P1-E01

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

Topical LUT014 Is Tolerable And May Be Efficacious For Grade 2 Radiation Dermatitis 75% of Patients in Part 1 Experienced Complete Resolution of Radiation Dermatitis Part 2 Data Showed Clinically Relevant Treatment Advantage of Approximately 30% in Patients on LUT014 Versus Placebo TEL AVIV, Israel, Feb. 21, 2024 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing dose limiting side effects, today announced the publication of data from its phase 1/2 trial of lead compound, LUT014, a topically applied, novel B-Raf inhibitor, for the treatment of radiation-induced dermatitis (RD) in patients with breast cancer. The data were published in the peer-reviewed, JAAD International, in an article entitled, "A Topical BRAF Inhibitor (LUT014) For Treatment of Radiodermatitis Among Women with Breast Cancer." "Our data suggest that LUT014 can be safely administered, with no serious adverse events (AEs) observed in either the open-label or randomized parts of the study," stated Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma. "In part 1 of the trial, by day 28, 6 of 8 (75%) of enrolled patients who developed grade 2 dermatitis at baseline, achieved complete resolution. Additionally, all 8 women in part 2 achieved treatment success, compared to 73% in the placebo arm, illustrating that a positive efficacy signal may be associated with this compound. Importantly, the results support the need for further study of LUT014 in this radiation-induced dermatitis indication, especially since several expert professional bodies such as the Oncologic Nursing Society (ONS), the American Society of Radiation Oncology (ASTRO) and the Multinational Association of Supportive Care in Cancer (MASCC) recently concluded that there is currently no standard treatment for radiation dermatitis." "Publication of the impressive results from our phase 1/2 trial in breast cancer patients with RD in such a highly regarded peer reviewed journal, one of the main scientific/educational arms of the American Academy of Dermatology; the largest and most influential professional organization of dermatologists in the U.S. & Canada, is a testament to the potential of LUT014 to improve patients' quality of life while accelerating their recovery from RD," added Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "Given that the majority of women with breast cancer will develop some form of RD, and that there remains a clinically meaningful, unmet medical need, with no current, effective treatment options, we believe LUT014 may be able to effectively treat this patient population." The phase 1/2 trial included an open-label part 1, followed by a double-blind placebo-controlled part 2. Part 1 results showed that, of the eight enrolled patients who developed grade 2 RD at baseline, 75% (6/8) had complete resolution, improving to grade 0 dermatitis, and 100% of patients had RD of 1 or 0 as assessed by the Common Terminology Criteria for Adverse Events (CTAE) after 28 days of daily, topically applied LUT014 gel. All of the patients derived benefit in quality of life by day 28 as assessed by the validated, self-reporting Dermatology Life Quality Index (DLQI) questionnaire, with seven of eight patients experiencing no or small effect of the dermatitis on their respective quality of life after the treatment course. The primary endpoint of the open-label part 1 was the incidence of Treatment-Emergent Adverse Events as assessed by CTAE at 12 weeks and the data showed that LUT014 was well tolerated, no severe or serious adverse events occurred, and no adverse events were associated with discontinuation of the study drug. These data were deemed to be sufficiently intriguing to trigger the randomized part of this phase 1/2 trial. The randomized, double-blind, placebo-controlled part two of the phase 1/2 study enrolled a total of 20 patients and was designed to evaluate the efficacy of topically administered LUT014 in breast cancer patients with RD. Patients were randomized in a 1:1 ratio to receive either topically administered LUT014 or placebo for 28 days, followed by a 2-month follow-up period. The primary endpoint of the double blinded part 2 of the phase 1/2 trial was the change in severity of radiation dermatitis, based on a validated self-reporting DLQI questionnaire at 14 days, as measured by improvement of at least 5 points on the DLQI at day 14, and was achieved by all eight women treated with LUT014, in comparison to 73% of the placebo arm at the same juncture. Improvement in the DLQI score at day 7 was 30%. Furthermore, 75% of patients in the intervention-arm showed improvement from grade 2 to grade 1 as early as day 7, in comparison to 55% of those assigned to the control arm. Moreover, 50% of the women assigned to the treatment arm experienced complete recovery at Day 21, versus 27% of those receiving only placebo (p=0.3765). Overall, four out of eight (50%) subjects had recovered completely in the LUT014 Gel group while four out of 11 (36%) subjects had recovered completely in the placebo group by the end of the study (Day 28) (p=0.6577). None of these differences reached conventional levels of statistical significance, however, this small study was not powered to show such differences. The mean and the median of the time to recovery were shorter in the LUT014 Gel group than in the placebo group: 30.5 vs. 46.6 days and 21.0 vs. 54.0 days, respectively. For more information about this clinical trial, please visit: , NCT04261387. 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 Radiation Dermatitis Radiation therapy results in ionization events that lead to damage of cellular macromolecules, including double-stranded DNA breaks. Within the epidermis, this DNA damage disrupts the normal proliferation and differentiation of basal keratinocytes, depleting the differentiated epidermal keratinocytes and ultimately resulting in the loss of the protective barrier provided by the skin. This, combined with DNA damage disruption within the dermis, which results in a complex sequence of effects including an immune response cascade, leads to the symptomology associated with radiation dermatitis, which can dramatically diminish a patient's quality of life. There is currently no FDA-approved drug whose labelled indication is for the prevention or treatment of radiation-induced dermatitis. Rather, patients are merely treated with supportive cutaneous care. The current treatment options – which have a weak evidence base -- have included topical steroids, non-steroidal anti-inflammatory topicals, and hyaluronic acid derivatives. To date, none has been definitively proved efficacious. 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