KIN-7136 / Xoma - LARVOL DELTA

Preclinical investigation of a novel brain penetrant combination therapy targeting RAF and MEK for melanoma brain metastasis (SNO 2024) - "Current BRAF/MEK inhibitors, such as dabrafenib and vemurafenib, have shown responses on the order of 50-60% in patients with BRAF-mutant melanoma; however, responses are not durable... In mice, the brain-to-plasma unbound partition coefficients (Kpuu) of KIN-7136 and KIN-8391 were 0.67 and 0.7 respectively, higher than the comparators binimetinib and belvarafenib, demonstrating improved brain exposure.The IC50s of KIN-7136/ KIN-8391 in melanoma cell lines were 27.0/36.5 nM in A375 (BRAF V600E), 78.6/35.4 nM in HMV2 (BRAF G469V), 183.0/699.0 nM in SK-MEL-2 (NRAS Q61R), and 53.9/110.0 nM in SK-MEL30 (BRAF D287H and E275K), respectively... These preclinical data confirm the synergistic effect of KIN-7136 and KIN-8391 in BRAF-mutant melanoma brain metastases models, supporting further research to advance its clinical translation."

Combination therapy • Preclinical • Melanoma • Oncology • Solid Tumor • NRAS

Preclinical investigation of a novel brain penetrant MEK inhibitor to target brain metastasis (SNO 2023) - "Despite the clinical success of BRAF/MEK inhibitors for the treatment of advanced melanoma, dabrafenib and vemurafenib have limited intracranial overall response rates of 42-50% and median progression-free survival of 3.6-5.5 months...KIN-7136 showed improved rodent brain exposure compared to conventional agents; the brain-to-plasma concentration ratio (Kp) of KIN-7136 was >1.0, much higher than comparators binimetinib and mirdametinib...In vivo, daily oral treatment with KIN-7136 was well tolerated and produced a significant extension of overall survival compared to the vehicle control (p=0.0289, log-rank test) in the A375 intracranial tumor model in athymic mice. These preclinical data confirm activity of KIN-7136 in BRAF-mutant melanoma brain metastases models and support further research to advance its clinical progression."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Kinnate Biopharma Inc. Announces Pipeline Updates, Strategic Reprioritization and Workforce Restructuring (GlobeNewswire) - "Paused KIN-7136 MEK inhibitor development and implementing a workforce restructuring, aligned with reprioritization plan...Kinnate previously announced that the FDA cleared the IND application for KIN-7136. Based on the reprioritization plan, the Company will not initiate a clinical trial for KIN-7136 at this time."

Pipeline update • Oncology • Solid Tumor

Kinnate Biopharma Inc. Reports Second Quarter 2023 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Received clearance from the U.S. Food and Drug Administration (FDA) for the Investigational New Drug (IND) application of KIN-7136, a potentially brain-penetrant mitogen-activated protein kinase (MEK) inhibitor. The Company expects to enter the clinic in the second half of 2023 with KN-3603, a Phase 1 trial, to evaluate KIN-7136 in adult participants with advanced solid tumors that are driven by the mitogen-activated protein kinase pathway, primarily non-small cell lung cancer, including in participants with brain metastases."

IND • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Kinnate Biopharma Inc. Reports First Quarter 2023 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Pipeline Updates:...(i) The company expects to provide an update in the second half of 2023 on the dose selection and additional escalation data for exarafenib plus binimetinib, and initial exarafenib monotherapy dose expansion data in the first half of 2024; (ii) A brain penetrant mitogen-activated protein kinase (MEK) inhibitor (KIN-7136), expected to enter the clinic in the second half of 2023."

New trial • P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer