Lutris Pharma Completes Enrollment in Phase 2 Trial of LUT014 for the Treatment of EGFRI-Induced Acneiform Rash in Patients with Metastatic Colorectal Cancer

Topline Results Expected in Q1 2025

TEL AVIV, Israel, Oct. 15, 2024 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicity, today announced that it has completed enrollment in the phase 2 trial of lead compound, LUT014, a topically-applied novel B-Raf inhibitor, for patients with metastatic colorectal cancer (mCRC) treated with epidermal growth factor receptor (EGFR) inhibitor therapy who develop dose-limiting acneiform rash. Topline results are expected in first quarter of 2025.

The phase 2, randomized, double-blind, placebo-controlled trial has enrolled a total of 117 subjects at 20 international sites, including Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center and Dana Farber Cancer Institute. The trial is evaluating the efficacy and safety of two strengths of LUT014 gel, 0.03% or 0.10%, applied once daily for 4 weeks, compared to placebo (with a randomization of 1:1:1), in patients with mCRC who develop Grade 2 or non-infected Grade 3 EGFR inhibitor-induced acneiform rash, with a 4-week follow up period. During an optional open label extension period for the placebo group, eligible subjects received the 0.03% concentration of LUT014.

The study's primary endpoint is the proportion of subjects in each treatment group who achieve treatment success, defined as an improvement (decrease) of at least one grade in the severity of the acneiform lesions from baseline to Day 28, based on common terminology criteria for adverse events (CTCAE) V5.0 skin and subcutaneous tissue disorders grading scale or, an improvement (increase) of at least 5 points in the total score for the skin-specific (first 13 questions) of the functional assessment of cancer therapy epidermal growth factor receptor inhibitor 18 (FACT-EGFRI-18) health related quality of life (HRQoL) questionnaire, from baseline to Day 28. Key secondary endpoints include adherence to EGFR inhibitor treatment.

"Enrollment of the last patient is an important milestone for Lutris Pharma and in the progress of the international phase 2 trial of LUT014," stated Antoni Ribas, M.D., Ph.D., Chairman and Founder of Lutris Pharma. "Although EGFR inhibitors are critical treatment options, approximately 75% of patients with mCRC receiving such therapy experience acneiform rash, which can be so disruptive to quality of life that many of these patients do not receive the optimal treatment against their cancer, either due to dose reduction or even discontinuation of the anti-EGFR therapy, caused by the rash. By reversing the inhibitory effect of anti-EGFR therapy on downstream signaling in the skin cells, we believe that LUT014 has the potential to address a toxicity of otherwise effective therapeutic regimens and can have a favorable impact for patients who currently have no other treatment options.

Dr. Ribas continued, "having generated positive phase 1 results in patients with mCRC, demonstrating safety, preliminary efficacy a dose response and a therapeutic benefit in all patients, we look forward to reporting topline results from the phase 2 study early next year and are planning present them at a major medical meeting."

"Reporting data on the use of LUT014 to treat acneiform rash induced by anti-EGFR inhibitors will be timely, given the encouraging data generated with new classes of EGFR inhibitors being developed for the treatment of cancer" added Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "These active anticancer agents have the same class-effect dose limiting skin toxicities that could be addressed with the topical application of LUT014, potentially broadening the clinical benefit to patients with cancer."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT04759664.

About EGFR Inhibitor-Induced Rash
EGFR is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the key pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is a protein encoded by the BRAF gene and is a downstream effector component of EGFR signaling pathway. EGFR has been shown to be over-activated in various human cancers, including colorectal, lung, head and neck, urinary bladder, pancreatic and breast cancers, eliciting downstream phosphorylation and activation of the MAP Kinase pathway.

Drugs called EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have failed prior chemotherapy. Although effective as anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have many adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience adverse dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About LUT014
LUT014 is a novel B-Raf inhibitor which is applied topically on the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.

About Lutris Pharma
Lutris Pharma is a clinical stage biopharmaceutical company focused on improving anti-cancer therapy effectiveness and quality of life for patients who are being treated with EGFR (Epidermal Growth Factor Receptor) inhibitors or with radiation, where dermal toxicity often leads to a reduction of anti-cancer therapy compliance. The company aims to provide novel topical therapies in order to mitigate these side effects. Lutris Pharma's lead asset, LUT014, a topical B-Raf Inhibitor, is a proprietary, first-in-class, small molecule currently in a phase 2 clinical trial in metastatic colorectal cancer patients with EGFR inhibitor induced acneiform lesions and has successfully completed a phase 1/2 study for the treatment of radiation-induced dermatitis in breast cancer patients.

For more information, please visit www.lutris-pharma.com.

Contacts:

Lutris Pharma
Noa Shelach, Ph.D.  
Chief Executive Officer 
ir@lutris-pharma.com

Rx Communications Group 
Michael Miller
+1-917-633-6086
mmiller@rxir.com

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