Kura Oncology, Inc. (NASDAQ:KURA) 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. Kura's lead product candidate, ziftomenib, has received Breakthrough Therapy Designation from the FDA for the treatment of relapsed or refractory NPM1-mutant acute myeloid leukemia (AML). The company is also advancing its farnesyl transferase inhibitor (FTI) programs, including tipifarnib and the next-generation FTI, KO-2806.
Business Overview
Kura Oncology is focused on developing targeted therapies for patients with genetically defined cancers. The company's lead product candidate, ziftomenib, is a potent, selective, reversible and oral small molecule inhibitor that blocks the interaction of two proteins, menin and the protein expressed by the Lysine K-specific Methyl Transferase 2A gene (KMT2A). Ziftomenib has demonstrated promising clinical activity in relapsed or refractory AML, particularly in patients with NPM1 mutations, which account for approximately 30% of all AML cases.
In addition to ziftomenib, Kura is also advancing its FTI programs. Tipifarnib, the company's second product candidate, is a potent, selective and orally bioavailable FTI that has shown compelling and durable anti-cancer activity in certain patients with a manageable side effect profile. Kura is evaluating tipifarnib in combination with the PI3 kinase alpha inhibitor, alpelisib, in patients with HNSCC whose tumors have HRAS overexpression and/or PIK3CA mutation and/or amplification. The company's newest product candidate, KO-2806, is a next-generation FTI that Kura believes demonstrates improved potency, pharmacokinetic and physicochemical properties relative to earlier FTI drug candidates.
Financials
For the full year 2023, Kura reported a net loss of 152.6 million, with no revenue generated. The company's annual operating cash flow was negative 124.8 million, and its annual free cash flow was negative 125.0 million.
In the first quarter of 2024, Kura reported a net loss of 49.5 million, compared to a net loss of 34.1 million in the same period of 2023. Research and development expenses increased to 36.3 million in Q1 2024, up from 25.2 million in Q1 2023, primarily due to increased clinical trial costs related to the company's ziftomenib and KO-2806 programs. General and administrative expenses also rose to 18.2 million in Q1 2024, compared to 11.4 million in Q1 2023.
As of March 31, 2024, Kura had 527.1 million in cash, cash equivalents and short-term investments, which the company believes will be sufficient to fund its current operating plan into 2027.
Ziftomenib: Breakthrough Therapy Designation and Promising Clinical Data
Kura's lead product candidate, ziftomenib, has received Breakthrough Therapy Designation from the FDA for the treatment of patients with relapsed or refractory NPM1-mutant AML. This designation is intended to expedite the development and review of drugs that treat serious or life-threatening conditions and demonstrate the potential for substantial improvement over existing therapies.
The FDA's decision to grant Breakthrough Therapy Designation for ziftomenib was based on data from Kura's ongoing KOMET-001 clinical trial in patients with relapsed or refractory NPM1-mutant AML. In the Phase 1b portion of the KOMET-001 trial, ziftomenib demonstrated durable activity in patients with heavily pretreated and co-mutated relapsed or refractory NPM1-mutant AML. As of the April 12, 2023 data cutoff, 35% of patients with NPM1-mutant AML treated at the recommended Phase 2 dose of 600 mg achieved a complete remission (CR) with full count recovery. Additionally, the overall response rate (ORR) in patients with NPM1-mutant AML treated at the 600 mg dose was 45%, and the median duration of response was 8.2 months.
Kura is currently enrolling a Phase 2 registration-directed trial of ziftomenib in relapsed or refractory NPM1-mutant AML, which is expected to complete enrollment of 85 patients by mid-2024. The company is also evaluating ziftomenib in combination with current standards of care, including venetoclax plus azacitidine and cytarabine plus daunorubicin (7+3), in patients with NPM1-mutant or KMT2A-rearranged AML.
In the KOMET-007 trial, the combination of ziftomenib with venetoclax plus azacitidine or 7+3 demonstrated an encouraging safety profile and promising early signs of clinical activity. As of the January 11, 2024 data cutoff, all five newly diagnosed patients with adverse risk NPM1-mutant or KMT2A-rearranged AML treated with ziftomenib and 7+3 achieved a complete remission with full count recovery. The overall response rate among the 15 relapsed or refractory patients treated with ziftomenib and venetoclax plus azacitidine was 53%, including a 40% ORR in patients who had received prior venetoclax.
Kura plans to identify the recommended Phase 2 dose of ziftomenib in combination with venetoclax plus azacitidine and in combination with 7+3 by mid-2024. The company will then initiate a Phase 1b expansion study to further evaluate the safety and efficacy of these combinations in various patient populations, including newly diagnosed and relapsed or refractory NPM1-mutant or KMT2A-rearranged AML.
Tipifarnib and KO-2806: Advancing FTI Programs
In addition to ziftomenib, Kura is also advancing its farnesyl transferase inhibitor (FTI) programs, including tipifarnib and the next-generation FTI, KO-2806.
Tipifarnib, Kura's second product candidate, has been studied in more than 5,000 cancer patients and has demonstrated compelling and durable anti-cancer activity in certain patients with a manageable side effect profile. The company is currently evaluating the combination of tipifarnib and the PI3 kinase alpha inhibitor, alpelisib, in patients with HNSCC whose tumors have HRAS overexpression and/or PIK3CA mutation and/or amplification in the KURRENT-HN trial.
Kura expects to complete enrollment of two expansion cohorts in the KURRENT-HN trial by the end of 2024 and present preliminary data from the study in the first half of 2025. The company believes the manageable safety and tolerability observed with the tipifarnib and alpelisib combination significantly derisks the development of its next-generation FTI, KO-2806.
KO-2806 is a next-generation FTI that Kura believes demonstrates improved potency, pharmacokinetic and physicochemical properties relative to earlier FTI drug candidates. The company is evaluating KO-2806 as a monotherapy and in combination with other targeted therapies, including tyrosine kinase inhibitors and KRAS inhibitors, in the FIT-001 Phase 1 trial. Kura dosed the first patient with KO-2806 in combination with cabozantinib in clear cell renal cell carcinoma in February 2024 and plans to dose the first patient in combination with adagrasib in KRAS G12C-mutated non-small cell lung cancer by mid-2024.
Risks and Challenges
While Kura's pipeline of targeted oncology therapies holds significant promise, the company faces several risks and challenges common to the biopharmaceutical industry. These include the inherent uncertainty of clinical development, the potential for adverse safety events, the ability to successfully navigate the regulatory approval process, and the need to secure adequate funding to support the company's ongoing operations and future growth.
Kura's reliance on the successful development and commercialization of its product candidates, particularly ziftomenib, exposes the company to the risk of clinical trial failures or delays, which could significantly impact its financial position and future prospects. Additionally, the company's ability to effectively manage its clinical trials, manufacturing, and supply chain operations will be critical to its success.
Furthermore, Kura operates in a highly competitive environment, with other biopharmaceutical companies developing targeted therapies for similar patient populations. The company's ability to differentiate its product candidates and maintain a competitive edge will be crucial to its long-term success.
Outlook
Kura Oncology is a promising oncology biotech company with a robust pipeline of targeted therapies, led by the Breakthrough Therapy-designated ziftomenib. The company's strong financial position, with 527.1 million in cash, cash equivalents and short-term investments as of March 31, 2024, provides the resources to advance its clinical programs and support its ongoing research and development efforts.
The rapid enrollment in Kura's ziftomenib studies, the encouraging safety and efficacy data observed to date, and the FDA's Breakthrough Therapy Designation for the treatment of relapsed or refractory NPM1-mutant AML suggest that ziftomenib has the potential to become a cornerstone of therapy for patients with acute leukemias. Additionally, the company's progress with its FTI programs, including the development of the next-generation KO-2806, further diversifies Kura's pipeline and provides opportunities for value creation.
Conclusion
As Kura continues to execute on its clinical development strategy and navigate the regulatory landscape, investors will closely monitor the company's ability to deliver on its milestones and demonstrate the long-term potential of its targeted oncology approach. With multiple catalysts on the horizon, Kura Oncology remains a biotech company to watch in the rapidly evolving field of precision medicine for cancer treatment.