Endometrioid carcinoma ovary

33% Response Rate and 100% Disease Control Rate Observed in Patients Evaluated for Efficacy Complete Response of Non-Target Tumor Also Observed Platinum-Resistant Ovarian Cancer is a Devastating Serious Condition of Unmet Medical Need with a Median Life Expectancy of Approximately One Year Fort Lee, NJ, March 14, 2024 (GLOBE NEWSWIRE) -- Nuvectis Pharma, Inc. (NASDAQ: NVCT) today announced preliminary data from the ongoing Phase 1b clinical trial of NXP800 in patients with platinum resistant ARID1a-mutated ovarian cancer, a deadly disease of unmet medical need. The NXP800 development program in this disease was granted Fast Track Designation by the U.S. Food and Drug Administration (“FDA”). The Phase 1b clinical trial is being conducted in top clinical centers in the United States and the United Kingdom. Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis, commented, “We are pleased to share the preliminary results from the NXP800 Phase 1b study in the target patient population of platinum resistant, ARID1a-mutated ovarian cancer patients. The clinical activity observed thus far includes a 33% response rate and 100% disease control rate, defined as partial response (“PR”) plus stable disease (“SD”), in patients evaluated for efficacy. While the data presented today is early, we are encouraged by the achievement of a PR as well as a complete response (“CR”) of the non-target lymph node disease in a patient with a progressive malignancy after a surgical resection and two prior lines of systemic combination chemotherapy, and stable disease in patients with similar stage disease. We believe that this provides an important initial signal that NXP800 can potentially be effective in this devastating and difficult to treat cancer.” Mr. Bentsur continued, “After a cautious start to the study, we are now seeing a ramp up in the number of participating clinical sites, which is already translating into increased rates of patient identification and enrollment. Moreover, similar to what has been done with other classes of potent drugs, dosing management procedures have recently been implemented to better manage the key side effects associated with treatment with NXP800. We believe that we can now make significant progress with this clinical trial and unlock the full potential of NXP800 in this disease setting.” Preliminary Clinical Data Summary Encouraging preliminary efficacy data was observed and includes data from the first four patients enrolled in the study, two treated with 75 mg/day and two treated with 50 mg/day. All patients failed at least two prior lines of systemic chemotherapy, including at least one prior platinum-based chemotherapy regimen. Three of the patients also failed prior treatment with bevacizumab (Avastin). Efficacy was evaluated in three of the four patients. One patient treated with 75 mg/day achieved a PR, unconfirmed, that also included a CR of her non-target lymph node disease. Both patients treated with 50 mg/day achieved SD and the fourth patient was not evaluated for efficacy. Three of these four patients experienced an adverse event of thrombocytopenia that was Grade 4 in intensity, these events were transient in nature with no concurrent bleeding events reported. Following these events, as mentioned above, a management procedure for the monitoring of platelets and dose adjustments, as necessary, has been implemented with the goal of minimizing dosing interruptions and increasing patient retention. No other ≥ Grade 3 hematological toxicities were reported. In addition, gastrointestinal adverse events were reported in all four patients, all Grade 1-2. About the Phase 1b Study The Phase 1b study is a multicenter, single arm, open-label clinical trial of NXP800 in patients with platinum-resistant, ARID1a-mutated ovarian cancer. The study is examining the safety and preliminary efficacy of NXP800 in this target patient population. The study is being conducted in the US and UK in collaboration with the European Network of Gynecological Oncological Trial Groups and the GOG Foundation, Inc., recognized as the world's leading gynecology oncology clinical trials consortia. About NXP800 NXP800 is an oral, small molecule, potentially first-in-class GCN2 kinase activator. NXP800 is also being evaluated in an investigator-initiated study conducted in collaboration with the Mayo Clinic for the treatment of cholangiocarcinoma, an indication for which the FDA granted NXP800 Orphan Drug Designation. The NXP800 development program in platinum-resistant, ARID1a-mutated ovarian cancer was granted Fast Track Designation by the FDA. NXP800 completed a Phase 1a dose-escalation study in the first half of 2023. Nuvectis licensed exclusive world-wide rights to NXP800 from the Institute of Cancer Research in London, UK. About Platinum-Resistant, ARID1a-Mutated Ovarian Carcinoma ARID1a-mutated ovarian carcinoma is comprised almost exclusively of two histologies, ovarian clear cell carcinoma (“OCCC”) and ovarian endometrioid carcinoma (“OEC”), each representing about 10% of the overall ovarian cancer cases in the U.S. with an annual incidence of approximately 2,200 patients per histology. Platinum resistant ovarian carcinoma is recognized as a serious condition of unmet medical need, given the lack of effective treatments and the poor patient prognosis in this setting, with median life expectancy estimated to be approximately one year. It is estimated that approximately 66% of patients with OCCC and 40% of patients with OEC have the ARID1a mutation. About Nuvectis Pharma, Inc. Nuvectis Pharma, Inc. is a biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology. The Company is currently developing two drug candidates, NXP800 and NXP900. NXP800 is an oral small molecule GCN2 activator currently in a Phase 1b clinical trial for the treatment for platinum resistant, ARID1a-mutated ovarian carcinoma and in an Investigator-sponsored clinical trial for the treatment of cholangiocarcinoma. The U.S. Food and Drug Administration granted Fast Track Designation to the NXP800 development program in platinum resistant, ARID1a-mutated ovarian carcinoma, and Orphan Drug Designation for the treatment of cholangiocarcinoma. NXP900 is a novel, small molecule SRC/YES1 kinase inhibitor currently undergoing a Phase 1a dose escalation study. Forward Looking Statements Certain statements in this press release constitute "forward-looking statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will," "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Nuvectis Pharma, Inc.'s current expectations, estimates, and projections about future events and trends that we believe may affect our business, financial condition, results of operations, prospects, business strategy, and financial needs. The outcome of the events described in these forward-looking statements are subject to inherent uncertainties, risks, assumptions, market and other conditions, and other factors that are difficult to predict and include statements regarding the conclusions and interpretation of the Phase 1a data generated for NXP800 and the timing and clinical expectations for the NXP800 Phase 1b study, including statements regarding NXP800's potential ability to become a therapeutic option for the treatment of platinum-resistant, ARID1a-mutated ovarian carcinoma and cholangiocarcinoma; whether the preliminary safety and efficacy data reported today from the Phase 1b study will translate into data that can lead to the successful completion of the Phase 1b study, whether the dosing management algorithms that include dose modifications to better manage the key side effects associated with treatment with NXP800 that have been implemented will lead to longer treatment periods and better patient retention and whether patient enrollment into the study will be satisfactory and lead to a timely completion of the study. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are subject to market and other conditions and described more fully in the section titled "Risk Factors" in our 2023 Form 10-K filed with the Securities and Exchange Commission ("SEC"). However, these risks are not exhaustive and new risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this press release or other filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date of this press release. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Company Contact Ron Bentsur Chairman, Chief Executive Officer and President 201-614-3151 rbentsur@nuvectis.com Media Relations Contact Christopher M. Calabrese LifeSci Advisors Tel: 917-680-5608 ccalabrese@lifesciadvisors.com

NEW YORK and SAN DIEGO, Aug. 01, 2023 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today announced the appointment of Kimberly Freeman as Chief Strategy Officer. In this role, she will support and implement Zentalis’ long-term portfolio strategy. Ms. Freeman joins Zentalis with over 25 years of clinical development and strategic leadership experience, including deep expertise in oncology, particularly in gynecologic malignancies and the DNA damage response (DDR) pathway. “Kimberly brings an outstanding track record of building and executing drug development and franchise strategies that will be invaluable to Zentalis as we seek to capitalize on the significant opportunity we see with azenosertib across a broad array of tumor types,” said Dr. Kimberly Blackwell, Chief Executive Officer of Zentalis. “We welcome her unique skill set, which is ideally suited to helping us advance azenosertib to patients with ovarian and uterine cancers, as well as expand to other Cyclin E1 positive tumor types where patients typically face poor prognosis. Kimberly has successfully driven multiple cancer programs from early clinical development to FDA approval, led a billion-dollar product franchise, and has a deep network in the gynecologic oncology community.” Prior to joining Zentalis, Ms. Freeman was Vice President, US Head of DDR Franchise, Oncology at AstraZeneca. She was responsible for overseeing the strategic direction and cross-functional efforts for LYNPARZA® (olaparib) and other therapies targeting the DDR pathway, which is an important hallmark in ovarian and other cancers. Previously, she held various leadership roles at biopharmaceutical companies including Adaptimmune, Boehringer Ingelheim and GlaxoSmithKline. Ms. Freeman has also served on the Alliance for Regenerative Medicine (ARM) Cell Therapy Advisory Committee and has been recognized by Women in Bio as a Female Pioneer in the Life Sciences. After receiving her Bachelor of Science in Biology from Cornell University, Ms. Freeman was a Research Scientist in the Department of Hematology/Medical Oncology at Weill Cornell Medical Center and later pursued Graduate Studies at SUNY Upstate Medical Center. Ms. Freeman also received Finance and Marketing Certificates from the Wharton School of the University of Pennsylvania. “It is a privilege to join the Zentalis management team at such an exciting time in the Company’s history. I look forward to working with the team to shape and advance the Company’s strategic priorities,” said Ms. Freeman. “I see tremendous opportunity for azenosertib to change the therapeutic paradigm in a number of solid tumor types as it continues to emerge as a promising new therapeutic for cancer patients.” About Zentalis Pharmaceuticals Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers. Utilizing its Integrated Discovery Engine, the Company is developing a focused pipeline of potentially best-in-class oncology candidates, which include azenosertib (ZN-c3), a WEE1 inhibitor for advanced solid tumors, ZN-d5, a BCL-2 inhibitor for hematologic malignancies and related disorders, and a heterobifunctional degrader of BCL-xL for solid and hematological malignancies. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders. Zentalis has operations in both New York and San Diego. For more information, please visit www.zentalis.com. Follow Zentalis on Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the anticipated contribution and value of management team members; our goal of capitalizing on the azenosertib opportunity; our goals of advancing azenosertib in ovarian and uterine cancer indications and expanding to other Cyclin E1 positive tumor types; and the potential opportunity with and benefits of azenosertib. The terms “advance,” “expand,” “look forward,” “opportunity,” “promising,” “seek,” “will,” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of any diagnostic tools, if needed; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. ZENTALIS® and its associated logos are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release. Contact:Katie Beach Oltsik Evoke CanaleKatherine.Beach@evokegroup.com

June 1, 2023 -- The National Cancer Institute (NCI) has launched a large precision medicine cancer initiative to test the effectiveness of treating adults and children with new drug combinations that target specific tumor alterations. Known as the Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH), the initiative is the largest of its kind to test combinations of cancer drugs guided by tumor biology. The endeavor aims to identify promising treatments that can advance to larger, more definitive clinical trials outside of ComboMATCH. NCI is part of the National Institutes of Health. ComboMATCH comprises numerous phase 2 treatment trials that will each evaluate a drug combination—usually either two targeted drugs or a targeted drug plus a chemotherapy drug. Some trials will include patients with specific changes in their cancer cells, no matter where the cancer arose in the body, whereas others will enroll patients with specific cancer types. “The majority of treatments that patients get nowadays are not genomically determined,” said James H. Doroshow, M.D., director of NCI’s Division of Cancer Treatment and Diagnosis. “With ComboMATCH, we’re trying to show that genomic abnormalities can be used to determine the most effective treatment combinations for patients.” ComboMATCH (NCT05564377) is a cross-group collaboration among NCI and all five U.S. clinical trial groups within NCI’s National Clinical Trials Network (NCTN). ComboMATCH is a successor to NCI-MATCH, NCI’s groundbreaking precision medicine clinical trial. In NCI-MATCH, people were assigned to treatment based on genetic changes in their tumor rather than their type of cancer. For the most part, NCI-MATCH evaluated single drugs targeting the mutation thought to be driving the growth of a patient’s tumor. However, many patients quickly developed resistance to these single drugs. “With ComboMATCH, we’re hoping that by attacking both the genetic driver and the mechanisms of resistance, we will obtain more durable clinical responses and more benefit to patients,” said Jeffrey Moscow, M.D., of the Investigational Drug Branch in NCI’s Division of Cancer Treatment and Diagnosis and a co-leader of ComboMATCH. The combinations will include both U.S. Food and Drug Administration-approved drugs and investigational agents contributed by pharmaceutical companies. Hundreds of thousands of potential drug combinations exist, so one challenge has been to narrow down and prioritize the most promising ones. The overarching ComboMATCH coordination effort is led by the ECOG-ACRIN Cancer Research Group. All five U.S. NCTN groups, which include the Alliance for Clinical Trials in Oncology, Children’s Oncology Group, ECOG-ACRIN Cancer Research Group, NRG Oncology, and SWOG Cancer Research Network, will lead ComboMATCH treatment trials. “An important strength of the study is that the combinations being evaluated in ComboMATCH will be based on preclinical data showing that indeed the combination is better than either agent alone, as well as safety data from phase 1 studies,” said James Ford, M.D., of Stanford University School of Medicine, a co-leader of ComboMATCH and lead investigator on the coordination effort by ECOG-ACRIN. "There will be agreement among all the NCTN trial group representatives to evaluate each combination.” There are several ways in which patients with locally advanced or metastatic solid tumors will be identified for possible participation in ComboMATCH. In recent years, genomic testing of tumors has become a standard part of care for people with many cancer types. A doctor at any of the community hospitals and cancer centers participating in ComboMATCH can refer their patient for additional eligibility screening if the patient’s test results show that they have a particular alteration being investigated in one of the treatment trials. Any one of the nearly 35 designated commercial and academic labs that are conducting genomic testing as part of standard of care can also identify patients who might be eligible for a ComboMATCH trial. Patients who are matched to a trial will be asked to provide a pretreatment tumor biopsy specimen for genomic profiling. This will enable ComboMATCH investigators to later probe other questions, such as why some treatments worked and others didn’t. Three ComboMATCH trials are already open for enrollment: A study testing the use of fulvestrant (Faslodex) and binimetinib (Mektovi) in patients with an NF1 mutation in hormone receptor-positive breast cancer that has spread (NCT05554354) A study testing the use of selumetinib (Koselugo) and olaparib (Lynparza) or selumetinib alone in women with a RAS mutation who have endometrial or ovarian cancer that has come back or persists despite treatment (NCT05554328) A study of chemotherapy plus ipatasertib in patients with AKT mutations who have solid tumors that have spread (NCT05554380) Six additional trials will be available in the coming months, with more to be added over time. Overall, NCI plans for ComboMATCH to include about 2,000 patients, but that number could grow. Unlike MATCH, which did not include children, but rather had a separate parallel trial called PediatricMATCH, some ComboMATCH trials will include children with cancer. NCI will be launching two additional precision medicine cancer treatment trials. ImmunoMATCH has started with a pilot study to determine how prospective characterization of the immune status of a tumor can be used to improve the response to targeted treatments using immunotherapy, with plans to expand into larger studies in the future. MyeloMATCH will test treatments based on genetic changes in the cancer cells of people with acute myeloid leukemia or myelodysplastic syndromes. About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237). About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. NIH…Turning Discovery Into Health ® Source: NIH Posted: June 2023