BUB1

NEWTOWN, Pa., March 15, 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 the publication of two abstracts that have been accepted for poster presentations at the American Association for Cancer Research (AACR) Annual Meeting, which is taking place at the Orange County Convention Center in Orlando, Florida from April 14 – 19, 2023. The full texts of the published abstracts can be found on the AACR Annual Meeting website. The corresponding posters will be presented during the “Cyclin-dependent Kinases and Cyclin-dependent Kinase Inhibitors” poster session, which is taking place from 9:00 a.m. – 12:30 p.m. ET on April 19, 2023. Additional information on the posters is shown below. Poster Title: Synergistic activity of the CDK4/6 antagonist narazaciclib (ON123300) with irreversible BTK inhibition in ibrutinib-resistant mantle cell lymphoma Abstract Number: 5974 This poster will describe studies evaluating narazaciclib in preclinical models of mantle cell lymphoma (MCL). Results from these studies demonstrated narazaciclib’s single-agent antitumor activity in MCL cell lines independent of their sensitivity to ibrutinib, which is a Bruton’s tyrosine kinase inhibitor (BTKi) approved by the U.S. Food and Drug Administration (FDA) for the treatment of MCL. When combining narazaciclib with ibrutinib, synergistic increases in antitumor activity against both BTKi-resistant and BTKi-sensitive MCL cell lines were observed. Additional analyses showed that narazaciclib’s antitumor activity against the evaluated MCL cell lines was superior to that of the FDA-approved CDK 4/6 inhibitors palbociclib and ribociclib, and similar to that of the FDA-approved CDK 4/6 inhibitor abemaciclib. Treatment with narazaciclib also led to tumor growth inhibition without detectable toxicity in a chicken embryo chorioallantoic membrane (CAM) xenograft model of MCL. Poster Title: Differential targets engaged by narazaciclib in comparison to the approved CDK4/6 inhibitors contribute to enhanced inhibition of tumor cell growth Abstract Number: 5987 This poster will describe cell-based, in vitro, and bioinformatic analyses comparing narazaciclib and palbociclib. Results from a cell-based murine mammary carcinoma model showed a stronger induction of programmed cell death with narazaciclib compared to palbociclib. In vitro and cell-based analyses revealed multiple targets that are engaged by narazaciclib but not by palbociclib. These targets included BUB1, the overexpression of which is correlated with poor survival in triple negative breast cancer. The results of additional cell-based assays that will be described in the poster suggest that narazaciclib may promote antitumor immunity and show that combining narazaciclib with autophagy inhibitors sensitizes breast cancer cells to cell death. 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 . 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

Medical researchers find an answer to the mystery of why most human embryos die young. New research by a scientist at the Milner Centre for Evolution at the University of Bath suggests that "selfish chromosomes" explain why most human embryos die very early on. The study, published in PLoS, Biology, explaining why fish embryos are fine but sadly humans' embryos often don't survive, has implications for the treatment of infertility. About half of fertilised eggs die very early on, before a mother even knows she is pregnant. Tragically, many of those that survive to become a recognised pregnancy will be spontaneously aborted after a few weeks. Such miscarriages are both remarkably common and highly distressing. Professor Laurence Hurst, Director of the Milner Centre for Evolution, investigated why, despite hundreds of thousands of years of evolution, it's still so comparatively hard for humans to have a baby. The immediate cause of much of these early deaths is that the embryos have the wrong number of chromosomes. Fertilised eggs should have 46 chromosomes, 23 from mum in the eggs, 23 from dad in the sperm. Professor Hurst said: "Very many embryos have the wrong number of chromosomes, often 45 or 47, and nearly all of these die in the womb. Even in cases like Down syndrome with three copies of chromosome 21, about 80% sadly will not make it to term." Why then should gain or loss of one chromosome be so very common when it is also so lethal? There are number of clues that Hurst put together. Firstly, when the embryo has the wrong number of chromosomes it is usually due to mistakes that occur when the eggs are made in the mother, not when the sperm is made in the father. In fact, over 70% of eggs made have the wrong number of chromosomes. Secondly, the mistakes happen in the first of two steps in the manufacture of eggs. This first step, it had been noticed before, is vulnerable to mutations that interfere with the process, such that the mutation can "selfishly" sneak into more than 50% of the eggs, forcing the partner chromosome to be destroyed, a process known as centromeric drive. This is well studied in mice, long suspected in humans and previously suggested to somehow relate to the problem of chromosome loss or gain. What Hurst noticed was that, in mammals, a selfish mutation that tries to do this but fails, resulting in an egg with one too many or one too few chromosomes, can still be evolutionarily better off. In mammals, because the mother continuously feeds the developing fetus in the womb, it is evolutionarily beneficial for embryos developing from faulty eggs to be lost earlier rather than be carried to full term. This means that the surviving offspring do better than the average. Hurst explained: "This first step of making eggs is odd. One chromosome of a pair will go to the egg the other will be destroyed. But if a chromosome 'knows' it is going to be destroyed it has nothing to lose, so to speak. Remarkable recent molecular evidence has found that when some chromosomes detect that they are about to be destroyed during this first step, they change what they do to prevent being destroyed, potentially causing chromosome loss or gain, and the death of the embryo. "What is remarkable, is that if the death of the embryo benefits the other offspring of that mother, as the selfish chromosome will often be in the brothers and sisters that get the extra food, the mutation is better off because it kills embryos." "Fish and amphibians don't have this problem," Hurst commented. "In over 2000 fish embryos not one was found with chromosomal errors from mum." Rates in birds are also very low, about 1/25th the rate in mammals. This, Hurst notes, is as predicted as there is some competition between nestlings after they hatch, but not before. By contrast, chromosome loss or gain is a problem for every mammal that has been looked at. Hurst commented, "It is a downside of feeding our offspring in the womb. If they die early on, the survivors benefit. It leaves us vulnerable to this sort of mutation." Hurst suspects that humans may indeed be especially vulnerable. In mice the death of an embryo gives resources to the survivors in the same brood. This is gives about a 10% increase in survival chance of the others. Humans, however, usually just have one baby at a time and the death of an embryo early on enables a mother to rapidly reproduce again -- she probably never even knew her egg had been fertilised. Preliminary data shows mammals such as cows, with one embryo at a time seem to have especially high embryo death rates owing to chromosomal errors, while those with many embryos in a brood, like mice and pigs, seem to have somewhat lower rates. Hurst's research also suggests that low levels of a protein called Bub1 could cause loss or gain of a chromosome in humans as well as mice. Hurst said: "The levels of Bub1 go down as mothers get older and as the rate of embryonic chromosomal problems goes up. Identifying these suppressor proteins and increasing their level in older mothers could restore fertility. "I would hope too that these insights will be one step to helping those women who experience difficulties getting pregnant, or suffer recurrent miscarriage."