Ikena Oncology, Inc. (NASDAQ:IKNA) is a clinical-stage targeted oncology company focused on developing differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance in the Hippo and RAS onco-signaling networks. The company's approach in each of its programs is to target both cancer-driving targets and mechanisms of resistance to other therapies.

Business Overview

Ikena Oncology's most advanced program, IK-930, is a selective inhibitor of the transcriptional enhanced associate domain 1 (TEAD1). The TEAD transcription factors (TEAD 1-4) execute the ultimate step in the Hippo signaling pathway, a known oncogenic pathway that also drives resistance to multiple targeted and chemo therapies. The company's program in the RAS pathway, IK-595, is a molecular glue designed to trap MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors.

Since commencing operations in 2016, Ikena Oncology has advanced multiple product candidates into clinical development. The company's most advanced targeted oncology product candidate, IK-930, is an oral, TEAD1-selective, small molecule inhibitor of the Hippo signaling pathway. The Hippo pathway is genetically altered in approximately 10% of human cancers and is widely accepted as a prevalent driver of cancer pathogenesis and a mediator of poor outcomes for patients.

In the company's ongoing first-in-human Phase 1 clinical trial, Ikena Oncology is focusing on indications that provide the potential to achieve rapid proof-of-concept, such as NF2 deficient mesothelioma and solid tumors with YAP1 or TAZ gene fusions, including epithelioid hemangioendothelioma (EHE). Approximately 40% of mesothelioma patients are genetically deficient for the tumor suppressor NF2, with approximately an additional 25-30% having partial NF2 alterations or protein loss, and 100% of EHE patients have oncogenic YAP1 or TAZ gene fusions.

In addition to the monotherapy approach, Ikena Oncology plans to assess IK-930 in combination with other targeted therapies across several indications with multiple targeted therapies. Based on the role that the Hippo pathway plays in resistance to other targeted therapies, the company believes that IK-930 may expand the patient populations that could benefit from therapies like epidermal growth factor (EGFR) inhibitors, KRAS inhibitors, and MEK inhibitors, among others. The company has an established clinical collaboration with AstraZeneca for the evaluation of osimertinib in combination with IK-930 for patients with EGFR-mutant lung cancers as a cohort in the clinical program.

In the company's RAS pathway program, IK-595 is designed to robustly inhibit MEK-RAF by gluing MEK and the RAFs (A, B, and C) in an inactive complex, thus more completely inhibiting RAS signals than existing inhibitors. IK-595's potential ability to complex CRAF, in particular, has been shown in preclinical models to prevent a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other MEK and RAF drugs in this class. In addition, trapping CRAF in an inactive complex has been shown in preclinical models to prevent 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.

Financials

For the full year 2023, Ikena Oncology reported annual net loss of $68.2 million, annual revenue of $9.2 million, annual operating cash flow of -$79.7 million, and annual free cash flow of -$80.2 million. For the first quarter of 2024, the company reported a net loss of $16.1 million, no revenue, and net cash used in operating activities of $18.3 million.

Liquidity

The company's cash, cash equivalents, and marketable securities totaled $157.3 million as of March 31, 2024. Based on the company's current operating plans, this cash position is expected to fund operations into the second half of 2026.

Recent Developments

In January 2024, Ikena Oncology's board of directors approved a plan to reduce the company's workforce by approximately 35% and discontinue discovery efforts. The Workforce Reduction is designed to align the company's workforce with its strategy to focus on its clinical stage, targeted oncology programs, IK-930 and IK-595. The company expects the Workforce Reduction to result in a reduction of operating expenses and extend its cash runway into the second half of 2026.

Risks and Challenges

Ikena Oncology faces several key risks, including the ability to successfully complete clinical trials for its targeted oncology programs, the rapidly evolving nature of the science underlying its approach, the capital-intensive nature of drug development, and the competitive landscape in the oncology space. The company also faces risks related to its reliance on third-party manufacturers and service providers, the potential for intellectual property disputes, and the regulatory environment for its product candidates.

Outlook

Despite these risks, Ikena Oncology's focus on innovative, targeted oncology therapies and its progress in advancing multiple programs into the clinic position the company as an interesting player in the oncology space. Investors will be closely watching the company's ability to execute on its clinical development strategy and deliver on the promise of its pipeline. With a cash runway into the second half of 2026 and a streamlined focus on its lead programs, Ikena Oncology appears well-positioned to continue advancing its targeted oncology efforts.