The human battle against viruses is an unending struggle for advantage. As we adapt and evolve to survive, pathogens evolve in response to us. This ongoing cycle is called the Red Queen hypothesis. Red Queen Therapeutics is named for this concept of evolutionary biology, and the startup is now out of stealth, revealing a technology platform and drug pipeline that could give humans the upper hand against prevalent viral threats.
Red Queen launched Tuesday backed by a $55 million Series A commitment from Apple Tree Partners, the venture capital firm that formed and incubated the Cambridge, Massachusetts-based startup.
While Red Queen, the company, is new, the world has already seen the Red Queen biological concept in action. The Covid-19 pandemic spurred research that led to the development and authorization of new antivirals. Viral mutations gave rise to variants resistant to these therapies. Many of these Covid-19 drugs were designed to interrupt a step in viral replication after a virus has already injected its nucleic acids to hijack a cell’s machinery, said Mark Mitchnick, president and CEO of Red Queen and a venture partner at Apple Tree.
Red Queen’s antivirals are peptides. Rather than blocking viral replication inside a cell, these peptides block a virus from fusing to the cell in the first place. Viral fusion is highly conserved, meaning it does not change even as viruses mutate. That makes it a valuable antiviral target. By blocking this highly conserved mechanism, Red Queen’s therapies have potential application to multiple viral families and their variants.
“Because they’re resistant to resistance, so to speak, should the next Covid variant or the next flu variant show up, it’s highly likely that the peptide we have now would have good activity,” Mitchnick said.
Red Queen is taking a new approach to an old idea. Fuzeon, an HIV drug approved in 2003 and currently marketed by Roche, is a peptide designed to block viral fusion. That drug employs the same fundamental science as Red Queen, though the startup brings new technology. Peptides by nature are unstable, and this instability is a disadvantage, Mitchnick said. Peptides require cold storage. After dosing, they are soon subject to breakdown by enzymes in the body. Peptide drugs also can’t be administered orally.
The antivirals of Red Queen are “stapled” peptides, meaning they are chemically stabilized in a particular conformation, Mitchnick explained. This stability overcomes some of the limitations of peptide drugs, making degradation by bodily enzymes less likely. Stability also enables storage at room temperature and dosing via a nasal spray, inhaler, or by injection. In addition to the stapling, Red Queen attaches a chunk of cholesterol to the peptide, which helps situate the molecule at the cell membrane.
Red Queen’s stapled peptide platform technology is based on research from Dr. Loren Walensky, attending physician in the department of pediatric oncology at the Dana-Farber Cancer Institute/Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School. Preclinical research from Walensky’s lab was published in January in Nature Communications.
Red Queen began its work about three years ago. A Covid-19 antiviral named RQ-01 is the startup’s lead program. The company has proof-of-concept data from a placebo-controlled Phase 1 study that enrolled 67 mildly symptomatic Covid-19 patients. Results show the nasal spray administered therapy’s safety was comparable to placebo. The small study was not powered to demonstrate efficacy, but results show a dose-dependent trend toward clearance of SARS-CoV-2 infection as well as activity of the peptide against infection progression. The data were presented in June during the American Society for Microbiology’s ASM Microbe meeting.
Red Queen is not Apple Tree’s first foray into stapled peptides. The VC firm was the founding investor of Aileron Therapeutics, whose peptide technology was based on Walensky’s earlier stapled peptide research. Aileron went public in 2017, raising money for a pipeline that included a lead program in development for cancer. The failure of a breast cancer study last year led Aileron to stop its cancer work. Last October, Aileron acquired Lung Therapeutics and shifted focus to lungs drugs that are not stapled peptides. There’s at least one other biotech developing stapled peptide drugs. Equillium has an orally administered stapled peptide in preclinical development for gastrointestinal indications. Mitchnick said he believes Red Queen is the first company to enter the clinic with a stapled peptide for infectious disease.
The potential of stapled peptides to combat infectious disease has drawn interest from the federal government. Earlier this year, the Biomedical Advanced Research and Development Authority (BARDA) awarded Red Queen a $750,000 contract to generate preclinical proof-of-concept data for a pan-influenza therapeutic. Mitchnick said this research is also looking at the drug’s activity against Ebola virus, Nipah virus, and hemorrhagic fevers. Studies are already underway testing the drug against avian influenza, which is of growing public health concern. A multi-state outbreak of bird flu in cattle has led to a small but growing number of infected farm workers. The Red Queen pipeline also includes RQ-02 in development for respiratory syncytial virus, human metapneumovirus, and human parainfluenza viruses, as well as RQ-04 for herpes.
With the new financing, Red Queen plans to advance its Covid-19 drug to a Phase 2 study in late 2025 enrolling immunocompromised patients. Mortality and morbidity in this group is high, and even when these patients recover, they don’t clear the virus very quickly, Mitchnick said. The trial will test RQ-01 and the standard of care compared to standard of care alone. The company is also exploring partnerships. Mitchnick said Red Queen has fielded inquiries from companies and government agencies. The stability of a Red Queen infectious disease therapeutic makes it suitable for stockpiling in advance of an epidemic or pandemic threat, Mitchnick said.
“When you talk about public health, if you can avoid a cold chain, that’s a huge plus, especially if you think about globally outside the U.S.,” he said.
Photo: Red Queen Therapeutics
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