Unmet Need
In the U.S., approximately 16% of non-small cell lung cancer (NSCLC) cases harbor epithelial growth factor receptor (EGFR) mutations, with insertions at exon 20 (EGFRex20ins) accounting for 12% of those mutations. Patients with EGFRex20ins mutations have poorer outcomes than those with more common EGFR mutations, such as exon 19 deletions. There remains a significant unmet need for therapies targeting EGFRex20ins mutations in NSCLC that are safer and more effective.
Unmet Need
A hallmark of cancer is the ability to avoid destruction by immune cells. Cancer cells develop escape mechanisms that can render them invisible to the human immune system. This immune evasion enables unrestricted tumor growth and potential metastasis. There is a significant unmet need for treatments that can help overcome immune-evasion mechanisms employed by tumors.
Development Plan
Unmet Need
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults with 20,050 new cases expected in the US in 2022. AML is a rapidly growing cancer. Patients are typically diagnosed at an average age of 72 and have a 5-year survival rate of 10% or less in the relapsed setting. A significant unmet need remains for a broadly applicable and accessible therapy that produces high and durable response rates.
Development Plan
News
Unmet Need
While checkpoint inhibitors have revolutionized immuno-oncology, only a minority of patients respond, often due to the tumor being "cold," which means it lacks an appreciable number of infiltrated, tumor-specific T cells. For several decades, preclinical researchers and clinical investigators have characterized the powerful role interleukin (IL)-2 and IL-12 play in stimulating the immune response to cancer and turning the tumor "hot." Previous attempts to administer IL-2 and IL-12 directly into the tumor have failed to improve efficacy due to leakage of drug from the injection site. Because of the systemic toxicities of both IL-2 and IL-12, delivery directly into the tumor is theoretically attractive as long as an effective retention strategy is leveraged.
Asset Potential
CLN-617 is a potential first-in-class cytokine therapy candidate for intratumoral injection and is the first to combine IL-2 and IL-12 in a single molecule. CLN-617 is effectively retained in tumor tissue in preclinical animal models to avoid systemic toxicity. Local administration of CLN-617 promotes broad systemic immunosurveillance, potentially enabling the treatment of advanced disease, including mediating the regression of non-injected distal tumors and generating a memory of T cell responses to enhance long-term survival. Collagen is the major component of the tumor microenvironment; binding to collagen helps keep CLN-617 in the tumor.
Development Plan
Development Plan
In ongoing Phase 1/2a study, zipalertinib (CLN-081/TAS6417) demonstrated promising efficacy in heavily pretreated patients, including patients who progressed on treatment with EGFR tyrosine kinase inhibitors (TKIs), with favorable safety and tolerability profile. Results are encouraging in heavily pretreated patients, including those who progressed with other EGFR TKI. The safety profile is amenable for long-term treatment at doses <150mg BID. Zipalertinib (CLN-081/TAS6417) demonstrates the potential to become a new standard of care to treat NSCLC harboring EGFRex20ins mutations.