KURA - Kura Oncology: Riding The Menin Hype Wave In AML Therapy

2023-12-12 15:32:16 ET

Summary

• Kura Oncology is an oncology-focused biotech developing targeted therapies for various forms of cancer with high unmet need.
• Their pipeline includes ziftomenib for AML, with promising phase 2 results and a potential data readout in 2024.
• They are also developing tipifarnib for HRAS-mutated HNSCC, with breakthrough therapy designation and positive response rates in early trials.

Topline Summary

Kura Oncology ( KURA ) is an oncology-focused biotech developing several different kinds of targeted therapy for different forms of cancer with high unmet need. In this article, I provide a synopsis of their pipeline, as well as the justification for my tentative optimism in the company. Overall, I think they're worth a good, hard look, and a consideration of a small position in your portfolio, if you don't have one already.

Pipeline Overview

Ziftomenib

The current main claim to fame for KURA is ziftomenib, an inhibitor of an emerging target called menin, which has demonstrated key potential in the setting of acute myeloid leukemia. In particular, Syndax's revumenib has generated a lot of interest in the space of AML for patients who harbor mutations in the KMT2A gene.

KURA is focusing development of ziftomenib on the subset of AML harboring NPM1 mutations, and the last we heard about this approach was at EHA 2023 back in June, where the company presented a late-breaking abstract demonstrating a 35% rate of complete remission in patients who received the recommended phase 2 dose of ziftomenib. The duration of response was reportedly 8.2 months, and ziftomenib showed early activity in patients with other actionable co-mutations like FLT3 and IDH1 . Although it should be noted that these were very small patient subsets.

The registrational portion of this trial (KOMET-001) began back in February 2023 , and in the latest quarterly filing they indicated that enrollment is proceeding well and is expected to be completed in the first half of 2024. Given that median follow-up in the phase 1 study was 8.8 months, I believe it is reasonable to expect a data readout either at EHA 2024 or ASH 2024, and KURA believes this phase 2 study will have "registrational potential."

KURA is also conducting a few combination trials of ziftomenib and other agents like venetoclax, azacitidine, and chemotherapy in the KOMET-007 and KOMET-008 studies, from which the company expects to have data in the first half of 2024. No results have been posted to date.

Tipifarnib

This farnesyl transferase inhibitor has been in development for a long time, having first been licensed from Janssen back in 2015. Farnesyl transferase is responsible for shuttling Ras protein to its proper location in the cell during signal transduction, and it is thought that inhibiting this enzyme could be one backdoor to inhibiting Ras function as a cancer target.

To date, none of the stories for tipifarnib have panned out, but KURA is continuing on with something promising. They currently have Breakthrough Therapy Designation for tipifarnib in the setting of HRAS- mutated head and neck squamous cell carcinoma (HNSCC), a form of cancer that remains a serious unmet need.

Indeed, they seem to have broken through with tipifarnib. In a late-breaking abstract at ESMO 2023 , KURA highlighted findings from 59 patients with HRAS -mutated HNSCC. Of the 38 patients who had evaluable disease, independently assessed responses were shown in 10 patients (1 with complete response). The median duration of response by independent assessment was 6.5 months.

This response rate is in general agreement with findings of other second-line studies , which show responses in just over 10% of patients. Toxicity led to discontinuation in 7% of the patients enrolled in the study. KURA has not guided on a timeline for initiating a pivotal trial or a possible path to approval, but these findings do provide a signal of efficacy for farnesyl transferase inhibitors in the setting of selected subgroups of HNSCC. They are also conducting a notable phase 1/2 trial of tipifarnib in combination with Novartis's PI3K inhibitor alpelisib in patients with PIK3CA -amplified or -mutated HNSCC.

KO-2806

Building on tipifarnib, KURA is also developing a next-generation farnesyl transferase inhibitor, with the intention of improving various pharmacokinetic and pharmacodynamic properties. The IND for KO-2806 was approved in January 2023, and the monotherapy trial had its first patient treated back in October .

Also of note, KURA announced a collaboration with Mirati Therapeutics to combine KO-2806 and the KRAS G12C inhibitor adagrasib in patients with KRAS G12C-mutated non-small cell lung cancer, signaling a potential future pathway for this agent.

Financial Overview

Per their Q3 2023 filing , KURA held $28.7 million in cash and equivalents, with another $423.9 million in short-term investments. Meanwhile, operating expenses reached $42.5 million for the quarter, up from $36.5 in the same period of 2022. After interest and other income, the company realized a net loss of $38.6 million.

With these reserves, KURA has an operational runway of 10-11 quarters.

Strengths and Risks

KURA presents an interesting investment case, with favorable early trial results in two very different targeted therapy areas. With tipifarnib, there aren't really any meaningful competitors. For ziftomenib, however, there are quite a few companies vying for the crown of menin inhibition. But the results of menin inhibition are looking good enough in general to support this as a therapeutic approach in AML, and a potential drug approval would be a net positive, even in the face of competition.

The cash reserves of KURA also represent a strength, in my opinion. With well over a year of runway, this should be plenty of time to see some critical clinical trial results and a possible path to accelerated approval demystified.

Bottom-Line Summary

KURA is entering a period of critical mass as far as clinical trial data go, and they've got the cash to support their efforts for the foreseeable future. This makes me optimistic overall about their prospects, and I would give it a "buy" recommendation. As always, take into consideration that there is a high risk of drug development failure, even when things look promising in these early stages. Furthermore, there is no guarantee that the studies they're conducting will end up being registrational, at which point we'll need to wait a much longer time for confirmatory, randomized trials to be completed. Still, there is much room for further growth for KURA.

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