KT-621, potential oral medication for COPD, cleared for human trials
Therapy is designed to target diseases marked by type 2 inflammation
The U.S. Food and Drug Administration has cleared the start of clinical trial testing of KT-621, Kymera Therapeutics’ oral therapy for chronic obstructive pulmonary disease (COPD) and other diseases marked by type 2 inflammation.
KT-621 is designed to target STAT6, a protein involved in type 2 inflammation, which is marked by high blood counts of eosinophils, a type of immune cell, and is thought to contribute to COPD-related lung inflammation.
The regulatory clearance “is a significant milestone for Kymera, patients, and the whole industry, allowing Kymera to be the first company to advance a [STAT6-targeted] medicine into clinical evaluation,” Nello Mainolfi, PhD, Kymera’s founder, president, and CEO, said in a company press release.
The company plans to launch later this month a placebo-controlled Phase 1 trial to assess the safety, tolerability, and pharmacological properties of single and multiples doses of KT-621 in healthy volunteers. Results are anticipated early next year.
“We are excited to advance KT-621 into Phase 1 clinical testing and look forward to sharing updates on this program in the near future,” Mainolfi said.
Oral medication could be more convenient option for treating COPD
COPD is an inflammatory lung disease that makes breathing hard due to limited airflow into the lungs. Many patients have flare-ups, in which symptoms suddenly get worse. People with high numbers of eosinophils, a hallmark of type 2 inflammation, often have more severe flare-ups despite treatment.
In the U.S., Dupixent (dupilumab), an antibody-based therapy, is approved as a maintenance treatment for adults with poorly controlled COPD. It is designed to block signaling of IL-4 and IL-13, two chemical messengers involved in type 2 inflammation.
The therapy is the first biologic, a type of medication that comes from a living organism or its products, available in the country to treat COPD. Dupixent is also approved for several other diseases marked by type 2 inflammation.
KT-621 is a small molecule that acts downstream in the IL-4/IL-13 signaling. It specifically targets STAT6, a protein whose production is triggered by IL-4/IL-13 signaling activation and that is considered the central driver of type 2 inflammation.
Developed with Kymera’s targeted protein degradation approach, KT-621 flags STAT6 for degradation within cells, stopping the signals that cause type 2 inflammation. The company believes KT-621, administered orally, may offer a more convenient alternative to Dupixent’s under-the-skin injections.
We believe that our oral STAT6 degrader, KT-621, has the potential to … transform the current treatment paradigm for atopic and allergic diseases.
Like Dupixent, KT-621 has the potential to treat a range of other conditions marked by type 2 inflammation, such as atopic dermatitis and asthma.
“Unlike traditional oral small molecule inhibitors, we believe that our oral STAT6 degrader, KT-621, has the potential to combine the complete pathway blockade of upstream biologics with the convenience of oral administration and in doing so has the opportunity to transform the current treatment paradigm for atopic and allergic diseases,” Mainolfi said.
Atopy refers to the genetic tendency to develop a heightened immune response to an allergen, a substance that triggers allergy.
Preclinical studies showed that KT-621 effectively promoted STAT6 breakdown and fully blocked IL-4/IL-13 signaling in several types of lab-grown human cells at lower doses than those needed with Dupixent to achieve the same effect.
Further experiments demonstrated that low doses of the therapy potently degraded STAT6 in blood and tissue samples from dogs and nonhuman animals. It also eased type 2 inflammation and was well tolerated, even at high doses, in mouse models of atopic dermatitis and asthma.
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