Alpelisib

BASEL, Switzerland I July 23, 2025 I Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission has approved Itovebi™ (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, for the treatment of adult patients with PIK3CA -mutated, oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment. “Itovebi is the first treatment of its kind to improve survival outcomes for those living with PIK3CA -mutated, ER-positive advanced breast cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “Therefore, the Itovebi-based regimen may help address an important unmet need for people with this subtype of breast cancer.” The approval is based on results from the phase III INAVO120 trial, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43; 95% CI: 0.32-0.59, p<0.001) in the first-line setting. 1 The PFS benefit was consistent across all pre-specified subgroups and the Itovebi-based regimen was well tolerated, with no new safety signals observed. 1 These results were reinforced by the INAVO120 final overall survival analysis that showed the Itovebi-based regimen reduced the risk of death by 33% (stratified HR=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). 5 Additionally, the treatment regimen substantially delayed the time to chemotherapy by approximately two years compared with palbociclib and fulvestrant alone (stratified HR=0.43; 95% CI: 0.30-0.60). 5 These data were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in the New England Journal of Medicine in May 2025. Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA -mutated, locally advanced or metastatic breast cancer in various combinations. 6-8 We are exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations. About Itovebi TM (inavolisib) Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer, who often have a poor prognosis and are in urgent need of new treatment options. 1,4,9 Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha. 10,11 In addition to the European Commission’s approval, the Itovebi-based regimen is also approved for the treatment of adults with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer in the United States, Switzerland, Canada, Australia, United Arab Emirates, China and Taiwan, with data from INAVO120 under review with several other global health authorities. About the INAVO120 study The INAVO120 study [ NCT04191499 ] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease. 12 The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. 12 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause. 12 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate. 12 Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III clinical studies in PIK3CA -mutated locally advanced or metastatic breast cancer in various combinations: About oestrogen receptor (ER)-positive breast cancer ER-positive is a subtype of hormone receptor (HR)-positive breast cancer, the most prevalent type of all breast cancers, accounting for approximately 70% of cases. 13,14 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth. 15 People diagnosed with ER-positive and HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. 14,16,17 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors. 9 About Roche in breast cancer Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers. 13,14 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com . All trademarks used or mentioned in this release are protected by law. References [1] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer. NEJM. 2024;391(17):1584-96. [2] Cizkova M, et al. Gene expression profiling reveals new aspects of PIK3CA mutation in ERalpha-positive breast cancer: major implication of the Wnt signaling pathway. PLoS One. 2010;30;5(12):e15647. [3] Schagerholm C, et al. PIK3CA mutations in endocrine-resistant breast cancer. Scientific Reports. 2024;14:12542. [4] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22(1):1002. [5] Jhaveri KL, et al. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. 2025;40454641. [6] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2025 June]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862 . [7] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA -Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (INAVO122) [Internet; cited 2025 June]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239 . [8] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/​6 Inhibitor and Letrozole vs Placebo + CDK4/​6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA -Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (INAVO123) [Internet; cited 2025 June]. Available from: https://clinicaltrials.gov/study/NCT06790693 . [9] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179. [10] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA -mutated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05. [11] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14. [12] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA -Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2025 June]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499 . [13] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2025 June]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html . [14] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696. [15] Wu VS, et al. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer? J Steroid Biochem Mol Biol. 2015 Sep;153:45-53. [16] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20. [17] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. SOURCE: Roche

– FDA Priority Review of New Drug Application (NDA) for ziftomenib in adults with R/R NPM1-m AML with Prescription Drug User Fee Act (PDUFA) target action date set for November 30, 2025 – – Fully engaged in commercial readiness activities in alignment with regulatory review timeline – – KOMET-017-IC (intensive chemotherapy) and NIC (non-intensive chemotherapy) phase 3 studies in newly diagnosed AML on track to start in 2H 2025 – – Three clinical abstracts from Kura’s farnesyl transferase inhibitors (FTI) development program accepted for presentation at the 2025 ESMO Congress – – $630.7 million in pro forma cash, together with anticipated collaboration agreement payments, expected to support ziftomenib commercialization through the frontline AML combination setting – – Management to host webcast and conference call today at 4:30 p.m. ET – SAN DIEGO , Aug. 07, 2025 (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 second quarter 2025 financial results and provided a corporate update. “FDA’s acceptance of our NDA for ziftomenib represents another important step toward addressing a high unmet need in patients with relapsed or refractory NPM1-mutant AML,” said Troy Wilson , Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “As a menin inhibitor, ziftomenib targets a fundamental disease driver in certain genetically defined subsets of AML, and along with our partners at Kyowa Kirin, we are committed to advancing ziftomenib as a potential therapy for patients throughout the continuum of care. With preparations underway for commercialization, upcoming initiation of two registrational trials of ziftomenib in the frontline setting and a strong pipeline to support future growth, we believe Kura is well-positioned to deliver meaningful benefit to patients and long-term value to stakeholders.” Recent Highlights FDA Priority Review of New Drug Application for ziftomenib with PDUFA target action date of November 30, 2025 – In June 2025 , Kura and Kyowa Kirin Co., Ltd. (Kyowa Kirin) announced the U.S. Food and Drug Administration (FDA) accepted Kura’s NDA seeking full approval for ziftomenib as a treatment for adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (NPM1-m). Ziftomenib is the only menin inhibitor to receive Breakthrough Therapy Designation (BTD) for this indication. The application has been granted Priority Review and assigned a PDUFA target action date of November 30, 2025. Commercial readiness activities advancing in line with the regulatory review timeline – Pre-launch efforts by medical affairs, market access, patient support, and sales continue. Hiring and onboarding of U.S. field sales team are now complete. Pre-approval information exchange with key stakeholders across the AML ecosystem is ongoing. Presentation of positive results from the KOMET-001 pivotal trial of ziftomenib in R/R NPM1-m AML at 2025 ASCO Annual Meeting – The study achieved a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 23%, an improvement over historical controls in a heavily pretreated patient population with limited survival and few treatment options. Key safety and tolerability measures, including manageable differentiation syndrome, low rates of ziftomenib-related myelosuppression and treatment discontinuation, absence of clinically significant QTc prolongation and minimal drug-drug interactions highlighted a potentially favorable benefit-risk profile for ziftomenib. Presentation of clinical data from the Phase 1b expansion cohort of KOMET-007 evaluating ziftomenib in combination with intensive chemotherapy (7+3) in newly diagnosed NPM1-m and KMT2A-rearranged AML at 2025 EHA Congress – High rates of CR and measurable residual disease (MRD) negativity with ziftomenib in combination with intensive chemotherapy in newly diagnosed NPM1-m and KMT2A-rearranged (KMT2A-r) AML were reported. Among patients achieving a composite CR, 68% of NPM1-m and 83% of KMT2A-r patients reached MRD-negative status at a median of ~4–5 weeks. At a median follow-up of 25 and 16 weeks, 96% and 88% of patients in the respective cohorts remained alive and on study. Ziftomenib was well tolerated, enabling patients to remain on treatment through consolidation and maintenance, without interruption, dose reduction, or added myelosuppression. Nomination of next-generation menin inhibitor designed for the treatment of Type 1 and Type 2 diabetes and menin-dependent cardiometabolic indications - In preclinical models of type 2 diabetes, ziftomenib has been shown to improve glucose control, enhance insulin production, reduce insulin resistance, and selectively induce beta-cell proliferation, supporting menin as a therapeutic target for beta-cell regeneration. Kura has nominated a next-generation menin inhibitor for evaluation in diabetes. Development plans and timelines will be announced in a future update. Three clinical abstracts from Kura’s farnesyl transferase inhibitor (FTI) program accepted for presentation at the 2025 ESMO Congress - The presentations will include the first clinical data on Kura’s lead investigational FTI therapy, KO-2806, in combination with cabozantinib in renal cell carcinoma (Poster #2604P), as well as KO-2806 monotherapy in advanced RAS-mutant solid tumors (Poster #981P). An additional abstract will highlight clinical data from the combination of the FTI tipifarnib and alpelisib in patients with PIK3CA-mutant head and neck squamous cell carcinoma (HNSCC) (Poster #1349P). Financial Results Collaboration revenue from our Kyowa Kirin partnership for the second quarter of 2025 was $15.3 million , compared to no revenue for the second quarter of 2024. Research and development expenses for the second quarter of 2025 were $62.8 million , compared to $39.7 million for the second quarter of 2024. General and administrative expenses for the second quarter of 2025 were $25.2 million , compared to $16.7 million for the second quarter of 2024. Net loss for the second quarter of 2025 was $66.1 million , compared to a net loss of $50.8 million for the second quarter of 2024. Net loss for the second quarter included non-cash share-based compensation expense of $6.9 million , compared to $8.4 million for the same period in 2024. As of June 30, 2025 , Kura had cash, cash equivalents and short-term investments of $630.7 million , compared to $727.4 million as of December 31, 2024 . Based on our current plans, we believe that our cash, cash equivalents and short-term investments as of June 30, 2025 will be sufficient to enable us to fund our current operating expenses into 2027, and, combined with anticipated funding under our collaboration agreement with Kyowa Kirin, should support our ziftomenib AML program through commercialization in the frontline combination setting. Forecasted Milestones Continued regulatory interactions with the FDA ahead of the November 30, 2025 PDUFA target action date for ziftomenib as a monotherapy for adult patients with relapsed or refractory NPM1-m AML. Initiate KOMET-017, two independent Phase 3 registration-enabling trials in frontline intensive chemotherapy and non-intensive chemotherapy AML settings, in the second half of 2025. Present preliminary clinical data from the KOMET-007 Phase 1b expansion cohort evaluating ziftomenib in combination with venetoclax and azacitidine in the second half of 2025. Initiate one or more FIT-001 expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the second half of 2025. Present data from the FIT-001 Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma at the 2025 ESMO Congress in October 2025 . Present data from the FIT-001 Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS-mutant solid tumors at the 2025 ESMO Congress in October 2025 . Present data from the KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent HNSCC at the 2025 ESMO Congress in October 2025 . 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, August 7, 2025 , to discuss the financial results for the second quarter of 2025 and to provide a corporate update. The live call may be accessed by dialing (800) 579-2543 for domestic callers and (785) 424-1789 for international callers and entering the conference ID: KURAQ2. A live webcast and archived replay of the event will be available here or online from the investor relations section of the Company’s website at www.kuraoncology.com. 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 designed to target cancer signaling pathways. Ziftomenib, a once-daily, oral menin inhibitor, is the first and only investigational therapy to receive Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory (R/R) NPM1-mutant (NPM1-m) acute myeloid leukemia (AML). In November 2024, Kura Oncology entered into a global strategic collaboration agreement with Kyowa Kirin to develop and commercialize ziftomenib for AML and other hematologic malignancies. Enrollment in KOMET-001, a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-m AML, has been completed, and in the second quarter of 2025, the companies announced the FDA’s acceptance of a New Drug Application for ziftomenib for the treatment of adult patients with R/R NPM1-m AML and assignment of a Prescription Drug User Fee Act target action date of November 30, 2025. Kura and Kyowa Kirin are conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-m and KMT2A-rearranged AML. Ziftomenib is also being evaluated in a Phase 1 dose-escalation trial (KOMET-015) in combination with imatinib for treatment of patients with advanced gastrointestinal stromal tumors (GIST). KO-2806, a next-generation farnesyl transferase inhibitor (FTI), is being evaluated in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy and in combination with targeted therapies for patients with various solid tumors. Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial (KURRENT-HN) in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma. For additional information, please visit the Kura website at https://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 Kura’s product candidates, ziftomenib, KO-2806 and tipifarnib; the expected timing of clinical trials; the expected timing and presentation of results and data from clinical trials; the potential duration of FDA’s review of the NDA; the potential FDA approval of product candidates; the success and impact of interactions with the FDA; 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 and, combined with anticipated collaboration funding under the Kyowa Agreement, to support Kura’s ziftomenib AML program through commercialization in the 1L combination setting. 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, 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, the risk that the collaboration with Kyowa Kirin is unsuccessful, 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 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 and media: Greg Mann 858-987-4046gmann@kuraoncology.com Source: Kura Oncology, Inc.