ARID1A

Fort Lee, NJ, March 19, 2024 (GLOBE NEWSWIRE) -- Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, today announced upcoming presentations for NXP800 and NXP900 at the upcoming 2024 American Association for Cancer Research Meeting (2024 AACR), taking place from April 5th to April 10th in San Diego, California. Presentation details are below: Abstract Title Poster Presentation Details NXP800 Pharmacokinetic and pharmacodynamic evaluation of NXP800, a novel GCN2 activator, in a first in human clinical trial Session Title First-in-Human Phase I Clinical Trials 1 Session Date / Time April 8th, 1:30 - 5:00 PM NXP800 Using acquired resistance to explore the mechanism of action of the integrated stress response/GCN2 activator NXP800 - a new developmental agent for platinum-resistant ARID1A mutant ovarian cancer Session Title Cell Cycle, Transcription Regulation, and Anticancer Drug Action Session Date / Time April 7th, 1:30 - 5:00 PM NXP800 Discovery of ARID1A loss as a patient biomarker for NXP800 – a developmental activator of the integrated stress response (ISR) and inhibitor of the HSF1 pathway in ovarian cancer Session Title Predictive Biomarkers 6 Session Date / Time April 9th, 1:30 - 5:00 PM NXP800 A novel GCN2 kinase activator demonstrates therapeutic efficacy in preclinical PDX models of human cholangiocarcinoma Session Title Novel Targets and Pathways Session Date / Time April 8th, 9:00 AM - 12:30 PM NXP900 Src family kinase inhibition demonstrates antitumor activity in vitro and in patient-derived xenograft models of human cholangiocarcinoma Session Title Kinase and Phosphatase Inhibitors 1 Session Date / Time April 7th, 1:30 - 5:00 PM NXP900 NXP900, a novel YES1/SRC kinase inhibitor in phase 1, demonstrates potent inhibition of proliferation in cell lines resistant to ALK and EGFR inhibitors Session Title Kinase and Phosphatase Inhibitors 1 Session Date / Time April 7th, 1:30 - 5:00 PM 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 ("FDA") 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 preclinical data generated to date for NXP800 and NXP900, 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, cholangiocarcinoma, and potentially other cancer indications, and timing of and expectations for the Phase 1a study for NXP900. 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 2022 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 Tel: 201-614-3151 rbentsur@nuvectis.com Media Relations Contact Christopher M. Calabrese LifeSci Advisors Tel: 917-680-5608 ccalabrese@lifesciadvisors.com

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

NXP800 preliminary data update expected this month from the Phase 1b study in platinum resistant, ARID1a mutated ovarian cancer, a program that has been granted Fast Track Designation by the FDA NXP800 Investigator-sponsored clinical trial in cholangiocarcinoma initiated with the Mayo Clinic NXP800 granted Orphan Drug Designation for the treatment of cholangiocarcinoma NXP900 Phase 1a dose escalation initiated Multiple clinical data readouts expected in 2024 FORT LEE, N.J., March 05, 2024 (GLOBE NEWSWIRE) -- Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, today reported its financial results for the fiscal year 2023 and provided an update on recent business progress. Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis, commented, "2023 was an eventful year for Nuvectis as we continued to make important strides with our two clinical-stage drug candidates, NXP800 and NXP900. For NXP800, we initiated the Phase 1b in platinum resistant ARID1a-mutated ovarian carcinoma and an investigator-sponsored clinical trial in cholangiocarcinoma in collaboration with the Mayo Clinic. Additional preclinical data presented during the year demonstrated the potency of NXP800 in ARID1A-mutated endometrial carcinoma, providing another potential development path for NXP800 within the gynecology-oncology space." Mr. Bentsur continued, "For NXP900, we initiated the Phase 1a dose escalation clinical trial and presented additional preclinical data that demonstrated the potential of NXP900 as a single agent and in combination with certain market-leading therapies." Mr. Bentsur added, "We expect several catalysts in 2024 for NXP800 and NXP900, starting with the preliminary clinical data update later this month from the NXP800 Phase 1b study in platinum resistant ARID1a-mutated ovarian cancer. We also expect to provide updates from all our clinical trials throughout the year." Mr. Bentsur concluded, "We remain cash efficient and highly focused on our mission of developing important precision medicines for the treatment of serious conditions of unmet medical need in oncology." Full Year 2023 Financial Results Cash, and cash equivalents were $19.1 million as of December 31, 2023, compared to $20.0 million as of December 31, 2022. The decrease of $0.9 million was a result of the Company's continued operations, offset primarily by the exercise of warrants issued in our 2022 PIPE transaction. The Company's net loss was $22.3 million for the year ended December 31, 2023, compared to $19.1 million for the year ended December 31, 2022, an increase in net loss of $2.2 million. Net loss for the 2023 fiscal year included $4.7 million in non-cash stock-based compensation and $2.3 million in one-time non-recurring expenses. Research and development expenses, including non-cash stock-based compensation and one-time non-recurring expenses, were $15.4 million for the year ended December 31, 2023, compared to $13.2 million for the year ended December 31, 2022, an increase of $2.2 million. General and administrative expenses, including non-cash stock-based compensation and one-time non-recurring expenses, were $7.5 million for the year ended December 31, 2023, compared to $6.0 million for the year ended December 31, 2022, an increase of $1.5 million. Interest income was $0.6 million for the year ended December 31, 2023, compared to $0.1 million for the year ended December 31, 2022, an increase of $0.5 million. 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 ("FDA") 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 preclinical data generated to date for NXP800 and NXP900, 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, cholangiocarcinoma and potentially other cancer indications, and timing of and expectations for the Phase 1a study for NXP900. 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 2022 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 safeharbor 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 NUVECTIS PHARMA, INC. BALANCE SHEETS (USD in thousands, except per share and share amounts) December 31, 2023 2022 Assets CURRENT ASSETS: Cash and cash equivalents 19,126 19,993 Other current assets 59 412 TOTAL CURRENT ASSETS 19,185 20,405 TOTAL ASSETS 19,185 20,405 Liabilities and Stockholders' Equity CURRENT LIABILITIES Accounts payables 2,771 2,910 Payable offering costs — 450 Accrued liabilities 415 445 Employee compensation and benefits 3,798 2,381 TOTAL CURRENT LIABILITIES 6,984 6,186 TOTAL LIABILITIES 6,984 6,186 COMMITMENTS AND CONTINGENCIES STOCKHOLDERS' EQUITY: Common Stock, $0.00001 par value – 60,000,000 shares authorized as of December 31, 2023, and December 31, 2022, respectively, 17,418,886, and 15,190,720 shares issued and outstanding as of December 31, 2023 and December 31, 2022, respectively * * Additional paid in capital 66,446 46,204 Accumulated deficit (54,245 ) (31,985 ) TOTAL STOCKHOLDERS' EQUITY 12,201 14,219 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY 19,185 20,405 NUVECTIS PHARMA, INC. STATEMENT OF OPERATIONS (USD in thousands, except per share and share amounts) For the year ended For the year ended December 31, 2023 December 31, 2022 OPERATING EXPENSES: Research and development 15,380 13,227 General and administrative 7,517 6,007 OPERATING LOSS (22,897 ) (19,234 ) Finance income 637 149 NET LOSS (22,260 ) (19,085 ) NET LOSS ATTRIBUTABLE TO COMMON STOCKHOLDERS (22,260 ) (19,085 ) BASIC AND DILUTED NET LOSS PER COMMON SHARE OUTSTANDING (1.43 ) (1.51 ) Basic and diluted weighted average number of common shares outstanding 15,556,655 12,657,651