• Two of two evaluable participants in an ongoing investigator-sponsored program of rigosertib in RDEB-associated squamous cell carcinoma (SCC) have achieved a complete response of all cancerous skin lesions
  
• First evaluable participant has been in complete remission with no signs of metastatic disease for >18 months; the second patient has achieved a complete response in all squamous cell skin lesions following four cycles of treatment and remains on therapy with additional scans to follow to evaluate metastatic disease
• Onconova plans to review initial data with regulators to gain insights on the optimal regulatory pathway for rigosertib in RDEB-associated SCC, an ultra-rare and invariably fatal condition

NEWTOWN, Pa., Feb. 07, 2023 (GLOBE NEWSWIRE) -- Onconova Therapeutics, Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the second of two evaluable participants in an investigator-initiated Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) achieved a complete response of all cancerous skin lesions following 4 treatment cycles and remains on oral rigosertib.

The Company previously announced that the RDEB-associated SCC program’s first evaluable participant achieved a RECIST-defined complete response. Both of the program’s evaluable participants remain on therapy, with the first participant in complete remission with no signs of metastatic disease for more than 18 months. Rigosertib continues to demonstrate a favorable safety profile in this indication that is similar to that displayed in prior studies in other indications.

“Though from only two participants, the emerging data from this Phase 2 program show rigosertib displaying a level of anti-cancer activity in RDEB-associated SCC that far exceeds what we have seen with currently available treatments,” said Professor Andrew P South from Sidney Kimmel Cancer Center, Thomas Jefferson University. “Given its ultra-orphan nature and the extremely high unmet need in RDEB-associated SCC, I believe regulatory discussions to enable rigosertib’s expeditious advancement to potential approval in this indication are warranted. In parallel, we plan to continue advancing this Phase 2 program and to report more detailed data at a future medical meeting.”

RDEB is caused by insufficient expression of type VII collagen protein, which is responsible for anchoring the skin’s inner layer to its outer layer. This leads to extreme skin fragility as well as chronic blistering and wound formation with recurrent infections in RDEB patients, many of whom go on to develop metastatic squamous cell carcinoma driven by over expression of polo like kinase 1 (PLK1). RDEB-associated SCC tumors show a highly aggressive and early metastasizing course that makes them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by ages 45 and 55, respectively^1,2. RDEB-associated SCC can appear in pediatric patients or in young adults. Currently available treatments such as targeted therapies and conventional chemo- and/or radiotherapy have demonstrated limited response rates and poor durability in RDEB-associated SCC^1,3.

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, “We are pleased to be building on this Phase 2 program’s initial single-patient data with a second participant showing complete resolution of all cancerous skin lesions, with the most recent patient notably seeing this result after only four cycles of therapy. We look forward to reviewing our findings with the FDA to determine the most expeditious regulatory path for rigosertib in RDEB-associated SCC. In addition, these findings may have important implications beyond this orphan indication, as they and prior preclinical data demonstrate rigosertib’s activity against the PLK1 protein. Although the company is focusing its resources mainly on the lead narazaciclib program, preclinical studies exploring rigosertib’s activity in other PLK1-dependent tumors are underway and will hopefully open a broader regulatory path for rigosertib.”

Onconova and a program investigator plan to present more detailed data on the first two evaluable participants from the Phase 2 RDEB-associated SCC program at a future medical meeting. In addition, preclinical data on rigosertib’s mechanism of action have been accepted for presentation at the American Association for Cancer Research (AACR) Targeting RAS Conference, which is taking place in Philadelphia, Pennsylvania from March 5 – 8, 2023.

About Rigosertib

Rigosertib is an investigational product candidate with a multi-faceted mechanism of action targeting proteins containing the RAS binding domain, allowing it to modulate the PI3K and PLK-1 pathways, as well as the tumor immune microenvironment. It is currently being evaluated in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer refractory to pembrolizumab, the current standard of care for these patients, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.

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 has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.

Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose escalation and expansion studies. These trials are currently underway in the United States and China. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also planning a combination trial of narazaciclib with estrogen blockade in advanced endometrial cancer, as well as its clinical study in additional indications.

Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies, 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, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.

For more information, please visit www.onconova.com. 

References

1. Mellerio et al. Br J Dermatol. 2016 Jan; 174(1):56-67. doi: 10.1111/bjd.14104.
2. Fine et al. J Am Acad Dermatol. 2009 Feb; 60(2):203-11. doi: 10.1016/j.jaad.2008.09.035.
3. Stratigos et al. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008.

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
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https://www.onconova.com/contact/

Investor Contact:
Bruce Mackle
LifeSci Advisors, LLC
646-889-1200
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