Onconova Therapeutics’ Rigosertib Poster Selected for AACR 2024
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Insights
The exploration of rigosertib's molecular targets presents a significant step in understanding its mechanism of action and potential synergies in cancer treatment. Rigosertib's influence on RAS-MAPK signaling and reactive oxygen species (ROS)-related proteins suggests a multi-faceted approach to oncogenesis inhibition. Particularly, the activation of the NLRP3 inflammasome could indicate a novel pathway for modulating the tumor microenvironment, potentially enhancing the efficacy of existing therapies such as checkpoint inhibitors.
From a research perspective, the utilization of Cellular Thermal Shift Assay (CETSA-MS) is noteworthy. This methodology allows for the precise identification of drug targets within living cells, which is crucial for validating the direct effects of rigosertib on its targets. The findings from these preclinical studies could be pivotal in designing future clinical trials, especially in cancers where current treatments are inadequate.
As an oncologist, the potential clinical implications of rigosertib's preclinical findings are of great interest. The focus on difficult-to-treat cancers is particularly relevant, as these conditions often have limited therapeutic options and poor prognoses. The modulation of RAS-MAPK signaling is a promising avenue, considering that abnormalities in this pathway are common in various malignancies and have been associated with resistance to therapy. Furthermore, the activation of JNK via ROS mediation and the subsequent reprogramming of the tumor microenvironment through NLRP3 could represent a novel approach to enhance anti-tumor immunity.
Understanding the interplay between rigosertib and the inflammatory response is critical, as inflammation can either support or inhibit tumor growth. The evidence pointing to rigosertib's ability to activate inflammation-related targets suggests a potential dual role in both direct cancer cell inhibition and the modulation of immune responses within the tumor milieu.
From a market perspective, the development of rigosertib could address a significant unmet need in the oncology sector. The ability to target cancers with limited treatment options could position Onconova Therapeutics favorably in the market. The preclinical success of rigosertib, especially if translated into clinical benefits, may lead to increased investor confidence and potentially enhance the company's valuation.
Furthermore, the strategic presentation of these findings at a prominent conference such as the American Association for Cancer Research Annual Meeting serves not only as a platform for scientific exchange but also as a signal to stakeholders of the company's commitment to advancing its pipeline. The focus on translational science underscores the company's dedication to bridging the gap between laboratory findings and clinical application, which is a key factor in attracting partnerships and funding.
Translational science to characterize pathways impacted by rigosertib may help to guide future clinical studies and combination treatment regimen for difficult-to-treat cancers
NEWTOWN, 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 Guerin
Onconova Therapeutics, Inc.
267-759-3680
ir@onconova.us
https://www.onconova.com/contact/
Investor Contact:
Bruce Mackle
LifeSci Advisors, LLC
646-889-1200
bmackle@lifesciadvisors.com
FAQ
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