Cetuximab

- Preclinical data demonstrates synergy of QTX3544 with EGFR inhibitors, broadly enhancing anti-tumor activity - - Data supports ongoing Phase 1 clinical trial for QTX3544 as monotherapy and in combination with cetuximab in patients with KRASG12V mutations - SOUTH SAN FRANCISCO, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- Quanta Therapeutics, a privately-held clinical-stage biopharmaceutical company leading the development of innovative, oral therapeutics for RAS-driven cancers, today announced late-breaking preclinical data for QTX3544, an oral, G12V-preferring, dual ON/OFF state, multi-KRAS inhibitor currently being evaluated in a Phase 1 clinical trial in patients with KRASG12V mutation. Data are being presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 being held April 25-30, 2025, in Chicago, Illinois. “There is a high unmet need for effective treatments in KRASG12V-mutated cancers, the second most prevalent in KRAS-driven cancers, for which there are no current targeted treatments, including colorectal and pancreatic cancers. Using a clinically validated approach against G12C mutations, we aim to combine allosteric KRAS inhibition and EGFR blockade to enhance the depth and durability of tumor response against G12V,” said Leonardo Faoro, MD, MBA, Chief Medical Officer of Quanta Therapeutics. “QTX3544 has shown high potency against multiple KRAS variants, particularly G12V. These preclinical data support the clinical strategy to combine QTX3544 and cetuximab to enhance the therapeutic activity against KRASG12V-driven cancers. We look forward to evaluating this combination in the ongoing Phase 1 clinical trial.” “We continue to generate promising data supporting our unique pipeline of KRAS-directed agents, as we advance three distinct candidates in the clinic targeting high prevalence KRAS mutations across solid tumors with major unmet need. QTX3034 and QTX3046 are being developed for G12D-mutant and QTX3544 for G12V-mutant KRAS-driven cancers,” said Perry Nisen, MD, PhD, Chief Executive Officer of Quanta. “We are building a compelling clinical package across our three lead programs and are on track to share proof-of-concept data later this year as our pipeline continues to progress.” Studies evaluating the potential synergy between QTX3544 and EGFR inhibitors (afatinib and cetuximab) in KRASG12V-driven cancer cell lines and tumor models demonstrated: QTX3544 synergized with EGFR inhibitors and potently inhibited KRASG12V-mutant cell proliferation in cell viability assays.Combined treatment of QTX3544 with afatinib led to a deeper suppression of MAPK signaling and enhanced inhibition of KRASG12V-driven cancer cell survival in colony formation assays.Combination treatment of QTX3544 with cetuximab significantly enhanced anti-tumor efficacy and elicited greater tumor regressions in pancreatic and colorectal KRASG12V-mutant cell line-derived xenograft models, as well as in a patient-derived colorectal tumor xenograft model. AACR presentation information:Title: QTX3544, a potent and selective G12V-preferring KRAS inhibitor, synergizes with EGFR inhibitors for enhanced anti-tumor activityDate and Time: Wednesday, April 30, 2025; 9:00 AM - 12:00 PMSession Name: Late-Breaking Research: Experimental and Molecular Therapeutics 4Abstract Number: LB430 Location: Poster Section 51 About QTX3544QTX3544 is an allosteric, G12V-preferring multi-KRAS inhibitor. The QTX3544 Phase 1 clinical trial is initially enrolling patients with KRASG12V mutation in dose escalation cohorts as monotherapy and in combination with cetuximab. The Phase 1 clinical endpoints include safety and tolerability, determination of the maximum tolerated dose/recommended Phase 2 dose, pharmacokinetic properties, anti-tumor activity, and molecular markers. The clinical trial is being conducted at clinical sites in the US. More information about the QTX3544 clinical trial (NCT06715124) can be found on https://clinicaltrials.gov/. About RAS and the MAPK PathwayThe mitogen-activated protein kinase (MAPK) pathway is a central signaling cascade that regulates cellular growth, proliferation, differentiation, and survival. When one of the proteins in the pathway is mutationally activated, it can drive tumor development and growth. RAS is the most frequently mutated oncogene in cancer, with KRAS mutations occurring in nearly one-quarter of all human cancers. RAS mutations impair the ability of RAS to convert from its active GTP-bound “ON” form into its inactive GDP-bound “OFF” state, leading to the sustained activation of the MAPK signaling pathway and ultimately driving tumorigenesis. KRAS mutations, especially G12D, G12V, and G12C, are highly prevalent in pancreatic, colorectal, and lung cancers. First-generation KRAS inhibitors have demonstrated clinical benefit, but their impact is limited to a subset of patients with a single type of KRAS mutation (G12C). About Quanta TherapeuticsQuanta Therapeutics is a private biopharmaceutical company focused on the most prevalent and elusive target in oncology—RAS. Our vision is to develop novel small molecule cancer medicines by selectively targeting protein-protein interactions that are key to oncogenic RAS activity. Driving Quanta's success is our unique high-throughput platform that applies Second Harmonic Generation (SHG) optical technology to identify allosteric modulators of protein complexes. The Quanta team has extensive drug development expertise and substantial research experience in the RAS space. By applying innovative medicinal chemistry and its unique protein conformation detection technology, Quanta aims to advance differentiated, next-generation RAS programs that address the resistance paradigms of targeted therapy in oncology. Quanta’s KRAS inhibitor pipeline includes three programs: QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3046, a G12D-selective KRAS inhibitor, currently in a Phase 1 clinical trial as monotherapy and in combination with cetuximab; QTX3544, a multi-KRAS inhibitor with G12V-preferring activity (G12V+ multi-KRAS) currently in a Phase 1 clinical trial as a monotherapy and in combination in patients with KRASG12V-driven solid tumors. Quanta is headquartered in South San Francisco, CA, and has a site in Radnor, PA. Find more information at https://www.quantatx.com/. Follow us on LinkedIn: Quanta Therapeutics. Quanta Therapeutics Heather Meeks 661-992-6907 heather.meeks@quantatx.com Media Contact Kelli Perkins kelli@redhousecomms.com

LUT014 Gel Shows Statistically Significant Reductions of Acneiform Rash in the Intention-to- Treat and Per-Protocol Patient Analyses as Compared to Placebo Patients Randomized to LUT014 Had Lower Rates of Interruption of Anti-EGFRI Therapy Due to Acneiform Rash Study Presented at the Clinical Trials Plenary Session TEL AVIV, Israel, April 28, 2025 /PRNewswire/ -- Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicity, presented data from its recently completed double-blind, placebo-controlled phase 2 randomized clinical trial of lead therapy, LUT014 gel, demonstrating statistically-significant reductions in dose-limiting acneiform rash in patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy. This new clinical data, showing that Lutris' topically-applied novel B-Raf inhibitor gel is optimized for paradoxical MAPK activation, was presented yesterday in an oral presentation at the Clinical Trials Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2025. Presentation Details: Presentation Title: A double-blind placebo-controlled randomized phase 2 clinical trial to assess the efficacy of a topical BRAF inhibitor for acneiform rash toxicities from anti-EGFR therapies Presenting Author: Anisha B. Patel, MD, Associate Professor, Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX Abstract Number: CT018 Session Title: New Frontiers in Precision Oncology "Due to the widespread use of EGFR inhibitors for cancer treatment and the frequent occurrence of dermal toxicities, many patients do not receive optimal cancer therapy. This is often because the toxicity leads to dose reductions or complete discontinuation of treatment," stated Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma. "By reversing the inhibitory effect of anti-EGFR therapy on downstream signaling in skin cells, we firmly believe LUT014 has the potential to be a key therapeutic, offering significant benefits to patients with no other effective treatment options. In the trial, as we expected, LUT014 demonstrated statistically significant improvement in acneiform rash compared to placebo, with highly successful outcomes in both intention-to-treat and per-protocol patient analyses. LUT014 was also shown to be safe and well tolerated, with fewer adverse events reported than in the placebo group, with the majority of adverse events being mild." "This was the first placebo-controlled randomized clinical trial demonstrating the benefit and safety of an agent for the treatment of the acneiform rash associated with anti-EGFR therapy. Therefore, having these overwhelmingly positive results for LUT014 selected for an oral presentation at the prestigious AACR Annual Meeting, is a testament to the potential of our lead asset and a significant milestone for the company," added Noa Shelach, Ph.D., Chief Operating Officer of Lutris Pharma. "In addition, our successful $30 million financing, completed in January 2025, allows us to continue advancing our clinical development program as we pursue our goal of commercializing LUT014 which will align with our mission to enhance the effectiveness of anti-cancer therapies and significantly improve the quality of life for patients." The trial enrolled 118 colorectal cancer patients from 23 clinical sites, all of whom had developed grade 2 or non-infected grade 3 acneiform rash while receiving cetuximab or panitumumab. Participants were randomized in a 1:1:1 ratio to receive either LUT014 gel 0.03%, LUT014 gel 0.1%, or a placebo gel. The gel was applied daily for 28 days. The primary endpoint was the proportion of patients who achieved treatment success, measured by an improvement of at least one grade in Common Terminology Criteria for Adverse Events (CTCAE) scoring or an improvement of at least 5 points in the Functional Assessment of Cancer Therapy (FACT)-EGFRI-18 HRQoL skin-specific assessment. The study employed both an intention-to-treat (ITT) analysis and a Per-Protocol (PP) analysis (i.e., patients who dropped out or did not discontinue their EGFR inhibitor for reasons unrelated to the rash, such as disease progression were excluded from the analysis). Sample size calculation was based on an expected treatment success of 20% for the placebo group and 50% for one of the treatment groups. A total of 117 patients were required for a two group ꭕ2 test with a 0.05 two-sided significance and 80% power. Efficacy is shown in the table below. In the ITT as well as the PP, the composite endpoint demonstrated statistically significant rates of success for the high dose LUT014 group, compared to placebo. 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 the 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. 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 progressed on prior chemotherapy treatments. Although effective as an 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 to 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 B-Raf Inhibitor, is a proprietary, first-in-class, small molecule formulated as a topical gel, has recently been studied in a phase 2 clinical trial in metastatic colorectal cancer patients with EGFR inhibitor induced acneiform lesions and previously had 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 Operating Officer [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE Lutris Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED