On November 28, 2022 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported that a next-generation mitogen-activated protein kinase (MEK)-RAF complex inhibitor, IK-595, has been nominated as the company’s first development candidate in the RAS pathway (Press release, Ikena Oncology, NOV 28, 2022, View Source [SID1234624641]).

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The RAS pathway is implicated in at least half a million new cancer diagnosis each year in the United States alone. Ikena aims to target the pathway on multiple levels, including preventing known resistance mechanisms to achieve deep and sustained responses. Ikena’s new development candidate, IK-595, traps MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors. IK-595’s ability to complex CRAF, in particular, prevents a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other drugs in this class. In addition, trapping CRAF in an inactive complex prevents the kinase independent anti-apoptotic function in RAS and RAF mutant cancers, a mechanism that cannot be addressed with first generation MEK inhibitors or pan-RAF inhibitors. IK-595 is being developed as an oral therapy, with a half-life enabling a pharmacokinetic profile potentially superior to other drugs, with the goal of developing an optimal therapeutic window for patients. The company plans to submit an investigational new drug application (IND) for IK-595 to the US Food & Drug Administration (FDA) in the second half of 2023.

"I am thrilled to announce this addition to our pipeline, one that adds to our holistic approach to the Hippo & RAS oncosignaling network. IK-595 inhibits multiple nodes of MEK-RAF signaling, including avoiding known mechanisms of resistance," said Mark Manfredi, PhD, Ikena’s Chief Executive Officer. "The industry’s excitement about MEK inhibition stems from its great potential as a target, but the challenges of CRAF bypass and achieving optimal target inhibition have kept first generation treatments from meeting the full potential of the target. We are hopeful that our MEK-RAF trapping approach with an optimized therapeutic window can make IK-595 a game-changing candidate for multiple indications in the RAS space."

Development Highlights, Corporate Updates, and Upcoming Milestones

Advancing new development candidate, IK-595, through IND-enabling studies, targeting MEK-RAF through novel mechanisms aiming to address existing gaps in the MEK inhibitor space
Preclinical differentiation data planned for presentation in the first half of 2023
IND targeted in the second half of 2023
Progressing novel, paralog-selective transcriptional enhanced associate domain (TEAD) inhibitor, IK-930, in the clinic and further defining differentiation profile from panTEAD inhibition
Monotherapy program progressing as planned, advanced through multiple dose escalation cohorts
Preclinical data on differentiation and advantages of paralog selectivity planned for presentation in first half of 2023
Initiation of osimertinib combination cohort clinical program expected in first half of 2023
Initial clinical data from IK-930 monotherapy program expected in second half of 2023
Following a portfolio review, discontinuing the internal clinical development of the EP4 antagonist IK-007 and exploring strategic alternatives for this program
Clinical data from IK-007 in microsatellite stable colorectal cancer (MSS-CRC) will be presented in a poster at 2022 European Society for Medical Oncology Immuno-Oncology Congress
Portfolio reprioritization and streamlining of discovery and clinical activities contribute to extension of cash runway into 2025
Runway does not include any potential licensing revenue from the aryl hydrocarbon receptor (AHR) antagonist IK-175 program, currently in development in collaboration with Bristol Myers Squibb and eligible for opt-in through early 2024
"Ikena has a strong track record of internal drug discovery and development that has built our robust clinical and early-stage pipeline," said Jotin Marango, MD, PhD, Chief Financial Officer and Head of Corporate Development of Ikena. "Our goal is to continue our leadership in targeted oncology by discovering and advancing best-in-class candidates like IK-930 and IK-595, therapies designed to address the needs of specific patient populations while at the same time building value for our shareholders."