New start-up aims to turn stapled peptides into antivirals

Around 3 years ago, Dana-Farber Cancer Institute scientist Loren Walensky approached the venture firm Apple Tree Partners (ATP) with an idea. He and his team had found a way to use chemically stapled lipopeptides to block the virus SARS-CoV-2, and they believed the same technology could be used for other enveloped viruses, such as respiratory syncytial virus, Ebola virus, and Nipah virus (Nat. Commun. 2024, DOI: 10.1038/s41467-023-44361-1).

ATP set to work testing that theory and quietly built a company around it. Now that start-up is emerging from stealth. Red Queen Therapeutics launched Tuesday with $50 million in venture backing, a contract with the Biomedical Advanced Research and Development Authority (BARDA), and a pipeline led by a drug candidate that has already been tested in humans.

Most antivirals work by stopping a virus from replicating. Paxlovid, for instance, blocks an enzyme that SARS-CoV-2 uses to make copies of itself. In contrast, the peptide made by Walensky’s team is designed to prevent a virus from infecting a cell at all.

As CEO Mark Mitchnick puts it, an enveloped virus will typically park itself on a cell membrane, find a receptor it likes, and then bring itself closer to the membrane so it fuses. That fusion process involves the folding of two helical protein structures belonging to the virus, usually the heptad repeat 1 and 2 domain α-helices (called HR1 and HR2). “It literally jackknives and brings the virus closer to the body of the protein where the fusion takes place,” Mitchnick says.

Red Queen’s peptide is designed to stop that folding process from happening. “We mimic the part of HR2 that binds to HR1 . . . so HR2 cannot fold onto HR1,” Mitchnick says. “It’s literally a wrench in the works.”

The Red Queen team has worked to make the peptide stabler—preventing it from hydrolyzing and protecting it from enzymatic degradation—by cross-linking certain amino acids. The researchers also added cholesterol to one end so that the peptide sits in the membrane and is thus “in the right place at the right time when [the virus] shows up,” Mitchnick says.

Red Queen recently completed a Phase 1 clinical trial of its COVID-19 antiviral and plans to begin enrolling patients in a Phase 2 study toward the end of 2025. The midstage trial will focus specifically on immunocompromised people, like those who have received organ transplants or chimeric antigen receptor (CAR)T-cell therapy or who consistently take immunosuppressive medications. These are the people who stand to benefit the most from new antivirals, since their immune systems cannot easily clear pathogens on their own, Mitchnick says. Crucially, in the context of COVID-19, many immunocompromised people cannot take Paxlovid because it interacts with multiple medications.

Meanwhile, Red Queen is also testing the same drug candidate as a paninfluenza antiviral through a project funded by BARDA. The agency awarded the start-up a grant of up to $750,000 in May to test the compound in preclinical models and to engineer it for pulmonary rather than nasal administration. Mitchnick expects to publish preclinical data in late 2025.

Red Queen’s third project will test its ability to develop a true broad-spectrum antiviral. The drug candidate RQ-02is designed to target parainfluenza virus, respiratory syncytial virus, and human metapneumovirus.

“We’ve got quite a deep bench of products,” Mitchnick says. “Infectious disease is always feast or famine. We’re heading into a feast portion again, meaning it’s going to be very busy.”