For a drug to work, the molecule must bind to its target. That’s tricky for elusive targets lacking typical binding sites, but that hurdle can be overcome with molecular glue, a molecule that brings together two proteins that don’t normally interact.
Molecular glues are a hot area of research in the context of targeted protein degradation, an emerging therapeutic approach that gets a disease-causing protein to go to the cell’s built-in protein disposal system. A molecular glue ensures that the enzyme tag marking a protein for disposal sticks to the target protein. Biotech companies have reached the clinic with this type of drug, but they’re all degraders. Brian Safina, president and chief scientific officer of Magnet Biomedicines, says molecular glues can do more, and the startup is now out of stealth to show how.
“It’s really all focused on degradation,” Safina said of current molecular glue research. “While that’s a great way to go, there are other biological mechanisms that one can take advantage of.”
Boston-based Magnet formally launched on Tuesday, backed by $50 million. The Series A financing was co-led by Newpath partners, which was the startup’s founding and initial investor, and Arch Venture Partners.
Molecular glues are already available via some old and widely prescribed medicines, such as cyclosporine A and rapamycin, Safina said. But as is the case with many older drugs, the mechanism of both immunosuppressants was not known at first. In the early 1990s, Stuart Schreiber, a Harvard University professor of chemistry and biology, revealed cyclosporin works as a molecular glue that induces protein-protein interactions. Schreiber has founded or co-founded biotech startups such as Jnana Therapeutics, Forma Therapeutics, and Belharra Therapeutics. Magnet, which Schreiber also co-founded, builds on the scientist’s decades of molecular glue research while also taking the therapeutic modality beyond degradation, Safina said.
“Now with degraders making inroads into disease and showing impact, Stuart found the time is right to expand beyond that in molecular discovery,” he said.
Rather than finding molecular glues by chance, Magnet takes a rational approach to discovering them. The company screens chemical libraries and analyzes human genetics and protein data to identify its molecular glues. Safina says his company’s molecules, called TrueGlues, prompt “cooperative interaction” between proteins.
Safina declined to disclose any of Magnet’s targets, though he said the company is initially focusing on targets that already have clinical and genetic validation. Therapeutic areas falling within that scope include immunology, oncology, and cardiovascular disease. The TrueGlue platform is indication agnostic, and that broad potential positions Magnet for partnering opportunities, Safina said. He added that the company is researching areas where “there is an opportunity to have a molecular glue to solve some of the problems that exist.”
What are those problems? A targeted protein degrader molecule resembles a barbell, with each end having a different function. But Safina says these bifunctional molecules are challenging to develop as oral formulations. A molecular glue can also imbue a Magnet drug with high specificity to its target, similar to the targeting ability of antibodies. Higher specificity reduces the risk of adverse effects that happen when a drug goes off target.
Magnet joins a growing group of companies researching molecular glues. Monte Rosa Therapeutics, which trades under the descriptive stock symbol “GLUE,” develops molecular glues for applications in targeted protein degradation. The Boston-based company’s most advanced program is in early clinical development for various cancers. Ambagon Therapeutics launched last year to develop glues that address the 14-3-3 family of proteins. Those glues can work in a variety of ways, such as stabilizing protein interactions, inhibiting function, restoring function, or protein degradation. The San Francisco-based startup’s preclinical pipeline currently spans six programs in cancer and one in neurodegeneration. Meanwhile, A-Alpha Bio discovers molecular glues that other companies use in their drug research. Disclosed partners of Seattle-based A-Alpha include Bristol Myers Squibb, Kymera Therapeutics, and Gilead Sciences.
Magnet drugs could work in a variety of ways. While targeted protein degradation is one potential mechanism, Safina reemphasized that Magnet aims to expand beyond degradation. The startup’s drugs could inhibit function like traditional small molecules. A Magnet drug could also stabilize a target protein. Safina said Magnet’s technology should produce drugs capable of binding to targets that are tough for small molecules.
Magnet will use its new capital to continue building the TrueGlue platform while applying it to a variety of targets. Safina said the Series A round will enable the startup to reach lead optimization with understanding of which types of targets are most amenable to the TrueGlue approach. The financing will also support the company through candidate nomination and preparation for an investigational new drug application, he said.
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