Invivyd Announces FDA Authorization for Emergency Use of PEMGARDA (Formerly VYD222) for Pre-exposure Prophylaxis (PrEP) of COVID-19 PEMGARDA (pemivibart) is authorized in the U.S. for PrEP of COVID-19 in certain adults a

Invivyd Announces FDA Authorization for Emergency Use of PEMGARDA (Formerly VYD222) for Pre-exposure Prophylaxis (PrEP) of COVID-19

WALTHAM, Mass., March 22, 2024 (GLOBE NEWSWIRE) Invivyd, Inc. (Nasdaq: IVVD), a biopharmaceutical company on a mission to

protect the vulnerable from serious viral infectious diseases, today announced that PEMGARDA (pemivibart), formerly VYD222, a half-life extended monoclonal antibody (mAb), has received

emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents

(12 years of age and older weighing at least 40 kg) who have moderate-to-severe immune compromise due to certain medical conditions or receipt of certain

immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination. Recipients should not be currently infected with or have had a known recent exposure

to an individual infected with SARS-CoV-2.

The PEMGARDA EUA marks a

transformational moment for Invivyd and for the many moderately to severely immunocompromised people who are vulnerable to COVID-19 disease in the U.S. This EUA milestone represents strategic proof-of-concept for our company and platform, affirming the unique strategy we embarked on over a year ago: to use rapid innovation and surrogate markers to bring new

antibodies to market repeatedly, said Dave Hering, Chief Executive Officer of Invivyd. PEMGARDA is the first authorized monoclonal antibody from our proprietary platform approach. We are committed to ongoing process improvement while

working with global regulatory agencies with the aim to increase the speed and efficiency of new mAb candidate development even further. Additionally, we are planning to explore the protective clinical benefits of mAb prophylaxis for symptomatic COVID-19 disease in future studies.

Mr. Hering added, We are proud that roughly one year after

initiating the Phase 1 trial of our mAb now known as PEMGARDA, we are expecting to have product available for order imminently, with initial supply already packaged and awaiting final release at our U.S.-based third-party logistics provider.

deeply grateful to our dedicated team members who made this achievement possible and everyone else who has supported our work, especially our clinical trial participants and investigators.

Finally, we also appreciate the continuous engagement from the FDA as they have worked with urgency to make this medicine available to populations in serious need.

People who are immunocompromised continue to be disproportionally impacted by COVID-19 even after receiving

multiple vaccine doses, said Cameron R. Wolfe, M.B.B.S., M.P.H., Professor of Medicine, Transplant Infectious Disease at Duke University School of Medicine. I m excited to have PEMGARDA as an additional COVID-19 preventive option for moderately to severely immunocompromised adult and adolescent patients, such as solid organ transplant recipients and those with hematological malignancies. These types of patients,

among others, continue to have both an impaired response to vaccines and a higher risk for severe COVID-19 outcomes.

COVID-19 continues to pose a significant threat and major concern to those who are moderately to severely

immunocompromised, said Jorey Berry, President and CEO of the Immune Deficiency Foundation and a steering committee member of the Immunocompromised Collaborative. As such, we are delighted that a new monoclonal antibody for pre-exposure prophylaxis of COVID-19 will be available soon for certain vulnerable populations.

Multiple medical conditions or treatments may result in moderate-to-severe

immune compromise and an impaired immune response to COVID-19 vaccination including, for example, hematologic malignancies (blood cancers) or treatment with immunosuppressive therapy after a solid organ or

stem cell transplant.1 Observational studies have demonstrated that people with immune dysfunction have a higher risk of

COVID-19-related hospitalization and death, despite vaccination, than the general population.2-3

The EUA of PEMGARDA is based on the totality of scientific evidence available, such as data showing that

immunobridging was established in the CANOPY clinical trial and that the calculated serum neutralizing antibody titers against JN.1 were consistent with the titer levels associated with efficacy in prior clinical trials of adintrevimab (ADG20), the

parent mAb for VYD222, and other monoclonal antibody products. JN.1 is currently the dominant variant circulating in the U.S. according to estimates from the Centers for Disease Control and Prevention (CDC).4 PEMGARDA (pemivibart) (4500 mg) is administered as an intravenous (IV) infusion.

Invivyd s first authorized mAb and the first mAb to receive EUA based on a rapid immunobridging trial design that is expected to be repeatable to help address the need to mitigate ongoing viral evolution. It was developed using INVYMABTM, the company s platform approach which combines state-of-the-art viral

surveillance and predictive modeling with advanced antibody engineering. INVYMAB is designed to enable the rapid, serial generation of durable mAbs targeting conserved epitopes that could be deployed to keep pace with

SARS-CoV-2 viral evolution or other viral threats. With a commitment to serial innovation, Invivyd aims to ensure that vulnerable populations, such as immunocompromised

people, have continuous access to innovative antibody therapies.

The Company estimates it had approximately $200.6 million of cash and cash

equivalents as of December 31, 2023. The estimated amounts are preliminary, have not been audited and are subject to change upon completion of the Company s audited financial statements for the year ended December 31, 2023. In

February 2024, the Company sold shares of common stock totaling $40.5 million in gross

proceeds under its At-the-Market facility further strengthening the Company s balance sheet ahead of PEMGARDA

launch. Based on current operating plans and excluding anticipated cash collections from PEMGARDA sales, Invivyd expects its existing total cash and cash equivalents will enable the company to fund its operating expenses and capital expenditure

requirements into the fourth quarter of 2024.

Interim CANOPY Clinical Data Update

CANOPY is an ongoing Phase 3 clinical trial of VYD222 (PEMGARDA) for the pre-exposure prophylaxis of COVID-19 which enrolled adults 18 years of age in two cohorts. Cohort A is a single-arm, open-label trial in adults who have moderate-to-severe immune compromise (n=306); Cohort B is a 2:1 randomized, placebo-controlled trial in which adults who do not have

moderate-to-severe immune compromise received VYD222 (n=317) or placebo (n=162). The interim data presented below are subject to further analysis.

Summary of CANOPY immunobridging data

approach was used in the CANOPY clinical trial, utilizing the relationship between serum virus neutralizing antibody (sVNA) titers and clinical efficacy that was demonstrated in the previous EVADE clinical trial of adintrevimab (ADG20), the parent

mAb for VYD222, and clinical trials of other mAbs that were previously authorized by the FDA. EVADE was a Phase 2/3 randomized, double-blind, placebo-controlled clinical trial of adintrevimab for PrEP and post-exposure prophylaxis of symptomatic COVID-19 in SARS-CoV-2 na ve, unvaccinated individuals, which showed that a neutralizing titer of 3514 on Day 90 was associated

with approximately 70% clinical efficacy in the PrEP cohort (approximately 70% relative risk reduction in development of symptomatic COVID-19 between the adintrevimab and placebo arms).

The CANOPY trial was designed to utilize current relevant SARS-CoV-2 variants

in the analyses of neutralizing titers. The primary immunobridging endpoint for Cohort A was based on calculated sVNA titers on Day 28 following VYD222 administration compared with the calculated Day 28 reference titer derived from historical Day 90

data from the EVADE trial. The most relevant SARS-CoV-2 variant circulating in the U.S. at the time of the analysis (JN.1), was selected as the variant for the analysis

of the primary immunobridging endpoint.

Summary of initial CANOPY immunobridging data from Cohort A (immunocompromised cohort):

Figure 1. Calculated sVNA titers against JN.1 based on observed pharmacokinetic

concentration by timepoints (Cohort A)

Summary of CANOPY safety data

The safety of VYD222 (PEMGARDA) is based on exposure of 623 participants who received at least one dose of VYD222 4500 mg IV in one of two cohorts in the

ongoing CANOPY trial. Cohort A is a single-arm, open-label trial in adults who have moderate-to-severe immune compromise

including complex underlying medical conditions (n=306). Cohort B is a randomized, placebo-controlled cohort that recruited adults without moderate-to-severe immune

compromise who are at risk of acquiring SARS-CoV-2 due to regular unmasked face-to-face

interactions in indoor settings. Cohort B participants were randomized 2:1 to VYD222 (n=317) or placebo (n=162). Interim safety data presented today included 296 people in Cohort A who received a second dose of VYD222 three months after the initial

dose. In Cohort B, 450 participants received a second dose of VYD222 or placebo three months after the initial dose. Cumulative safety with the first two doses of VYD222 is assessed only in Cohort A because unblinded safety data in Cohort B were not

available after Day 28.

Anaphylaxis was observed in four of 623 (0.6%) participants in CANOPY, all in Cohort A. Two participants had anaphylaxis during

the first infusion, for whom treatment included diphenhydramine. Two participants had anaphylaxis during the second infusion. All four reactions led to permanent discontinuation of VYD222. Three participants had complete resolution, and one

participant had acute resolution with sequelae related to a flare of an underlying condition. For the two participants who experienced anaphylaxis with the second dose, both incidents were reported as life-threatening, and they experienced symptoms

during the infusion and following discontinuation of the infusion. Both participants were treated with diphenhydramine and epinephrine. One participant also received oral prednisone and metoprolol for an associated flare of an underlying condition.

Please see PEMGARDA Important Safety Information below, including a boxed warning for anaphylaxis.

The systemic infusion-related reactions and hypersensitivity reactions observed in Cohort A are summarized

in Table 1. The severity of the reactions was generally mild (17/27) or moderate (8/27), but two reactions were life-threatening.

(Open-label cohort with moderate-to-severe immune compromise) Systemic infusion-related reactions and hypersensitivity reactions

*These two events were initially classified as mild or moderate hypersensitivity adverse reactions. Subsequently,

during the review of the EUA application, the FDA reclassified these hypersensitivity adverse reactions as anaphylaxis adverse reactions.

through Day 28 from Cohort B (post-first dose only) were also analyzed in support of the EUA filing, including randomized data on systemic infusion-related and hypersensitivity reactions, as shown in Table 2. As of Day 28, there were no observations

of anaphylaxis in the Cohort B VYD222 arm. Unblinded safety data in Cohort B were not available yet after Day 28.

Table 2. Cohort B (Randomized,

placebo-controlled cohort without moderate-to-severe immune compromise at risk of acquiring

SARS-CoV-2 due to regular unmasked face-to-face interactions) Systemic

infusion-related reactions and hypersensitivity reactions

Other than systemic infusion-related reactions and hypersensitivity reactions described previously for Cohort A, the most

common ( 2%) treatment-emergent adverse events in Cohort A across both the first and second dose cumulatively, irrespective of causality, observed with VYD222 in participants who have moderate-to-severe immune compromise in CANOPY were upper respiratory tract infection (6%), infusion site infiltration/extravasation/vein rupture (5%), viral infection (4%),

influenza-like illness (3%), fatigue (3%), headache (2%), nausea (2%), and local infusion site reactions (2%).

This press release features downloadable multimedia content. View the full suite of assets here: https://www.multivu.com/players/English/9254151-invivyd-announces-fda-authorization-pemgarda-formerly-vyd222-pre-exposure-prophylaxis-covid-19/

Conference Call & Webcast

Invivyd will host a conference call and webcast today, Friday, March 22 at 4pm ET. A live audio webcast will be available at

https://investors.invivyd.com/. Listeners can register for the webcast via this link. Analysts wishing to participate in the question-and-answer session should

use this link. A replay of the webcast will be available in the investor section of the company s website approximately two hours after the end of the call. Those who plan on participating are advised to join 15 minutes prior to the

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS

PEMGARDA is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of PEMGARDA.

WARNINGS AND PRECAUTIONS

Hypersensitivity Including

Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been observed with PEMGARDA. If signs and

symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration, and initiate appropriate medications and/or supportive therapy. Clinically monitor individuals during infusion and observe

for at least two hours after infusion is complete.

Risk of Cross-Hypersensitivity

With COVID-19 Vaccines

PEMGARDA contains polysorbate 80, which is in some COVID-19 vaccines and is structurally similar to polyethylene glycol (PEG), an ingredient in other COVID-19 vaccines. For individuals with a history of severe hypersensitivity

reaction to a COVID-19 vaccine, consider consultation with an allergist-immunologist prior to PEMGARDA administration.

Risk for COVID-19 Due to SARS-CoV-2 Viral Variants Not Neutralized by PEMGARDA

Certain SARS-CoV-2 viral variants may emerge that are not neutralized by monoclonal antibodies such as PEMGARDA. PEMGARDA may not be effective at preventing COVID-19 caused by