LUT-014

According to Lutris’ CEO, approximately 75% of cancer patients taking EGFR inhibitors develop some form of acneiform rash. Credit: sruilk via Getty Images. Lutris Pharma has secured a US Food and Drug Administration (FDA) orphan drug designation for its BRAF inhibitor LUT014, an investigational treatment for epidermal growth factor receptor (EGFR) inhibitor-induced acneiform rash. EGFR inhibitors are used as cancer treatments, however dermatological side effects such as acneiform lesions, a skin condition that appears as small red bumps or pustules on the skin, seen with the treatment affect a patient’s quality of life. Approximately 75% of cancer patients taking EGFR inhibitors develop some form of an acneiform rash, according to Lutris’ CEO Noa Shelach. The candidate is currently being investigated in a Phase II clinical trial (NCT04759664), where 117 colorectal cancer patients with acneiform lesions receive either one of two strengths of LUT014 gel once a day for four weeks, or a placebo. EGFR, found on cell surfaces including skin, regulates crucial cell functions such as growth and differentiation. It is overexpressed in cancer cells, so EGFR inhibitors prevent cancer cells from receiving the signals needed for growth and division, inhibiting tumour growth and progression. See Also: Market cap upturn for top 20 biopharma companies with obesity drug successes in 2023 LUT014 is a BRAF inhibitor that is applied topically on the skin. BRAF, a protein translated from the BRA gene, is part of the EGFR signalling pathway. LUT014 helps to shrink tumours with mutated BRAF proteins while promoting cell growth in normal cells, helpful for conditions such as an acneiform rash. In the announcement accompanying the orphan drug designation, Shelach said: “Receipt of orphan drug designation for LUT014 is strategically important for Lutris, as it reflects the significant unmet need for patients treated with EGFR inhibitors. “The [orphan drug designation] also qualifies us for incentives including tax credits for qualified clinical trials, exemption from user fees and potentially seven years of marketing exclusivity for LUT014, should it gain approval for the treatment of EGFRI inhibitor acneiform rash.” In March 2023, the FDA approved Novartis’ Tafinlar and Mekinist BRAF/MEK inhibitor combination therapy to treat BRAF V600E low-grade glioma in paediatric patients starting at one year of age. Findings from the Phase II/III TADPOLE trial listed acneiform rash as one of the most common adverse reactions observed.

TEL AVIV, Israel, Feb. 28, 2024 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing dose limiting side effects, today announced that the U.S. Food and Drug Administration's (FDA) Office of Orphan Products Development has granted Orphan Drug Designation (ODD) to lead compound, LUT014, a novel topically applied B-Raf inhibitor, for the treatment of EGFR (Epidermal Growth Factor Receptor) inhibitor induced acneiform rash. Currently, no drug or treatment is approved by the FDA for the prevention or treatment of EGFR inhibitor induced acneiform lesions. "Receipt of orphan drug designation for LUT014 is strategically important for Lutris, as it reflects the significant unmet need for patients treated with EGFR inhibitors, approximately 75% of whom develop some grade of acneiform rash, and allows for an expedited FDA regulatory pathway for LUT014," stated Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "The ODD also qualifies us for incentives including tax credits for qualified clinical trials, exemption from user fees and potentially seven years of marketing exclusivity for LUT014, should it gain approval for the treatment of EGFRI inhibitor acneiform rash. The ODD designation is, therefore, a meaningful milestone for this program, as our mission from the start has been to improve anti-cancer therapy effectiveness, as well as the quality of life for patients who are being treated with EGFR inhibitors. It will be integral to our ability to potentially bring this important treatment to patients faster." "As a result of the dermal toxicity caused by EGFR inhibitors, many of these patients do not receive the optimal treatment against their cancer, either due to dose reduction or even discontinuation, caused by the rash," added Antoni Ribas, M.D., Ph.D., Chairman and Founder of Lutris Pharma. "Importantly, results from our phase 1 trial of LUT014 in patients with metastatic colorectal cancer who had developed grade 2 rash demonstrated the safety of the approach as well as provided preliminary favorable efficacy results and a dose response. We look forward to reporting results from the ongoing phase 2 randomized clinical trial of LUT014 in treating skin toxicities caused by EGFR inhibitors in the future." 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 most important pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is protein encoded by the BRAF gene and is a downstream effector component of EGFR signaling pathway. EGFR is 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 a number of 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 cancer, 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 . 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