Gilteritinib Fumarate

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, February 27th, 2025 – Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, today reported financial results for the fourth quarter ended December 31, 2024 and provided a corporate update on recent developments. “The publication of the final dataset from the REIMAGINE study on aggression in autism, ADHD, and borderline personality disorder (BPD) in a prestigious specialized journal has allowed the scientific and investment community to better contextualize and appreciate the relevance of vafidemstat’s results in treating aggression in our Phase IIb PORTICO trial,” said Dr Carlos Buesa, Oryzon’s Chief Executive Officer. “As we mentioned in the previous Note, we received the official minutes from our End-of-Phase II meeting with the FDA, confirming that we can proceed to a Phase III. The FDA also indicated that agitation/aggression in BPD may be an acceptable indication, and agreed that we may use the same aggression scale that showed the strongest signal in Phase II. With this positive feedback, we are continuing the preparations to submit the full Phase III protocol to the FDA within the next 1–2 months. We have also continued patient recruitment in our ongoing EVOLUTION trial in schizophrenia in Spain.” Dr Buesa continued, “In oncology, we continue our efforts to further evaluate iadademstat in first line unfit AML patients through two ongoing trials in combination with azacitidine and venetoclax - one under our CRADA agreement with the NCI and another as an investigator-initiated study (IIS) at Oregon Health & Science University (OHSU). The OHSU-led trial has already enrolled the first two cohorts, representing a significant progress in our oncology program and potentially expanding our clinical development options, if results are positive. Additionally, a new IIS sponsored by the Medical College Wisconsin in combination with azacitidine in patients with myelodysplastic syndrome has started to enroll patients. In June, we presented promising initial data from our FRIDA Phase Ib trial at the EHA Conference, showing that iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML was safe and showed strong antileukemic activity, with encouraging response rates and a faster time to response compared to historical data on gilteritinib alone. With the third cohort enrolled, and as the data matures, we plan to present additional results at ASH in December.” Dr Buesa added, “As the company transitions into a Phase III organization for the first time, we are restructuring our Board of Directors to be more U.S.-centric. The Board will now have three Directors based in the Bay Area, with extensive Nasdaq and industy experience. This will enhance our outreach and strengthen our dialogue with corporate partners and Tier-1 investors. While maintaining strict budgetary discipline and leveraging our Convertible Notes program, we also anticipate additional financial support from the recently approved IPCEI grant from the EU. This funding will be instrumental in advancing our R&D efforts in personalized medicine for CNS and oncology. Meanwhile, the company continues discussions with corporate partners and actively evaluates additional financing opportunities.” Fourth Quarter and Recent Highlights Vafidemstat in large multifactorial CNS indications: Following positive feedback from the end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), Oryzon is advancing in the preparations for Phase III, including the preparation of a full protocol for the PORTICO-2 Phase III trial to submit to the FDA for study approval. The trial will use STAXI-2 Trait anger as a primary efficacy endpoint measure. Secondary endpoints will include both patient-rated and clinician-rated scales to assess agitation/aggression and overall BPD improvement. The estimated total sample size for PORTICO-2 is 350 patients (randomized 1:1 vafidemstat or control), with a trial duration of 18 weeks in total. Subject to FDA’s review of the final data, the PORTICO-2 Phase III study has the potential to be one of the two registrational trials required by the FDA. The company expects to obtain FDA’s approval for PORTICO-2 in 1H2025. The final results of the Phase IIa REIMAGINE study, which evaluated the safety and efficacy of vafidemstat on aggression in adult patients with BPD, attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD), have been published online in the clinical psychiatry journal Psychiatry and Clinical Neurosciences. As reported in the publication, the study showed that vafidemstat was safe and well-tolerated and elicited significant and consistent reduction in agitation/aggression in patients with BPD, ADHD, and ASD. REIMAGINE was a proof-of-concept trial that laid the foundation for the subsequent PORTICO Phase IIb clinical trial in BPD. A summary of the final data from REIMAGINE had been previously released at the 2020 European Psychiatry Association (EPA) annual meeting. Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter, with an additional “Decision to grant” communication in its patent family titled “Methods of treating borderline personality disorder”, now in Russia. Oryzon has also received “Decision to grant” communications for corresponding patent applications in Europe and Mexico, and a patent has already been granted in Japan, with patent applications pending in other relevant markets. These patents will not expire until at least 2040, excluding potential patent term extensions that may provide additional protection. Additionally, Oryzon recently secured granted patents in Europe, Australia, Korea, Malaysia, Philippines, and Russia under another patent family that covers the use of vafidemstat for the treatment of aggression and social withdrawal, with patent applications pending in additional countries. These patents will not expire until at least 2038, excluding any potential patent term extension that may provide additional years of protection. The EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia continues to enroll participants. This study aims to assess the efficacy of vafidemstat, with a primary focus on improving negative symptoms. As secondary endpoints the trial will explore vafidemstat’s efficacy in improving cognitive impairment and positive symptoms in schizophrenia. The project is partially funded by the Spanish Ministry of Science and Innovation and is being conducted at multiple hospitals across Spain. Vafidemstat in monogenic CNS indications: We continue to evaluate the feasibility of a new precision medicine trial in Kabuki Syndrome. The company will decide on a possible submission of an IND for HOPE to the FDA in 2025. Iadademstat in oncology: FRIDA, an open-label, multicenter Phase Ib clinical trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), continues to enroll patients. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity. The primary objectives of the trial are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination, while the secondary objectives focus on assessing treatment efficacy. The study is being conducted in the U.S. and will accrue up to approximately 45 patients. If successful, Oryzon and the FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much-in-need AML population. The first patient has been dosed in the Phase I dose-finding clinical trial of iadademstat in combination with venetoclax and azacitidine in newly diagnosed acute myeloid leukemia (AML), sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI. This Phase I dose-finding study is now actively enrolling patients. Additionally, the Investigator-initiated study (IIS) sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute also evaluating the combination of iadademstat with venetoclax and azacitidine in first line AML continues to enroll patients. The first patient has been dosed in the IIS Phase I dose-finding trial of iadademstat in combination with azacitidine inmyelodysplastic syndrome (MDS), led by the Medical College of Wisconsin (MCW). This Phase I dose-finding study is now actively enrolling patients. The collaborative Phase II basket trial of iadademstat in combination with paclitaxel in platinum R/R small cell lung cancer (SCLC) and extrapulmonary high-grade neuroendocrine tumors (NET trial) continues to enroll patients. This trial is being conducted in the U.S. under a collaborative clinical research agreement with the Fox Chase Cancer Center. The Phase I/II trial with iadademstat plus immune checkpoint inhibitors in first line SCLC patients with extensive disease under the CRADA agreement with the NCI, already approved by the FDA, is ready to start enrolling patients. The trial is entitled “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer” and will be conducted and sponsored by the NCI, with Dr. Charles Rudin from the Memorial Sloan Kettering Cancer Center (MSKCC) as the main PI for the trial, and Dr. Noura Choudhury from University of Chicago as co-PI. A number of prestigious cancer centers in the US, including the MSKCC, the JHU Sidney Kimmel Comprehensive Cancer Center and many others will participate. The trial plans to enroll 45-50 patients and is expected to start enrolling patients in 1Q2025. Earlier stage programs: ORY-4001, Oryzon’s highly selective histone deacetylase 6 (HDAC6) inhibitor nominated as a clinical candidate for the treatment of certain neurological diseases such as Charcot-Marie-Tooth disease (CMT), Amyotrophic Lateral Sclerosis (ALS) and others, continues to progress through IND enabling studies to prepare it for clinical studies. Financial Update: Fourth Quarter 2024 Financial Results Research and development (R&D) expenses were $2.1 million and $8.7 million for the quarter and twelve months ended December 31, 2024, compared to $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023. As a result of the completion of the PORTICO clinical trial, the company saves $7.9M with respect to the twelve months ended December 31, 2023. General and administrative expenses were $0.9 and $3.7 million for the quarter and twelve months ended December 31, 2024, compared to $1.2 and $4.2 million for the quarter and twelve months ended December 31, 2023. Net losses were $1.0 and $4.6 million for the quarter and twelve months ended December 31, 2024, compared to $1.4 and 5.0 million for the quarter and twelve months ended December 31, 2023. The result is as expected, given the biotechnology business model where companies in the development phase typically have a long-term maturation period for products and do not have recurrent income. Negative net result was $3.8 million (–$0.06 per share) for the twelve months ended December 31, 2024, compared to a negative net result of $3.7 million (–$0.06 per share) for the twelve months ended December 31, 2023. Cash, cash equivalents, and marketable securities totaled $5.8 million as of December 31, 2024.

药械追踪 No.1 / AskBio帕金森病基因疗法获FDA RMAT认定 2025年2月19日，拜耳全资拥有并独立运营的基因治疗公司AskBio宣布，其针对帕金森病（PD）的在研基因疗法AB-1005已获得美国食品药品监督管理局（FDA）授予再生医学先进疗法（RMAT）认定。 AB-1005是一种基于2型腺相关病毒载体（AAV2）的基因疗法，内含人神经胶质细胞系衍生的神经营养因子（GDNF）转基因，注射后可在大脑局部区域稳定连续地表达GDNF。开放标签、非对照研究的Ib期临床试验表明，AB-1005耐受性良好，未出现与治疗相关的严重不良事件。接受AB-1005治疗的中度帕金森病队列在36个月时，在多个帕金森病相关临床量表上显示出改善或稳定的趋势，包括运动障碍协会-统一帕金森病评定量表（MDS-UPDRS）和患者自我报告的帕金森病运动日记，以及帕金森病药物（左旋多巴等效日剂量[LEDD]）用量减少的趋势。轻度帕金森病队列的大多数受试者临床表现整体稳定，MDS-UPDRS、自我报告的帕金森病运动日记或LEDD几乎没有变化。目前，AB-1005的II期REGENERATE-PD研究已在美国启动患者入组。 ->点击文末阅读原文，解锁完整双语新闻 No.2 / 安斯泰来吉瑞替尼在华获常规批准上市 2025 年2月18日，安斯泰来宣布，国家药监局于2025年1月26日正式授予适加坦（吉瑞替尼）常规批准。本次常规批准是基于COMMODORE的研究结果。COMMODORE是一项在FLT3突变型复发性或难治性 AML患者中比较吉瑞替尼与补救性化疗的开放性、多中心、随机、Ⅲ期研究。 适加坦是类FMS样酪氨酸激酶3（FLT3）抑制剂，用于治疗采用经充分验证的检测方法检测到携带FMS样酪氨酸激酶3（FLT3）突变的复发性或难治性急性髓系白血病（AML）成人患者。该药是安斯泰来与 Kotobuki 制药有限公司通过研究合作发现的药物，安斯泰来拥有吉瑞替尼的全球开发、制造和商业化推广的独占权利。此前，吉瑞替尼于2020年7月在华获优先审评资格，并在2020年11月被列入第三批临床急需境外新药名单，2021年1月30日获国家药监局附条件批准上市。 ->点击文末阅读原文，解锁完整双语新闻 企业动态 No.1 / 被指低估中国市场法律风险，AZ在美面临集体诉讼 近日，美国多家律师事务所对阿斯利康（纳斯达克代码：AZN）提起集体诉讼，指控其最近在中国市场的不当行为，这些行为的后果包括前中国区总裁王磊被捕。英国《金融时报》特别指出，阿斯利康最近公布的2024年财报显示，2024年12月，有人代表阿斯利康股份持有人向美国加利福尼亚中区联邦地区法院提起了证券集体诉讼。 该诉讼指控阿斯利康在其早些时候的财务报告中低估了中国市场的法律风险，做出了“与该公司中国业务相关的重大虚假和误导性陈述”。而王磊的被捕正暴露了这些风险，阿斯利康表示，中国有关部门正在对公司现任和前任雇员进行一些个人调查，调查包括医疗保险欺诈、非法药物进口和个人信息泄露的指控。 值得注意的是，尽管处于调查风波中，阿斯利康在中国的表现迄今为止几乎没有受到影响。该公司财报显示，2024年第四季度中国市场收入下降了3%，原因是年终医院预算变化和呼吸系统药物市场需求不足。此外，中国有关部门调查的消息被公布后，阿斯利康的股价在2024年底下跌了近20%，但此后已大致恢复至正常水平。 ->点击文末阅读原文，解锁完整双语新闻 行业政策 No.1 / 国务院发布2025年稳外资行动方案，深化医药领域对外开放 2025年2月17日，国务院办公厅发布《2025年稳外资行动方案》（简称《方案》），推动扩大医疗等多个领域开放试点。 《方案》支持生物技术、外商独资医院等试点政策落地，支持符合条件的外资企业参与生物制品分段生产试点，加快省级试点方案、质量监管方案审核，推动生物医药产业优化资源配置，及时协调解决试点过程中企业遇到的困难问题。研究完善医药领域开放政策，便利创新药加快上市，优化药品带量采购，进一步提高医疗器械产品采购可预期性。 《方案》鼓励外资在华开展股权投资。要求落实《外国投资者对上市公司战略投资管理办法》，制定发布实施战略投资的操作指引，加大对上市公司、境外基金和投资机构等的宣介力度，引导更多优质外资长期投资我国上市公司。此外还鼓励养老服务、医疗等领域吸引利用外资，满足多层次服务消费需求。 ->点击阅读原文，解锁完整双语新闻 全球医疗情报领导者 解锁隐藏在数据中的商业潜力  关于 G B I ” 自从2002年成立以来，GBI始终以技术为驱动，为药企、器械及行业相关服务商提供贯穿生命周期的全球药品市场竞争数据、全球行业资讯、HCPs洞察、全国医疗器械数据等商业信息与洞察，助力企业在进行战略布局和决策时，脱颖而出。历经20余年的深耕细作GBI已成为95%以上跨国药企、国内头部药企、咨询与投资机构等医疗圈灯塔用户值得信赖的长期合作伙伴。 联系我们 数据库 | 咨询服务 | 资讯追踪 ▶ 点击左下“阅读原文”完成表单填写 点击阅读原文，解锁完整双语新闻