Kura Oncology Files Prospectus: A Decade of Precision Oncology Innovation Following a One-Year-to-IPO Trajectory

Precision medicine is reshaping the blueprint of cancer treatment.

With the growing demand for personalized medicine, coupled with rapid advancements in genomic sequencing technologies and the interdisciplinary application of bioinformatics and big data science, precision medicine has emerged. It is grounded in individualized patient diagnosis and treatment, analyzing and validating disease onset and progression at the genetic and molecular levels to accurately identify disease etiologies and drug targets, thereby achieving optimal therapeutic efficacy with minimal adverse effects.

Currently, the role of precision medicine in oncology is becoming increasingly prominent, with leading pharmaceutical companies such as Pfizer, Novartis, and Amgen all establishing a presence in this sector. According to data released by Mordor Intelligence, the global precision medicine market reached $77.02 billion in 2023. Driven by factors such as the rising number of cancer cases and unmet patient needs, the market is expected to grow to $99.24 billion by 2028.

Kura Oncology (hereinafter referred to as “Kura”) is a biotechnology company in the field of precision medicine, dedicated to developing targeted therapies for solid tumors and hematologic malignancies. The company’s diversified pipeline consists of small molecules targeting cancer signaling pathways. Its drug development strategy focuses on addressing broader patient populations and leveraging combination therapies to prevent tumor resistance, ultimately delivering improved therapeutic outcomes for patients.

Kura was founded in 2014 and is led by its President and Chief Executive Officer, Dr. Troy Wilson. Under Dr. Wilson’s leadership, Kura rapidly assembled a distinguished leadership and R&D team, striving to break through the red ocean of the precision medicine market with innovative therapies. Just one year later, Kura successfully completed an initial public offering (IPO) on the U.S. OTCQB market. Over the past decade, the company has secured investments from prominent investors such as Bristol-Myers Squibb, Hercules Capital, and EcoR1 Capital, raising $1 billion across ten rounds of financing.

In 2015, as the wave of precision medicine swept across the globe, how did Kura Oncology win the favor of investors and achieve rapid growth?

The story of Kura’s 10-year development begins in 2007.

In 2007, Kura’s core founding team was established, including Dr. Troy Wilson and Professor Kevan M. Shokat, a member of the U.S. National Academy of Sciences. Both are industry experts with extensive experience and specialized expertise. Prior to founding Kura, Dr. Wilson served as President and Chief Executive Officer, as well as a board member, for multiple biotechnology companies. Professor Shokat participated in the founding of several biotechnology companies, serving as a technical partner.

The story of Kura began with Wilson and Shokat. Building on Shokat’s research, the two founded Intellikine in 2007, a drug development company focused on the PI3K (phosphoinositide 3-kinase) pathway, which was acquired by Takeda Pharmaceutical Company in 2011. Over the next four years, Intellikine advanced three candidate drugs into clinical trials. Among them, duvelisib, a small-molecule drug for the treatment of small lymphocytic lymphoma, received FDA approval and was launched in 2018.

In 2012, after the sale of Intellikine, Shokat proposed the idea of founding a new company to develop covalent inhibitor small-molecule drugs targeting the oncogenic protein KRAS G12C, building on his pioneering research conducted in his academic laboratory at the University of California, San Francisco (UCSF). Thus, Araxes Pharma was established.

The name “Araxes Pharma” was proposed by Shokat, derived from the Araxes River. The Araxes flows through Turkey, Armenia, Azerbaijan, and Iran, running along the southern side of the Lesser Caucasus Mountains before converging with the Kura River and emptying into the Caspian Sea. Additionally, Shokat was drawn to “Araxes” because it translates to “A Ras,” or simply “Ras,” referring to the RAS signaling pathway, which has been the focus of his research at UCSF.

Rather than stopping at Araxes, they traced the “river” upstream in hopes of finding the “source” of innovation. Consequently, they soon founded Wellspring Biosciences (a subsidiary of Araxes Pharma)—with “Wellspring” signifying the “source” of innovation.

During this period, Wilson and Shokat took notice of tipifarnib, a farnesyltransferase (FTase) inhibitor. At the time, tipifarnib was an investigational Phase II clinical drug under development by Janssen Pharmaceuticals and had demonstrated efficacy in certain cancer patient populations. Wilson and Shokat believed that tipifarnib could be further optimized through appropriate strategies. Consequently, after communicating with Janssen, they secured a license agreement. Leveraging the foundational developments from their two previous companies, Wilson and Shokat established a new company in 2014.

When naming the new company, they sought a name that would reflect Tipifarnib’s ability to target cancers driven by proteins “downstream” of KRAS. Thus, they continued with the metaphor of rivers representing the RAS pathway. This time, they turned their attention to the Kura River, which lies downstream of the Araxes, and named the new company Kura Oncology.

“Kura” carries a dual meaning: on one hand, the Kura River flows from the north side of the Caucasus Mountains and converges with the Aras River on the south side, symbolizing the core team’s interest in “downstream” targets of the KRAS protein. On the other hand, Kura serves as a link, connecting the team’s past efforts in oncology drug development with Kura’s future endeavors to inhibit central signaling pathways that drive cancer.

Leveraging the development experience of Araxes and Wellspring, and driven by Wilson and his team, Kura Oncology has embarked on a path of rapid growth, launching two wholly owned small-molecule drug development pipelines, with all three investigational products advancing into clinical development. As a result, Kura Oncology was honored with The Scrip Awards’ “2023 Best Oncology Drug Development Progress Award.”

Kura focuses on the R&D of Menin inhibitors and farnesyltransferase inhibitors (FTIs), with its specific products in development being Ziftomenib, Tipifarnib, and KO-2806.

Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults. Among these, KMT2A rearrangements (KMT2A-r) and NPM1 mutations (NPM1-m) are common protein alterations in AML. Research data indicate that approximately 5%–10% of AML patients harbor KMT2A rearrangements[1], while about 30% of AML patients have NPM1 mutations[2].

Despite the availability of numerous treatment options for acute myeloid leukemia (AML) and the high response rates to first-line therapy among patients with NPM1-mutated AML, patient prognosis remains poor, with high relapse rates. Furthermore, NPM1 mutations frequently co-occur with other disease-associated gene mutations, such as those in FLT3, DNMT3A, and IDH1/2. The presence of these co-mutations increases the likelihood of severe adverse outcomes.

Data show that in patients with NPM1-mutated AML who experience relapse or have refractory disease, the median overall survival (OS) is 6.1 months, and the 12-month OS rate is only 30%³. Patients with KMT2A rearrangements have an even poorer prognosis; under current standard-of-care treatment, they exhibit high rates of drug resistance and relapse, with a 5-year survival rate below 20%⁴.

Ziftomenib is an oral, selective menin inhibitor that suppresses the interaction between menin and the KMT2A/MLL protein complex for the treatment of AML patients harboring specific genetic mutations. In preclinical models, ziftomenib inhibited the KMT2A/MLL protein complex and demonstrated potent anti-leukemic activity.

Clinical trial data showed that among 20 patients with NPM1-mutated acute myeloid leukemia (AML) treated with ziftomenib at the recommended phase 2 dose (RP2D), 7 patients (35%) achieved complete remission with full hematologic recovery (CR). Notably, 33% (2/6) of patients with FLT3 co-mutations and 50% (4/8) of patients with IDH1/2 co-mutations achieved complete remission following ziftomenib treatment. The median overall survival (OS) for all patients with NPM1 mutations was 8.2 months. The incidence of adverse events (AEs) was low, with grade 1/2 AEs occurring in 15% of cases and grade 3 AEs in 5%.

Owing to its favorable safety profile, resistance profile, and patient compliance, ziftomenib has been granted orphan drug designation by the FDA for the treatment of AML. Furthermore, ziftomenib was named one of the top ten “star” small molecules of 2022 by DrugHunter.com5.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. According to data released by the Global Cancer Observatory, HNSCC accounts for approximately 890,000 new cases and 450,000 deaths annually, representing about 4.5% of all cancer diagnoses and deaths. Among these, approximately 4%–8% of HNSCC patients harbor HRAS gene mutations.

Despite some advances in treatment in recent years, the prognosis for HNSCC remains poor, particularly in patients with recurrent or metastatic disease. Data show that the 5-year survival rate for patients with stage III or IV HNSCC is only approximately 15%–35%6.

Tipifarnib is an oral selective farnesyltransferase inhibitor (FTI) for the treatment of patients with HRAS-mutant head and neck squamous cell carcinoma (HNSCC). By inhibiting the farnesylation process catalyzed by farnesyltransferase, it prevents the localization of the HRAS protein to the cell membrane, thereby suppressing signal transduction through the HRAS pathway. Preclinical studies have demonstrated its specific anticancer activity in cancer models harboring HRAS gene mutations.

Data from its Phase II clinical trial (AIM-HN) showed that, among 59 evaluable patients with HRAS-mutant head and neck squamous cell carcinoma (HNSCC), the tipifarnib treatment group achieved an objective response rate (ORR) of 30%, a median duration of response (DOR) of 5.6 months, and a median progression-free survival (PFS) of 3.7 months.

Currently, Kura is advancing a Phase 1/2 dose-escalation study of tipifarnib in combination with the PI3Kα inhibitor alpelisib to evaluate the safety and recommended dose of this combination therapy in patients with PIK3CA-mutant head and neck squamous cell carcinoma (HNSCC).

KO-2806 is a potent next-generation FTI designed to improve the potency, pharmacokinetics, and physicochemical properties of early FTI candidates, and to meet the treatment needs of patients with advanced solid tumors through combination therapy.

With the successful development of drugs such as KRAS G12C inhibitors, TKI inhibitors, and EGFR inhibitors, cancer patients have achieved significant clinical benefits; however, acquired drug resistance still emerges, and unmet patient needs persist. KO-2806 is designed specifically to overcome this challenge.

Preclinical data indicate that combining KO-2806 with various classes of targeted therapies—including TKI inhibitors, KRAS G12C inhibitors, and KRAS G12D inhibitors—has the potential to overcome or prevent cancer cell resistance to certain drug classes.

Currently, Kura is conducting a Phase 1 clinical trial (FIT-001) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of KO-2806 as both monotherapy and combination therapy in adult patients with advanced solid tumors. Recently, Kura announced that the first patient has been dosed.

In February 2015, China established the Expert Group on National Precision Medicine Strategy. In March, the first national expert conference on precision medicine strategy proposed that China would invest RMB 60 billion in the field of precision medicine by 2030. In 2016, the “Notice on the 2016 Project Application Guidelines for Key Special Projects such as Precision Medicine Research under the National Key R&D Program” was released, listing precision medicine research as one of the key special projects to be prioritized and officially launched in 2016, thereby entering the implementation phase.

In 2022, the National Development and Reform Commission released the “14th Five-Year Plan for Bioeconomy Development,” proposing to enhance original innovation capabilities with a focus on advanced diagnostic and therapeutic technologies and equipment, precision medicine, and testing and inspection. Although China’s precision medicine sector has a relatively short development history, its overall trajectory is positive.

According to the "Report on Global Precision Medicine Industry Development Prospects Forecast and Investment Strategic Planning Analysis" released by Qianzhan Industry Research Institute, from 2016 to 2022, the annual average growth rate of the domestic precision medicine industry market size reached 18.5%. In 2022, this market size exceeded RMB 200 billion, representing a year-on-year increase of approximately 14%. In the future, China's precision medicine market size will maintain its growth trend.

As of June this year, there were 4,887 registered enterprises in China’s precision medicine industry. Among them, BGI Genomics, New Horizon Health, Vcanbio, and Dian Diagnostics are upstream players in the precision medicine sector, providing services for precision prevention and precision diagnosis, such as cell storage and therapy, genetic testing and diagnosis, immunodiagnostics, and molecular diagnostics.

In the future, will more companies emerge that focus on the downstream segment of precision medicine, innovate precision therapeutics, and meet patient needs? Time will tell.

References:

1. Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest. 2020;130(2):981-997. 2.

2. Prata PH, Bally C, Prebet T, et al. NPM1 mutation is not associated with prolonged complete remission in acute myeloid leukemia patients treated with hypomethylating agents. Haematologica. 2018;103(10):e455-e457.

3. Angenendt L, Röllig C, Montesinos P, et al. Chromosomal abnormalities and prognosis in NPM1-mutated acute myeloid leukemia: a pooled analysis of individual patient data from nine international cohorts. J Clin Oncol. 2019;37(29):2632-2642.

4. Issa GC, Zarka J, Sasaki K, et al. Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements. Blood Cancer J. 2021;11(9):162.

5. molecules of the year 2022，Retrieved March 14th, 2023, from https://drughunter.com/molecules-of-the-year/2022/

6. Ridge JA, Glisson BS, Lango MN. Head and neck tumors. February 18, 2011. Accessed April 4, 2023. https://www.cancernetwork.com/view/head-and-neck-tumors