Idiopathic pulmonary fibrosis (IPF) is a progressive, deadly condition marked by a buildup of collagen in the lungs, which stiffens the tissue, reduces oxygen exchange and makes breathing hard. More than 250,000 people in the U.S.live with lung fibrosis, with 50,000 new diagnoses annually, and up to 40,000 deaths each year. Currently, lung transplantation is the only cure. The two approved drugs for IPF have limited efficacy and come with some serious side effects. Now, Randi Silver, PhD, Professor of Physiology and Biophysics at the Weill Cornell Medicine, and her team at Adiutrix Therapeutics have developed a novel compound that may be both safer, but more effective.
Rethinking the Collagen Pathway
Approved in 2014 for IPF, nintedanib (Ofev) and pirfenidone (Esbriet) slow the rate of lung scarring. They target the TGF-beta pathway, an upstream molecular route involved in collagen production. But up to half of patients stop these treatments due to their toxicity. "No one was focusing on other pathways, so I decided to take a deep dive into the mechanisms underlying collagen formation," explained Silver. She discovered that in a different collagen production pathway, an enzyme called C-P4H was necessary to stabilize the collagen. Silver and her colleagues created ADX1001, a first-in-class inhibitor of C-P4H. In preclinical models, ADX1001 restored lung function and normalized collagen formation — potentially offering a transformative alternative for fibrosis care.. If successful, ADX1001 could also have applications for other diseases where fibrosis is a hallmark, such as scleroderma, chronic kidney disease and impaired wound healing. In recognition of the promise of this technology, Silver and her team have been named a finalist in the 2025 XSeed Award, which provides grants of up to $250,000 to New York City minority- and women-led life science and healthcare startups working on novel preclinical drug development projects. Winning teams also join the ecosystem of Cure, a healthcare innovation campus headquartered in New York City.
A Researcher’s Journey from Lab to Clinic to Startup
Silver’s path to entrepreneurship began with diverse scientific interests. As an undergraduate at Skidmore College, Silver's interests were split between scientific research and art conservation. She even spent time in the field monitoring the migration of humpback whales. But lab research won out, she earned her PhD in physiology at Brown University, and her completed her first postdoc at Weill Cornell, where she has been ever since. Silver has been studying fibrosis for more than two decades. Initially researching renal fibrosis, she had a lab colleague had an uncle with IPF who subsequently died. She became increasingly interested in pulmonary disease after hearing repeatedly from clinicians about the poor prognosis for IPF patients, who have an average life expectancy of only five years after diagnosis. At the heart of her exploration are mast cells, which she began investigating in the early 2000s. "They're usually ignored, but mast cells are involved in many diseases and are always associated with a fibrotic response," she contended. It turns out that mast cells, the enzyme renin and the hormone angiotensin — all implicated in kidney disease — also play key roles in lung fibrosis, with angiotensin receptors present on fibroblasts, cells with contribute to making connective tissues. "I studied mast cells to see what could trigger a fibroblast to actually make collagen," she added. Through a series of experiments, Silver and her lab team zeroed in on C-P4H as the rate-limiting enzyme for stable collagen production and developed AX1001 to inhibit it. "I'm a basic scientist doing wet lab work, but I might actually bring something to the clinic that helps humankind. It's like a dream come true and underscores the value of basic scientific research," Silver added. "I love having a 'Eureka!' moment and I haven't had too many in science, but when you have them, it's extremely fulfilling and it keeps you going."
Go Where the Science Takes You
Despite her confidence as a lab researcher, Silver had never envisioned launching a company. She credits Weill Cornell's technology transfer office and a course sponsored by the BioVenture eLab about entrepreneurship, how to translate basic science findings to the clinic, and how to do a pitch for funding. She met cell biologist Ron Lennox, PhD, who has managed multiple spin-outs from academic labs. With J. Mark Junewicz, MBA, they founded Adiutrix, with Lennox as CEO and Junewicz as CFO/CBO. "I never considered myself an entrepreneur. I've learned a lot from Ron and I'm very pleased because we're making great progress," Silver noted. "Working as a team is also really important. I'm very big on collaborating with people to come together and push a project forward." She advises other academic investigators considering a startup launch to build a team, stay involved, use resources wisely and keep moving forward. "Be very conscious of how you spend your money and how you design each experiment, because every experiment counts," she recommended. "It takes years for a therapeutic startup to have something at the end. Stay focused. Go where the science takes you."
How an XSeed Award could fulfill a dream
The grant from an XSeed Award would enable Adiutrix Therapeutics to accomplish critical development milestones to enable the translation of ADX1001 to the clinic. These include in vivo pharmacokinetics, dose-finding studies and efficacy studies in mouse models of organ fibrosis, all of which could enable an Investigational New Drug submission to the FDA. A number of consultants have come on board, including Weill Cornell IPF clinicians Robert Kaner, MD, and Fernando Martinez, MD, to design the clinical development strategy; computational biophysicist George Khelashvili, PhD; and Peter Meinke, PhD, who leads the Sanders Tri-Institutional Therapeutics Discovery Institute and provides guidance on drug assays and design. "Winning an XSeed Award would really bring us to an infection point to take us to the next stage," Silver said. Adiutrix also looks forward to the opportunity to be part of Cure's healthcare innovation ecosystem.
A vision for broader impact for fibrotic diseases
In five years, Silver hopes the company will have a family of drugs tailored for lung fibrosis in different formulations, such as oral medications or nebulized preparations. The medication could potentially be formulated as a topical preparation for fibrotic diseases that affect the skin. "A mechanism is a mechanism. It doesn't matter where the fibroblast is — we're targeting the same rate-limiting enzyme, whether it's in the lung, skin or kidney," Silver stated. A nebulized preparation, for example, could make it possible to treat premature infants with bronchopulmonary dysplasia, who may be at risk of chronic obstructive pulmonary disease as adults. She concluded, "If we could change the trajectory of someone's health and Adiutrix made a contribution to that, then I have fulfilled my dream as a scientist." Learn more about the XSeed Award and past winners.