On April 8, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that it will present data from the company’s lead RAF kinase inhibitor program, KIN-2787, and its clinico-genomics study investigating the occurrence of BRAF Class II and Class III alterations across solid tumors (Press release, Kinnate Biopharma, APR 8, 2022, View Source [SID1234611710]). The three separate poster presentations will be delivered at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana taking place April 8-13, 2022.

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"Kinnate continues to make progress with KIN-2787 in our RAF program. KIN-2787 has shown its potential as both a promising next-generation RAF inhibitor and to address a larger than previously understood unmet need among patients with BRAF and/or NRAS-altered cancers who are not currently benefiting from approved RAF inhibitors," said Richard Williams, MBBS, Ph.D., Chief Medical Officer at Kinnate. "We look forward to sharing these updates with the cancer research community at this year’s annual AACR (Free AACR Whitepaper) meeting."

The presentations to be delivered at the AACR (Free AACR Whitepaper) Annual Meeting include:

Abstract title: Occurrence of BRAF class II and III alterations is common across solid tumors and is associated with inferior clinical outcomes in NSCLC and melanoma (PAN# 4122)
Session: Real-world Data (RWD) and Real-world Evidence (RWE) / Outcomes Research (PO.CL13.01)
Section: 32
Presenter: Paul Severson, Ph.D., Senior Director of Translational Medicine & Bioinformatics at Kinnate
Session date and time: April 13, 2022, 9:00 AM – 12:30 PM ET

This presentation will highlight analyses conducted utilizing the GuardantINFORM platform and suggest that the prevalence of BRAF Class II and Class III alterations across patients with advanced and metastatic solid tumors screened via liquid biopsy-based comprehensive genomic profiling may be higher than previously understood. Among the nearly 6,000 patients who were identified as having BRAF alteration-positive cancers, approximately 55% were found to be harboring Class II and Class III alterations across all tumor types. When looking across common tumor types – Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer and Melanoma – approximately 65%, 30% and 20% of oncogenic BRAF alterations, respectively, are BRAF Class II and Class III. NSCLC and melanoma patients with BRAF Class II and Class III alterations experienced inferior clinical outcomes and represent populations that could benefit from novel targeted therapies.

Abstract title: Design and rationale of a first in human (FIH) Phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF- and NRAS-mutation positive solid tumors (PAN# CT248)
Session: Phase I Trials in Progress 2 (PO.CT01.04)
Section: 35
Presenter: Meredith McKean, M.D., M.P.H., Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology
Session date and time: April 13, 2022, 9:00 AM – 12:30 PM ET

This presentation will provide an overview of KN-8701 (NCT04913285), a first-in-human, multicenter, non-randomized, open-label, Phase 1 trial of KIN-2787 in adult patients with BRAF-altered advanced and metastatic solid tumors (AMST). KIN-2787 is given orally bid continuously in 28-day cycles until drug intolerance or disease progression. Planned sample size is approximately 155 patients in two parts: Part A of the trial has a dose-escalation design to establish the optimal dose for further evaluation and will enroll patients with AMST driven by BRAF Class I, Class II or Class III genomic alterations and patients with NRAS-mutant melanoma; Part B will evaluate a selected dose of KIN-2787 in three cohorts of patients with melanoma, NSCLC, or other AMST, each driven by BRAF Class II or Class III alterations. Standard Phase 1 enrollment criteria are required, and key exclusion criteria include known clinically active brain metastases from non-brain tumors, and prior receipt of BRAF-, MEK-, or MAPK-directed inhibitor therapy (except for cases in which these inhibitors were used in FDA-approved indications).

Abstract title: Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human RAF/RAS mutant melanoma (PAN# 2674)
Session: Signaling Pathway Inhibitors (PO.ET06.04)
Section: 25
Presenter: Nichol Miller, Ph.D., Senior Director of Translational & Discovery Biology at Kinnate
Session date and time: April 12, 2022, 9:00 AM – 12:30 PM ET

This presentation will highlight preclinical activity of KIN-2787 in human melanoma models. Cellular activity of KIN-2787 was evaluated across a panel of melanoma cell lines, including those harboring Class I, Class II and III BRAF alterations, NRAS mutations, KRAS mutation, and wild type RAF/RAS cell lines. In contrast to approved therapies targeting Class I V600E BRAF mutant tumors, KIN-2787 was active across all classes of BRAF-altered melanoma cells. Daily KIN-2787 treatment resulted in tumor growth inhibition in human melanoma xenograft models bearing Class I, II and III BRAF alterations as well as NRAS mutation and was associated with MAPK pathway suppression. Additionally, KIN-2787 was efficacious in a pre-/post-treatment melanoma PDX pair in which the original tumor was driven by a Class I BRAF V600E alteration but acquired a Class II BRAF kinase domain duplication upon progression on dabrafenib + trametinib.

Additional information about AACR (Free AACR Whitepaper) 2022 is available at: www.aacr.org/meeting/aacr-annual-meeting-2022.

About KIN-2787
KIN-2787, is an orally available small molecule pan-RAF inhibitor being developed for the treatment of patients with lung cancer, melanoma, and other solid tumors. KIN-2787 has been designed to target both monomeric and dimeric forms of the mutant BRAF kinase and minimize paradoxical activation, a liability often observed with other RAF inhibitors that can adversely impact tolerability and require addition of a MEK inhibitor to suppress pathway activation. KIN-2787 has also shown preclinical proof-of-concept as single agent and in combination with a MEK inhibitor in NRAS mutant melanoma. Unlike currently available treatments that target only Class I BRAF kinase alterations, KIN-2787 targets Class II and Class III BRAF alterations, where it has the potential to be a first-line targeted therapy, in addition to covering Class I BRAF alterations. The ongoing KN-8701 clinical trial (NCT# 04913285) of KIN-2787 is actively enrolling patients across multiple centers in the United States and one in Perth, Australia. For more information, please visit www.kinnate.com/patients.