Press Release

Three poster presentations highlight the unmet need for targeted therapies in BRAF and/or NRAS-altered cancers, including non-small cell lung cancer and melanoma

SAN FRANCISCO and SAN DIEGO, April 08, 2022 (GLOBE NEWSWIRE) -- 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, today announced 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. The three separate poster presentations will be delivered at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, Louisiana taking place April 8-13, 2022.

“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 meeting.”

The presentations to be delivered at the AACR 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 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.

About Kinnate
Kinnate is focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers. Kinnate’s mission is to expand the reach of targeted therapeutics by developing products that are designed to address significant unmet need. Kinnate utilizes its deep expertise in structure-based drug discovery, translational research, and patient-driven precision medicine, which it refers to as the Kinnate Discovery Engine, to develop targeted therapies. Based in San Francisco and San Diego, California, the Kinnate team is composed of drug discovery experts supported by a distinguished group of scientific advisors. For more information, please visit www.kinnate.com.

Forward Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. These forward-looking statements include, without limitation, statements regarding the potential benefits of our product candidates, including KIN-2787, and statements by our Chief Medical Officer. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are also intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and trends. Such expectations and projections may never materialize or may prove to be incorrect. These forward-looking statements are subject to a number of risks, uncertainties, assumptions and other factors, including risks related to recently transitioning to operating as a clinical-stage biopharmaceutical company with a limited operating history; our ability to raise additional capital to finance our operations; our ability to discover, advance through the preclinical and clinical development of, obtain regulatory approval for and commercialize our product candidates; the novel approach we are taking to discover and develop drugs; our ability to timely file and obtain approval of investigational new drug applications for our planned clinical trials; the potential for any clinical trial results to differ from our preclinical study results; negative impacts of the COVID-19 pandemic on our business, including ongoing and planned clinical trials and ongoing and planned preclinical studies; competition in our industry; regulatory developments in the United States and other countries; our ability to attract, hire and retain highly skilled executive officers and employees; difficulties in managing our growth; our ability to protect our intellectual property; reliance on third parties to conduct our preclinical studies and any ongoing or planned future clinical trials, and to manufacture our product candidates; general economic and market conditions; and other risks. These and other risks, uncertainties, assumptions and other factors are further described under the heading “Risk Factors” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2021 that we have filed with the Securities and Exchange Commission (the “SEC”), as well as in our subsequent filings we make with the SEC. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. Investors should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Our forward-looking statements speak only as of the date of this release, and except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason in the future.

Contacts:

Investors:
Patti Bank
ICR Westwicke
415-513-1284
investors@kinnate.com 

Media:
Colin Sanford
203-918-4347
colin@bioscribe.com