On April 17, 2023 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported that it will present preclinical data in two poster presentations highlighting the Company’s novel Hippo pathway inhibitor, IK-930, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Orlando, FL from April 14-19, 2023 (Press release, Ikena Oncology, APR 17, 2023, View Source [SID1234630157]).

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Data being shared today reveals that IK-930 selectively binds and inhibits TEAD1 and further describes the mechanism for its antitumor activity. Key advantages demonstrated in the nonclinical studies include IK-930’s superior tolerability and comparable antitumor activity compared to panTEAD inhibition, resulting in a significantly improved projected therapeutic window in cancer patients. IK-930 was designed as a TEAD1-selective inhibitor to avoid on-target renal toxicity expected from panTEAD inhibition. TEAD1 is the most highly expressed TEAD paralog in mesothelioma and epithelioid hemangioendothelioma (EHE). The data being presented support the ongoing IK-930 Phase 1 program in patients with Hippo mutated cancers and the planned expansion into combinations of IK-930 with other targeted therapies in multiple cancer types, including across EGFR and RAS mutated cancers, to potentially delay or even reverse therapeutic resistance.

"IK-930’s selectivity profile is the ultimate example of what we are aiming to do at Ikena – creating effective and safe targeted oncology treatments that have the potential to benefit both patients with primary-defined cancers and prevent resistance to other targeted therapies. Targeted oncology came to fruition as a way to develop highly specific therapies that can benefit patients — to spare healthy tissue instead of causing widespread toxicity — it is crucial to take into account a target’s function outside of a patient’s cancer," said Mark Manfredi, Ph.D., Chief Executive Officer of Ikena Oncology. "Tolerability across multiple nonclinical species, including non-human primates, was central to our design of IK-930 and our enthusiasm about its potential in the clinic."

Highlights from the data in today’s poster include:

In nonclinical models and species, IK-930 demonstrated selective inhibition of TEAD1 with equivalent activity to broad TEAD inhibitors and a significantly improved tolerability profile

IK-930 promotes repressive TEAD1 activity by driving interactions with VGLL4, a signaling partner that reduces expression of pro-growth and anti-apoptotic genes

Through its binding with TEAD1 and VGLL4, IK-930 potentially blocks chromatin binding of other TEAD paralogs

In assessing the potential on-target renal toxicity of targeting TEAD, average urinary protein-to-creatinine ratios and histopathology in non-human primates predicted a therapeutic index of less than one for panTEAD inhibitions and a broad therapeutic window for IK-930

In addition, tomorrow the Company will present a poster that highlights IK-930’s ability to reduce and reverse resistance to other targeted therapies in preclinical models. Highlights include:

Treatment with IK-930 in combination with multiple targeted agents, such as EGFR, KRAS G12C, and MEK inhibitors, demonstrated a reduction in emergence of drug resistant "persister" cells

"IK-930 was designed by leveraging TEAD biology to rebalance the oncogenic activity of the Hippo pathway, providing a potentially differentiated and tolerable therapeutic option for patients," added Jeff Ecsedy, Ph.D., Ikena Chief Development Officer. "The data presented at AACR (Free AACR Whitepaper) today demonstrate the beauty of IK-930’s ability to preferentially keep TEAD1 in a transcriptionally repressive state, and to likely block other TEAD paralogs from activating oncogenic transcription. We are thrilled to be able to share this essential differentiation today and look forward to sharing more later this year from our progress with IK-930 in the clinic."

Presentation Details:

Poster Title: IK-930 A TEAD Paralog Selective Inhibitor for Treating YAP/TAZ-TEAD Dependent Cancers

Session: Novel Antitumor Agents 4

Presenter: Nathan Young, Ph.D., Associate Director of Molecular and Cellular Oncology at Ikena Oncology

Date: Monday, April 17, 2023

Time: 9:00 AM – 12:30 PM ET

Poster Title: IK-930, A Paralog Selective Novel TEAD-Inhibitor, Effectively Attenuates Drug-Tolerant Persister Cell Proliferation

Session: Drug Resistance in Molecular Targeted Therapies 3

Presenter: Daniel Hidalgo, Ph.D., Scientist I, Translational Science at Ikena Oncology

Date: Tuesday, April 18, 2023

Time: 9:00 AM – 12:30 PM ET

Both posters will be available on Ikena’s Resources Page on their website following the conference.

About IK-930

IK-930 is an oral, paralog-selective TEAD inhibitor targeting the Hippo signaling pathway. IK-930 selectively binds to TEAD1 and prevents transcription of multiple genes that drive cancer progression. By targeting the Hippo pathway, a key driver of cancer pathogenesis that is genetically altered in approximately 10% of all cancer types, IK-930 could have a differentiating impact across many cancers with high unmet need. Ikena is advancing IK-930 both as a monotherapy in patients with Hippo pathway mutated cancers and in combination with other approved targeted therapies to combat therapeutic resistance. IK-930 is currently being studied in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors with or without gene alterations in the Hippo pathway, including NF2-deficient malignant mesothelioma, Epithelioid Hemangioendothelioma (EHE) with documented TAZ/CAMTA1 fusion genes as well as other solid tumors with either NF2 deficiency or with YAP/TAZ genetic fusions (NCT05228015).