PI3Kα

The European Medicines Agency (EMA) released a report detailing the reasons for the withdrawal of Novartis marketing authorisation application for Vijoice. Credit: Bloomberg via Getty Images. The European Medicines Agency (EMA) recently released its main concerns with Novartis ’ Vijoice (alpelisib) application which led to the company withdrawing its conditional authorisation application for a group of rare genetic disorders last autumn. In Europe, Novartis was pursuing a label for the treatment of adults and children aged two years and above with severe or life-threatening symptoms of PIK3CA-Related Overgrowth Spectrum (PROS) requiring systemic therapy. In an updated withdrawal assessment report that was released earlier today (14 March), the EMA explained that the long-term safety profile of Vijoice, especially its impact on growth and development in the paediatric population, is still unknown. Furthermore, it questioned whether the assessment of tumour size was an adequate measure of patient benefit in the group of patients with the target indication. The US Food and Drug Administration (FDA) approved Vijoice in April 2022 as the first and only treatment for select patients with PROS. In May 2019, the regulator also granted approval to alpelisib, under the brand name Piqray . The treatment was made available for postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated advanced or metastatic breast cancer. PROS are a group of genetic disorders in which mutations occur in the PIK3CA gene, causing overgrowth of certain body parts. Vijoice treats the condition by inhibiting the PI3K/Akt signalling pathway. See Also: Novartis exercises option to acquire IFM Due for $835m Novartis files patent for combination therapy for b-cell lymphoma with CD19 car and BCL2 inhibitor In October 2023, Novartis withdrew its EU marketing authorisation application for Vijoice following an EMA evaluation. At the time of withdrawal, the agency reported concerns that the clinical data, provided from the EPIK-P2 study (NCT04589650), was not sufficient in demonstrating the exact effect of the medicine on tumour size and whether patients experienced significant reductions in tumour size. In a letter to the EMA released in the same month, Novartis had also expressed the need to acquire further data to support the drug’s benefit/risk assessment. Novartis submitted the initial application based on real-world evidence from a retrospective chart review study. However, the Swiss company was unable to answer all questions from the Committee for Medicinal Products for Human Use (CHMP) within the necessary timeframe. At the time, the Swiss company announced intentions to submit a new marketing authorisation application once it collects new data. The EMA designated the drug as an orphan medicine on 26 March 2021 for the treatment of PROS. In the EU, there are currently no disease-modifying treatments available for PROS.

– 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

SAN DIEGO, March 01, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (the “Company”) (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced that on March 1, 2024, the Compensation Committee of the Company’s Board of Directors (the “Compensation Committee”) granted inducement awards consisting of nonstatutory stock options to purchase 93,000 shares of common stock to two (2) new employees under the Company’s 2023 Inducement Option Plan. The Compensation Committee approved the stock options as an inducement material to such employees’ employment in accordance with Nasdaq Listing Rule 5635(c)(4). Each stock option has an exercise price per share equal to $21.59 per share, the Company’s closing sales price on March 1, 2024, and will vest over four years, with 25% of the underlying shares vesting on the one-year anniversary of the applicable vesting commencement date and the balance of the underlying shares vesting monthly thereafter over 36 months, subject to the new employees’ continued service relationship with the Company through the applicable vesting dates. The stock options are subject to the terms and conditions of the Company’s 2023 Inducement Option Plan and the terms and conditions of an applicable stock option agreement covering the grant. 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 www.kuraoncology.com and follow us on X and LinkedIn. Contacts Investors:Pete De SpainExecutive Vice President, Investor Relations &Corporate Communications(858) 500-8833pete@kuraoncology.com Media:Alexandra WeingartenAssociate Director, Corporate Communications & Investor Relations(858) 500-8822alexandra@kuraoncology.com