BMY - Kura Oncology: Targeted AML Therapy Continues To Deliver

2023-07-12 16:23:16 ET

Summary

• Kura Oncology, Inc. has additional updated results released from the KOMET-001 study, as part of an oral late-breaker presentation shown on June 11, 2023 at the EHA; 35% achieved CR with full count recovery.
• The global Acute Myeloid Leukemia market is expected to reach $2.69 billion by 2028; 30% of AML patients have the NPM1 mutation and 5% to 10% have the KPT2A-rearranged mutation.
• KOMET-007 and KOMET-008 are two studies being launched to explore the synergistic effects of combining ziftomenib with other standard of care therapies for 1st line NPM1 and/or KMT2A-rearranged AML patients.
• The KURRENT-HN study is exploring the use of tipifarnib for the treatment of patients with PIK3CA-dependent head and neck squamous cell carcinoma.

Kura Oncology, Inc. ( KURA ) is advancing the use of its drug ziftomenib as a monotherapy for the treatment of patients with relapsed/refractory NPM1-mutant acute myeloid Leukemia [AML]. It continues to make progress in this area, which is why I believe that it may offer some value to investors.

Kura is currently running a registration directed phase 2 study, which is using this drug to specifically target this AML patient population who have this NPM1 genetic mutation. It presented additional data from the phase 1/2 KOMET-001 study using ziftomenib for this AML patient population back on June 11, 2023 at the European Hematology Association [EHA] Annual Congress. This updated data was presented as part of a late-breaking oral session.

The company is not just stopping here in only targeting NPM1-mutant AML patients who are relapsed/refractory. Its goal is to advance other studies which are to be known as KOMET-007 and KOMET-008. These studies are being launched to test ziftomenib in combination with other treatments.

The reason why is so that it could possibly expand the use of ziftomenib to target first line NPM1-mutant and KMT2A-rearranged AML patients with combinations. It expects to dose the first patients for both of these studies in the coming months. Another expected event is that it plans to select the most optimal dose for the phase 1/2 KURRENT-HN trial it is running. This particular study is using tipifarnib in combination with alpelisib for the treatment of patients with PIK3CA dependent head and neck squamous cell carcinoma [HNSCC]. Such a dose selection is expected to happen at some point in mid-2023. With continued progress in helping patients with NPM1-mutant AML, plus potential to expand to earlier lines of therapy targeting this AML mutant patient population, I believe that investors might be able to benefit by any potential gains made here in the coming months.

Ziftomenib Continues To Deliver Promising Results For Specific Acute Myeloid Leukemia Patient Population

A good thing about Kura Oncology is that it had established some great proof of concept over the years in being able to use its drug ziftomenib to treat patients with NPM1-mutant acute myeloid Leukemia. It is also hoping to be able to expand to targeting KMT2A-rearranged AML patients as well with ziftomenib. Acute myeloid leukemia is a type of cancer of the blood and bone marrow whereby excess immature white blood cells are present. It progresses rapidly, which is bad since it greatly interferes with the production of normal white blood cells, red blood cells, and platelets in the body. Symptoms that these AML patients might experience are as follows:

• Fatigue
• Being bruised easily
• Recurrent infections.

It is a pretty large market opportunity as well for Kura Oncology. That's because it is expected that the global Acute Myeloid Leukemia market is expected to reach $2.69 billion by 2028 . However, as I noted above in the beginning, this company is only targeting a specific portion of the AML population. It is going after relapsed/refractory AML patients who have the NPM1-mutation. It is not a bad population to go after, because it is said that about 30% of AML patients harbor the NPM1 mutation.

Then, you have to consider the two expansion opportunities I highlighted above as well. The first expansion opportunity would be the targeting of KMT2A-rearranged AML patients. It is said that between 5% to 10% have this specific mutation. Secondly, there will be an exploration of using ziftomenib in combination with other SOC drugs to go after earlier lines of therapy for AML patients [First-line treatment]. Therefore, as you can see, there are additional ways to expand the use of ziftomenib for this AML patient population.

As I noted above, Kura Oncology continues to make positive progress in being able to use monotherapy ziftomenib for the treatment of patients with AML. It reported additional results from the KOMET-001 study, as part of a late-breaking oral session at the European Hematology Association [EHA] Annual Congress in Frankfurt Germany. Such data from this particular study, using ziftomenib to treat relapsed/refractory NPM1-mutant AML patients was presented on June 11, 2023. It was shown that as of the data cutoff date of April 12, 2023, 7 out of 20 patients [35%] with NPM1-mutant AML treated with a recommended phase 2 dose [RP2D] of 600 mg of ziftomenib, had achieved a complete response [CR] with full count recovery . There were other additional positive data highlighted from the study as well, which were as follows:

• 2 out of 6 [33%] patients with FLT3 co-mutations achieved CR when given ziftomenib
• 4 out of 8 [50%] patients with IDH co-mutations achieved CR when given ziftomenib
• 2 patients that had a stem cell transplant remain in remission as of data cutoff, including one on post stem cell transplant treatment ziftomenib maintenance therapy
• An 8th patient who had a CR with incomplete recovery eventually became a complete responder and remains on the study.

While this data is indeed good, there are two clinical findings that were far more intriguing. For starters, the data also showed that patients with prolonged exposure use of ziftomenib monotherapy, were less likely to evolve with MEN1 mutations over time. A second finding, which I believe is far more important, is that the drug had strong evidence of mechanistic synergy with standard of care [SOC] drugs such as venetoclax and FLT3 inhibitors. Why was this an important finding? That's because such a finding can be evolved to advance the use of ziftomenib + combination regimens to target earlier lines of patients with NPM1-mutant and KMT2A-rearranged AML.

Ziftomenib Synergistic Combinations Will Allow Expansion Of Possible AML Patients To Be Targeted

Ziftomenib alone as a monotherapy is pretty good, but it remains to be see how well it does in the phase 2 registration directed study, whereby the first patient was dosed in February of 2023 . It is expected that a total of 85 patients with relapsed/refractory NPM1 mutant relapsed/refractory AML will be recruited. The primary endpoint for this study is complete response [CR] or CR with partial hematologic recovery [CRh]. How can Kura Oncology benefit with respect to the advancement of ziftomenib monotherapy? It is because there are no approved targeted therapies for this specific AML patient population - yet.

The next move for this company, with this positive clinical data achieved to date, is to expand upon the possible AML patients that can be targeted with ziftomenib. As such, it expects to advance two clinical studies in 2023, which are going to be known as KOMET-007 an KOMET-008. With respect to KOMET-007, this study is going to explore the use of ziftomenib in combination with other therapies to treat patients with NPM1-mutant and KMT2A-rearranged AML. It is hoping to combine its menin inhibitor drug ziftomenib with other standard of care [SOC] therapies such as:

• Ventoclax plus azacitidine
• FLT3 inhibitors
• Standard induction cytarabine plus daunorubicin [7+3].

Kura Oncology is on track to dose the first patients for the KOMET-007 this quarter. Besides the possibility of finding an effective combination treatment in this study, it is also looking to launch another study as well. I'm talking about the plan for this biotech to initiate another study, which will evaluate ziftomenib combination treatments for NPM1-mutant and KMT2A-rearranged AML patients, expected in the coming months. This other trial is going to be known as KOMET-008, but unlike KOMET-007, it is going to use different SOC regimens to treat these specific AML patients. The other therapies that Kura hopes to combine with ziftomenib are as follows: Giltertinib, Flag IDA and LDAC.

Financials

According to the 10-Q SEC Filing , Kura Oncology had cash, cash equivalents and short-term investments of $405.9 million as of March 31, 2023. It should be good on cash for a very long time and the reason why I state that is because of the projection that it gave investors with respect to the most recent earnings release. It stated that with the current cash on hand, it believes that it has enough to fund its operations into Q4 of 2025.

Not only does it have a long cash runway, but it has been able to raise cash through several other methods. For starters, in November of 2022 it entered into a loan and security agreement "Loan Agreement" with Hercules Capital, Inc. (HTGC) to provide up to $125 million in a series of term loans.

It borrowed $10 million upon making this loan agreement and still has up to an additional $115 million it can draw upon should it need to. Not only that, but around the same time it also raised $25 million with an equity investment from Bristol-Myers Squibb ( BMY ) as well. Prior to this, in February of 2022 it entered into a new Common Stock Sales Agreement with SVB Securities LLC, Credit Suisse Securities [USA] LLC and Cantor Fitzgerald & Co., or ATM Facility, whereby it could sell from time to time up to $150 million. As you can see, Kura Oncology has several options it could take if it intends to raise additional cash when needed.

Risks To Business

There are several risks that investors should be aware of before investing in Kura Oncology. The first risk to consider would be with respect to the ongoing phase 2 registration-directed study, which is using ziftomenib for the treatment of patients with relapsed/refractory AML with the NPM1-mutation. While data continues to come in strong from the phase 1/2 KOMET-001 study, there is no guarantee that a similar positive outcome will be achieved in the ongoing phase 2 registration-directed study.

A second risk to consider would be the advancement of testing out ziftomenib in combination with other SOC therapies for the treatment of first-line AML patients with the NPM1 or KMT2A-rearranged mutations. While it appears as though ziftomenib has synergistic effects together with other therapies like venetoclax, azacitidine and others, there is no assurance that such combinations will end up doing better than ziftomenib monotherapy.

A third risk to consider would be with respect to the ongoing advancement of the phase 1/2 KURRENT-HN study. This trial is exploring the combination of tipifarnib plus alpelisib for the treatment of patients with PIK3CA dependent head and neck squamous cell carcinoma [HNSCC]. There is no guarantee that the most optimal dose will be found with respect to this study by mid-2023. Another risk to consider is that should efficacy data not be good from this KURRENT-HN trial, then Kura might decide to stop it entirely.

Conclusion

Kura Oncology has done well to specifically target relapsed/refractory AML patients with the NPM1 mutation with ziftomenib monotherapy. This is evidenced with the release of updated results from the KOMET-001 study, whereby as of the April 12, 2023 cutoff date, it was noted that 35% of NPM1 mutant AML treated patients had achieved a CR with full count recovery with the recommended phase 2 dose of 600 mg of ziftomenib. It has potential to expand the use of ziftomenib with other SOC therapies by going after first-line NPM1 and KMT2A-rearranged mutant AML patients with combinations.

A good thing about Kura Oncology, Inc. is that it is not purely relying on the use of ziftomenib to boost shareholder value. It is also exploring the use of a farnesyl transferase inhibitor [FTI] known as tipifarnib for the treatment of patients with PIK3CA-dependent HNSCC. The use of this drug for the treatment of this patient population is being explored in the ongoing KURRENT-HN trial. A recommended phase 2 dose [RP2D] might be obtained by mid-2023 and this would then allow for the next stage of clinical testing. Speaking of an FTI drug, it is advancing a next-generation FTI known as KO-2806. The FDA has cleared the submitted IND for this drug candidate, and it is expected that it will be used to treat patients with advanced solid tumors.

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