FLT3

– Company anticipates dosing of KO-2806 in combination with adagrasib in KRASG12C-mutant NSCLC next quarter – – Dose escalation of KO-2806 as a monotherapy continues in parallel – SAN DIEGO, March 06, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced dosing of the first patient with KO-2806, the Company’s next-generation farnesyl transferase inhibitor (FTI), in combination with the tyrosine kinase inhibitor (TKI) cabozantinib in the clear cell renal cell carcinoma (ccRCC) cohort of the Phase 1 portion of the FIT-001 trial. “Dosing of the first patient in combination in our Phase 1 trial of KO-2806 marks a significant milestone for our next-generation FTI program,” said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. “This innovative, first-in-human trial builds upon our leadership position in the development of FTIs as well as a growing body of preclinical data demonstrating that combining KO-2806 with certain tyrosine kinase inhibitors, including cabozantinib, has the potential to address mechanisms of innate and adaptive resistance of targeted therapies, while driving tumor regressions and enhancing both duration and depth of antitumor response in preclinical models of ccRCC. With this achievement, we are now one step closer to realizing our vision for broad application of KO-2806 as an ideal combination partner to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies.” FIT-001 is a first-in-human, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of KO-2806 when administered as monotherapy and in combination with targeted therapies. Concurrent with the monotherapy dose escalation, Kura is evaluating KO-2806 in dose-escalation combination cohorts with other targeted therapies, beginning with cabozantinib in ccRCC. The Company expects to begin dosing in combination with adagrasib in KRASG12C-mutant non-small cell lung cancer (NSCLC) next quarter. For more information regarding FIT-001, please visit www.clinicaltrials.gov (identifier: NCT06026410). About KO-2806 KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Kura presented promising preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Additional information about clinical trials for KO-2806 can be found at https://kuraoncology.com/clinical-trials/#farnesyl-transferase-inhibitor. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined AML patients with high unmet need. Kura is currently enrolling patients in a Phase 2 registration-directed trial of ziftomenib in NPM1-m R/R AML (KOMET-001). The Company is also conducting a series of studies to evaluate ziftomenib in combination with current standards of care, beginning with ven/aza and 7+3 in NPM1-m and KMT2A-r newly diagnosed and R/R AML (KOMET-007) and with the FLT3 inhibitor gilteritinib, FLAG-IDA or LDAC in NPM1-m and KMT2A-r R/R AML (KOMET-008). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent HNSCC (KURRENT-HN). Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with cabozantinib in ccRCC and with adagrasib in KRASG12C-mutated NSCLC (FIT-001). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of KO-2806, potential benefits of combining KO-2806 with appropriate standards of care and expected timing for enrollment in the NSCLC cohort of the FIT-001 trial. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, risks associated with Kura’s cash needs, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission (SEC), including the Company’s Form 10-K for the quarter ended December 31, 2023 filed with the SEC on February 27, 2024, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investors: Pete De Spain Executive Vice President, Investor Relations & Corporate Communications (858) 500-8833 pete@kuraoncology.com Media: Alexandra Weingarten Associate Director, Corporate Communications &Investor Relations(858) 500-8822 alexandra@kuraoncology.com

– Positive preliminary combination data from KOMET-007 trial of ziftomenib in NPM1-m and KMT2A-r AML, including effective mitigation of differentiation syndrome – – First patient dosed in KOMET-008 trial of ziftomenib in combination with additional standards of care, including gilteritinib, FLAG-IDA and LDAC, in AML – – Completion of enrollment in registration-directed trial of ziftomenib in NPM1-m AML anticipated by mid-2024 – – $570 million in pro forma cash provides runway into 2027 – – Management to host webcast and conference call today at 4:30 p.m. ET – SAN DIEGO, Feb. 27, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported fourth quarter and full year 2023 financial results and provided a corporate update. “Given its best-in-class safety and efficacy pro well as optimal pharmaceutical properties, we believe ziftomenib is well positioned to become a cornerstone of therapy for patients with acute leukemias,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “This belief is supported by strong enthusiasm among both physicians and patients, as evidenced by rapid enrollment across our ongoing ziftomenib studies. We continue to be encouraged by the rate of enrollment in KOMET-001, our Phase 2 registration-directed trial of ziftomenib in patients with relapsed/refractory NPM1-mutant AML, and we remain on pace to complete enrollment of all 85 patients in the trial by the middle of this year. We also are seeing robust enrollment in our ongoing KOMET-007 study, which is investigating ziftomenib in combination with current standards of care in the frontline and relapsed/refractory settings. And with our recent financing, we remain in a strong financial position, which enables us to invest aggressively in research, development and pre-commercial activities to maximize the value of ziftomenib and support our other pipeline assets.” Recent Highlights Encouraging safety and tolerability pro ziftomenib in combination with 7+3 and ven/aza – In January 2024, Kura reported preliminary clinical data from the first 20 patients in KOMET-007, a Phase 1 dose-escalation trial of ziftomenib in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine (ven/aza), in patients with NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) AML. The first 20 patients were enrolled between July 2023 and November 2023 and included five newly diagnosed patients with adverse risk NPM1-m or KMT2A-r AML and 15 patients with refractory/relapsed (R/R) NPM1-m or KMT2A-r AML. Continuous daily dosing of ziftomenib at 200 mg was well tolerated, and the safety pro consistent with features of underlying disease and backbone therapies. No differentiation syndrome events of any grade were reported, and no dose-limiting toxicities, evidence of QTc prolongation, drug-drug interactions or additive myelosuppression were observed. Encouraging evidence of clinical activity for ziftomenib combinations in NPM1-m and KMT2A-r AML – As of the data cutoff on January 11, 2024, all five newly diagnosed patients treated with ziftomenib and 7+3 achieved a complete remission with full count recovery, for a complete remission (CR) rate of 100%. The overall response rate (ORR) among the 15 R/R patients treated with ziftomenib and ven/aza was 53%, including a 40% ORR in the 10 patients who had received prior venetoclax. The CR/CRh (CR with partial hematologic recovery) rate among the nine R/R patients who were menin inhibitor naïve was 56%. As of the data cutoff, 16 of the first 20 patients remained on trial, including all 11 NPM1-mutant patients. To date, enrollment at the 400 mg dose of ziftomenib is ongoing in the R/R ven/aza cohorts and in the frontline NPM1-mutant 7+3 cohort. First patient dosed in KOMET-008 trial of ziftomenib in combination with additional standards of care in AML – Yesterday, Kura announced dosing of the first patient in its KOMET-008 trial of ziftomenib in combination with the FLT3 inhibitor gilteritinib, FLAG-IDA or LDAC for the treatment of relapsed/refractory NPM1-m or KMT2A-r AML. Roughly half of patients with relapsed or refractory hNPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is poor. Preclinical data for ziftomenib in combination with FLT3 inhibitors demonstrate strong synergistic effects compared to either single agent alone. Completion of enrollment in registration-directed trial of ziftomenib in NPM1-m AML anticipated by mid-2024 – The KOMET-001 registration-directed trial of ziftomenib in NPM1-m R/R AML is expected to enroll a total of 85 patients in the U.S. and Europe. In the Phase 1 trial, ziftomenib demonstrated a 35% CR rate and 45% overall response rate in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose (RP2D). NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Addressing the continuum of care for patients with acute leukemias– Kura remains committed to developing new treatment options across the continuum of care for patients with acute leukemias, where poor outcomes and significant unmet medical need remain. In December 2023, the Company announced that ziftomenib was selected by the Leukemia & Lymphoma Society for the Pediatric Acute Leukemia (PedAL) Master Clinical Trial. As part of the study, ziftomenib will be evaluated in combination with chemotherapy in pediatric patients with R/R KMT2A-r, NPM1-m or NUP98-rearranged acute leukemia. In addition, Kura recently began dosing with ziftomenib in patients with R/R KMT2A-r acute lymphoblastic leukemia, a relatively small population with a large unmet medical need. Positive results from registration-directed trial of tipifarnib in HRAS-mutant HNSCC – In October 2023, Kura presented positive results from its AIM-HN registration-directed trial of tipifarnib as a monotherapy in patients with HRAS-mutant head and neck squamous cell carcinoma (HNSCC). The Company continues to evaluate tipifarnib in combination with alpelisib in patients with PIK3CA-dependent HNSCC as part of its ongoing KURRENT-HN dose-escalation trial. Dose escalation continues in first-in-human trial of KO-2806 – In October 2023, Kura announced that the first patient was dosed in its FIT-001 Phase 1 dose-escalation trial of its next-generation FTI, KO-2806. Concurrent with dose escalation as a monotherapy in the FIT-001 trial, the Company also plans to evaluate KO-2806 in dose-escalation combination cohorts with cabozantinib in clear cell renal cell carcinoma (ccRCC) and with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). Preclinical data support clinical combinations of KO-2806 with targeted therapies – In October 2023, Kura presented preclinical data supporting its rationale to combine KO-2806 with cabozantinib in ccRCC and with adagrasib in KRASG12C-mutated NSCLC. The new findings illustrate the potential for FTIs to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies such as tyrosine kinase inhibitors and KRAS inhibitors. Clinical collaboration with Mirati to evaluate KO-2806 and adagrasib in KRASG12C-mutated NSCLC – In November 2023, Kura announced a clinical collaboration and supply agreement with Mirati Therapeutics to evaluate the combination of KO-2806 and adagrasib in patients with KRASG12C-mutated NSCLC. Kura anticipates dosing the first patients with KO-2806 and adagrasib in KRASG12C-mutated NSCLC by mid-2024. Financial Results Research and development (R&D) expenses for the fourth quarter of 2023 were $32.5 million, compared to $22.7 million for the fourth quarter of 2022. R&D expenses for the full year 2023 were $115.2 million, compared to $92.8 million for the prior year. General and administrative (G&A) expenses for the fourth quarter of 2023 were $14.2 million, compared to $12.5 million for the fourth quarter of 2022. G&A expenses for the full year 2023 were $50.6 million, compared to $47.1 million for the prior year. Net loss for the fourth quarter of 2023 was $42.8 million, compared to a net loss of $33.1 million for the fourth quarter of 2022. Net loss for the full year 2023 was $152.6 million, compared to a net loss of $135.8 million for the prior year. Net loss for the fourth quarter and full year 2023 included non-cash, share-based compensation expense of $7.2 million and $28.1 million, respectively. This compares to $6.8 million and $26.3 million for the same periods in 2022. As of December 31, 2023, Kura had cash, cash equivalents and short-term investments of $424.0 million, compared to $438.0 million as of December 31, 2022. Pro forma for $146 million in approximate net proceeds from the company’s private placement completed in January 2024, Kura had $570 million in cash, cash equivalents and short-term investments at December 31, 2023. Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027. Forecasted Milestones Initiate the post-transplant maintenance program for ziftomenib in the first quarter of 2024. Complete enrollment of 85 patients in the KOMET-001 registration-directed trial of ziftomenib in NPM1-m AML by mid-2024. Initiate an expansion cohort evaluating ziftomenib as a monotherapy in patients who have neither NPM1-mutant nor KMT2A-rearranged AML by mid-2024. Determine the RP2D for ziftomenib in combination with ven/aza and initiate dose validation/expansion in frontline AML by mid-2024. Determine the RP2D for ziftomenib in combination with 7+3 by mid-2024. Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with cabozantinib in ccRCC by mid-2024. Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with adagrasib in KRASG12C-mutated NSCLC by mid-2024. Complete enrollment of two expansion cohorts to support determination of the optimal biologically active dose for tipifarnib in combination with alpelisib by the end of 2024. Conference Call and Webcast Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, February 27, 2024, to discuss the financial results for the fourth quarter and full year 2023 and to provide a corporate update. The live call may be accessed by dialing (888) 886-7786 for domestic callers and (416) 764-8658 for international callers and entering the conference ID: 02911668. A live webcast and archive of the call will be available online from the investor relations section of the company website at . About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined AML patients with high unmet need. Kura is currently enrolling patients in a Phase 2 registration-directed trial of ziftomenib in NPM1-m R/R AML (KOMET-001). The Company is also conducting a series of studies to evaluate ziftomenib in combination with current standards of care, beginning with ven/aza and 7+3 in NPM1-m and KMT2A-r newly diagnosed and R/R AML (KOMET-007). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent HNSCC (KURRENT-HN). Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with cabozantinib in ccRCC and with adagrasib in KRASG12C-mutated NSCLC (FIT-001). For additional information, please visit Kura’s website at and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of Kura’s product candidates, ziftomenib, tipifarnib and KO-2806, progress and expected timing of Kura’s drug development programs and clinical trials and submission of regulatory filings, the presentation of data from clinical trials, plans regarding regulatory filings and future clinical trials, the regulatory approval path for tipifarnib, the strength of Kura’s balance sheet and the sufficiency of cash, cash equivalents and short-term investments to fund its current operating plan to 2027. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission, which are available at Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. KURA ONCOLOGY, INC. Statements of Operations Data (unaudited) (in thousands, except per share data) Three Months Ended Year Ended December 31, December 31, 2023 2022 2023 2022 Operating Expenses: Research and development $ 32,533 $ 22,668 $ 115,235 $ 92,812 General and administrative 14,229 12,488 50,569 47,053 Total operating expenses 46,762 35,156 165,804 139,865 Other income, net 3,976 2,042 13,173 4,025 Net loss $ (42,786 ) $ (33,114 ) $ (152,631 ) $ (135,840 ) Net loss per share, basic and diluted $ (0.55 ) $ (0.49 ) $ (2.08 ) $ (2.03 ) Weighted average number of shares used in computing net loss per share, basic and diluted 77,337 67,781 73,229 66,990 KURA ONCOLOGY, INC. Balance Sheet Data (unaudited) (in thousands) December 31, December 31, 2023 2022 Cash, cash equivalents and short-term investments $ 423,957 $ 437,985 Working capital 397,218 422,369 Total assets 448,935 456,306 Long-term liabilities 16,399 11,971 Accumulated deficit (721,439 ) (568,808 ) Stockholders’ equity 397,273 420,278 Contacts Investors: Pete De Spain Executive Vice President, Investor Relations & Corporate Communications (858) 500-8833 pete@kuraoncology.com Media: Alexandra Weingarten Associate Director, Investor Relations & Corporate Communications (858) 500-8822 alexandra@kuraoncology.com

Topline data from vafidemstat's PORTICO Phase IIb trial in Borderline Personality Disorder (BPD) reported with promising results in secondary endpoints of overall severity and control of agitation/aggressionCompany planning to request an End-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III trial in BPDContinues to enroll patients in Phase IIb EVOLUTION trial with vafidemstat in schizophreniaContinues to recruit patients in FRIDA trial with iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patientsResearch and development (R&D) expenses of $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023, respectively MADRID, Spain and BOSTON, Feb. 26, 2024 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with a strong unmet medical need, today reported financial results for the fourth quarter ended December 31, 2023 and provided a corporate update on recent developments. Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon continued with a strong path in its clinical programs in the fourth quarter. In CNS, we recently presented topline results for our Phase IIb PORTICO trial evaluating vafidemstat as a treatment for Borderline Personality Disorder (BPD). Although the primary endpoints were not met, two important secondary endpoints evaluating improvement in overall BPD disease severity and in agitation/aggression reached nominal statistical significance, and the results across all the primary and secondary efficacy endpoints favored vafidemstat over placebo. This is the first time, to the best of our knowledge, that a large, randomized Phase II trial in BPD had two secondary endpoints that met statistical significance reflecting clinically meaningful improvements in overall BPD severity and in agitation/aggression. In a disease with currently no approved drugs, and no established regulatory endpoints yet, PORTICO’s results across these two important endpoints are paving the way, in our opinion, to define a registrational Phase III trial, based for the first time on a well-controlled study that has enrolled a truly representative real-world BPD population. Once the full analysis is completed, the company will request an End-of-Phase II meeting with the FDA to discuss the design of a Phase III. Our Phase IIb trial with vafidemstat in schizophrenia, EVOLUTION, has also continued to enroll patients. We continue working for a future submission of an IND to initiate HOPE in 2024, the first randomized Phase I/II personalized medicine trial with an LSD1 inhibitor, in Kabuki Syndrome patients.” Dr Buesa continued: “In oncology, we also continued to make progress this quarter in both iadademstat’s ongoing clinical trials. In the FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, the second cohort is fully enrolled and ongoing, and the company’s assessment on the initial preliminary data looks very promising when compared to gilteritinib alone in historical data. We expect to communicate some preliminary data at the EHA Conference next June in Madrid. The collaborative trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in neuroendocrine tumors is also actively recruiting patients. In addition, we are expanding iadademstat’s clinical development through additional clinical trials under our CRADA with the NCI and through investigator-initiated studies in SCLC in combination with ICIs and in first line AML in combination with venetoclax and azacitidine.” Dr Buesa added: “While we have experienced a clear advance in our clinical pipeline, on the financial side, the company has continued its budgetary discipline. This, and the combination of non-dilutive funds (private and public grants and loans from commercial Spanish banks) with the withdrawal of €10 million from our €45 million Convertible Bond program allows us to extend the runway until 2025 and to focus now on the next conversations with the FDA and EMA and our clinical execution.” Fourth Quarter and Recent Highlights Vafidemstat in large multifactorial CNS indications: Topline results from PORTICO, a multicenter, double-blind, randomized, placebo-controlled Phase IIb conducted in the U.S. and EU to evaluate the efficacy and safety of vafidemstat in BPD patients, were reported on January 5, 2024. The primary endpoints, improvement in Borderline Personality Disorder Checklist (BPDCL) and in agitation/aggression by the Clinical Global Impression – Severity Agitation/Aggression (CGI-S A/A), did not reach statistical significance. However, nominal statistical significance was achieved on the secondary endpoint Borderline Evaluation of Severity (BEST), an overall measure of BPD disease severity, at weeks 8-12 (p = 0.042), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 28.9%. Nominal statistical significance was also achieved on the secondary endpoint State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger, a measure of agitation and aggression, at weeks 8-12 (p = 0.026), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 46.7%. Results across all primary and secondary efficacy endpoints consistently favored vafidemstat over placebo. Global Statistical Test (GST p-values) confirmed a consistent trend across efficacy endpoints. Vafidemstat was safe and well-tolerated. Adverse events (AEs) were generally consistent with the safety profile of vafidemstat seen to date, with no new safety findings. Based on the efficacy and safety results, Oryzon intends to request an end-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III study for the treatment of BPD. The company is currently completing the full data analysis and plans to provide a full data presentation at a psychiatric conference later this year, as well as in a peer-reviewed journal publication.The EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia continues to enroll patients. This Phase IIb study aims to evaluate the efficacy of vafidemstat on negative symptoms and cognitive impairment in patients with schizophrenia. This project is partially financed with public funds from the Spanish Ministry of Science and Innovation and is being carried out in various Spanish hospitals. Vafidemstat in monogenic CNS indications: We continue the preparations of a new precision medicine trial in Kabuki Syndrome (KS). The company is in a dialogue with the regulatory agencies to refine the final design of this trial and expects to submit an IND for HOPE to the U.S. Food and Drug Administration (FDA) in 2024. 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. The first cohort has been completed (six patients), and the combination was safe and showed strong antileukemic activity. The second cohort (six patients) is fully enrolled and ongoing. 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. Secondary objectives include the evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the Duration of Responses (DoR), and the assessment of Measurable Residual Disease (MRD). 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 Company is further expanding the clinical development of iadademstat in AML through an Investigator-initiated study (IIS). This trial will be a Phase Ib dose-finding study to evaluate iadademstat in combination with venetoclax and azacitidine in first-line AML patients, led by Oregon Health & Science University (OHSU). The trial received FDA IND approval in 4Q2023 and is expected to begin enrolling patients in 1Q2024.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 FCCC, under which the FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug, and technical expertise.A new clinical trial of iadademstat in combination with an immune checkpoint inhibitor (ICI) in first-line metastatic SCLC, which will be conducted under the Cooperative Research and Development Agreement (CRADA) signed with the National Cancer Institute (NCI) in the United States, is under preparation. This trial will be led by the Memorial Sloan Kettering Cancer Center (MSKCC), which plans to file the IND with the FDA in 1Q2024.The STELLAR trial, a randomized, multicenter Phase Ib/II study of iadademstat plus a checkpoint inhibitor in first-line extensive-stage SCLC, will be informed and refined from the findings of the CRADA-MSKCC trial in the same space and with the same design that is expected to start in 1Q2024, as mentioned above. The company believes that STELLAR could potentially support an application for accelerated approval. 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, is progressing through IND enabling studies to prepare it for clinical studies. The Company recently announced that is has received a 0.5 million USD grant from the ALS Association in the U.S. to support the regulatory preclinical development of ORY-4001 for ALS. ORY-4001 has been previously shown to reverse disease progression symptoms in a CMT mice model which reliably recapitulates many of the symptoms of this condition in humans, improving myelination and restoring axon integrity in the sciatic nerve, and improving compound muscle action potential and nerve conduction. These results are fruit of a collaboration entered in 2022 between Oryzon and the CMT Research Foundation (CMTRF), a U.S.-based patient-led, non-profit organization focused on delivering treatments and cures for CMT.Oryzon has received two new grants to further explore the role of epigenetic targets in the treatment of neuronal pathologies. These are two collaborative projects with public research centers, focused on the discovery and validation of novel biomarkers and epigenetic targets for the treatment of neuronal pathologies. The projects have a global budget of 2.3 million euros, of which Oryzon will receive up to 1.4 million euros. Financial Update: Fourth Quarter 2023 Financial Results Research and development (R&D) expenses were $3.9 and $16.6 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $5.0 and $18.1 million for the quarter and twelve months ended December 31, 2022. General and administrative expenses were $1.2 and $4.2 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $1.2 and $4.8 million for the quarter and twelve months ended December 31, 2022. Net losses were $1.4 and $5.0 million for the quarter and twelve months ended December 31, 2023, respectively, compared to $1.6 and $5.9 million for the quarter and twelve months ended December 31, 2022. 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 $3.7 million (–$0.064 per share) for the twelve months ended December 31, 2023, compared to a negative net result of $4.5 million (–$0.085 per share) for the twelve months ended December 31, 2022 Cash, cash equivalents and marketable securities totaled $13.5 million as of December 31, 2023. ORYZON GENOMICS, S.A.BALANCE SHEET DATA (AUDITED)1(Amounts in thousands US $) December 31st, 2023 December 31st, 2022 Cash and cash equivalents13,544 22,737Marketable securities0 0Total Assets118,125 110,606 Deferred revenue12 0Total Stockholders' equity90,361 77,405 ORYZON GENOMICS, S.A. STATEMENTS OF OPERATIONS (AUDITED)1 (US $, amounts in thousands except per share data) Three Months Ended December 31st Twelve Months Ended December 31st 20232022 20232022 Collaboration Revenue 00 00 Operating expenses: Research and Development 3,8675,033 16,63118,050 General and administrative 1,1871,249 4,2474,822 Total operating expenses 5,0546,282 20,87822,872 Loss from Operations -5,054-6,282 -20,878-22,872 Other income, net 3,6194,693 15,85117,016 Net Loss -1,435-1,589 -5,027-5,856 Net Financial & Tax -468-863 1,3221,342 Net Result -1,903-2,452 -3,705-4,514 Loss per share allocable to common stockholders: Basic -0.03-0.05 -0.06-0.08 Weighted average Shares outstanding Basic 58,451,07054,284,176 57,616,23653,336,257 1 Spanish GAAP * Exchange Euro/Dollar (1.1050 for 2023 and 1.0666 in 2022) About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About Iadademstat Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers; a first trial in combination with ICI in SCLC is under preparation. In total iadademstat has been dosed so far to more than 130 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has also been observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Vafidemstat is being investigated in neuropsychiatric disorders in two double-blind, randomized, placebo-controlled Phase IIb trials: one in schizophrenia, named EVOLUTION (recruitment ongoing), and another one in Borderline Personality disorder (BPD), named PORTICO, recently finalized, with topline data and in the process of completing the full data analysis. Based on PORTICO’s topline results, the company is planning to request an End-of-Phase II meeting with the FDA to discuss options for a registrational Phase III trial in BPD. The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is preparing a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. IR, USIR & Media, EuropeSpainOryzonAshley R. RobinsonSandya von der WeidPatricia Cobo/Mario CorderaEmili TorrellLifeSci Advisors, LLCLifeSci Advisors, LLCAtreviaChief Business Officer+1 617 430 7577+41 78 680 05 38+34 91 564 07 25+34 673 33 97 65+34 93 515 1313arr@lifesciadvisors.comsvonderweid@lifesciadvisors.compcobo@atrevia.commcordera@atrevia.cometorrell@oryzon.com