SNDX - Kura Oncology: Good Cash Some Good Data A Few Problems

Summary

• Kura Oncology, Inc. has two assets, and both produced decent data.
• Each asset has its own set of problems.
• Kura Oncology is set for cash.

I covered Kura Oncology, Inc. ( KURA ) two years ago, when I said that, although I like the company’s science, per se, lead asset tipifarnib does not have adequate patent protection. It is an old, ex-Janssen molecule, and the composition of matter patent expired in 2016. What they have left is NCE exclusivity, which is given for 5-years to a drug, no active ingredient of which is approved for any other indication. The same molecule is, however, being pursued by Eb Pharma

About this, Kura said in a 10-K filing:

EB Pharma has licensed rights from Janssen to develop tipifarnib in virology indications. If EB Pharma obtains regulatory approval for tipifarnib in a virology indication before we obtain regulatory approval in one of our oncology or other non-virology indications, the five-year exclusivity period would commence on the date upon which EB Pharma obtains regulatory approval, and as a result, the period of regulatory exclusivity to which we may be entitled may be reduced or eliminated and the commercial prospects for tipifarnib could be harmed as a result.

Additionally, if EB Pharma obtains approval of tipifarnib for a virology indication, EB Pharma may sell tipifarnib at a lower price, which could adversely affect the price at which we could sell tipifarnib for oncology or other non-virology indications.

However, I could not find tipifarnib on EB Pharma’s list of drugs it is pursuing for approval - see here . EB Pharma is a Taiwanese subsidiary of Eiger Pharma. Just to be thorough, I checked Eiger’s website as well, and could not find tipifarnib among its pipeline drugs. Thus, it could quite well be that we are needlessly worrying about tipifarnib getting earlier approval at EB Pharma.

Also, it appears that Kura has now pushed ziftomenib higher in the hierarchy of its pipeline . Although tipifarnib still has the later stage trial - in Head & Neck Cancer - this move appears significant. Here’s a look at its current pipeline:

Ziftomenib is a “menin inhibitor” which is targeting NPM1-mutant AcuteMyeloid Leukemia ((AML)) as a monotherapy in the Komet-001 trial. This is a phase 1/2a trial open-label, dose-escalation and dose-validation/expansion study. In December, the company published data for ziftomenib at the ASH. The data was from the r/r AML patient population. Data showed that treatment with ziftomenib produced just one complete remission ((CR)) with no evidence of minimal residual disease ((MRD)) among 30 R/R AML patients in an all-comer trial. This was a patient who had received 7 prior lines of therapy, and was now on remission using ziftomenib for two years.

The company said that the patient with CR, who had received seven prior lines of therapy, remains on ziftomenib after two years. However, in NPM1-mutant AML patients in a phase 1a dose-escalation trial, there was a 30% CR rate at 600mg dose, and 17% CR at 200 mg dose. 30% of all new AML cases are NPM1-mutant.

Of the two randomized expansion cohorts in this 53-patient trial, some patients had KMT2A-rearranged AML. The trial performed poorly in this population. Kura explained:

Although meaningful clinical benefit was observed in patients with KMT2A rearrangements, symptoms of differentiation syndrome prevented most patients from receiving sufficient therapy to attain response criteria for CR or CR with partial hematologic recovery ((CRH)), and only one patient achieved a CR/CRh.

The company plans to do further studies in this population. They will also begin a registration-directed phase 2 trial in NPM1-mutant patients at 600mg dose in Q1 2023.

Interestingly, at ASH, rival menin inhibitor developer Syndax ( SNDX ) also published data. This was a Phase 1/2 trial for its lead candidate revumenib (SNDX-5613) in relapsed/refractory AML or acute lymphoid leukemias ((ALL)). Ruvemenib showed a 53% ORR and 30% CR/CRh in efficacy evaluable AML patients. Other key data for Ruvemenib:

CR/CRh rate stood at 27% in both mNPM1 (3/11) and KMT2Ar (MLLr) (10/37) R/R acute leukemia patients treated at recommended Phase 2 dose (RP2D).

As for safety, 10% treated at the RP2D and 13% treated at all doses experienced asymptomatic Grade 3 QT prolongation, which, the company said, was the only dose-limiting toxicity. No patients discontinued the treatment due to related adverse events.

However, as for safety, note that two years earlier, Kura’s ziftomenib also produced some troubling safety data:

severe (Grade 3) tumor lysis syndrome (a deadly complication of blood cancers) at 50 mg and a severe embolic (blood clotting) event at 100 mg.

I'm struck by the contrast in an update 10 months later:

On the safety front, there have been no drug discontinuations due to treatment-related adverse events, and the continuous daily dosing of KO-539 has been well tolerated with a manageable safety profile to date.

Indeed, a year later, this molecule was placed on a partial clinical hold after a patient's death due to complications arising out of differentiation syndrome, something we also saw in the latest data update. The hold was lifted a few months later after the FDA discussed a mitigation strategy for differentiation syndrome with Kura.

Thus the SNDX data appeared much better than Kura’s, and investors punished Kura with a 14% drop on that day, while SNDX gained 14%. Two years earlier, too, SNDX was the leader that was able to pull the menin inhibition space up. At that time, SNDX posted positive data that helped pull up KURA stock, not just SNDX. However, as the two assets are becoming increasingly differentiated, that sort of “sympathetic detonation” is not happening any longer. Syndax has its own problems with cardiac toxicity, but revumenib targets a broader population.

Thus, both of Kura’s assets have problems. I discussed tipifernib in my earlier article. I noted that one of their problems, that the FDA has asked them for a diagnostic plan for tipifernib patients, has been on the path to resolution after the company teamed up with Illumina for the diagnostic effort. However, today we now see that the other asset, ziftomenib, too has not provided stellar data. Kura has no other major assets. Ziftomenib’s NPM1 population showed competitive data with Syndax, however in KMT2A patients ziftomenib had nothing wile rivumenib had decent data.

Financials

KURA has a market cap of $950mn and a cash balance of $428mn. In November, they received a $25 million equity investment from Bristol Myers Squibb and $125 million term loan facility from Hercules Capital. Research and development expenses for the third quarter of 2022 were $25.0 million, while general and administrative expenses were $11.6 million. That gives them a runway till 2026 with their current cash runway.

Bottom Line

Kura Oncology, Inc. is set for cash for a number of years, and its assets have produced competitive data in some respects. However, both assets have some issues; tipifarnib has its IP problem, while ziftomenib has its rival, Syndax. I would like to see more of this company, but not planning an investment in Kura Oncology, Inc. right now.

For further details see: