British biotech, Autolus, is best known for its work on next-generation CAR T-cell therapies. However, as the pandemic coronavirus spread around the world last year, Autolus put together a team focused on addressing two issues it felt were being overlooked early in the crisis.
“The first was the risk of mutational drift, which was known for coronaviruses in general, but at the time, not well established for SARS-CoV-2. And the second was the challenge this viral infection could pose for our patients with B-cell malignancies with multiple myeloma, who would likely only have limited ability to benefit from future vaccines,” Autolus CEO Christian Itin told investors.
Those areas of focus drove Autolus to consider how to develop a product that would be active against the pandemic coronavirus and all future variants. That thinking led Autolus to zero in on the ACE2 receptor the coronavirus uses to enter human cells.
The result is a molecule that combines an “enzymatically inactive form of the extracellular domain of ACE2 and a mutated constant domain from an IgG to avoid unwanted immune activation.” Mutating the Fc domain is expected to extend the half-life of the candidate.
If Autolus is right, ACE2 Fx will reduce the binding of all variants of SARS-CoV-2 to human cells and, in doing so, neutralize the virus. The mechanism of action should work against other viruses that rely on ACE2 to enter human cells, such as the coronavirus behind the 2003 SARS outbreak and any other similar pathogens that make the leap from animals in the future.
The infectious disease candidate is well outside of Autolus’ focus on immuno-oncology but could still make a difference to the patients targeted by its cell therapy prospects.
Many therapies given to patients with hematological malignancies are B-cell depleting. Using such a therapy is likely to both increase susceptibility to severe COVID-19 and diminish immune responses to vaccines.
Typically, clinical practice guidelines recommend waiting months after a patient undergoes anti-B cell therapy before giving them a vaccine, although exceptions to that rule are made for influenza and, now, COVID-19.
Autolus thinks those patients need effective passive immunization against SARS-CoV-2. Having put its receptor decoy through preclinical studies, Autolus is now seeking a partner to help it find out if its candidate can address that need.