An experimental Kymera Therapeutics therapy now has clinical data showing it can address a target long thought to be undruggable. The early results give confidence to Kymera’s partner, Sanofi, which has decided to advance the program to Phase 2 testing in two inflammatory skin disorders.

Kymera announced the Phase 1 results on Wednesday. Shares of the biotech company rose nearly 15% on the news.

Watertown, Massachusetts-based Kymera is one of several biotechs working in an emerging field of drug research called targeted protein degradation. This approach leverages a built-in cellular mechanism for disposing of old proteins as a way of eliminating proteins that cause disease.

Kymera’s lead program, KT-474, addresses IRAK4, a protein with known roles in inflammation and cancers. Research efforts to develop small molecules inhibitors for this protein haven’t panned out. Rather than block IRAK4, Kymera aims to degrade it. Cells have a disposal system that gets rid of proteins that are marked with certain molecular tags. Kymera’s drugs are small molecules that bring the target protein together with the right tag.

KT-474 is designed to address two skin disorders, hidradenitis suppurativa (HS) and atopic dermatitis (AD). The Phase 1 study was designed to test various doses in healthy volunteers and patients with HS or AD. The data reported Wednesday are from a group of 21 participants: 13 HS patients and 8 AD patients. Those patients received a 75 mg dose of KT-474 once daily for 28 days, and were then followed for an additional two weeks.

According to the results reported Wednesday, treatment with KT-474 knocked down levels of IRAK4. The maximum degradation of the target protein reported in a patient topped 90%. Kymera said that degradation of the target protein was similar across HS and AD patients in both the blood and the skin. The Kymera drug was well tolerated by patients and no serious adverse events were reported in the study. Side effects reported include headache, fatigue, and diarrhea. Kymera described those problems as mild, adding that all of them fully resolved.

The data reported are encouraging for the Kymera program and for the broader field of targeted protein degradation. Most of protein degradation research has focused on cancer. Kymera’s data bring validation to applications of this approach in inflammation. Based on these promising early data, Kymera said Sanofi plans to advance KT-474 into Phase 2 testing in both HS and AD. The first study is expected to start in 2023.

“The HS and AD patient data are encouraging as they highlight the broad potential of KT-474 and continue to validate Sanofi’s commitment to the target and to [targeted protein degradation’s] unique ability to unlock this critical pathway,” Naimish Patel, MD, head of global development, immunology and inflammation at Sanofi, said in a prepared statement. “We look forward to advancing the program into Phase 2 studies, and the potential that KT-474 offers to patients with a variety of immunological conditions.”

Sanofi paid $150 million up front in 2020 to partner with Kymera on its inflammation research. The IRAK4 research is one of the programs partnered with Sanofi. The other one, addressing an undisclosed target, is still in the discovery stage. Under the terms of the agreement, Sanofi will be responsible for the development of KT-474 in inflammation going forward; Kymera retains rights to develop the molecule in cancer. Under the deal terms, Kymera could earn more than $2 billion in milestone payments tied to the progress of the Sanofi-partnered programs.

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