NXP-800

FORT LEE, NJ, Feb. 04, 2025 (GLOBE NEWSWIRE) -- Nuvectis Pharma, Inc. (Nasdaq: NVCT), 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 that it has commenced an underwritten public offering of its common stock. All of the shares to be sold in the offering will be offered by Nuvectis. In addition, Nuvectis intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the public offering. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. Lucid Capital Markets is acting as sole book runner for the offering. Nuvectis intends to use the net proceeds from this offering to continue to advance the development programs of NXP800 and NXP900 or any future product candidate, hiring of additional personnel, capital expenditures, costs of operating as a public company and other general corporate purposes. The securities described above are being offered by Nuvectis pursuant to its shelf registration statement on Form S-3 (File No. 333-270657) with the U.S. Securities and Exchange Commission (“SEC”) on March 17, 2023 and declared effective by the SEC on March 29, 2023. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at https://www.sec.gov/. Copies of the final prospectus supplement and the accompanying prospectus relating to these securities may also be obtained, when available, by contacting Lucid Capital Markets, LLC, 570 Lexington Avenue, 40th floor, New York, NY 10022. The offering of these securities is being made under an effective shelf registration statement on file with the SEC. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. About Nuvectis Pharma 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 clinical-stage 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. NXP900 is an oral small molecule inhibitor of the SRC Family of Kinases (SFK), including SRC and YES1. NXP900 has a unique mechanism of action in that it inhibits both the catalytic and scaffolding functions of the SRC kinase thereby providing complete shutdown of the signaling pathway. NXP900 is currently in a Phase 1a dose escalation study. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties, including the risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the proposed public offering. 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, including safety and efficacy data generated to date for NXP800 and NXP900, 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 and data regarding the preclinical studies for NXP800 and NXP900, and the Phase 1a data for NXP800 and the NXP900 Phase 1a study to date, as well as the clinical expectations for the ongoing NXP800 Phase 1b study in platinum-resistant, ARID1a-mutated ovarian carcinoma, including the potential ability of a higher dose intensity going forward in the NXP800 Phase 1b study to generate satisfactory safety and efficacy results, 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 the timing for completion of the clinical trials, including the ongoing NXP800 investigator-initiated study in cholangiocarcinoma and statements regarding NXP900's therapeutic potential and the expected timing for the start of the NXP900 Phase 1b program. 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 3Q 2024 Form 10-Q and our other public filings 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

Prostate cancer that has become resistant to hormone therapy could be treated using a new drug that is currently in clinical trials for ovarian and bile duct cancer, according to research published in the journal Clinical Cancer Research. Scientists from The Institute of Cancer Research, London, showed that the drug, NXP800, discovered at the same institute, slowed the growth of prostate cancer cells, including in cancer cells that are resistant to the hormone therapy enzalutamide. Although hormone therapies like enzalutamide and abiraterone transform the lives of thousands of men with advanced prostate cancer every year, most patients will eventually become resistant to these treatments. Researchers are searching for new ways to overcome drug resistance. NXP800 works in an innovative way, by targeting the Heat Shock Factor 1 (HSF1) pathway – a ‘master switch’ in cells that is hijacked to support the growth of cancer cells, helping them withstand the stresses they come under as a tumour develops. The pathway controls the production of heat shock proteins that help to protect the cancer cell during stressful conditions. The team at The Institute of Cancer Research (ICR) studied data from 439 advanced prostate cancer samples. In research funded largely by Prostate Cancer UK, Movember, and the Prostate Cancer Foundation, they found an association between higher levels of heat shock proteins and more androgen receptor signalling, which drives the development and growth of prostate cancer. They also found an association between patients who had higher levels of these proteins and poorer overall survival. In one cohort they studied, patients with more of these proteins survived for 22.0 months, compared with 33.5 months for those with fewer heat shock proteins, suggesting that prostate cancers with more of these proteins may be better equipped to survive and harder to treat. The researchers attempted to block these heat shock proteins using the drug NXP800, which was discovered at the ICR in its Centre for Cancer Drug Discovery. The drug underwent an early clinical trial in advanced cancer, led by the ICR and its hospital partner The Royal Marsden NHS Foundation Trust, and sponsored by Nuvectis Pharma. In the lab, the researchers found that NXP800 slowed the growth of prostate cancer cells – even for cells which were resistant to the hormone therapy enzalutamide. In biopsies of patients with advanced prostate cancer grown as mini tumours in the laboratory, the new drug slowed the growth of the tumours, whereas enzalutamide only had a small effect at very high concentrations. In mice with hormone therapy-resistant prostate cancers, NXP800 significantly slowed tumour growth. Without the drug, 100 per cent of tumours had doubled in size by 38 days – when treated with the drug, only 37.5 per cent of tumours had reached that size in that time. The researchers from the ICR, which is both a research institute and a charity, hope these findings will lead to trials of NXP800 for advanced prostate cancer, to provide patients with alternative treatments when hormone therapies have stopped working. The team carried out mechanistic studies which confirmed that NXP800 blocks the activity of HSF1 in prostate cancer cells and reduces the levels of heat shock proteins. They also discovered that it modulates a pathway called the unfolded protein response – a pathway connected to the cells’ response to stress – and impacts other protein molecules that are important in controlling gene activity in prostate cancer. Understanding the mechanism of the drug’s action will be important for future research to discover which patients will respond best. NXP800 has been granted Fast-Track and Orphan Drug Designation by the US Food and Drug Administration (FDA) for its potential to treat ARID1a-deficient ovarian, fallopian tube, and peritoneal cancers, and Orphan Drug Designation for hard-to-treat bile duct cancer. This is to speed up the review of, and provide financial benefits for, drugs which show promise to treat rare diseases. Until this study, it had not been considered for use in prostate cancer. Study co-leader Dr Adam Sharp, Leader of the Translational Therapeutics Group at The Institute of Cancer Research, London, and Honorary Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust said: “While hormone therapies have extended the lives of lots of men with advanced prostate cancer, drug resistance is inevitable. We need to tackle the problem from a new angle. “With this research, we’ve shown that targeting the heat shock response pathway – a pathway responsible for enabling tumours to withstand stress and keep growing – is a potential new avenue for treating advanced prostate cancer. The pathway impacts the hormone signalling that drives cancer, but it’s not susceptible to the usual mutations that drive drug resistance. “Excitingly, we’ve shown that targeting this pathway can slow the growth of prostate cancer tumours – even for tumours that are resistant to hormone therapy. The next step will be to assess if certain prostate cancer patients would respond better than others. “The researchers Jon Welti, Denisa Bogdan and Ines Figueredo, played a critical role in this research to establish the effect of NXP800 on prostate cancer.” Study co-leader Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust said: “We have shown that people with prostate cancers with higher levels of heat shock proteins have significantly worse outcomes. If targeting these proteins proves effective in clinical trials, patients with advanced prostate cancer will be able to look forward to longer and better-quality lives.” Professor Kristian Helin, Chief Executive at The Institute of Cancer Research, London, said: “Drug resistance is one of the biggest problems we face in treating cancer. Finding drugs that can slow down cancer’s growth when all other treatments have stopped working is critical. “This research uses an innovative drug to target prostate cancer through a novel mechanism of action. We’ve been delighted to see the ICR-discovered NXP800 drug make great progress in clinical studies for ovarian cancer, so it is very exciting to see that it could potentially also benefit prostate cancer patients for whom hormone therapy has stopped working. “NXP800 is one of the 13 ICR-discovered drugs we’ve taken into clinical trials for cancer patients since 2005. That track record is unrivalled in the academic world.” Professor Paul Workman, Harrap Professor of Pharmacology and Therapeutics at The Institute of Cancer Research, London, who led the original research at the ICR to discover NXP800 and is a co-author of this study, said: “The NXP800 drug is an example of the incredible drug discovery and development that is possible through partnerships between academics, clinicians and private enterprise. Through our Centre for Cancer Drug Discovery and our close partnership with The Royal Marsden, the ICR has unparalleled capabilities for discovering and developing totally new types of treatment for patients with hard-to treat cancers. “I’m thrilled about the exciting results we’ve obtained in prostate cancer models, which means that the drug could benefit even more patients beyond the current focus on ovarian and bile duct cancer. “NXP800 works through a highly innovative mechanism and I very much hope to eventually see the drug, now licenced to the US biotechnology Nuvectis Pharma, progress into additional trials including for advanced prostate cancer.” Simon Grieveson, Assistant Director of Research at Prostate Cancer UK, said: "For men with advanced prostate cancer, treatment with hormone therapy can be very effective at delaying cancer progression, however eventually these treatments are likely to stop working. This is a critical problem we need to address through continued research into brand new approaches to treating prostate cancer, and this is a fantastic example. “We’re thrilled to have funded this research in partnership with Movember, which could make a marked impact on the lives of men with hormone resistant prostate cancer and who have very few treatment options remaining. These findings provide valuable insight into the role of heat shock proteins, which we now know are at a higher level among advanced prostate cancer patients and associated with worse outcomes. Targeting these proteins with this novel drug could give men with hormone resistant prostate cancer a new option for treatment and, crucially, more valuable time with their loved ones. Clinical trials are now needed, but this is an exciting step towards a new solution to tackling treatment resistance in prostate cancer." Howard R. Soule, PhD, Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation, said: “These findings fill a therapeutic gap for patients with advanced prostate cancer. We applaud the discovery and clinical translational expertise of the ICR in advancing a new target and novel experimental therapy to the patients PCF serves.”