A biotech startup founded at Penn was awarded $22 million in federal funding to advance clinical testing of a drug that mimics the effect of estrogen.
Linnaeus Therapeutics will launch clinical trials on cancer and age-related disease treatments with the five years of funding from the Advanced Research Projects Agency for Health. The company — co-founded by 2018 Perelman School of Medicine graduate Christopher Natale and Penn Medicine physician and associate professor of dermatology Todd Ridky — is developing a once-a-day pill that provides estrogen benefits without activating the hormone.
While at Penn, Natale conducted doctoral work studying differences in melanoma outcomes between men and women which informed the company’s research. Prior research found that women with melanoma have lower mortality and recurrence rates than men, leading Natale to treat cells with estrogen — which is often seen in woman at higher levels.
Natale told the Philadelphia Inquirer that he thought his research could become “more than an academic project.”
While testing, Natale found that estrogen inhibited melanoma cell growth by activating a receptor known as the G protein-coupled estrogen receptor. Linnaeus Therapeutics later developed LNS8801 to activate this receptor without engaging other estrogen pathways in the body.
“We know that estrogen has a lot of anti-aging properties in general,” Natale told the Inquirer.
Linnaeus Therapeutics is one of seven teams nationwide selected for the ARPA-H PROactive Solutions for Prolonging Resilience program, which focuses on preventing or delaying age-related diseases. The company’s research uses “observed sex differences to identify mechanisms like GPER activation that link tumor suppression, vascular health, metabolism, and brain function.”
The drug, LNS8801, has been tested in clinical trials for melanoma since 2019 and has received Orphan Drug and Fast Track designations — but it has not yet been approved by the Food and Drug Administration. In early trials involving approximately 100 cancer patients, “no serious adverse events” were reported.
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Researchers have also observed effects beyond cancer treatment, with some trial participants experiencing improvements in cardiometabolic markers, including indicators associated with diabetes risk. The trials will examine whether LNS8801 can also help preserve physical and cognitive function in older adults.
In November 2024, researchers at the School of Engineering and Applied Science and the Medical School received a four-year, $7 million grant to develop artificial intelligence systems that support personalized medical treatment.
