Azacitidine

Fourth quarter 2024 total revenue of approximately $57.6 million, which includes TAVALISSE® net product sales of $31.0 million, REZLIDHIA® net product sales of $7.4 million and GAVRETO® net product sales of $8.1 million 2024 total revenue of approximately $179.3 million, which includes TAVALISSE® net product sales of $104.8 million, REZLIDHIA® net product sales of $23.0 million and GAVRETO® net product sales of $17.1 million R289 granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS and Orphan Drug designation for the treatment of MDS by the FDA 2025 Outlook: Total revenue of approximately $200 to $210 million Conference call and webcast scheduled today at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., March 4, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today reported financial results for the fourth quarter and full year ended December 31, 2024, including sales of TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP); REZLIDHIA® (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and GAVRETO® (pralsetinib) for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) and advanced or metastatic thyroid cancer, and recent business progress. "2024 was a year of significant accomplishments for Rigel. We continued to focus on commercial expansion and execution, achieving record net product sales of $144.9 million, an increase of 39% compared to 2023. Coupled with Rigel's commitment to financial discipline, for the first time we generated full-year net income of more than $17 million and increased our cash balances by more than $20 million," said Raul Rodriguez, Rigel's president and CEO. "These outstanding commercial and financial results provide us the resources to advance our promising internal development programs in 2025, including our ongoing Phase 1b clinical study of R289 for the treatment of lower-risk MDS and the initiation of a Phase 2 clinical study of olutasidenib for the treatment of recurrent glioma." Business Update Commercial Commercial strength continued in the fourth quarter for all products with record bottles shipped to patients and clinics and total bottles sold. The following table summarizes total bottles shipped for the fourth quarter: Rigel's partner Kissei Pharmaceutical Co., Ltd. (Kissei) announced in January that The Korean Ministry of Food and Drug Safety approved TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic idiopathic thrombocytopenic purpura who have had an insufficient response to a previous treatment. In the first quarter of 2025, Rigel will recognize a $3.0 million regulatory milestone earned from Kissei in connection with the approval. In December, Rigel's partner Knight Therapeutics announced Mexico's Comisión Federal para la Protección contra Riesgos Sanitarios approved TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. Rigel entered into an exclusive license agreement with Dr. Reddy's Laboratories Ltd. (Dr. Reddy's) in November to develop and commercialize REZLIDHIA in all potential indications throughout Dr. Reddy's territory, which includes Latin America, South Africa, certain countries in the Commonwealth of Independent States (CIS), India, certain countries in Southeast Asia and North Africa, Australia and New Zealand. Rigel received an upfront cash payment of $4.0 million with the potential for up to $36.0 million in future regulatory and commercial milestone payments. Clinical Development R2891, a novel and selective dual IRAK1/4 inhibitor, has been granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS and Orphan Drug designation for the treatment of MDS by the U.S. Food and Drug Administration (FDA). Rigel continues to advance its Phase 1b clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of R289 in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). Enrollment in the fifth dose level (500mg / 250mg split dose) is complete and the new sixth dose level (500 mg twice daily) is now open for enrollment. Rigel presented initial data from the ongoing Phase 1b clinical study of R289 at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in December, demonstrating that R289 was generally well tolerated with preliminary signs of efficacy in this heavily pretreated R/R lower-risk MDS patient population, the majority of whom were high transfusion burden (HTB) at baseline. Also at the ASH Annual Meeting, four posters were presented on olutasidenib, which included data that adds to the growing body of evidence supporting the benefits of its use in patients with mIDH1 AML. CONNECT, an international collaborative network of pediatric cancer centers, in collaboration with Rigel, opened for enrollment the "TarGet-D" study, a Phase 2 study (NCT06161974) evaluating olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy, as maintenance therapy for newly diagnosed adolescent and young adult patients (ages 12 to 39 years) with a high-grade glioma (HGG) harboring an IDH1 mutation. Rigel and The University of Texas MD Anderson Cancer Center (MD Anderson) have now opened for enrollment the four studies outlined in the multi-year strategic development alliance. Olutasidenib will be studied in disease areas where mIDH1 can play a role, including AML; higher-risk MDS, chronic myelomonocytic leukemia (CMML) and advanced myeloproliferative neoplasms (MPN); clonal cytopenia of undetermined significance (CCUS) and lower-risk MDS/CMML; and as post-transplant maintenance therapy. In November, the National Comprehensive Cancer Network® (NCCN®) added olutasidenib to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes. Olutasidenib was added as a recommended option to the following treatment algorithms: Management of Lower-Risk Disease, Management of Lower-Risk Disease - Evaluation of Related Anemia and Management of Higher-Risk Disease, and was recommended as NCCN Category 2B in all circumstances. If mIDH1 positive, olutasidenib was either recommended as a single agent, in combination with azacitidine, or both.* *NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Publication Highlights A paper titled "Long‑term safety and efficacy of fostamatinib in Japanese patients with primary immune thrombocytopenia," was published in January by Masataka Kuwana, M.D., Ph.D., professor and chairman of the Department of Allergy and Rheumatology at Nippon Medical School Graduate School of Medicine in the International Journal of Hematology. The paper reported the 3-year safety and efficacy data from the Phase 3 trial of fostamatinib in Japanese patients with ITP, which included no new safety signals and a sustained platelet response during treatment. A paper titled "Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial," was published in January by Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator, in the Journal of Hematology and Oncology. A paper titled "Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm," was published in December by Stéphane de Botton, M.D., Ph.D., head of translational research in hematology, Institut Gustave Roussy, France, in the British Journal of Haematology. Fourth Quarter and Full Year 2024 Financial Update For the fourth quarter ended December 31, 2024, total revenues were $57.6 million, consisting of $31.0 million in TAVALISSE net product sales, $7.4 million in REZLIDHIA net product sales, $8.1 million in GAVRETO net product sales, and $11.1 million in contract revenue from collaborations. TAVALISSE net product sales grew 21% compared to $25.7 million in the same period of 2023. REZLIDHIA net product sales grew 92% compared to $3.9 million in the same period of 2023. GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations primarily consisted of a $4.0 million upfront cash payment from Dr. Reddy's; $3.6 million of revenue from Grifols S.A. (Grifols) related to delivery of drug supplies and earned royalties; $2.9 million of revenue from Kissei Pharmaceutical Co., Ltd. (Kissei) related to delivery of drug supplies; and $0.3 million of revenue from Medison Pharma Trading AG (Medison) related to delivery of drug supplies and earned royalties. Total costs and expenses were $40.9 million compared to $33.8 million for the same period of 2023. The increase in costs and expenses was mainly due to higher research and development costs driven by timing of clinical activities, increased personnel-related costs and increased commercial-related activities. In addition, cost of product sales increased, driven primarily by increased products sales, higher royalties and a sublicensing revenue fee, and higher amortization of intangible assets. Rigel reported net income of $14.3 million, or $0.81 basic and $0.80 diluted per share, compared to a net income of $0.7 million, or $0.04 basic and diluted per share, for the same period of 2023. The basic and diluted share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split effected on June 27, 2024 on a retroactive basis. For the full year 2024, total revenues were $179.3 million, consisting of $104.8 million in TAVALISSE net product sales, $23.0 million in REZLIDHIA net product sales, $17.1 million in GAVRETO net product sales, and $34.4 million in contract revenue from collaborations. TAVALISSE net product sales grew 12% compared to $93.7 million in the same period of 2023. REZLIDHIA net product sales grew 118% compared to $10.6 million in the same period of 2023. As mentioned above, GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations primarily consisted of $20.4 million from Kissei related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies; $9.1 million from Grifols and $0.5 million from Medison related to delivery of drug supplies and earned royalties; and $4.0 million from Dr. Reddy's related to an upfront fee from sublicensing olutasidenib. Total costs and expenses were $155.1 million compared to $137.4 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales driven primarily by increased products sales, sublicensing revenue fees and increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs, stock-based compensation expense and commercial-related expenses. These increases were partially offset by decreased research and development costs due to the timing of clinical trial activities related to R289, Rigel's dual IRAK 1/4 inhibitor program, as well as reduced trial activities related to the completed Phase 3 clinical trial of fostamatinib in patients with warm antibody hemolytic anemia (wAIHA). Rigel reported net income of $17.5 million, or $0.99 basic and diluted per share, compared to a net loss of $25.1 million, or $1.44 basic and diluted per share, for the same period of 2023. As discussed above, the share and per share amounts have been restated to reflect the 1-for-10 reverse stock split on a retroactive basis for the respective periods presented. Cash, cash equivalents and short-term investments as of December 31, 2024 was $77.3 million, compared to $61.1 million as of September 30, 2024 and $56.9 million as of December 31, 2023. 2025 Outlook Rigel anticipates 2025 total revenue of approximately $200 to $210 million, including: Net product sales of approximately $185 to $192 million. Contract revenues from collaborations of approximately $15 to $18 million. The company anticipates it will report positive net income for the full year 2025, while funding existing and new clinical development programs. Conference Call and Webcast with Slides Today at 4:30pm Eastern Time Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time). Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company's website at . The webcast will be archived and available for replay after the call via the Rigel website. About ITP In patients with immune thrombocytopenia (ITP), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. Patients suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 22,010 new cases in the United States, most in adults, in 2025.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About NSCLC It is estimated that over 226,000 adults in the U.S. will be diagnosed with lung cancer in 2025. Lung cancer is the leading cause of cancer death in the U.S, with non-small cell lung cancer (NSCLC) being the most common type accounting for 85-90% of all lung cancer diagnoses.5 RET fusions are implicated in approximately 1-2% of patients with NSCLC.6 About TAVALISSE® TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Please click here for Important Safety Information and Full Prescribing Information for TAVALISSE. About REZLIDHIA® REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. Please click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING, for REZLIDHIA. About GAVRETO® GAVRETO is indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).* *Thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Please click here for Important Safety Information and Full Prescribing Information for GAVRETO. To report side effects of prescription drugs to the FDA, or call 1-800-FDA-1088 (800-332-1088). TAVALISSE, REZLIDHIA and GAVRETO are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 16, 2025. Accessed January 31, 2025: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed January 31, 2025: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed January 31, 2025. doi: The American Cancer Society. Key Statistics for Lung Cancer. Revised January 16, 2025. Accessed January 31, 2025: Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin Cancer Res. 2017;23(8):1988-1997 doi: 10.1158/1078-0432.CCR-16-1679 Forward Looking Statements This press release contains forward-looking statements relating to, among other things, expected commercial and financial results for the fourth quarter and year ended December 31, 2024, projected financial performance and outlook for 2025, expectations to grow and advance our commercial portfolio and hematology and oncology pipeline, results of our study of R289 in lower-risk MDS including safety and efficacy data, continued ability for developing and commercializing TAVALISSE, REZLIDHIA, and GAVRETO domestically and in certain international markets, and expectations for Rigel's partnering and collaboration efforts. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "anticipates", "plan", "outlook", "potential", "may", "look to", "expects", "will", "initial", "promising", and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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.