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Translational science to characterize pathways impacted by rigosertib may help to guide future clinical studies and combination treatment regimen for difficult-to-treat cancersNEWTOWN, Pa., March 08, 2024 (GLOBE NEWSWIRE) -- Onconova Therapeutics, Inc. (NASDAQ: ONTX), (“Onconova” or “the Company”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the Company will present an abstract related to preclinical studies conducted by the Company and its collaborators to further characterize the mechanism of rigosertib at the American Association for Cancer Research Annual Meeting 2024 (AACR 2024), taking place April 5-10, 2024 in San Diego, CA. “The ability to impact multiple targets is an important characteristic of Onconova’s two lead clinical programs, rigosertib and narazaciclib. We are pleased to present new preclinical studies that explore the molecular targets for rigosertib, in clinical development through a series of investigator initiated studies (IIS),” commented Steven Fruchtman, M.D., President and Chief Executive Officer of Onconova. “The studies provide additional prospective on the main cellular pathways impacted by rigosertib, including RAS-MAPK signaling and reactive oxygen species (ROS)-related proteins. In addition, the studies highlight rigosertib’s impact on the tumor microenvironment through the activation of inflammation–related targets, such as an NLRP3. We hope to apply this translational science to help guide the clinical program to enable the potential use of rigosertib in difficult-to-treat cancers.” Poster Information:Poster Title:Rigosertib promotes anti-tumor activity of cancer cells via CETSA revealed novel targets and activates NLRP3-dependent inflammatory responses (2033/16)Session:Microenvironment, Immunity, and DNA Repair in Therapeutic Response (PO.ET05.02)Date/Time:Monday, April 8 9:00a-12:30p PT Brief Overview: Onconova and its collaborators conducted a series of biochemistry and molecular and cell biology assays to study rigosertib’s molecular and inflammation-based targets. The team used a specialized mass spectrometry assay (a Cellular Thermal shift Assay or CETSA-MS) as one of the tools to identify new targets which were then validated as novel targets of rigosertib. Conclusions: This work identified a series of cellular and inflammatory targets that may be affected by rigosertib. In particular, the research highlighted target activity through RAS-MAPK signaling, ROS-mediation JNK activation, and tumor microenvironment reprogramming through NLRP3 activation, which may contribute to preclinical and clinical synergistic effects with checkpoint inhibitors. The identification of these targets and signaling pathways may be helpful in the design of clinical trials to address difficult-to-treat cancers. About Onconova Therapeutics, Inc. Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company’s product candidates, narazaciclib and rigosertib, are proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Narazaciclib, Onconova’s novel, multi-kinase inhibitor (formerly ON 123300), is being evaluated in a Phase 1/2 combination trial with the estrogen blocker letrozole, in advanced endometrial cancer (NCT05705505). Based on preclinical and clinical studies of CDK4/6 inhibitors, Onconova believes narazaciclib has broad potential and is also evaluating opportunities for combination studies with narazaciclib and letrozole in additional indications, including breast cancer, ovarian cancer, multiple myeloma, and mantle cell lymphoma. Rigosertib is being studied through an IIS strategy to evaluate the product candidate in multiple indications, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer (NCT04263090), a Phase 2 program evaluating oral or IV rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) (NCT03786237, NCT04177498), and a Phase 2 trial evaluating rigosertib in combination with pembrolizumab in patients with metastatic melanoma (NCT05764395). For more information, please visit www.onconova.com. Forward Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding its clinical development and trials, its product candidates, its business and financial position including the potential to initiate IISs in metastatic breast cancer and relapsed/refractory multiple myeloma, and initiate enrollment in H2 2024 and potential that the results will provide data on new treatment options for patients with metastatic breast cancer and relapsed/refractory multiple myeloma. Onconova has attempted to identify forward-looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should," “preliminary,” “encouraging,” "approximately" or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova's clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading "Risk Factors" in Onconova's most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. Company Contact:Mark GuerinOnconova Therapeutics, Inc.267-759-3680ir@onconova.ushttps://www.onconova.com/contact/ Investor Contact:Bruce Mackle LifeSci Advisors, LLC646-889-1200bmackle@lifesciadvisors.com

With dovitinib snatched back from Allarity’s pipeline, it’s unclear whether this is the end of the road for the multi-kinase inhibitor. Already reeling from the controversial termination of its CEO, Allarity Therapeutics has now been told that Novartis is rescinding the rights to a troubled cancer drug after the biotech failed to keep up with its payments. Allarity, under its previous Oncology Venture moniker, licensed the rights to the small molecule multi-kinase inhibitor dovitinib from Novartis back in 2018. But Allarity revealed in an SEC filing yesterday that the Big Pharma had written to the biotech a week ago “indicating their decision to terminate the agreement based on material breach for lack of financial payment.” Novartis had once touted dovitinib as a highly promising kidney cancer drug based on the strength of mid-phase data. But by the time Allarity got interested, the candidate had shown itself unable to outperform Bayer’s Nexavar in a phase 3 trial of metastatic renal cell cancer patients previously failed by anti-angiogenic therapies. Allarity was willing to give the drug a second chance. It licensed the asset in return for an undisclosed package of upfront and milestone payments, hoping to prove dovitinib’s worth by using its DRP biomarker platform to better select tumor patients who could benefit. By 2022, the company was forced to abandon plans to develop the drug as a monotherapy for a type of advanced kidney cancer after the FDA responded to Allarity’s application with a refusal to file letter. The biotech responded by refocusing its pipeline on combination therapies. As part of that retooled strategy, Allarity launched a phase 1b/2 study of stenoparib, a PARP inhibitor, in combination with dovitinib for second-line or later treatment of metastatic ovarian cancer. In the filing yesterday, Allarity said it remains “fully committed and primarily focused” on a phase 2 trial of stenoparib in ovarian cancer. The biotech reiterated that “encouraging results” were seen from the first five evaluable patients in December 2023 from that study. With dovitinib snatched back from Allarity’s pipeline, it’s unclear whether this is the end of the road for the multi-kinase inhibitor. Fierce Biotech has asked Novartis whether it has any plans to pick up development of the drug. The loss of the dovitinib license isn’t the only drama at Allarity. The company first revealed in December that CEO James Cullem was leaving the company. In yesterday’s filing, Allarity explained that Cullem had been fired “for ‘cause’ under his employment agreement,” although Cullem has apparently disputed this rationale. Allarity also attached Cullem’s letter resigning from the biotech’s board last week, in which the former CEO accused the company’s directors of “acts and omissions … that I consider directly injurious to the company, its shareholders and its creditors.” “We and our continuing members of the board disagree with the claims made by Mr. Cullem in the resignation email and take exception to Mr. Cullem’s characterizations of facts and his conclusions,” the company added in yesterday’s filling. Cullem had only been in the CEO role since June 2022, when he took over after Steve Carchedi stepped down to “pursue other opportunities.” Cullem has been replaced by co-founder and board member Thomas Jensen.

Preclinical data show that narazaciclib treatment led to significant tumor growth inhibition, demonstrating synergy with standard-of-care ibrutinib, in ibrutinib-sensitive and -resistant settings Early Phase 1/2 studies suggest potential for an improved pro daily dosing Dose escalation is underway in lead indication of Low Grade Endometrioid Endometrial Carcinoma (LGEEC), with plans to define the Recommended Phase 2 Dose (RP2D) and prepare for registrational studies, with a planned update in H1 2024 NEWTOWN, Pa., Dec. 12, 2023 (GLOBE NEWSWIRE) -- Onconova Therapeutics Inc. (NASDAQ: ONTX), (“Onconova” or “the Company”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced preclinical data, highlighting narazaciclib’s preclinical activity in Bruton’s kinase inhibitor (BTKi)-resistant mantle cell lymphoma (MCL), in a poster presented on December 11, 2023 at the 65th Annual Meeting of the American Society for Hematology (ASH 2023) in San Diego. “We are pleased to have shared data at ASH 2023 from preclinical studies with narazaciclib in MCL models. These results, which are consistent with data presented this year at the international MCL conferences, demonstrate that treatment with narazaciclib led to significant tumor growth inhibition when used as a single agent and that combination with ibrutinib demonstrated synergy, in both ibrutinib-sensitive and -resistant in vitro and in vivo settings,” said Steve Fruchtman, M.D., President and Chief Executive Officer. “These data are important because they provide further evidence for the potential use of narazaciclib in cancers with cyclin over-expression and elaborate our understanding of narazaciclib’s mechanism of action, including its ability to promote G1 cell cycle blockade.” Dr. Fruchtman continued, “We believe that these data, along with the preclinical data presented on Friday, December 8th at the San Antonio Breast Cancer Symposium (SABCS), further underscore the impressive and differentiated pro narazaciclib. The data presented at SABCS highlight narazaciclib’s multi-kinase activity, its ability to target resistance pathways missed by other CDK4/6 inhibitors, and its differentiated anti-tumor and immunomodulatory activity. The data presented at ASH 2023 show that narazaciclib, in combination with BTKi’s such as ibrutinib, also trigger metabolic reprogramming alongside DNA damage.” “The totality of these data is helping us to shape the clinical program for narazaciclib, including the lead indication of LGEEC, with further potential to expand into additional investigator-sponsored studies in breast, ovarian, and other cancers. We are pleased with the early Phase 1/2 data for narazaciclib monotherapy and in combination with letrozole, showing lower levels of neutropenia and diarrhea, and the potential for once daily dosing. Both of these attributes could position narazaciclib as a differentiated and improved CDK4/6i. Looking ahead, we are enthusiastic to advance the clinical program for narazaciclib in 2024 and to update our stakeholders regarding our progress, including the planned completion of dose escalation studies, definition of an RP2D, and development of our registrational trial plans for LGEEC. The data presented at ASH suggest narazaciclib is a drug with the potential to target a variety of cancer indications with an unmet medical need, including MCL,” concluded Dr. Fruchtman. Poster Highlights Title: Narazaciclib, a differentiated CDK4/6 antagonist, prolongs cell cycle arrest and metabolomic reprogramming, enabling restoration of ibrutinib sensitivity in BTKi-resistant mantle cell lymphoma Objectives: To evaluate the activity and mechanism of action of narazaciclib as a single agent and in combination with ibrutinib, in comparison to the standard-of-care ibrutinib, in preclinical models of MCL that are sensitive and resistant to ibrutinib treatment. Snapshot of the Results and Conclusions: Tumor Growth Inhibition: Narazaciclib showed safety and efficacy as a single agent in preclinical MCL models, including ibrutinib-resistant settings, with significant reductions in cell viability. Combination Synergy: The narazaciclib plus ibrutinib combination showed synergy in vitro and in vivo, especially in ibrutinib-resistant models, with overall greater synergy, measured by lower “Combination Index” values, versus ibrutinib-sensitive cells. Cell Cycle Blockade: The combination of narazaciclib plus ibrutinib induces a superior G1 cell cycle blockade in both ibrutinib-sensitive and ibrutinib-resistant MCL cells. Metabolic programming: In ibrutinib-resistant cases, the synergy between narazaciclib and ibrutinib triggers metabolic reprogramming alongside DNA damage, mediated by the USP24 and P53 axis, as evidenced by several assays to assess mitochondrial metabolism. Together, these preclinical data suggest that narazaciclib has important single agent activity and the potential to restore ibrutinib sensitivity in BTKi-resistant models, successfully meeting the primary objective of the study. A copy of the poster is available on the “Scientific Presentations” section of the Onconova website. About Onconova Therapeutics, Inc. Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company’s product candidates, narazaciclib and rigosertib, are proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Narazaciclib, Onconova’s novel, multi-kinase inhibitor (formerly ON 123300), is being evaluated in a Phase 1/2 combination trial with the estrogen blocker letrozole in advanced endometrial cancer (NCT05705505). Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova believes narazaciclib has broad potential and is also evaluating opportunities for combination studies with narazaciclib and letrozole in additional indications, including breast cancer, ovarian cancer, multiple myeloma, and mantle cell lymphoma. Rigosertib is being studied in an investigator-sponsored trial strategy to evaluate the product candidate in multiple indications, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer (NCT04263090), a Phase 2 program evaluating oral or IV rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) (NCT03786237, NCT04177498), and a Phase 2 trial evaluating rigosertib in combination with pembrolizumab in patients with metastatic melanoma (NCT05764395). For more information, please visit . Forward Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, and involve risks and uncertainties. These statements relate to Onconova’s expectations regarding its clinical development and trials, its product candidates, its business and financial position. Onconova has attempted to identify forward-looking statements by terminology including "believes," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should," “preliminary,” “encouraging,” "approximately" or other words that convey uncertainty of future events or outcomes. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including the success and timing of Onconova's clinical trials, investigator-initiated trials and regulatory agency and institutional review board approvals of protocols, Onconova’s collaborations, market conditions and those discussed under the heading "Risk Factors" in Onconova's most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q. Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. Company Contact: Mark Guerin Onconova Therapeutics, Inc. 267-759-3680 ir@onconova.us Investor Contact: Bruce Mackle LifeSci Advisors, LLC 646-889-1200 bmackle@lifesciadvisors.com