Darolutamide

SAN DIEGO, May 30, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced that enrollment has been completed and dosing initiated for the fifth dose cohort of its Phase 1/2 study of ONCT-534 for the treatment of patients with metastatic castration-resistant prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). Patients in the fifth cohort are receiving ONCT-534, the company’s dual-action androgen receptor inhibitor (DAARI), at a dose of 600 mg taken orally once each day. The decision to proceed to this higher dose level was made by the study’s Safety Review Committee (SRC) after reviewing data from the fourth dose level of 300 mg ONCT-534 daily. An initial update on ONCT-534 safety and efficacy based on prostate-specific antigen (PSA) levels from this study is expected in the third quarter of 2024 and will include data from this 600 mg dose cohort. “We are encouraged by the rapid enrollment in the dose escalation portion of our Phase 1/2 study with ONCT-534. The drug has been well tolerated, with no dose limiting toxicities observed to date. We continue to open new sites and patient demand continues to be strong,” said Salim Yazji M.D., Chief Medical Officer at Oncternal Therapeutics. “We are looking forward to sharing initial safety and efficacy data soon, which will include a larger, more robust set of clinical and biomarker results, as well as longer follow-up from the initial dosing cohorts.” About Study ONCT-534-101Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of ONCT-534 in patients with mCRPC who have relapsed or are refractory to approved ARPIs including enzalutamide, abiraterone, apalutamide, and darolutamide. After the safety and tolerability and preliminary antitumor activity of ONCT-534 have been assessed in Phase 1, Phase 2 will commence to further evaluate the safety and antitumor activity of ONCT-534 to support selecting an optimal dose. About Oncternal TherapeuticsOncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. Study ONCT-534-101 (NCT05917470) has completed enrollment in four dose cohorts and continues to enroll and dose patients for treatment with mCRPC. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced, compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options. Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905). More information on our company and programs is available at https://oncternal.com/. Forward-Looking InformationOncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding anticipated timing for study enrollment and announcing clinical data. Forward-looking statements are subject to risks and uncertainties inherent in Oncternal’s business, including risks associated with the clinical development and process for obtaining regulatory approval of Oncternal’s product candidates, such as potential delays in the commencement, enrollment and completion of clinical trials; the risk that interim results of a clinical trial do not predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues, and as more patient data become available; and other risks described in Oncternal’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact Information: InvestorsRichard Vincent 858-434-1113rvincent@oncternal.com MediaCorey Davis, Ph.D. LifeSci Advisors 212-915-2577 cdavis@lifesciadvisors.com

The Phase 3 clinical trial will evaluate gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer who are endocrine therapy resistantReceived an additional term loan of approximately $62 million in conjunction with an amendment to an existing debt facility agreement MINNEAPOLIS, May 30, 2024 (GLOBE NEWSWIRE) -- Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, today announced that it plans to initiate a Phase 3 clinical trial to evaluate gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer (“ABC”) who are endocrine therapy resistant. In conjunction with its plan to conduct this study, Celcuity today entered into an amendment to an existing debt facility agreement and received an additional term loan of approximately $62 million. “There is an urgent need for better first-line treatment options for HR+/HER2- advanced breast cancer patients whose disease progressed while on or within 12 months of completing adjuvant endocrine for early breast cancer,” said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. “We are very encouraged by the preliminary clinical data for gedatolisib as first-line treatment in patients with advanced breast cancer. In our Phase 1b trial that evaluated gedatolisib in combination with palbociclib and letrozole, median progression free survival was 48.6 months, and the ORR was 79%. These results highlighted the potential benefit of inhibiting the PI3K/AKT/mTOR pathway in treatment naïve patients.” Phase 3 VIKTORIA-2 Clinical TrialThe Phase 3 VIKTORIA-2 clinical trial will be an open-label, randomized study to evaluate the efficacy and safety of gedatolisib combined with fulvestrant plus a CDK4/6 inhibitor in comparison to fulvestrant plus a CDK4/6 inhibitor as first-line treatment for patients with HR+/HER2- ABC who are endocrine therapy resistant. For the CDK4/6 inhibitor, investigators may choose either ribociclib or palbociclib. The safety profile of gedatolisib combined with fulvestrant and palbociclib is well described, but the investigational combination of gedatolisib with ribociclib has not yet been clinically tested. Therefore, a safety run-in of approximately 12-36 subjects will evaluate the safety profile of gedatolisib combined with ribociclib and fulvestrant. The safety run-in will be completed, and gedatolisib’s Phase 3 dose confirmed, before enrolling patients in the Phase 3 portion of the study. For the Phase 3 study, approximately 638 subjects who meet the eligibility criteria will be assigned to a cohort based on their PIK3CA mutation status. After the investigator selects the CDK4/6 inhibitor for a subject, the subject will then be randomly assigned on a 1:1 basis to either Arm A (gedatolisib, fulvestrant, and Investigator’s choice of ribociclib or palbociclib) or Arm B (fulvestrant and Investigator’s choice of ribociclib or palbociclib). The clinical trial primary endpoints are progression free survival ("PFS"), per RECIST 1.1 criteria, as assessed by blinded independent central review. The primary PFS endpoints will be evaluated separately in subjects who are PI3KCA wild type and PI3KCA mutant. The study’s design was reviewed and discussed with the U.S. Food and Drug Administration ("FDA") during a Type C meeting. This global trial is expected to enroll subjects at up to 200 clinical sites across North America, Europe, Latin America, and Asia. Celcuity expects to enroll the first patient in the second quarter of 2025. “We are excited to have secured the additional capital so we could accelerate initiation of our second Phase 3 study,” said Brian Sullivan, CEO and co-founder of Celcuity. “Allowing investigators to choose between ribociclib or palbociclib as the CDK4/6 inhibitor for their patients, and separately randomizing patients according to their PIK3CA status, are important elements of the trial design. We are pleased that the FDA concurred with our approach.” Amended debt financing agreement with Innovatus Capital Partners, LLC and Oxford Finance LLCToday, Celcuity also amended its existing debt financing agreement with an affiliate of Innovatus Capital Partners, LLC (“Innovatus”) and added Oxford Finance LLC (“Oxford”) as a new lender to provide Celcuity with up to $180 million in term loans, a $105 million increase from the current debt financing agreement. At the closing of this amendment to the debt financing agreement, Celcuity will receive $61.7 million and will have $100 million of total debt outstanding. Celcuity will be able to draw an additional tranche of $30 million and an additional tranche of $50 million upon achievement of certain clinical trial and regulatory milestones. The amended debt facility has a 36-month interest only period, which can be extended to a 48-month period if certain conditions are met. The loans will mature on the fifth anniversary of the amended agreement date. The loan agreement includes customary warrant coverage and is secured by all of Celcuity’s assets. Armentum Partners LLC acted as sole advisor to Celcuity on this transaction. About CelcuityCelcuity is a clinical-stage biotechnology company focused on development of targeted therapies for treatment of multiple solid tumor indications. The company's lead therapeutic candidate is gedatolisib, a potent, pan-PI3K and mTOR inhibitor. Its mechanism of action and pharmacokinetic properties are highly differentiated from other currently approved and investigational therapies that target PI3K or mTOR alone or together. A Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant with or without palbociclib in patients with HR+/HER2- advanced breast cancer is currently enrolling patients. More detailed information about the VIKTORIA-1 study can be found at ClinicalTrials.gov. A Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer, is enrolling patients. A Phase 3 clinical trial, VIKTORIA-2, evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer is expected to begin enrolling patients in the second quarter of 2025. The company’s CELsignia companion diagnostic platform is uniquely able to analyze live patient tumor cells to identify new groups of cancer patients likely to benefit from already approved targeted therapies. Celcuity is headquartered in Minneapolis. Further information about Celcuity can be found at www.celcuity.com. Follow us on LinkedIn and Twitter. About Innovatus Capital Partners, LLCInnovatus Capital Partners, LLC, is an independent adviser and portfolio management firm with approximately $1.7B in assets under management. Innovatus adheres to an investment strategy that identifies disruptive and growth opportunities across multiple asset categories with a unifying theme of capital preservation, income generation, and upside optionality. The firm has a dedicated team of life sciences investment professionals with deep experience in healthcare, including life sciences. Innovatus and its principals have significant experience providing debt financing to medical device, diagnostics, and biotechnology companies that address unmet medical needs, improve patient outcomes, and reduce overall healthcare expenditures. About Oxford FinanceOxford Finance LLC is a specialty finance firm providing senior secured loans to public and private life sciences and healthcare services companies worldwide. For over 20 years, Oxford has delivered flexible financing solutions to over 700 companies, allowing borrowers to maximize their equity by leveraging their assets. Since 2002, Oxford has originated more than $11 billion in loans. Oxford is headquartered in Alexandria, Virginia, with additional offices serving the greater San Diego, San Francisco, Boston and New York City metropolitan areas. Cautionary Note Regarding Forward-Looking StatementsThis press release contains statements that constitute “forward-looking statements” including, but not limited to, the design of our clinical trials; the timing of initiating and enrolling patients in, and receiving results and data from, our clinical trials; the costs and expected results from any ongoing or planned clinical trials; the market opportunity for gedatolisib; other expectations with respect to gedatolisib and our CELsignia platform; the expected use of proceeds from our recent financing activities; and the strength of our balance sheet. In some cases, you can identify forward-looking statements by terminology such as “may,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “intends” or “continue,” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward-looking statements are subject to numerous risks, uncertainties, and conditions, many of which are beyond the control of Celcuity. These include, but are not limited to, unforeseen delays in our clinical trials, our ability to obtain and maintain regulatory approvals to commercialize our products, and the market acceptance of such products, the development of therapies and tools competitive with our products, and those risks set forth in the Risk Factors section in Celcuity’s Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on March 27, 2024. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Celcuity undertakes no obligation to update these statements for revisions or changes after the date of this press release, except as required by law. View source version of release on GlobeNewswire.com Contacts: Celcuity Inc.Brian Sullivan, bsullivan@celcuity.comVicky Hahne, vhahne@celcuity.com763-392-0123 ICR WestwickeMaria Yonkoski, maria.yonkoski@westwicke.com (619) 228-5886 SOURCE: Celcuity Inc.