OUR APPROACH

To enable our founding vision, our discovery efforts are focused on broadly neutralizing antibodies that target conserved epitopes across multiple members of the coronavirus family.

OUR APPROACH

To enable our founding vision, our discovery efforts are focused on broadly neutralizing antibodies that target conserved epitopes across multiple members of the coronavirus family. 

Coronaviruses: the driver of the pandemic

Coronaviruses comprise a large family of viruses that are grouped into four genera: alphacoronavirus, betacoronavirus, gammacoronavirus and deltacoronavirus. Over the past 20 years, three pathogenic novel betacoronaviruses have spilled over into the human population from animal reservoirs to cause outbreaks of deadly pneumonia, including COVID-19, SARS and MERS.

COVID-19, the disease caused by SARS-CoV-2 and its variants, has given rise to a global pandemic that swept rapidly throughout the world in 2020. The genome of SARS-CoV-2 encodes a spike, or S, protein, which is the surface protein common to all members of the coronavirus family and mediates attachment and entry into host cells. The S protein is the major antigen target for the host immune response, and neutralizing antibodies to this protein are associated with protection from infection and disease. For this reason, S protein is the primary target for currently available vaccines and therapeutic mAbs.

Of significant current concern is the emergence of a number of SARS-CoV-2 variants with increased transmissibility and/or the ability to evade neutralizing antibodies. While multiple agents, including other antibody-based therapies and vaccines have been developed to address the pandemic, the emergence of variants may limit their efficacy. Further, challenges with vaccine rollout and adoption emphasize the need for additional treatment and prevention options that are broadly neutralizing and easily administered across multiple care settings.

Our approach to addressing a global pandemic

Our discovery efforts are focused on broadly neutralizing antibodies that target conserved epitopes across multiple members of the coronavirus family. We believe that a mAb therapy with the following characteristics will have the potential to address the limitations of currently available treatment and prevention options for COVID-19 as well as future diseases that may arise from SARS-like viruses with pandemic potential:

  • High potency and broad neutralizing activity to address SARS-CoV-2, including variants of concern, and additional SARS-like viruses
  • Multiple mechanisms of action, including direct virus neutralization by blocking viral entry into the host cell and elimination of infected host cells through innate immune effector activity to clear infection
  • Convenient outpatient administration as a single-dose intramuscular injection
  • Ability to provide both rapid and durable protection with potential protection against COVID-19 for up to one year

Pipeline

We are developing a pipeline of antibody-based solutions not only for the current COVID-19 pandemic, but also to address future potential coronavirus outbreaks. Our pipeline is led by ADG20, which is in pivotal trials for both the treatment and prevention of COVID-19. Beyond ADG20, we are developing additional product candidates, such as ADG10, for
potential use in combination with ADG20 for the treatment and prevention of COVID-19 and have initiated discovery programs focused on preventative agents for additional coronaviruses as well as seasonal and pandemic influenza.

ADG20: our solution for the treatment and prevention of COVID-19

Our founding scientists discovered and engineered a highly potent and broad mAb therapeutic candidate for both the treatment and prevention of COVID-19. They focused on isolating an antibody capable of broadly neutralizing the entire clade of SARS-like viruses from the sarbecovirus lineage, including diverse family members such as SARS-CoV-1, WIV1, SHC014 and SARS-CoV-2, as opposed to only neutralizing SARS-CoV-2.

This work led to the discovery and engineering of ADG20, our lead product candidate, which is designed to be a potent, broadly neutralizing antibody for both the treatment and prevention of COVID-19, including disease caused by variants, as either a single or combination agent. Unlike other antibody-based therapies targeting SARS-CoV-2, ADG20 has demonstrated an ability to potently neutralize SARS-CoV-2, including variants of concern, as well as a broad range of sarbecoviruses. In addition, ADG20 can be conveniently administered as a single-dose intramuscular injection.

ADG20 employs a unique binding strategy which provides it with broader neutralizing capabilities compared to most other antibodies, either authorized for clinical use or in development.

ADG20 is currently being evaluated in two, global Phase 2/3 clinical trials, STAMP and EVADE, for the treatment and prevention of COVID-19, respectively.

ADG20 Potential to Address Significant Global Need

We don’t expect that vaccines alone will be able to adequately address the COVID-19 pandemic and the need for safe and effective treatments that are broadly accessible remains a significant need. We believe that vaccine hesitancy and access challenges could leave billions of people around the world with inadequate or no protection.

ADG20 has the potential to address this need, offering the potential to provide both treatment and preventative benefit with a single injection. We have identified four distinct patient segments where we think ADG20 could play an important role:

  1. Treatment: Patients recently diagnosed with COVID-19.
  2. Post-Exposure Prophylaxis: Non-vaccinated patients with close exposure to a SARS-CoV-2-infected patient.
  3. Vaccine Supplement: Patients seeking to supplement their vaccine protection against SARS-CoV-2 and/or who are deterred by potential booster doses due to vaccine side effects.
  4. Pre-Exposure Prophylaxis:This group represents the remainder of the population, including nonvaccinated individuals as well certain vaccinated individuals for whom vaccines are likely to provide suboptimal protection, such as those who are immunocompromised.

PUBLICATIONS

PUBLICATIONS

Relevant Publications by
Adagio Scientists:

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Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases

Nature Medicine

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Prolonged evolution of the human B cell response to SARS-CoV-2 infection

Science Immunology

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Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections

MDPI

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Rational Vaccine Design in the Time of COVID-19

Cell Host Microbe

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Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody

Science

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An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19

BioRxiv

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Wec AZ et al. Broad neutralization of SARS-related antibodies by human monoclonal antibodies. Science. 2020 Jun 15.

Science

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Wec AZ et al. Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6675-6685.

Proceedings of the National Academy of Sciences (PNAS)

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Shehata L et al. Systematic comparison of respiratory syncytial virus-induced memory B cell responses in two anatomical compartments. Nat Commun. 2019 Mar 8; 10(1):1126.

Nature Communications

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West BR et al. Structural basis of broad ebolavirus neutralization by a human survivor antibody. Nat Struct Mol Biol. 2019 Mar; 26(3):204-212.

Nature Structural and Molecular Biology

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Bornholdt ZA et al. A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates. Cell Host Microbe. 2019 Jan 9; 25(1):49-58.e5.

Cell Host and Microbe

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Wec AZ et al. Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection. Cell Host Microbe. 2019 Jan 9; 25(1):39-48.e5.

Cell Host and Microbe

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Saphire EO et al. Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection (2018). Cell. Aug 09; 174(4):938-952.

Cell

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Goodwin E et al. Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation (2018). Immunity. Feb 20; 48(2):339-349

Immunity 

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Walker LM et al. Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray (2018). Nat Rev Immunol. May; 18(5):297-308.

Nature Reviews Immunology

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Rogers TF et al. Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors (2017). Sci Immunol. Aug 18; 2(14). 

Science Immunology 

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Wec AZ et al. Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses (2017). Cell. May 18; 169(5):878-890.

Cell

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Gilman MS et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors (2016). Sci Immunol. Dec 16; 1(6).

Science Immunology 

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Badarau A et al. Context matters: The importance of dimerization-induced conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of neutralizing antibodies (2016). MAbs. Jul 28:0.

mAbs

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Bornholdt ZA et al. Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak (2016). Science. Mar 4;351(6277):1078-83.

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Testing

Walker LM et al. Broad neutralization coverage of HIV by multiple highly potent antibodies (2011). Nature. Aug 17;477(7365):466-470.

Nature

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Walker LM et al. Rational antibody-based HIV-1 vaccine design: current approaches and future directions (2010). Curr Opin Immunol. Jun; 22(3):358-66. 

Science Direct

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Walker LM et al. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target (2009). Science. 326(5950):285-9.  

Science

RELEVANT RESOURCES

Adagio Perspective

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Adagio Therapeutics’ Tillman Gerngross on Bringing Covid-19 Antibodies to Clinical Trials

GV

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Eyeing variants, Adagio starts phase 1 trial of COVID-19 antibody

Fierce Biotech

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Mutating strains and newly emerging viruses: how can one drug protect against future pandemics?

BioTechniques

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GV steps up to back Tillman Gerngross’ new antibody play against Covid-19 — and he’s already thinking about the IPO

Endpoints News

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Adagio Named a Winner of Fierce Biotech’s “Fierce 15 2020”

Fierce Biotech

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Investors think Lebanon biotech startup may be a winner in the fight against the coronavirus

Valley News

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An Audience With: Tillman Gerngross

Nature

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The Case for Antibodies

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Antibodies as Covid Insurance

WSJ

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Monoclonal antibodies could fill the COVID-19 treatment gap until vaccines arrive — but at a cost

Seattle Times

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It Will Take More Than a Vaccine to Beat COVID-19

The New Yorker

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Antibody drugs could be one of the best weapons against Covid-19. But will they matter?

Stat

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Antibody therapies could be a bridge to a coronavirus vaccine — but will the world benefit?

Nature

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Antibody Drugs Could Help Curb the Pandemic. What Investors Need to Know.

Barron’s

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Why Vaccines May Not Be Enough

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Peter Marks on Covid-19 vaccine efficacy, EUAs and challenge trials

Endpoints

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Coronavirus herd immunity may be ‘unachievable’ after study suggests antibodies disappear after weeks in some people

Business Insider India

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Coronavirus antibodies may disappear after mere months in some people, research shows. But it’s not necessarily a reason to panic.

Yahoo!

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After Trumps’ diagnosis: Vaccine or not, COVID-19 isn’t going away

USA TODAY

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Nature / COVID Research Updates

Nature