On January 28, 2025 Genialis, the RNA biomarker company, reported an extension of its collaboration with Debiopharm, a Swiss-based global biopharmaceutical company, to develop a predictive biomarker for WEE1-targeted therapy (Press release, Genialis, JAN 28, 2025, View Source [SID1234649918]). This extension builds on a 2024 agreement to define and discover biomarkers within the DNA damage response (DDR) biological space to predict the clinical benefit of one or more drugs in Debiopharm’s pipeline. Debiopharm’s WEE1 asset is currently in Phase 1 clinical research and is being studied in monotherapy and in combination in collaboration with international partners.

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"As an industry, we must redefine what it means to develop a biomarker that is highly effective in selecting patients for the right therapies," said Luke Piggott, PhD, Principal Scientist at Debiopharm. "Genialis is leveraging advanced artificial intelligence and RNA-sequencing data to classify patients into responder/non-responder groups based on a comprehensive evaluation of relevant biological mechanisms. This approach has shown great promise in our early work together, and we look forward to further refining this innovative solution to get therapies that are more precisely targeted and effective for patients."

DDR is a promising arena for the development of precision medicines, highlighted by the approvals of various PARP inhibitors indicated for ovarian, breast, pancreatic, and prostate cancers associated with BRCA mutations. Other druggable DDR targets, such as ATR, ATM, and WEE1, show potential in preclinical and early clinical trials, but also face challenges balancing toxicity and efficacy. While BRCA-indicated PARP therapies have received approvals in various clinical settings, most drugs under development lack accurate and informative biomarkers to guide clinical trial and treatment decisions.

One solution addressing the lack of biomarkers in the DDR space is the Genialis Supermodel, an AI-powered foundation model known as a large molecular model, or "LMM." This technology enables rapid configuration of biomarkers across the entire landscape of cancer drug targets, including DDR. Trained on hundreds of thousands of globally diverse RNA-seq samples, the Genialis Supermodel generates biomarkers that stratify response groups, identify mechanisms of response and resistance, and suggest combination therapies.

"A persistent challenge in developing DDR therapies is the lack of truly predictive biomarkers to guide patient selection and optimize clinical outcomes. Most cancers cannot be adequately characterized by individual mutations or proteins, or even a composite of these," said Rafael Rosengarten, Ph.D., CEO of Genialis. "The Genialis Supermodel is the cornerstone of our biomarker programs, driving innovation across a broad range of cancer drug targets. We’re taking the success we’ve had with KRAS-targeted therapies and applying a similar approach to the DDR drug space. I am confident our work with Debiopharm will move the needle for WEE1 and am excited to explore the rest of the target-rich DDR landscape."

Today’s announcement follows the recent dispatch from Tempus AI (NASDAQ: TEM), a leader in AI-driven precision medicine, announcing a multi-year agreement with Genialis to leverage Tempus’ multimodal dataset for the validation of new RNA-based biomarker algorithms across various cancer types.

Genialis will be attending the 8th Annual DDR Inhibitors Summit in Boston, January 28-30, 2025, and presenting an abstract with Debiopharm at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 meeting in April. To schedule a meeting or learn more about Genialis Supermodel, please visit www.genialis.com or email [email protected].

On January 28, 2025 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported that its management team will be attending the BTIG Annual MedTech, Digital Health, Life Science & Diagnostic Tools Conference on Tuesday, February 11, 2025, at The Cliff Lodge in Snowbird, UT (Press release, Personalis, JAN 28, 2025, View Source [SID1234649917]).

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On January 28, 2025 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose-limiting toxicity, reported that it has secured a $30 million financing to advance the development of LUT014, an innovative topically applied gel aimed at reducing EGFRi-induced rashes, a common adverse side effect of these cancer-fighting therapies (Press release, Lutris Pharma, JAN 28, 2025, View Source [SID1234649916]). The round was led by Columbus Venture Partners and Pontifax Venture Capital, an existing investor, with Peregrine Ventures and aMoon Fund also participating.

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While EGFRi therapies are highly effective for the treatment of cancer, they have dose-limiting skin toxicities, leading to substantial discontinuation of patients’ treatment in less than three months due to intolerable acneiform rashes. LUT014, a novel B-Raf inhibitor, is used for patients who develop dose-limiting rashes, potentially allowing them to continue EGFRi treatment with an improved quality of life.

"We are grateful to these investors who recognize the potential of LUT014 to address the significant unmet need caused by the toxicity of EGFRi therapies, which are otherwise effective therapeutic regimens. This financing will enable us to continue the clinical development of LUT014 with the goal of treating the acneiform rash to improve life quality and enabling adherence to EGFRi therapies," stated Noa Shelach, Ph.D., Chief Executive Officer of Lutris Pharma. "The development and ultimate commercialization of LUT014 aligns with our mission to improve anti-cancer therapy effectiveness and to meaningfully impact the quality of life for patients."

In October 2024, Lutris successfully completed enrollment in the international phase 2 trial of LUT014 in patients with metastatic colorectal cancer (mCRC) treated with EGFRi therapy who develop dose-limiting acneiform rash. The company expects to report top-line results from this trial during the first half of 2025 at a major medical meeting.

"Based on the broad use of EGFRi’s to treat cancer and the dermal toxicity that often emerges, many of these patients do not receive the optimal treatment against their cancer, either due to dose reduction or outright discontinuation in response to the intolerable dermal toxicity," stated Antoni Ribas, M.D., Ph.D., Chairman and Founder of Lutris Pharma. "Despite extensive research efforts in the past, no standard of care has emerged to deal with this prevalent issue, leading to a significant unmet medical need. By reversing the inhibitory effect of EGFRi therapy on downstream signaling in the skin cells, we believe that LUT014 has the potential to become an important therapeutic for EGFR inhibitor induced skin toxicity and can have a tremendous impact for patients who currently have no other effective treatment options."

"Acneiform rash is the most common side effect of EGFRi therapies, with up to 90% of patients experiencing an adverse dermatologic event, taking a toll which can be detrimental to their therapy. It is all too common that patients terminate treatment due to these effects, leading to continued disease progression and prolonged treatment. The need to manage this condition is crucial and Lutris is doing just that with the advent of LUT014," said Dr. Yael Gruenbaum-Cohen, DMD, PhD, Partner at aMoon Fund. "As development of LUT014 proceeds, we can foresee a paradigm shift wherein EGFRi treatment will be regularly coupled with LUT014 as a valuable adjunct. This aligns with aMoon’s mission of helping people live longer, healthier lives, and we are proud to support Lutris on their journey towards success."

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. Accordingly, LUT014 has the potential to impact not only on quality of life but also on oncologic outcome.

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 reactivate the MAPK pathway and reverse the rash induced by the inhibition of this signaling pathway.

On January 28, 2025 Intensity Therapeutics, Inc. (Nasdaq: INTS), ("Intensity" or "the Company") a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that following its most recent periodic review meeting, the Data Monitoring Committee (DMC) overseeing the Company’s ongoing Phase 3 sarcoma study of INT230-6 (INVINCIBLE-3) (NCT06263231) has agreed that the study should continue without modification (Press release, Intensity Therapeutics, JAN 28, 2025, View Source [SID1234649915]). The DMC reviewed data covering the six months from July to December 2024.

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"The Data Monitoring Committee is designed to confidentially review data to determine whether safety concerns with the data collected to date exist. We are encouraged by the continuation of the trial and continue to believe that INT230-6 represents important potential in a treatment area that has significantly unmet medical need. We look forward to continuing enrollment and to providing further updates as they develop," commented Lewis H. Bender, Intensity’s President and Chief Executive Officer.

INVINCIBLE-3 Study Overview

The INVINCIBLE-3 Study is a global open-label, randomized, controlled study designed to evaluate INT230-6 administered intratumorally by an interventional radiologist or an equivalently trained physician using image guidance compared to systemically dosed standard of care ("SOC") chemotherapy. The study endpoints are overall survival and safety, along with an exploratory quality of life (QoL) assessment using the EORTC-30 survey. The study is testing the efficacy and safety of INT230-6 intratumoral (IT) injection compared to any of three standard-of-care therapies (pazopanib, trabectedin, or eribulin) in approximately 333 adult participants with locally recurrent, inoperable, or metastatic soft tissue sarcoma ("STS") patients who had disease progression prior to study enrollment following standard therapies, which must have included an anthracycline-based regimen unless contraindicated. Participants may also have received a maximum of one additional regimen. Randomization will occur after screening and eligibility confirmation. As this is a survival study, there is no crossover allowed between SOC and INT230-6. Disease progression will be determined by the World Health Organization (WHO) criteria. Participants will be prospectively stratified into 1 of 3 histologically defined STS strata:

leiomyosarcoma
liposarcoma (dedifferentiated, myxoid, round cell and pleomorphic)
undifferentiated pleomorphic sarcoma
The comparator agents used are all U.S., Europe, Canadian and Australian-approved agents for sarcomas: pazopanib tablets, trabectedin, and eribulin mesylate. Authorizations for the INVINCIBLE-3 Study have been obtained from the U.S. FDA, Health Canada, the European Medicines Agency, and Australia’s Therapeutic Goods Administration. Sites will be opened in 8 countries and the study is presently recruiting participants in the U.S., Canada, and Europe.

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.

On January 28, 2025 Cordance Medical, a pioneer in non-invasive medical technologies for brain disease treatment, and EXACT Therapeutics (Euronext Growth: EXTX), a clinical-stage precision medicine company, reported initial positive results indicating more than a doubling (+127-145%) of the uptake of a radiopharmaceutical in brain tumors of mice inoculated with glioblastoma cancer cells, one of the most aggressive and hard-to-treat brain cancers (Press release, Cordance Medical, JAN 28, 2025, View Source [SID1234649914]). The increased uptake resulted from combining Exact Therapeutics’ proprietary Acoustic Cluster Therapy (ACT) with a device designed by Cordance Medical to deliver ultrasound energy non-invasively into the brain. The studies were performed at The Arctic University of Norway and University Hospital North-Norway in Tromsø by Dr. Mathias Kranz.

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The combination of ACT and the device can be used in a wide range of brain diseases to potentially access large regions of the brain. The combination can stimulate bioeffects including increasing the uptake of therapeutic agents and temporarily making the blood-brain barrier more permeable in these regions. The combination of ACT and the device may be utilized for both diagnostic and targeted therapeutic brain applications. Further experiments are ongoing to expand the early data, and the results will be submitted for publication in scientific journals.

"The combination of the Cordance technology and the ACT microcluster technology from Exact Therapeutics provides exciting possibilities for accessing and opening larger volumes in the brain without necessarily increasing the focused ultrasound procedure time or the total amount of ultrasound energy," said Dr. Bhaskar Ramamurthy Cofounder and CEO of Cordance Medical.

"These positive results in glioblastoma provide additional early evidence of the versatility of the noninvasive ACT microcluster technology in cancer therapy. Oncology is the key focus for Exact Therapeutics, spearheaded by our ongoing Phase 2 trial in locally advanced pancreatic cancer, which received IND clearance at the end of 2024," said Dr. Per Walday, CEO of Exact Therapeutics.