Some one million people in the United States are affected by heart failure with preserved ejection fraction (HFpEF), a condition marked by the stiffening of a heart chamber that makes it harder for blood to circulate. This disease has limited approved therapies and high mortality rates.
Researchers have long considered the hormone relaxin as a possible treatment for cardiovascular diseases, including HFpEF. Relaxin is known to help prevent fibrosis, stop veins and arteries from hardening, and support necessary changes in the heart during pregnancy. However, using relaxin as a drug has been difficult because the body removes these small molecules too quickly for them to be effective.
“The pharmacokinetics are not really suitable to use it as a drug,” said Grant Zimmermann, director of business development at Harvard Office of Technology Development (OTD).
A turning point came in 2017 after Andrew Kruse, professor of biological chemistry and molecular pharmacology at Harvard Medical School’s Blavatnik Institute, made a discovery in his lab. “Andrew came to us,” Zimmermann recalled, “and said, ‘I think I know how to fix this.’”
Kruse’s team was studying the structure of relaxin and its receptor. They found they could engineer relaxin from its natural two-chain form into a single-chain molecule and attach an antibody Fc-domain to extend its presence in the body. Sarah Erlandson, the graduate student leading the project, explained that native relaxin is hard to produce due to its structure. The new design allowed them to fuse relaxin with an antibody component so it would remain longer in circulation.
Erlandson noted there was no single moment when they realized their work’s significance: “Our work relied on iterative design improvements. I remember our growing excitement as we made progress on the engineered protein. That’s when it started to feel like we could have a tangible impact on relaxin therapeutics.”
Kruse saw potential beyond basic research. OTD secured intellectual property protections and began exploring ways to move toward commercialization. Zimmermann brought the project to colleagues at the Blavatnik Biomedical Accelerator (BBA), which provided funding through grants and business development support.
Zimmermann described relaxin as a “prototypical example” of BBA-funded innovations—technologies with clear clinical paths that need help attracting industry partners for further development or licensing.
With BBA support, Kruse’s team conducted animal studies on pharmacokinetics and validated their findings enough for Kruse to start Tectonic Therapeutic—a company aimed at advancing this research into clinical settings.
“All of these things were really critical for us to be able to out-license this molecule, to show that it actually had some real promise,” Kruse said. “The Blavatnik Accelerator is really what allowed us to go from a pure research compound to something that was ultimately a clinical candidate.”
Kruse also worked closely with Timothy A. Springer, Latham Family Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School’s Blavatnik Institute. Springer co-founded Tectonic with Kruse after initial discussions about moving academic discoveries into commercial ventures; he contributed early funding and technical expertise.
Since licensing the technology, Tectonic has continued engineering efforts under Kruse’s guidance as adviser and Springer as board member while expanding their platform for developing drugs targeting G-protein coupled receptors (GPCRs). Alise Reicin, CEO of Tectonic Therapeutic, stated that about 30 percent of all approved drugs target GPCRs but only address a small subset; many remain untapped due to challenges in drug development.
“There is a lot of biology there that could be important in drug discovery and development, but many of those GPCRs…were considered hard to drug or undruggable,” Reicin said.
Tectonic focuses on RXFP1—a GPCR involved in various bodily processes including cardiovascular function—which binds with relaxin making tissues more flexible. Their lead treatment candidate TX45 is currently undergoing Phase 2 clinical trials.
“I think there’s lots of reason for optimism that this story is going to play out in the way we envisioned all those years ago,” Zimmermann said.
In January 2025, Tectonic received data suggesting its relaxin-based therapy may benefit patients with pulmonary hypertension related to HFpEF; similar results were seen later among patients whose heart failure involves reduced ejection fraction alongside pulmonary hypertension—a group facing higher risks than other heart failure patients. The company plans next year to begin testing treatments for pulmonary hypertension linked with interstitial lung disease using relaxin-based approaches.
“I’m a big believer that it’s the academic-pharma-biotech partnership that has driven innovation in all of the great drug-development programs over the last few decades that have improved the lives of patients,” Reicin said.
