and the coadministration of VYD2311 with an mRNA COVID vaccine. Primary assessments include safety and tolerability, serum virus-neutralizing antibody responses, and pharmacokinetics across all 3 arms.

The trial is designed to characterize not only the standalone safety profile of VYD2311 but also whether antibody and vaccine coadministration produces additive or interactive immunologic effects relevant to clinical practice.

VYD2311 is a novel monoclonal antibody candidate engineered for COVID-19 prevention, sharing the same antibody backbone as pemivibart, which holds emergency use authorization from the FDA for preexposure prophylaxis of symptomatic COVID-19 in certain immunocompromised patients, and adintrevimab, an investigational antibody with phase 2/3 clinical data in COVID-19 prevention and treatment.¹ The shared backbone provides Invivyd with an established safety dataset to support VYD2311’s clinical development, while the new candidate is being evaluated across dosing regimens and populations not covered under pemivibart’s current authorization.

The Phase 3 DECLARATION Trial

LIBERTY’s first dosing follows Invivyd’s June 1, 2026, announcement of completed enrollment in DECLARATION (NCT07298434), the company’s BLA-enabling phase 3 pivotal trial of VYD2311.¹ DECLARATION is a randomized, triple-blind, placebo-controlled study enrolling 1770 adults and adolescents with and without underlying risk factors for progression to severe COVID-19.¹ Participants receive either a single dose or monthly doses of VYD2311 by IM injection versus placebo, with the primary endpoint of symptomatic COVID-19 prevention at 3 months.

Topline data from DECLARATION are expected in mid-2026, and positive results would support a BLA submission to the FDA for VYD2311 as a prophylactic antibody for COVID-19.¹

The simultaneous advancement of LIBERTY and DECLARATION positions Invivyd to generate both comparative tolerability data and placebo-controlled efficacy data for VYD2311 within the same clinical development window. For immunocompromised patients who mount suboptimal vaccine responses and for individuals who decline or are unable to receive mRNA vaccines, a rigorously studied prophylactic monoclonal antibody could fill a meaningful gap in the COVID-19 prevention armamentarium.

Background on VYD2311 and REVOLUTION Clinical Program

Just prior to IDWeek 2025, Invivyd announced FDA clearance of its Investigational New Drug application for VYD2311, a monoclonal antibody candidate designed as a vaccine alternative for COVID-19 prevention.³ The FDA also provided feedback supporting advancement of the company's REVOLUTION clinical program.

In an interview with Contagion at the time, Chief Scientific Officer Robert Allen, PhD, explained the core distinction between antibody-based prevention and traditional vaccination. Rather than prompting the immune system to generate its own antibody response, VYD2311 delivers preengineered monoclonal antibodies with potent neutralizing activity against SARS-CoV-2 directly. Invivyd monitors circulating variants through clinical and wastewater surveillance to ensure ongoing coverage—including against variants that may not yet be circulating at high levels—giving the program what Allen describes as a "future-tested, durable" profile.

Allen highlighted particular promise for immunocompromised patients, a population that has seen limited benefit from COVID-19 vaccines. For patients managing transplants, oncologic conditions, or complex medication regimens, a respiratory virus interruption can be especially consequential. If VYD2311 can reliably neutralize circulating variants in this group, Allen noted, clinicians may be able to effectively remove SARS-CoV-2 from the differential when a patient presents with respiratory symptoms—freeing them to focus on other causes and treatments.

REFERENCES

1. Invivyd. Invivyd Announces First Participants Dosed in LIBERTY, a Phase 3 Clinical Trial to Evaluate the Safety and Tolerability of VYD2311 Antibody Versus mRNA COVID Vaccine and to Characterize the Safety and Immunology of Antibody and mRNA Vaccine Co-Administration. Published June 9, 2026. Accessed June 9, 2026. https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-first-participants-dosed-liberty-phase-3

2. Centers for Disease Control and Prevention. Attitudes toward COVID-19 vaccination: concerns about side effects. CDC COVID-19 Vaccination Program Data. Accessed June 9, 2026. https://www.cdc.gov/covid/vaccines/index.html

3. Invivyd Announces U.S. IND Clearance and Alignment with U.S. FDA on Pivotal Clinical Program for VYD2311, a Vaccine-Alternative Antibody to Prevent COVID. Invivyd press release. October 6, 2025. Accessed June 9, 2026. https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-us-ind-clearance-and-alignment-us-fda-pivotal