The mastermind behind the COVID-19 vaccine pivots to the antibody track: Invivyd CEO bets on long-acting monoclonal antibodies
After COVID-19 monoclonal antibodies successively withdrew due to viral mutations, Invivyd is advancing early clinical trials of its next-generation antibody VYD222. CEO David Hering, who previously participated in the launch of Pfizer's vaccine, now targets the unmet needs of immunocompromised populations and attempts to address continuous viral mutations through engineered modifications.
When the dust settled in the COVID drug race, vaccines were hailed as heroes against the pandemic, while monoclonal antibodies (mAbs), once on the front lines, gradually faded from view.
In December of last year, the U.S. Food and Drug Administration (FDA) revoked the Emergency Use Authorization (EUA) for Eli Lilly and Co.'s bebtelovimab, citing that it was no longer effective against two Omicron subvariants. In January of this year, AstraZeneca's Evusheld met the same fate. Before that, these two therapies were the last antibodies still in use—earlier, as Omicron became the dominant strain, other monoclonal antibodies from companies like GSK and Regeneron had already been phased out in previous years, as these treatments gradually lost their effectiveness.
But the quest to develop a durable monoclonal antibody that can withstand COVID mutations has not ended—Invivyd is working to provide an antibody for immunocompromised or unvaccinated patients who currently have no treatment options.
"COVID is still the third leading cause of death, and the disease burden remains heavy," said David Hering, CEO of Invivyd. "Monoclonal antibodies are not a substitute for vaccines... but there are 8 million immunocompromised people in the U.S. Among them are cancer patients, organ transplant recipients, or those with vaccine contraindications. We often talk to advocates who don't dare go out without masks or social distancing—they desperately want products like this."
At the end of March, Invivyd, formerly known as Adagio Therapeutics, completed dosing of the first patient in a Phase 1 clinical trial for its new monoclonal antibody candidate, VYD222, and the company hopes to obtain initial data in the second quarter. If the candidate ultimately makes it through clinical trials and reaches the FDA approval stage, it would be a notable success for this startup that has weathered ups and downs in the COVID antibody field.
The COVID Rollercoaster
Adagio was founded in 2020 to develop COVID-related therapies and was once a biotech star that emerged from the pandemic. In 2021, the company raised $336 million in a Series C funding round, followed by an additional $309 million after its initial public offering (IPO). Its lead candidate, adintrevimab, once had a bright outlook and advanced smoothly to Phase 2/3 clinical trials. But ultimately, it was shelved due to poor efficacy against emerging variants.
"There are no other (monoclonal antibody) products on the market, and we saw the need to move quickly."
— Dave Hering, CEO of Invivyd
"The mood inside the company was disappointment," Hering said. "For most biotech companies, if the outcome after a setback isn't good, you can't always keep going. But we knew the product was safe and that the mechanism of action looked promising."
Then, in early 2022, its CEO Tillman Gerngross abruptly left, and Hering moved from the chief operating officer role to the top position. By the fall of 2022, Adagio announced it was advancing VYD222, a re-engineered version of adintrevimab, and as this new hope progressed, the company was renamed Invivyd.
Despite the setbacks, Invivyd now believes it has cracked the code for developing COVID monoclonal antibodies that remain effective over time.
Next-Generation Antibodies
Hering's experience in combating infectious disease threats is substantial. During his tenure at Novartis, Hering held various roles, including leading the "Medical Countermeasures" group, where he was responsible for the company's response to H1N1 influenza. And during his six years at Pfizer, Hering played a key role in the preparation and launch of the company's COVID vaccine, helping secure the first contracts with the U.S. government and the partnership with the Gavi vaccine alliance.
Now, with a cash reserve that can sustain operations through the second half of 2024, Hering is also leveraging the experience gained from the company's first compound to push VYD222 into clinical development.
"We've proven that we can move from an IND (Investigational New Drug application) to pivotal data in a short time," he said.
To accelerate drug progress, Hering said Invivyd is in discussions with the FDA to use alternative biomarkers so that its studies do not need to demonstrate "event-driven endpoints."
The company has also adopted a new strategy to counter variants.
"When an antibody attaches to the viral target, the virus cannot enter human cells to cause disease. But the virus undergoes small mutations that hide or alter these attachment points," he explained. "VYD222 is re-engineered from adintrevimab, adjusting a few amino acids to restore binding ability lost due to Omicron, enabling VYD222 to bind and block viral entry. We are currently the only company engineering COVID antibodies in this way."
However, Hering acknowledged that future mutations could pose new challenges to antibodies on the market, and the current goal is to stay ahead of variants and maintain that lead. The company has other antibodies in its pipeline, and in the long term, it envisions gaining approval for a platform that can rapidly produce new therapies.
"It's like the seasonal flu vaccine, updated each year for new strains, but from the same product platform," he explained.
As the industry shifts toward treating COVID as an endemic disease, Hering sees long-term market potential, noting that Eli Lilly's and AstraZeneca's antibody therapies, before being withdrawn from the market, "each had annual sales of about $2 billion."
If Invivyd ultimately outsmarts the virus, it could dominate this market. Although many academic institutions are still researching antibody therapies to treat COVID, pharmaceutical companies are continuing to exit the field. In June of last year, Celltrion abandoned development of its inhaled antibody therapy; in February of this year, GSK exited its antibody partnership with Vir Biotechnology, leaving the latter to advance its antibody candidate alone.
"There are no other products on the market, and we saw the need to move quickly," Hering said.