Docetaxel

PRESS RELEASE MASITINIB RECEIVES FDA AND EMA AUTHORIZATION FOR CONFIRMATORY PHASE 3 TRIAL IN METASTATIC CASTRATE-RESISTANT PROSTATE CANCER, WITH BIOMARKER-DRIVEN PATIENT SELECTION TARGETING POPULATION MOST LIKELY TO BENEFIT Paris, July 4, 2025, 8am CET AB Science SA (Euronext - FR0010557264 - AB) today announced that a confirmatory phase 3 trial of masitinib in metastatic castrate resistant prostate cancer (study AB22007) has been authorized by FDA and EMA (harmonized protocol approved through step 1 of Clinical Trials Information System), with a biomarker that targets patients with less advanced metastatic disease. Professor Olivier Hermine, MD, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France said, “The authorization of our confirmatory Phase 3 study by both the FDA and EMA represents a critical milestone for masitinib in metastatic castrate-resistant prostate cancer. With a validated biomarker guiding patient selection, this trial has the potential to establish the first targeted combination with docetaxel in nearly two decades for mCRPC.” Design of phase 3 study Study AB22007 is a prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to confirm the efficacy and safety of docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) plus masitinib 6.0 mg/kg/d, versus docetaxel plus placebo in metastatic castrate resistant prostate cancer (mCRPC). The study will enroll 600 patients (randomization 1:1) with confirmed mCRPC eligible to docetaxel and with a biomarker (as measured by baseline alkaline phosphatase level) indicative of less advanced metastatic disease. The study’s primary endpoint will be radiographic progression free survival (rPFS), supported by overall survival as the first secondary endpoint. Masitinib is positioned in metastatic castrate resistant prostate cancer eligible to docetaxel, a high unmet medical need Masitinib is positioned in combination with docetaxel as a treatment of mCRPC patients who are eligible to docetaxel; that is to say, it is administered directly following resistance or relapse after the metastatic hormone-sensitive prostate cancer (mHSPC) treatments. While there are numerous treatments in the mHSPC treatment space, there is currently no drug registered for use in combination with standard of care treatment docetaxel in patients who have relapsed on hormone treatments, i.e., patients with mCRPC, despite docetaxel having been approved almost 20 years ago. Although localized disease is associated with high survival rates, metastatic prostate cancer still represents an unmet medical need with a 5-years survival rate of about 30% [1]. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop CRPC within 5 years, and at least 84% of these will have metastases at the time of CRPC diagnosis [2]. Practically all patients with metastatic disease become resistant to androgen-deprivation therapy. Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year [2]. The estimated prevalence of people living with prostate cancer is 113 per 100,000 [3], with approximately 15% of the patients having mCRPC eligible to chemotherapy [4]. As such, the population with mCRPC eligible to chemotherapy is around 75,000 in the EU and 50,000 in the USA. Results from study AB12003 demonstrated that the biomarker Alkaline Phosphatase predicts response of masitinib in mCRPC. The combination of masitinib plus docetaxel may provide a new first-line treatment option for mCRPC patients with low metastatic involvement Primary analysis: AB12003 was a prospective, placebo controlled, double blind, randomized, phase 3 trial, evaluating masitinib (6.0 mg/kg/d) in combination with docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) as a first-line treatment of mCRPC. Eligible patients were chemo-naïve with confirmed mCRPC, who had progressed on previous abiraterone treatment or were indicated for docetaxel treatment, and had a ECOG ≤1. Primary analysis was performed on a pre-specified targeted subgroup, defined as patients with baseline alkaline phosphatase levels (ALP) ≤250 IU/L, and on the overall population. Primary endpoint was progression free survival (PFS) (PCWG2 definition). The study was successful if improvement in median PFS relative to control reached a 3.9% level of significance for the target subgroup (alpha split with fallback procedure to conserve overall type-I error at 5% for the overall study cohort). Primary analysis was based on 450 patients in the targeted subgroup (ALP ≤ 250 IU/L). There was a total of 712 patients in the overall study cohort. Masitinib (6.0 mg/kg/day) plus docetaxel confers a significant PFS benefit in mCRPC patients with ALP ≤ 250 IU/L. Hazard ratio of 0.79 [0.64;0.97] (p=0.0087), corresponding to a 21% reduction in risk of progression relative to control. Assessment of PFS rates was convergent with this primary outcome; 12, 18, and 24-month PFS rates showed significant improvement in favor of masitinib plus docetaxel relative to control: 1.6-fold (p=0.0035), 1.9-fold (p=0.0001) and 1.9-fold (p=0.0028), respectively. ALP as a biomarker: Importantly, a progressively greater masitinib treatment effect was observed for lower baseline ALP levels (less advanced metastatic disease), with a significant 47% reduced risk of progression in patients with ALP≤100 IU/L (hazard ratio=0.53, p=0.002). The efficacy and response of masitinib was in fact correlated to the level of ALP. The use of biomarker ALP for the confirmatory phase 3 study has been validated by FDA and EMA. The establishment of a biomarker predictive of the response to masitinib is a potentially important discovery. ALP measures the involvement in the bones and in the liver of metastasis. When used sufficiently early, masitinib in combination with docetaxel was able to slow down the progression of the metastatic cancer even resistant to hormone treatments. The masitinib plus docetaxel safety profile was acceptable with respect to control; consistent with the known masitinib profile and no new safety signals observed. Historically, there has been a high failure rate of trials studying combinations of docetaxel and new targeted agents, with study AB12003 being a rare example of a phase 3 clinical trial that showed improvement in progression-free survival (PFS) for masitinib in combination with docetaxel. Patent protection until 2042 Based on the results from AB12003 study, AB Science filed a patent application relating to methods of treating mCRPC (i.e. a secondary medical use patent) with its lead compound masitinib. The European Patent Office has granted this patent (EP4175639). It provides protection until 2042 for masitinib and related compounds for treatment of mCRPC in the patient subpopulation with low metastatic involvement (as measured by baseline alkaline phosphatase levels), which is the patient population in the approved phase 3 study of masitinib in mCRPC. Counterpart patent applications have also been filed in other major international markets, including the United States. References : [1] Cancer stat facts: prostate cancer. National Cancer Institute/ Surveillance, Epidemiology, and End Results Program. Accessed September 10, 2021. https://seer.cancer.gov/statfacts/html/prost.html[2] Crawford ED, Petrylak D, Sartor O. Navigating the evolving therapeutic landscape in advanced prostate cancer. Urol Oncol. 2017 May;35S:S1-S13. doi: 10.1016/j.urolonc.2017.01.020. [3] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. [4] Scher 2015 – PLoSONE - Symptomatic mCRPC that has not been treated with or not progressed on chemotherapy About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment Authorisation Ph3 mRCPC VENG VF

iStock, Grandbrothers The FDA delivered two notable approvals for RSV immunization, UroGen overcame a negative advisory committee vote to secure an approval in bladder cancer, and more key regulatory nods from the past month. Moderna Expands mRNA RSV Shot—But CDC Recommendation Still Uncertain The FDA on June 13 signed off on the broader use of Moderna ’s mRNA vaccine mResvia for respiratory syncytial virus, opening up inoculation for at-risk adults aged 18 through 59 years. For analysts at William Blair, however, approval is just the first regulatory hoop the vaccine will have to go through. “In our view, investor focus will likely shift to the CDC’s Advisory Committee on Immunization Practices (ACIP)’s next meeting,” they wrote in a note at the time, noting that the shot—and the broader vaccine market—could be battered by more headwinds still if the ACIP recommends “restrictive” guidelines. Currently, the CDC recommends a narrower use of RSV shots, where blanket vaccination is only recommended in adults 75 and older. In those 60 through 74 years of age, the CDC endorses immunization for those who are at risk of severe RSV. Earlier this month, Health and Human Services Secretary Robert F. Kennedy Jr. purged the ACIP of all 17 members in a move he claimed was “necessary to reestablish public confidence in vaccine science.” The next day, he named eight new panelists , many of whom have a documented history of vaccine skepticism and two who have previously spoken out specifically against the mRNA technology that underpins Moderna’s mResvia. The new committee members met on June 25 and 26 but did not vote on mResvia. The RSV vaccine was first approved in May 2024 for all adults 60 and above. Merck’s RSV Antibody Clears FDA Bar to Challenge Sanofi, AstraZeneca The FDA approved the use of Merck ’s anti-RSV antibody clesrovimab in infants on June 10. Merck will market the therapy under the brand name Enflonsia. The approval covers the use of Enflonsia to prevent RSV-related lower respiratory tract disease in newborns and infants who are entering their first season of circulating respiratory diseases. According to Merck, Enflonsia provides “rapid and durable” RSV protection persisting for five months, the length of a typical RSV season. Enflonsia is dosed at 105 mg regardless of patient weight. Enflonsia’s approval was backed by data from the Phase IIb/III CLEVER study, which found that in preterm and full-term infants up to 1 year, the antibody reduced RSV-associated medically attended lower respiratory infections by 60.5% versus placebo. Enflonsia also cut RSV hospitalizations by 84.3% as compared with placebo. Additional supporting data came from the Phase III SMART trial, which compared Enflonsia against Sobi’s Synagis, which is also a monoclonal antibody designed to prevent RSV. Interim results announced in October 2024 showed that Enflonsia could match Synagis’ safety and efficacy profiles through five months of observation. With Enflonsia, Merck will now go up against Sanofi and AstraZeneca, which own the immunizing antibody Beyfortus. Approved in July 2023 , Beyfortus has since become a top-performing asset for the companies, hitting blockbuster status in its first full commercial year with €1.7 billion (approximately $1.9 billion) in sales. On June 26, the CDC’s Advisory Committee for Immunization Practices gave Merck another win, voting to recommend Enflonsia to cover babies less than eight months who are not protected by maternal antibodies. Bayer Broadens Use of Nubeqa in Prostate Cancer On June 4, the FDA allowed the use of Bayer’s oral androgen receptor blocker Nubeqa for patients with metastatic castration-sensitive prostate cancer (mCSPC), regardless of concurrent chemotherapy. Before this approval, Nubeqa could only be used in the castration-sensitive patient population when it was combined with docetaxel, according to its label . The drug, taken twice daily, was originally approved in July 2019 for men whose cancers had yet to metastasize and were resistant to castration before winning an expansion in August 2022 for metastatic hormone-sensitive prostate cancer. Nubeqa’s latest approval was backed by data from the Phase III ARANOTE trial, a randomized, double-blinded and placebo-controlled trial with nearly 670 participants. Patients were given 600-mg Nubeqa on top of androgen deprivation therapy (ADT). Results, published in September 2024, showed that the Nubeqa regimen significantly improved radiographic progression-free survival, resulting in a 46% drop in the risk of disease progression or death as compared with placebo plus ADT. This efficacy was maintained in patients with high-volume mCSPC, who saw a 40% risk reduction, and was improved in those with low-volume disease, in which the risk was reduced by 70%. Nubeqa brought in €1.523 billion, or around $1.75 billion for Bayer in 2024. UroGen Surmounts AdComm Apprehension to Win Bladder Cancer Approval Despite failing to secure the backing of an external panel of advisors, UroGen won the FDA’s approval on June 13 for its intravesical drug mitomycin for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer. UroGen will market the drug under the brand name Zusduri. Zusduri is the first FDA-approved therapy for this indication and is meant for use in adults with recurrent disease, according to UroGen’s announcement. The drug, which is administered via a catheter directly into the bladder in an out-patient procedure, will be available “on or around” July 1. The Phase III ENVISION study, which is still ongoing, supported the regulatory decision with a 79.6% complete response rate at three months. The single-arm pivotal trial documented an 80.6% duration of response at 18 months, according to the latest data, released in April. Zusduri’s approval comes as a bit of a surprise, given that the FDA’s Oncologic Drugs Advisory Committee last month recommended against it—though only narrowly so. With a 5–4 split, the independent panel of experts pointed to several issues with UroGen’s application package, including the lack of a completely randomized study and the short follow-up in ENVISION. UroGen has promised to see the ENVISION trial through to completion “to further characterize the clinical benefit of Zusduri” and will provide the FDA with yearly updates regarding the drug’s duration of response for all treated patients with ongoing complete responses. Nuvation Wins First Commercial Approval With Lung Cancer Drug Ibtrozi On June 12, the FDA approved Nuvation Bio’s oral ROS1 blocker taletrectinib, which will be sold as Ibtrozi. The approval covers the drug’s use in non-small cell lung cancer. Ibtrozi is Nuvation’s first commercial product. Ibtrozi’s approval was backed by data from the Phase II TRUST-I and TRUST-II trials, which together account for “one of the largest global clinical trial programs in ROS1+ NSCLC [non-small cell lung cancer] to date,” according to Nuvation’s Wednesday release. Over 300 patients were enrolled across both trials. Results from TRUST-I showed a confirmed overall response rate (cORR) of 90% in patients with no prior exposure to tyrosine kinase inhibitor (TKI). TRUST-II confirmed these findings with an 85% cORR. Because of the single-arm nature of the TRUST program, progression-free survival isn’t included in Ibtrozi’s label. The TRUST studies also specifically looked at the benefits of Ibtrozi in patients with brain metastases—which Nuvation on Wednesday called “among the most common and devastating complications” in ROS1-positive NSCLC—and found high rates of treatment response. In patients with measurable brain metastasis at baseline, Ibtrozi demonstrated an intracranial response of 73% in the TKI-naïve subgroup and 63% in those who had previously been exposed to TKI treatments. Analysts at Jefferies at the time said that while Ibtrozi’s approval was positive for Nuvation, “patience may be needed by investors with several quarters to execute and demonstrate strong launch momentum.” BeOne Secures Approval for Twice-Daily Brukinsa Schedule BeOne—formerly known as BeiGene—received FDA approval on June 12 for a new tablet formulation of the tyrosine kinase inhibitor Brukinsa to be taken twice-daily. This label expansion covers all approved indications of Brukinsa , including mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma and Waldenström’s macroglobulinemia. “The recommended dose of Brukinsa remains at 320 mg daily,” BeOne noted in a news release announcing the approval. The new formulation delivers a 160-mg dose of the drug in each tablet, giving patients the option to “take two tablets daily rather than four of the current 80 mg capsules.” With the tablet nod, Brukinsa has become “the only BTK inhibitor to offer the flexibility of once or twice daily dosing,” with some leeway to adjust the schedule based on patient needs, the company said. Supporting the FDA’s decision are bioequivalence data generated from two Phase I crossover trials of healthy adults, which showed that the tablets are as safe and as effective as the capsules. Matt Shaulis, North America general manager of BeOne, said the tablet approval makes “treatment simpler and more convenient” for patients. BeOne expects to completely replace the 80-mg capsules with the 160-mg tablets by October 2025. AbbVie’s Mavyret Becomes First Antiviral for Acute Hepatitis C Also notching a notable regulatory nod this month is AbbVie, which on June 11 won the FDA’s first approval for an acute hepatitis C virus (HCV) drug. The approval of Mavyret, an oral antiviral, was supported by data from a Phase III single-arm prospective trial that enrolled nearly 300 treatment-naïve adults who had acute infection. Mavyret was given once-daily for eight weeks. Results, which are reflected in the drug’s label , show that Mayret elicited a sustained virological response of 96% 12 weeks post-treatment. None of the study participants experienced virologic failure. According to AbbVie, the label expansion allows doctors to treat patients “immediately at the time of diagnosis.” While hepatitis C infection is a curable disease, it often goes undiagnosed, as per the pharma’s news release announcing the approval. “If left untreated, people with acute HCV could progress to chronic disease, including liver-related complications” like cancer and cirrhosis. Mavyret is a direct-acting antiviral tablet that delivers a combination of drugs: glecaprevir , a protease inhibitor that disrupts the replication of the virus’ genetic material, and pibrentasvir , which blocks viral RNA replication while also preventing the formation of the viral particle itself. First approved in August 2017 , Mavyret is the first-ever product to be indicated for all types of HCV. Mavyret brought in roughly $1.3 billion in 2024 , a nearly 7% decline year-on-year. AstraZeneca, Daiichi Sankyo Earn Accelerated Approval for Datroway in NSCLC Datroway, an antibody-drug conjugate jointly developed and commercialized by AstraZeneca and Daiichi Sankyo, can now be used for patients with advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations. The FDA granted the biologic accelerated approval in this indication on June 24. The regulatory decision was backed by data from a subgroup analysis of the Phase II TROPION-Lung05 study, also supported by findings from the Phase III TROPION-Lung01 trial. Findings from these studies showed that Datroway elicits a confirmed objective response rate of 45% in patients who had undergone prior lines of treatment. This includes 4.4% complete responses and 40% partial responses. Median duration of response was 6.4 months. As per the terms of the FDA’s accelerated pathway, AstraZeneca and Daiichi Sankyo will need to validate Datroway’s clinical benefit in future confirmatory trials to maintain this approval. Datroway won its first U.S. approval in January 2025, allowing its use in patients with unresectable or HR-positive, HER2-negative breast cancer who had been previously treated. The therapy works by binding to TROP2, a surface protein found on many tumor cells, and delivering its topoisomerase I inhibitor payload, according to its label . This mechanism damages DNA in cancer cells, ultimately leading to their death.