As COVID-19 showed so convincingly, we need a deeper arsenal of drugs to address the ever-growing threats of viral pandemics. Vaccines are a key foundational defense but are only part of the answer, especially as the viruses continually evolve. Decoy Therapeutics is developing a new class of protective antiviral drugs that can be optimized for emerging threats, manufactured surprisingly quickly and delivered as a nasal spray. The company recently made a lead-quality drug candidate for the viral family that includes measles and mumps in three days.
Decoy also plans to use its platform to design novel therapeutics to block aberrant protein-to-protein interactions that cause many cancers, inflammatory diseases and neurological conditions.
Leveraging research by MIT chemistry professor Bradley Pentelute, Decoy is creating “peptide conjugate” drugs that effectively act as chemical decoys for viruses, says Rick Pierce, co-founder and chief executive officer of the STEX25 company.
These drugs will protect against infections such as COVID-19 by blocking the virus from fusing to cells in the nose or lung. Moreover, the drugs can be tailored to protect against multiple members of a given viral family such as coronaviruses, and to variants that will evolve in that family.
Affordable and self-administered, these drugs could become important safeguards for people who can't take a vaccine, or are at particularly high risk, or must go into crowded social situations when the risk of spreading disease is high. “You want to have a second line of defense above and beyond the vaccine,” Pierce says. “Antivirals are a very effective way of providing that.”
Decoy's lead candidate is engineered to protect against COVID-19, SARS and MERS coronaviruses and has proven 100% effective in animal studies, Pierce says. The startup aims to launch a first clinical trial in 2024.
Founded in 2020, Decoy has enlisted an experienced team of executives and scientists, and gathered support from the Gates Foundation, Johnson & Johnson (J&J), the U.S. Biomedical Advanced Research and Development Authority (BARDA) and private investors, Pierce says. The startup is seeking partnerships for licensing, distribution and manufacturing its products, and for pursuing other types of disease targets.
Conjugate concepts
Also known as “fusion inhibitors”, the class of peptide conjugates that Decoy is building use linker molecules to connect peptides (short proteins) with lipids (fats and other oily molecules). The lipids target the cells in the nose and lungs to which a specific virus normally attaches. The peptide “warheads” are exquisitely designed to block the attachment by acting as a kind of molecular decoy. The linkers hold the warhead and the lipid together until the conjugate is confronted by a virus, at which point the warhead will block the virus from entering the healthy cell, says Pierce.
Not only can we make novel chemistry, and conjugate it with lipids that can target warheads that can be switched out, but we can make these drugs at incredibly fast speeds
The company's goal is to build a plug-and-play library of peptide warheads and targeting lipids with linkers that can connect them all, built on research in the Pentelute lab.
In addition to his expertise in linker chemistry, Pentelute “happens to be the inventor of the world's fastest peptide synthesizer,” Pierce says. “So not only can we make novel chemistry, and conjugate it with lipids that can target warheads that can be switched out, but we can make these drugs at incredibly fast speeds. Give us a viral genetic sequence of interest and within a matter of hours, we can begin to print out drugs to test against a viral threat.”
The COVID-19 drug candidate uses a peptide developed from the virus's genetic code as the warhead. Future generations of drugs could use multiple warheads, targeting multiple components of the virus, Pierce says. Other drugs also eventually might employ DNA, RNA or small molecules as warheads.
Decoy collaborates with Philip Kim, a professor of molecular genetics at the University of Toronto, to design antiviral drugs with peptides that aren't found in the human body. This approach potentially helps to lengthen the action and life of the drugs, and to make them less prone to inflicting side effects, Pierce says.
The coronavirus drug candidate will work against multiple members of the coronavirus family because it targets the machinery by which all those viruses fuse to healthy cells, he says. Another research partnership, with University of Waterloo professor of applied mathematics Mohammed Kohandel, aims to ensure that this ability is maintained by exploiting artificial intelligence techniques to study how the viruses might evolve.
Pushing conjugates toward the clinic
Decoy began with a phone call from Pentelute early in the COVID-19 pandemic. Pentelute's lab was the first to engineer a peptide based on the virus's genetic sequence, and the MIT professor was looking for ways to bring that milestone accomplishment forward towards a clinical product.
“Through that phone call, Decoy Therapeutics was born,” says Pierce, a veteran pharmaceutical executive and venture capitalist. His co-founders include chief scientific officer Barbara Hibner, chief business officer Peter Marschel and operations director Jodi Cooper, who had worked together at biotech giant Takeda Pharmaceuticals.
Based in Cambridge, Decoy has 10 employees and draws on research performed by the Pentelute lab, a University of Massachusetts/Lowell lab, and at JLABs, a J&J/BARDA health science incubator in New York City. The startup has raised $7 million from J&J and BARDA, the Gates Foundation, the Commonwealth of Massachusetts and three venture capital investment funds. It recently won a J&J/BARDA, Blue Knight Quick Fire Challenge award and expects significantly more non-dilutive funding to support preclinical and clinical development of its COVID-19 drug candidate in coming months.
Decoy's pipeline also includes a drug targeting respiratory syncytial virus (RSV) infections, which can prove dangerous for infants and the elderly. Pierce expects strong demand for an RSV antiviral for patients who can't take vaccines, or for quick general protection in outbreaks of RSV, since it would take weeks for any vaccine to become effective.
The nice thing about our drugs is they are pretty easy to scale up and can be manufactured right now on any continent on the planet
Moreover, the startup is engineering an antiviral against multiple members of the paramyxovirus family. This family includes measles, mumps, and other infections, some of which can be deadly.
Decoy is currently negotiating terms for non-dilutive funding for clinical trials through Phase2a for its lead drug candidates. The startup also is discussing potential partnerships with multiple pharmaceutical companies for licensing or distributing its products, as well as for manufacturing at scale. “The nice thing about our drugs is they are pretty easy to scale up and can be manufactured right now on any continent on the planet,” says Pierce.
Additionally, the company is seeking collaborations to develop peptide conjugate drugs for oncology, inflammation and neurological diseases. “It would not be too difficult with a large partner to extrapolate from what we've learned and built to date, and take our platform into new therapeutic areas,” he says.
“We set out to create drugs that are affordable, safe to use, self-administered, and can be made on every continent,” Pierce sums up. “And we literally can send the genetic sequence and the chemistry, manufacturing and control protocols to manufacturers in different parts of the world and have them begin scaling up and manufacturing our drugs in real time.”