Kymera and Sanofi shared positive results for an IRAK4 degrader for hidradenitis suppurativa and atopic dermatitis.
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Kymera and Sanofi shared positive results for an IRAK4 degrader for hidradenitis suppurativa (HS) and atopic dermatitis (AD), breaking ground to take protein degradation outside the field of oncology and into inflammatory disease indications.
In Part C of the Phase I study, 13 HS patients and 8 AD patients were dosed with Kymera’s KT-474. The therapy knocked down IRAK4 in blood and skin by more than 90%.
Before dosing, levels of IRAK4 in the skin of HS and AD patients had been twice as high as healthy volunteers. The IL-1R/TLR pathway has been identified with a key role in several inflammatory and autoimmune diseases.
Participants also experienced a systemic anti-inflammatory response with improved skin lesions and other painful symptoms of their conditions.
For Kymera, these results validate the company’s entire protein degradation platform.
“We’re excited about is what this data means for Kymera and this drug, but also what this data means for targeted protein degradation,” Kymera’s CEO Nello Mainolfi told BioSpace.
“I think being at the forefront of new development in these difficult inflammatory diseases and showing that the technology can do that is a really big deal.”
Kymera’s stock leaped 30% on the heels of the study data.
Sanofi will take over from here. The French pharma will move forward with a Phase II trial of KT-474 next year in the HS and AD populations.
Sanofi already has a treatment on the market for AD – dupixent. Dupixent blocks the IL-4 and IL-13 signaling pathways, two key sources of inflammation. The treatment consists of an injection every two to four weeks and carries side effects like injection site reactions, eye and eyelid inflammation, sometimes with blurred vision, cold sores and eosinophilia.
KT-474 is delivered orally. The Phase I study found it safe and well-tolerated with mild side effects, including headache, fatigue and diarrhea, which were all fully resolved.
“This was early dose escalation in patients, and we were able to demonstrate that the degradation profile that we saw in preclinical species is confirming in patients as well,” Mainolfi said. “This really sets us up for starting to think about clinical responses in the right patient population.”
Mainolfi added that the Phase II study may expand “beyond those two indications.”
