IK-175 / Ikena Oncology - LARVOL DELTA

IK-175, an oral AHR inhibitor, as monotherapy and in combination with nivolumab in patients with urothelial carcinoma resistant/refractory to PD-1/L1 inhibitors. (ASCO 2024) - P1 | "IK-175 showed a predictable, consistent safety profile as a monotherapy and in combination with nivolumab. Meaningful clinical benefit and objective, durable, prolonged responses were demonstrated in both monotherapy and combination arms in heavily pretreated UC patients with tumors refractory to CPI and supports further development of this asset in solid tumors."

Clinical • Combination therapy • IO biomarker • Monotherapy • Endocrine Disorders • Fatigue • Immunology • Nephrology • Oncology • Pneumonia • Renal Disease • Rheumatology • Solid Tumor • Urothelial Cancer

Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Ikena Oncology | Phase classification: P1b ➔ P1 | N=54 ➔ 0 | Trial completion date: Jul 2025 ➔ Apr 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jul 2024 ➔ Apr 2023

Combination therapy • Enrollment change • Metastases • Phase classification • Trial completion date • Trial primary completion date • Trial withdrawal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Phase 1a/b Study of IK-175 as a Single Agent and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: Ikena Oncology | Recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Jul 2023 | Trial primary completion date: Sep 2022 ➔ Jul 2023

Checkpoint inhibition • Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Ikena Oncology Reports First Quarter 2023 Financial Results and Highlights Advancements Across Targeted Oncology Pipeline (GlobeNewswire) - "Initial clinical data from the monotherapy portion of the ongoing Phase 1 clinical trial of IK-930, including patients from the dose escalation cohorts and backfilling, is planned for the fourth quarter of 2023....Investigational new drug (IND) application submission for IK-595 planned for the second half of 2023....IK-175: AHR Inhibitor in Collaboration with Bristol Myers Squibb...The Phase 1 clinical trial in urothelial carcinoma has completed enrollment; treatment is ongoing and the program is eligible for opt-in from Bristol Myers Squibb through early 2024."

Enrollment closed • IND • P1 data • Genito-urinary Cancer • Mesothelioma • Oncology • Solid Tumor • Urothelial Cancer

Ikena Oncology Reports Fourth Quarter and Full Year 2022 Financial Results (GlobeNewswire) - "Phase 1 trial of IK-930 in Hippo altered cancers (NCT05228015) continues to advance as expected, with multiple dose escalation cohorts cleared....Initial clinical data from the monotherapy portion of the Phase 1 study is expected in the second half of 2023....Investigational new drug application (IND) submission for IK-595 to the U.S. Food & Drug Administration (FDA) planned for the second half of 2023. IK-175: AHR Inhibitor in Collaboration with Bristol Myers Squibb....The program is eligible for opt-in from Bristol Myers Squibb through early 2024."

IND • P1 data • Genito-urinary Cancer • Mesothelioma • Oncology • Solid Tumor • Urothelial Cancer

Analytical validation of a novel immunohistochemistry assay to determine nuclear AHR expression in human bladder cancer (SITC 2021) - P1 | "IK-175 is being evaluated in an ongoing phase 1 clinical study as a single agent and in combination with nivolumab for bladder cancer patients (NCT04200963). Conclusions A novel and robust nuclear AHR IHC assay for bladder cancer was developed and analytically validated in a CLIA certified lab and showed ≥95% accuracy, specificity, sensitivity, and precision, enabling its implementation in an IK-175 Ph1b clinical study (NCT04200963) for prospective patient enrichment. Trial Registration NCT04200963"

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • AHR

Computational biology and tissue-based approaches to inform indication selection for a novel AHR inhibitor (SITC 2021) - P1 | "This study provides rationale for therapeutic targeting of AHR in bladder cancer patients. Ikena is currently evaluating the anti-tumor activity of IK-175 as a single agent and in combination with nivolumab in bladder cancer in a Phase 1a/1b clinical study (NCT04200963)."

Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Oncology • Solid Tumor • Urothelial Cancer

[VIRTUAL] Discovery of clinical candidate IK-175, a selective orally active AHR antagonist (SITC 2020) - P1 | "In addition, IK-175 in combination with liposomal doxorubicin demonstrates antitumor activity in syngeneic mouse models of colorectal cancer (CT26.WT and MC38). Overall, our data demonstrates that IK-175 is a selective orally active AHR antagonist that inhibits tumor growth and reverses immune suppression in mouse tumors models. IK-175 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors and urothelial carcinoma (Clinicaltrials.gov NCT04200963)."

Clinical • IO Biomarker • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • Urothelial Cancer • AHR • CYP1A1 • IDO1

[VIRTUAL] Discovery of clinical candidate IK-175, a selective orally active AHR antagonist (SITC 2020) - P1 | "In addition, IK-175 in combination with liposomal doxorubicin demonstrates antitumor activity in syngeneic mouse models of colorectal cancer (CT26.WT and MC38). Overall, our data demonstrates that IK-175 is a selective orally active AHR antagonist that inhibits tumor growth and reverses immune suppression in mouse tumors models. IK-175 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors and urothelial carcinoma (Clinicaltrials.gov NCT04200963)."

Clinical • IO Biomarker • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • Urothelial Cancer • AHR • CYP1A1 • IDO1

Ikena Oncology Receives FDA Fast Track Designation for Novel AHR Antagonist IK-175 in Combination with Nivolumab to Treat Urothelial Carcinoma (GlobeNewswire) - "Ikena Oncology...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for IK-175, the Company’s novel aryl hydrocarbon receptor (AHR) antagonist, in combination with immune checkpoint inhibitors in patients with advanced urothelial carcinoma who have progressed on or within three months of receiving the last dose of checkpoint inhibitors....IK-175 is the second of Ikena’s candidates to receive Fast Track designation....IK-175 targets AHR, a compelling cancer-driving transcription factor that prevents immune recognition in a multitude of cancers by modulation of innate and adaptive immunity."

Fast track designation • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

IK-175 Monotherapy or Plus Nivolumab Shows Early Activity in Urothelial Cancer (OncLive) - P1a/1b | N=93 | NCT04200963 | Sponsor: Ikena Oncology | "The selective, small molecule AHR inhibitor, IK-175 was found to be well tolerated in patients with advanced solid tumors and to elicit responses in those with urothelial cancer when used alone or in combination with nivolumab (Opdivo), according to initial data from an ongoing phase 1a/b study (NCT04200963). Findings from the dose-escalation portion of the research showed that 3 of the 15 patients who received IK-175 alone, and 2 of the 5 patients who received the agent in combination with nivolumab, experienced prolonged stable disease which ranged from 16 to 74 weeks. Moreover, in the dose-expansion cohort of patients with urothelial disease (n = 20), 1 patient who received the monotherapy (n = 10) and 2 patients who received the combination (n = 10) achieved a partial response. In these patients, the duration of response (DOR) ranged from 4.5 to 14.9 months....Data...[were] presented during the 2022 SITC Annual Meeting."

P1 data • Oncology • Solid Tumor • Urothelial Cancer

A Phase 1b open-label, single-arm dose expansion study of IK-175, an oral AHR inhibitor, in combination with nivolumab in patients with primary PD-1 inhibitor resistant advanced head and neck cancer (SITC 2022) - P1b | "Estimated enrollment is approximately 54 patients; the study started in July 2022. Trial Registration NCT05472506 Ethics Approval The study was approved by Advarra Central IRB, approval number MOD01366597"

Clinical • Combination therapy • IO biomarker • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IDO1 • TDO2

Initial results from a Phase 1a/b study of IK-175, an oral AHR inhibitor, as a single agent and in combination with nivolumab in patients with advanced solid tumors and urothelial carcinoma (SITC 2022) - P1 | "Based on the objective responses observed in stage 1 of both cohorts, investigation of AHR inhibition with IK-175 in urothelial carcinoma is ongoing. Trial Registration NCT04200963 Ethics Approval This trial was approved by all participating IRBs."

Clinical • Combination therapy • IO biomarker • P1 data • Oncology • Solid Tumor • Urothelial Cancer

Ikena Oncology Announces Initial Clinical Data from IK-175 Program in Urothelial Carcinoma (GlobeNewswire) - P1 | N=93 | NCT04200963 | Sponsor: Ikena Oncology | "IK-175 monotherapy: 1 confirmed partial response with a duration of response (DoR) of 14.9 months and ongoing; 1 stable disease patient. 10% overall response rate (ORR), 20% disease control rate (DCR)....IK-175 combination with nivolumab: 2 confirmed partial responses with DoR 4.5-6 months and ongoing; 2 stable disease patients....IK-175 was well tolerated, with a predictable and manageable safety profile."

P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

UPDATE -- Ikena Oncology Reports Third Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Initial Clinical Data from IK-175 in Urothelial Carcinoma to be Presented at SITC 2022...The Phase 1a/1b trial of IK-175 (NCT04200963) in metastatic urothelial carcinoma is an ongoing clinical study and continues to recruit patients who have progressed on prior lines of therapy, including checkpoint inhibitors...As of July 2022, at abstract submission, a total of 43 patients were enrolled across dose escalation and expansion; population is heavily pre-treated and in late lines of therapy"

Trial status • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

UPDATE -- Ikena Oncology Reports Third Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Phase 1b Trial of IK-175 in Combination with Nivolumab in Head & Neck Cancer (NCT05472506) Trial-in-Progress Poster to be Presented at SITC 2022...Title: A Phase 1b open-label, single-arm dose expansion study of IK-175, an oral AHR inhibitor, in combination with nivolumab in patients with primary PD-1 inhibitor resistant advanced head and neck cancer "

Trial status • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase 1a/b Study of IK-175, an Oral AHR Inhibitor, Alone and in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma (SITC 2021) - "Exploratory biomarkers of IK-175 mediated PD effects, PK-PD correlations, and correlative analyses of predictive and PD measurements with response and resistance will be performed. The study started in January 2020 and is ongoing"

Clinical • Combination therapy • IO biomarker • P1 data • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • IDO1 • IL2 • IL9 • TDO2

Phase 1a/b open-label study of IK-175, an oral AHR inhibitor, alone and in combination with nivolumab in patients with locally advanced or metastatic solid tumors and urothelial carcinoma. (ASCO 2022) - P1 | "Key eligibility criteria include patients with histologically confirmed solid tumors (including urothelial carcinoma) who have locally recurrent or metastatic disease that have progressed on or following all standard of care therapies deemed appropriate by the treating physician including prior checkpoint inhibitors. Estimated enrollment is 93 patients; the study began in January 2020 and is ongoing."

Clinical • Combination therapy • IO biomarker • P1 data • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer • IDO1 • TDO2

Ikena Oncology to Present Initial Phase 1a/b Results from Novel AHR Inhibition Program at the 2022 Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting (GlobeNewswire) - "Ikena Oncology, Inc...announced that two abstracts highlighting the company’s Aryl Hydrocarbon Receptor (AHR) antagonist program, IK-175, will be presented at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting, which will be held in-person in Boston, MA and virtually on November 8-12, 2022....The initial results from the first-in-human Phase 1a/b clinical trial presented at SITC will include data from the dose-escalation cohorts and initial data from the urothelial carcinoma expansion cohorts. Both monotherapy and combination with nivolumab patients will be included....A trial-in-progress poster will also be presented on the ongoing head and neck cancer clinical trial, which is evaluating IK-175 in combination with nivolumab in PD-1 resistant patients."

P1 data • Trial status • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Ikena Oncology Reports Second Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "IK-175: AHR Inhibition Program Partnered with Bristol Myers Squibb (BMS): The Phase 1a/1b trial of IK-175 (NCT04200963) in metastatic urothelial carcinoma continues to recruit patients who have progressed on prior lines of therapy, including checkpoint inhibitors, in the second stage of both the monotherapy and combination expansion cohorts; Ikena plans to present initial clinical data from this trial in the second half of 2022; The FDA cleared the IND for the Phase 1b trial of IK-175 in head & neck cancer (NCT05472506) and Ikena is expected to dose a first patient before the end of the year."

IND • P1 data • Trial status • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Urothelial Cancer

Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer (clinicaltrials.gov) - P1b | N=54 | Not yet recruiting | Sponsor: Ikena Oncology

Combination therapy • New P1 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Discovery and characterization of a novel aryl hydrocarbon receptor inhibitor, IK-175, and its inhibitory activity on tumor immune suppression. (PubMed, Mol Cancer Ther) - "These studies provide rationale for targeting AHR in cancer patients. IK-175 is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CYP1A1 • IL17A • IL22

Ikena Oncology Reports First Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Ikena Oncology, Inc...today announced financial results for the first quarter ended March 31, 2022....The FDA granted IK-930 orphan designation as a potential novel treatment in mesothelioma in March 2022...Ikena plans to submit the initial clinical data from this trial to an oncology conference in the second half of 2022, and plans to initiate a second Phase 1b trial of IK-175 in combination with nivolumab in head and neck squamous cell carcinoma in the second half of 2022..."

New P1 trial • Orphan drug • P1 data • Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Mesothelioma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Ikena Oncology to Present at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting (GlobeNewswire) - "Ikena Oncology, Inc...announced that it will be presenting two trial-in-progress posters at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting. The presentations will include overviews of the clinical trials for Ikena’s novel TEAD inhibitor, IK-930, and aryl hydrocarbon receptor (AHR) antagonist, IK-175. Both posters will be presented by the trials’ investigators."

P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Ikena Oncology Reports Fourth Quarter and Full Year 2021 Financial Results and Corporate Update (GlobeNewswire) - "IK-175: IK-175 clinical data presentation is planned for a major medical conference in the second half of 2022; In addition to the bladder cancer clinical trial, a second Phase 1b clinical trial is planned to start in the second half of 2022 in head & neck squamous cell carcinoma (HNSCC)."

Clinical data • New P1 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck