Venetoclax

Safety Review Committee endorses escalation to 160 mg TUS dosing Cohorts with 120 mg, 80 mg, 40 mg TUS dosing completed with no dose-limiting toxicities Excellent safety and complete remissions (CRs) in some of the most difficult-to-treat AML populations No dose reductions required to the standard-of-care VEN/AZA with TUS dose cohorts TUS+VEN+AZA triplet continues to achieve CRs and minimal residual disease (MRD)-negativity with favorable safety in newly diagnosed AML patients Aptose receives third advance under the Loan Agreement with Hanmi Pharmaceutical SAN DIEGO and TORONTO, Aug. 06, 2025 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (OTC: APTOF, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, today announced that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of TUS in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has approved escalating from 120 mg TUS dose to 160 mg TUS dose based on its favorable review of safety and efficacy data from patients in the first three cohorts (40 mg, 80 mg, and 120 mg TUS dose levels) of the trial. Enrollment is open for dosing subjects at the 160 mg TUS dose level. Aptose also announced that it has received an additional advance of US$1.1M from Hanmi Pharmaceutical Co. Ltd. (“Hanmi”), as part of a US$8.5M loan facility agreement with Hanmi (the “Loan Agreement”) announced prior on June 20, 2025 (press release here). To date, Aptose has received an aggregate of US$5.6M under the Loan Agreement. The TUS+VEN+AZA triplet is being developed as a one-of-a-kind, safe and mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. Aptose reports that at the 120 mg TUS dose level, as with the prior reported 40 mg and 80 mg dose cohorts, no significant safety concerns or dose limiting toxicities (DLTs) have been reported in the TUSCANY trial, including no prolonged myelosuppression in Cycle 1 of subjects in remission. All patients treated in the 120 mg dose cohort remain on study while enrollment is open for the 160 mg dose cohort. Aptose previously reported that the first two dose cohorts have demonstrated safety, CRs, and minimal residual disease (MRD) negativity across patients with diverse mutations in an oral presentation at the European Hematology Association Congress (EHA 2025) in June (press release here). “Data from three cohorts, with a 40, 80 or 120 mg dose of TUS in the TUS+VEN+AZA triplet, continue to build a strong case for TUS as a therapeutic option for some of the most difficult to treat AML populations,” said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. “In particular, patients with adverse biallelic TP53 or FLT3-ITD mutations, and those without FLT3 mutations, were able to safely achieve complete remissions with MRD negativity. After review of the most recent safety and efficacy data, our CSRC recommended that we continue to escalate dosing.” TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study The tuspetinib-based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Indeed, responses were also noted in R/R AML patients with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes. The TUSCANY triplet Phase 1/2 study, being conducted at 10 leading U.S. clinical sites by elite clinical investigators, is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS is being administered in 28-day cycles. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by late 2025. Data will be released as it becomes available. More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here). About Aptose Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company’s lead clinical-stage, oral kinase inhibitor tuspetinib (TUS) has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit www.aptose.com. Forward Looking Statements This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential and safety profile of tuspetinib (including the triplet therapy) and its clinical development, the anticipated enrollment rate in the TUSCANY trial and the timing thereof, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein. For further information, please contact: Aptose Biosciences Inc. Susan Pietropaolo Corporate Communications & Investor Relations 201-923-2049 spietropaolo@aptose.com Released August 6, 2025

iStock, SergeyNivens From tariffs to drug pricing to the FDA, biopharma CEOs find themselves pulled into policy discussions on this year’s second quarter earnings calls. President Donald Trump has been re-raising many issues that pharmaceutical CEOs were happy to have left behind in the first quarter as earnings reporting season continues. Across the pharma landscape, CEOs are doing their best to project the idea that there is nothing to worry about as the pressure from Washington grows. Last week, the president sent a round of letters to a batch of pharma CEOs , asking them to get to work implementing Most Favored Nation drug pricing. Tariffs of 15% were placed on Europe , which could have implications on the industry, while the president threatened tariffs as high as 250% on imported pharmaceutical products specifically—although not any time soon. Then there was the high-profile resignation of an FDA official , which some reports say can be traced all the way back to the White House. Inevitably, these issues were raised as companies reported second quarter earnings over the past week. On the CEO Letters Pfizer CEO Albert Bourla couldn’t dodge the questions about those letters . Analyst after analyst tried to chip away at Bourla’s well-trained responses, seeking any inkling of how the high-pro leader is faring in discussions with the president. “I’m happy the way that they listen to us, in the way that we are trying collectively to find solutions that, from one hand, could make medicines affordable in the U.S., on the other hand, will make our industry even more competitive compared to China,” Bourla said. Bourla was one of very few pharma CEOs who was personally named by the president in the letters. While most were the same, Bourla’s had his full name scratched out and his first name written, apparently in Trump’s handwriting. This signaled to analysts that he had a close connection with the president, which traces back to Pfizer’s Operation Warp Speed effort to develop the COVID-19 vaccine during the pandemic. Bourla confirmed that he had spoken directly to Trump to discuss the matters in the letter. But who is Trump’s closest pharma pal? If you ask Regeneron CEO Leonard Schleifer, it isn’t him. Queried about the president’s personalization of the letters, Schleifer said he hasn’t been to Washington lately to discuss drug pricing or other issues. The Regeneron chief executive was asked if he, or any of his peers at Eli Lilly or Pfizer, might have some sway over policy these days. “I think the president probably knows Regeneron and my first name, given that it was Regeneron’s cocktail for COVID that may have saved his life,” Schleifer said. “Beyond that, I don’t have any great insights to the policies.” His counterparts at Lilly and Pfizer have been more active in attempting to influence policy at this time, Schleifer added. Bourla confirmed as much in his earnings comments days later, while Lilly has yet to report. On the specifics of the drug pricing plan, Schleifer said he agrees with the president that European nations are not paying their fair share for drugs. He said to change this “complicated” reality, policy and trade need to be adjusted, because companies can’t do it alone. “American consumers should not be paying for all of the innovation. The solution is simply not to lower prices in the U.S. without some equilibrating in Europe because then there’ll be no innovation,” Schleifer said. AstraZeneca’s Pascal Soriot agreed, saying that his company has been lobbying the Trump administration and offering some policy proposals that could achieve what the president is trying to do. But he also noted that access to new medications needs to be considered as the pricing discussion continues. “In many countries in Europe, patients wait for years to get access to medicines that could save their lives,” Soriot said on AstraZeneca’s earnings call last week. AbbVie’s Robert Michael, meanwhile, credited the president’s One Big Beautiful Bill Act with expanding the orphan drug exemption to the benefit of cancer therapy Venclexta. Michael said the company had assumed that drug would be subject to price negotiations soon under the Inflation Reduction Act, but with the change in the newer bill, Venclexta is not expected to be subject. “That’s an example of a good policy change where innovation is being rewarded and not penalized,” Michael said during AbbVie’s call last week. On FDA Disruption If anyone has insight into the inner workings of the FDA drug approval machine right now, it’s Moderna’s regulatory team. On a Friday earnings call , President Stephen Hoge said the company was pleased with the three approvals they received in the past quarter. “I will note that they happened on time, and that was through the incredibly diligent work of the folks at FDA to conduct those reviews in a rigorous way, and we continue to feel that those productive dialogues are going on now even on our existing files for the seasonal update,” he said. Hoge pledged to work closely with the FDA to transparently respond to any questions, even after the much-publicized changes within the Center for Biologics Evaluation and Research (CBER), and the CDC, including at the agency’s Advisory Committee on Immunization Practices . When any questions are received by the agencies to help inform public health, Hoge said that Moderna will make sure to provide that information. On Tariffs Many CEOs—of Vertex Pharmaceuticals, Moderna, Takeda, Regeneron and many more—brushed off the threat of tariffs to the pharmaceutical industry, especially for near term impacts this year. There’s still too much uncertainty on what exactly will be taxed, so the executives weren’t willing to speculate. But AbbVie’s Michael went a bit further, noting that one of his company’s largest products, Skyrizi, is made in the U.S. for the domestic market. Longer term, AbbVie plans to add even more U.S. manufacturing capacity, as part of a $10 billion capital investment announced on last quarter’s earnings call. This would include four sites for active pharmaceutical ingredients, peptide dug products and devices. Otherwise, Michael, like his fellow CEOs, will wait for the Section 232 process to complete before commenting further on how tariffs will impact AbbVie. Merck’s Robert Davis took a shot at providing some clarity to analysts about what a 15% tariff would be like for the Keytruda-maker. While he wouldn’t give specific guidance, he said that if 15% tariffs were implemented today, the impact would be minimal as Merck has conducted inventory management and moved manufacturing to the U.S. already. Similarly, AstraZeneca CFO Aradhana Sarin explained that since the first quarter, the company has been managing the potential tariff impact through inventory. AstraZeneca is also starting tech transfers for some products that are not currently manufactured in the U.S. Still, Sarin expects little impact. For its part, Pfizer included potential impacts of Most Favored Nation drug price changes and tariffs in its guidance this quarter—specifically factoring in the currently implemented tariffs on Canada, China and Mexico—but declined to provide actual numbers, to the chagrin of analysts on the call. Bourla, like his fellow pharma execs, said that Pfizer will await the conclusion of the Section 232 investigation before elaborating on tariffs’ impact to the company, though he did note that Pfizer is talking with trade officials about tariffs.