NUP98

– 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

BMF-219 demonstrated early signs of clinical activity and ability to achieve durable and sustained complete responses (CRs) with minimal residual disease negativity (MRD-neg) in acute myeloid leukemia (AML) patientsPharmacodynamic data further supports the mechanism of action of BMF-219 as a menin inhibitor; in-line with preclinical models, BMF-219 downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1BMF-219, the first and only investigational covalent oral menin inhibitor in clinical development for AML, was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuationsClinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B) REDWOOD CITY, Calif., Dec. 11, 2023 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, presented positive clinical data for BMF-219, an investigational covalent menin inhibitor, in relapsed / refractory AML patients with menin-dependent mutations at the 65th American Society of Hematology (ASH) Annual Meeting. The poster can be viewed at Biomea’s website at https://biomeafusion.com/publications. “We are very excited to present the clinical update at ASH on our targeted, covalently binding menin inhibitor, BMF-219, achieving durable and sustained CRs in patients with menin inhibitor-sensitive acute leukemia, even at suboptimal dosing levels. The gene expression data we presented here validates the proposed mechanism of action of BMF-219 and is in-line with our preclinical models,” said Steve Morris, M.D., Chief Development Officer at Biomea. As of the October 31, 2023, out of 29 patients dosed in the Phase I of COVALENT-101, nearly half (45%) of the participants received prior Hematopoietic Stem Cell Transplant (HSCT) and the median prior lines of therapy was 3. A total of 7 patients were selected as evaluable for efficacy. The efficacy evaluable population includes AML patients who meet the following criteria: dosed at or near predicted efficacious dose (500 mg or above [Arm A – non-CYP inhibitor Arm]; 125 mg or above [Arm B]), had known menin-dependent mutations, and completed at least two cycles of therapy. Within this patient population 2 Complete Responses (CRs) (CR rate 2/7 = 29%) were observed with a mean time to response of 1.8 months (1 CR patient had a NUP-98 mutation and 1 CRi patient had a NPM1 mutation). In the CYP inhibitor arm, BMF-219 showed increasing plasma pharmacokinetic (PK) exposure with escalating dose levels, and the ability to achieve systemic exposures predicted to be efficacious based on preclinical acute leukemia models. Further dose escalation is still needed to achieve target AUC. Pharmacodynamic data from a case study of an AML patient containing NUP98-NSD1 mutation showed suppression of key leukemogenic genes (e.g. HOXA9, MEIS1) as well as downregulation of MEN1, without noticeable increases in differentiation markers (e.g. CD14, ANPEP, ITGAM) in contrast to non-covalent menin inhibitors. Across all patients enrolled in the trial as of the data cutoff date (n=29), BMF-219 was generally well-tolerated with no dose-limiting toxicities observed and without treatment discontinuations due to toxicity. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, with onset 1-3 weeks after initiation of therapy and an average duration of 10 days, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Initially, patients were enrolled agnostic to mutational status; subsequently, the study protocol was amended to enrich for patients with AML harboring menin-dependent mutations. Dose Level 4 is the first dose level which focused primarily on enrolling patients with known menin-dependent mutations. Biomea is planning to amend the dosing protocol to explore higher dosing levels in Arm B. Dose escalation is to be followed by a dose optimization/expansion to determine the recommended phase 2 dose. About BMF-219 BMF-219 is a covalently binding inhibitor of menin, a protein known to play an essential role in oncogenic signaling in genetically defined leukemias as well as in diabetes. Preclinically, BMF-219 has demonstrated in well-established acute leukemia cell lines robust downregulation of key leukemogenic genes in addition to menin itself. Additionally, BMF-219 has shown anticancer activity in multiple in vitro, in vivo, and ex vivo models of acute leukemia, multiple myeloma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia. BMF-219 is currently being evaluated in first-in-human clinical trials enrolling patients with specific menin-dependent mutations in liquid and solid tumors as well as patients with diabetes. About COVALENT-101 COVALENT-101 is a Phase I, open-label, multi-center, dose-escalation and dose-expansion study designed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics of oral dosing of BMF-219 in patients with relapsed/refractory (R/R) acute leukemias — including subpopulations where menin inhibition is expected to provide therapeutic benefit (e.g., patients with MLL1/KMT2A gene rearrangements or NPM1 mutations). The study is designed to enroll subsets of acute leukemia patients who are receiving a CYP3A4 inhibitor and also those not receiving a CYP3A4 inhibitor. COVALENT-101 is also investigating the dosing of BMF-219 in other patient populations where preclinical studies have shown high menin dependence, such as multiple myeloma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. Additional information about this Phase I clinical trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05153330. About Acute Myeloid Leukemia (AML) AML is the most common form of acute leukemia in adults and represents the largest number of annual leukemia deaths in the U.S. and Europe. AML originates within the white blood cells in the bone marrow and can rapidly move to the blood and other parts of the body, including the spleen, central nervous system, and other organs. Approximately 30,000 people in the U.S. and Europe are diagnosed with AML each year, and the five-year overall survival rate in adults is roughly 29%. Among patients with relapsed/refractory disease, the need is greatest, as the overall survival is only approximately 3 to 9 months. It is estimated that upwards of 45% of AML patients have menin-dependent genetic drivers (MLL1-r, NPM1 mutant, and certain additional less common but recurrent gene mutations). About Biomea Fusion Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. The company is utilizing its proprietary FUSION™ System to advance a pipeline of covalent-binding therapeutic agents against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion is a leader in advancing next-generation covalent small molecule medicines designed to maximize clinical benefit to treat various cancers and metabolic diseases. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding our cash runway, the clinical and therapeutic potential of our product candidates and development programs, including BMF-219, the potential of BMF-219 as a treatment for various types of cancer, our research, development and regulatory plans, including the progress of our ongoing COVALENT-101 clinical trial of BMF-219, the availability of data from the trial, and the timing of such events, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in the initiation, conduct and completion of preclinical studies, including IND-enabling studies, the submission and clearance of IND applications, and our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

BMF-219 demonstrated early signs of clinical activity and ability to achieve durable and sustained complete responses (CRs) with minimal residual disease negativity (MRD-neg) in acute myeloid leukemia (AML) patients Pharmacodynamic data further supports the mechanism of action of BMF-219 as a menin inhibitor; in-line with preclinical models, BMF-219 downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1 BMF-219, the first and only investigational covalent oral menin inhibitor in clinical development for AML, was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuations Clinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B) REDWOOD CITY, Calif., Dec. 11, 2023 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, presented positive clinical data for BMF-219, an investigational covalent menin inhibitor, in relapsed / refractory AML patients with menin-dependent mutations at the 65th American Society of Hematology (ASH) Annual Meeting. The poster can be viewed at Biomea’s website at . “We are very excited to present the clinical update at ASH on our targeted, covalently binding menin inhibitor, BMF-219, achieving durable and sustained CRs in patients with menin inhibitor-sensitive acute leukemia, even at suboptimal dosing levels. The gene expression data we presented here validates the proposed mechanism of action of BMF-219 and is in-line with our preclinical models,” said Steve Morris, M.D., Chief Development Officer at Biomea. As of the October 31, 2023, out of 29 patients dosed in the Phase I of COVALENT-101, nearly half (45%) of the participants received prior Hematopoietic Stem Cell Transplant (HSCT) and the median prior lines of therapy was 3. A total of 7 patients were selected as evaluable for efficacy. The efficacy evaluable population includes AML patients who meet the following criteria: dosed at or near predicted efficacious dose (500 mg or above [Arm A – non-CYP inhibitor Arm]; 125 mg or above [Arm B]), had known menin-dependent mutations, and completed at least two cycles of therapy. Within this patient population 2 Complete Responses (CRs) (CR rate 2/7 = 29%) were observed with a mean time to response of 1.8 months (1 CR patient had a NUP-98 mutation and 1 CRi patient had a NPM1 mutation). In the CYP inhibitor arm, BMF-219 showed increasing plasma pharmacokinetic (PK) exposure with escalating dose levels, and the ability to achieve systemic exposures predicted to be efficacious based on preclinical acute leukemia models. Further dose escalation is still needed to achieve target AUC. Pharmacodynamic data from a case study of an AML patient containing NUP98-NSD1 mutation showed suppression of key leukemogenic genes (e.g. HOXA9, MEIS1) as well as downregulation of MEN1, without noticeable increases in differentiation markers (e.g. CD14, ANPEP, ITGAM) in contrast to non-covalent menin inhibitors. Across all patients enrolled in the trial as of the data cutoff date (n=29), BMF-219 was generally well-tolerated with no dose-limiting toxicities observed and without treatment discontinuations due to toxicity. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, with onset 1-3 weeks after initiation of therapy and an average duration of 10 days, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Initially, patients were enrolled agnostic to mutational status; subsequently, the study protocol was amended to enrich for patients with AML harboring menin-dependent mutations. Dose Level 4 is the first dose level which focused primarily on enrolling patients with known menin-dependent mutations. Biomea is planning to amend the dosing protocol to explore higher dosing levels in Arm B. Dose escalation is to be followed by a dose optimization/expansion to determine the recommended phase 2 dose. About BMF-219 BMF-219 is a covalently binding inhibitor of menin, a protein known to play an essential role in oncogenic signaling in genetically defined leukemias as well as in diabetes. Preclinically, BMF-219 has demonstrated in well-established acute leukemia cell lines robust downregulation of key leukemogenic genes in addition to menin itself. Additionally, BMF-219 has shown anticancer activity in multiple in vitro, in vivo, and ex vivo models of acute leukemia, multiple myeloma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia. BMF-219 is currently being evaluated in first-in-human clinical trials enrolling patients with specific menin-dependent mutations in liquid and solid tumors as well as patients with diabetes. About COVALENT-101 COVALENT-101 is a Phase I, open-label, multi-center, dose-escalation and dose-expansion study designed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics of oral dosing of BMF-219 in patients with relapsed/refractory (R/R) acute leukemias — including subpopulations where menin inhibition is expected to provide therapeutic benefit (e.g., patients with MLL1/KMT2A gene rearrangements or NPM1 mutations). The study is designed to enroll subsets of acute leukemia patients who are receiving a CYP3A4 inhibitor and also those not receiving a CYP3A4 inhibitor. COVALENT-101 is also investigating the dosing of BMF-219 in other patient populations where preclinical studies have shown high menin dependence, such as multiple myeloma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. Additional information about this Phase I clinical trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05153330. About Acute Myeloid Leukemia (AML) AML is the most common form of acute leukemia in adults and represents the largest number of annual leukemia deaths in the U.S. and Europe. AML originates within the white blood cells in the bone marrow and can rapidly move to the blood and other parts of the body, including the spleen, central nervous system, and other organs. Approximately 30,000 people in the U.S. and Europe are diagnosed with AML each year, and the five-year overall survival rate in adults is roughly 29%. Among patients with relapsed/refractory disease, the need is greatest, as the overall survival is only approximately 3 to 9 months. It is estimated that upwards of 45% of AML patients have menin-dependent genetic drivers (MLL1-r, NPM1 mutant, and certain additional less common but recurrent gene mutations). About Biomea Fusion Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. The company is utilizing its proprietary FUSION™ System to advance a pipeline of covalent-binding therapeutic agents against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion is a leader in advancing next-generation covalent small molecule medicines designed to maximize clinical benefit to treat various cancers and metabolic diseases. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding our cash runway, the clinical and therapeutic potential of our product candidates and development programs, including BMF-219, the potential of BMF-219 as a treatment for various types of cancer, our research, development and regulatory plans, including the progress of our ongoing COVALENT-101 clinical trial of BMF-219, the availability of data from the trial, and the timing of such events, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in the initiation, conduct and completion of preclinical studies, including IND-enabling studies, the submission and clearance of IND applications, and our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact: Investor Relations Chunyi Zhao, PhD Sr. Manager of Investor Relations & Corporate Development czhao@biomeafusion.com Media Relations Neera Chaudhary, PhD Chief Commercial Officer – Diabetes nchaudhary@biomeafusion.com