WHO Grade II Glioma

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

Doctors often prescribe radiation along with surgery to treat a brain tumor called meningioma that originates in the protective membranes surrounding the brain. But side effects from radiation can be serious, including memory loss and cognitive decline, so it's important to know which patients really need it. Now, researchers at UC San Francisco and Northwestern Medicine, in collaboration with 10 other medical centers, have found a highly accurate way to predict the best treatment for patients based on patterns of gene expression -- which genes are turned on and off -- in their tumors. Doctors often prescribe radiation along with surgery to treat a brain tumor called meningioma that originates in the protective membranes surrounding the brain. But side effects from radiation can be serious, including memory loss and cognitive decline, so it's important to know which patients really need it. Now, researchers at UC San Francisco and Northwestern Medicine, in collaboration with 10 other medical centers, have found a highly accurate way to predict the best treatment for patients based on patterns of gene expression -- which genes are turned on and off -- in their tumors. Screening tumors using this new approach could change the course of treatment for nearly 1 in 3 people with meningioma, the most common form of brain tumor diagnosed in 42,000 Americans each year. Unlike other brain tumors, meningiomas occur most often in female, Black and elderly patients. In a paper appearing Nov. 9, 2023 in Nature Medicine, the team concluded that just 1 in 5 patients with low-grade tumors (those less likely to regrow) may need radiation, while around 2 in 5 with higher-grade tumors may be better off without radiation, based on the results of the new gene-expression test. "There's been a lot of controversy in the field in terms of who should receive radiotherapy and who shouldn't," said David Raleigh, MD, PhD, a radiation oncologist in the UCSF Brain Tumor Center and a senior author of the study, along with Stephen Magill, MD, PhD, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. "Our biomarker takes the guessing game out of this and shows us which patients are likely to benefit from radiotherapy and which may get toxicity and possibly no benefit from radiation." From microscopes to molecules Because meningiomas grow slowly, a patient may be unaware of their tumor until they start to experience neurological symptoms like numbness, vision loss or personality changes. There are no pharmaceutical treatments, so doctors rely on surgery to remove the tumor and radiation to prevent it from growing back. Doctors treat these tumors based on guidance from the World Health Organization, which stages them according to severity. Pathologists currently classify meningiomas by looking at them under a microscope for features that indicate whether they may grow back, a system that is very good but not perfect. Patients with Grade 1 tumors don't usually receive radiation treatment if their tumors can be removed completely during surgery. Yet approximately 20% of the time, the tumors recur. Those with Grade 2 and 3 tumors, which are much more aggressive and more likely to grow back after surgery, are often treated with radiation after surgery. It has been unclear how many of these patients, particularly those with Grade 2 tumors, actually need radiation treatment. Raleigh, along with Magill and lead author William Chen, MD, decided to look at classifying tumors according to which of their genes are turned on and off, thereby offering clues to how aggressive they might be. "Gene-expression tests like this, that analyze a small number of genes at a time, are widely available for breast, prostate and some other cancers, and they've proven to be a very accurate and inexpensive alternative to other types of tests," said Chen. How to turn guesses into answers Raleigh and Chen and their multidisciplinary team suspected that gene expression could more accurately point out the patients who would be helped by radiotherapy. Using samples from 1,856 meningioma patients at 12 medical centers in the U.S., Europe and Hong Kong, Raleigh's team came up with a set of 34 genes whose gene expression patterns had the potential to predict whether a tumor would return. One-fifth of the Grade 1 tumors -- the same number that grow back after surgery -- expressed the patterns that Raleigh's team found could predict a tumor's regrowth. This fraction of patients may benefit from radiation. The researchers also found that two-fifths of patients with Grade 2 and 3 tumors did not have a recurrence, and this, too, could be predicted by the tumor's gene expression. "When to proceed with additional surgery, radiotherapy or simply to observe a small residual meningioma is not always clear," said Magill. "This test adds information that can let us tailor our surgical and radiation approach to provide the best outcome for each patient and maximize both quality and quantity of life." The team's next step is to test the approach in two clinical trials currently being developed. Funding: This study was supported by NIH grants (P50 CA097257, P50 CA221747, U01 CA180868, U10 CA180822, R01 CA262311, F32 CA213944, F30 CA246808, T32 GM007618) and philanthropy. For a full list of funders, please see the study.

NEW YORK--(BUSINESS WIRE)-- AnHeart Therapeutics (“AnHeart”), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, today announced the first patient has been dosed in a Phase 2 clinical trial, G203, evaluating safusidenib in patients with Grades 2 or 3 recurrent or progressive mutant isocitrate dehydrogenase 1 (mIDH1) glioma, one of the most common types of adult primary brain cancer. Oncogenic mutations in IDH1 are frequently found in gliomas and current treatment options, including chemotherapy and radiotherapy, can cause significant impact on neurocognition and quality of life. Safusidenib is a novel, selective, potent, oral mIDH1 inhibitor. Safusidenib has shown high blood-brain barrier penetration in both pre-clinical and clinical studies. Encouraging anti-tumor activity was observed in a Phase 1 clinical trial in patients with recurrent IDH1-mutant gliomas. “IDH1 mutations are now known to be a key driver in the development of IDH-mutant gliomas and we are excited by the potential of IDH targeted therapy for our patients, who tend to be in the prime of their life at diagnosis,” said Professor David Reardon, the leading Principal Investigator of the G203 clinical trial and Clinical Director at the Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston. “Early data suggest safusidenib may have a role in IDH1-mutant gliomas, notably in high-risk populations, and we look forward to further evaluating this investigational therapy in the G203 trial.” “This marks an important milestone for AnHeart, as we now have two investigational precision therapies in late-stage clinical trials,” said Jerry Wang, PhD, Chief Executive Officer of AnHeart. “Our mission is to improve the lives of people with cancer. Our strategy is to target known genetic drivers of cancer with the goal of bringing next-generation medicines that raise the bar for what patients should expect from cancer treatment. We look forward to sharing additional updates as we continue to progress our clinical programs.” About the G203 Phase 2 Safusidenib Trial G203 (NCT05303519) is a global Phase 2, multicenter, open-label, two-part clinical trial evaluating the efficacy and safety of safusidenib as a monotherapy in approximately 95 patients with recurrent or progressive WHO Grade 2 or Grade 3 IDH1-mutant glioma. The trial is divided into two parts. Part 1 is designed to confirm the optimal dose of safusidenib. Part 2 will evaluate the efficacy and safety of safusidenib in Grade 2 or Grade 3 glioma. Currently, patients are being enrolled in the United States, with expansion to other countries planned for Part 2 of the trial. About Safusidenib Safusidenib is a novel, selective, potent, oral mIDH1 inhibitor. Safusidenib has shown high blood-brain barrier penetration in both pre-clinical and clinical studies. Encouraging anti-tumor activity was observed in a Phase 1 clinical trial (NCT03030066) evaluating safusidenib in patients with recurrent or progressive WHO Grades 2 to 4 IDH1-mutant gliomas. In the trial, the objective response rate (ORR) was 33% (4/12) and 17% (6/35) in patients with contrast non-enhancing and enhancing tumors, respectively. Tumors that show enhancement on MRI scans tend to have more vascularization and disruption to the blood-brain barrier and are generally associated with a higher degree of malignancy compared with non-enhancing tumors. Safusidenib demonstrated a tolerable safety profile. Most adverse events (AEs) were Grades 1 or 2. 43% of patients experienced at least one Grade 3 treatment emergent AE. No Grade 4 or 5 AEs or serious treatment-related AEs were reported. AnHeart licensed safusidenib from Daiichi Sankyo in 2020 and owns global rights for safusidenib, excluding Japan where Daiichi Sankyo retains development and commercial rights. About Glioma Glioma is the most common type of adult brain cancer. Approximately 30,000 patients are diagnosed with IDH1-mutant gliomas in the United States, Europe, and China annually. Patients are typically diagnosed in the prime of their life in their mid-forties to early-fifties. IDH1 mutations are present in the majority of Grade 2 or 3 diffuse gliomas and IDH-mutant gliomas are recognized as distinct tumor subtypes by the World Health Organization (WHO). There are no targeted treatments approved for IDH-mutant glioma. Current treatment options include surgery, radiation, and chemotherapy, which can cause significant impact on neurocognition and quality of life. About AnHeart Therapeutics AnHeart Therapeutics (“AnHeart”) is a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer. Our lead investigational therapy, taletrectinib, is a next-generation ROS1-inhibitor currently in pivotal Phase 2 trials for ROS1-positive non-small cell lung cancer (NSCLC). Taletrectinib has been granted Breakthrough Therapy Designation by both the U.S. Food and Drug Administration and the China National Medical Products Administration. AnHeart’s second investigational therapy, safusidenib, is a mIDH1-inhibitor being evaluated in a Phase 2 trial for IDH1-mutant glioma. Our mission is to improve the lives of people with cancer. We are supported by leading life sciences investors and have built an organization with deep oncology drug discovery and development expertise, with offices in New York and Shanghai. For more information, visit or follow us on LinkedIn at .