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$KURA - Kura Oncology

$KURA – Kura Oncology

Overview:

Kura Oncology was created in 2007 and is based in California.  The company is utilizing the genomic revolution to transform how cancer is treated, understanding that a patient’s response to treatment depends partially on the cancer’s genetic makeup.  With an advancing pipeline of precision medicines for the treatment of both solid tumors and blood cancers, their small-molecule candidates specifically target signaling pathways and other drivers of cancers where there is a strong scientific and clinical rationale to improve the outcomes by identifying patients most likely to benefit from treatment.

The CEO of the company is well versed in the biotech industry as he is not only CEO of Kura, but also a member of the board of directors for Puma Biotechnology, Zosano Pharma, as well as president and CEO of Wellspring Biosciences, Araxes Pharma, and Avidity Biosciences.  Along with his history in the biotech industry, his management, advisory, and leadership teams are all stacked with extensive experience.  While the resume is quite impressive, it does strike concern in me that this man is a member of several executive boards as well as CEO and president of several different companies.  I believe a pharma company that is pushing multiple candidates in their pipeline through Phase I and II studies should not have his attention diverted between 5+ different companies. 

Anyways, the company has three primary focuses for their development.  Precision Medicines, Targeted Therapeutics, and Biomarkers.  Utilizing precision medicine, they want to discover and develop innovative therapies designed to inhibit abnormally functioning cellular pathways that drive cancer growth.  These two categories will be paired with molecular diagnostics to identify biomarkers specific to tumors to better decide which patients will likely respond to treatments.

Pipeline:

The company currently has 3 different candidates within its pipeline, with their flagship product being Tipifarnib.  This oral, investigational drug candidate is currently being evaluated in multiple Phase II clinical trials for four different indications.

 

Tipifarnib – Farnesyl Transferase Inhibitor

KO-947 – ERK Inhibitor

KO-539 – Menin-MLL Inhibitor

 

Tipifarnib is the most advanced drug in their pipeline, the furthest developed at Phase II while the others are in Phase I and preclinical.  We will discuss Tipifarnib below. 

KO-947 is being evalued in Phase I, and operates by blocking the activity of the enzyme extracellular signal-regulated kinase (ERK), which is a critical component of signaling pathways that has been implicated in various cancer processes, including survival, growth, and proliferation of tumor cells.  Phase I clinical trials are being conducted on patients with locally advanced unresectable or metastatic, relapsed, and/or refractory non-hematological malignancies.  Below is a poster presentation of the studies and function of this drug candidate. 

https://kuraoncology.com/wp-content/uploads/Burrows-AACR-2018.pdf

 

KO-539 is being evaluated in preclinical testing for treatment of specific types of leukemia.  Functioning by blocking the interaction of two proteins, menin and MLL that together, are critically important for survival, growth, and proliferation of certain kinds of leukemia cells.  Below is a poster presentation of the research being conducted on this candidate.

https://kuraoncology.com/wp-content/uploads/2017-AACR-NCI-EORTC-Menin-Formatted-Poster-2017-10-18.pdf

 

Specific Drug:

While Kura has a relatively new pipeline, their main candidate is Tipifarnib.  This flagship product is being studied for four different indications at the company, however we are focused on one specifically.  For the indication of Head and Neck Squamous Cell Carcinomas (HNSCC), this mid October the company is going to be presenting updated data from their Phase II study at the European Society for Medical Oncology.  In conjunction with that presentation, the company plans on initiating a pivotal trial in Phase III in the second half of 2018, which could very well land right around their presentation, providing a great opportunity for price action moving upwards.

Tipifarnib, an oral drug that functions by blocking the activity of an enzyme called farnesyl transferase.  Protein farnesylation is a key signaling process implicated in various cancer processes, including survival, growth, and proliferation of tumor cells.  With more than 5,000 oncology patients having been studied on the drug and observed to have manageable side effects, it is suggested that tipifarnib has the potential to provide benefits to specific cancer patients with limited treatment options.

For the specific indication and use in patients with Head and Neck Cancers, the company is evaluating tipifarnib in patients that carry HRAS mutations.  HRAS is a proto-oncogene, a gene that has the potential to cause cancer, that when mutations occur or there is an increased expression, can cause this normal gene to become cancerous.  Proto-oncogenes code for proteins that help regulate cell growth and differentiation, and HRAS is mutated or expressed in certain head or neck squamous cell carcinoma tumors.  HRAS has been known for over 40 years, yet there are no targeted therapies for tumors with the mutated form of HRAS.  The company hopes that its product tipifarnib will selectively inhibit farnesyltransferase, a critical enzyme for the activity in HRAS.  The relapsed or refractory HNSCC patient population has a survival rate of six to eight months and existing therapeutic options only produce a response rate of 10 to 20 percent. For this reason, HRAS is often called an undruggable oncogene. 

HRAS mutations are observed in 5% of HNSCC cases, generating a direct need that has no products to fill.  Early research shows that tipifarnib induces deep, sustained regression in HRAS mutations.  Clinical proof -of-concept has been achieved in HRAS mutated HNSCC cases with durable responses being observed.  So farm, Kura’s research is demonstrating that HRAS is a targetable mutation in HNSCC and illustrates that there is potential for tipifarnib in the treatment of additional HRAS-mutant squamous cell carcinomas. 

So far, preliminary Phase II data which will be updated soon demonstrates many positive points.  Tipifarnib demonstrates an overall response rate of 83% in its patients and is not only generally well tolerated, but also shows a benefit in use.  HRAS mutant HNSCC patients saw no benefit from prior therapies including chemotherapy, cetuximab, and immunotherapy, however patients had responded well or provided a partial response when treated with tipifarnib.  This data is displaying that the mutant HRAS oncogenes are targetable as well as providing evidence that tipifarnib is effective for recurrent or metastatic HNSCC carrying HRAS mutations.  This was confirmed in 5 of 6 HNSCC patients and did so with rapid responses where other treatments had failed to provide any response.  

Here is a poster presenting the data, research, and more of the indication of tipifarnib in HNSCC.

https://kuraoncology.com/wp-content/uploads/Kessler-AACR-2018.pdf

https://kuraoncology.com/wp-content/uploads/KO-TIP-001-HN-Scottsdale-Poster-44-in-by-40-in-v2018-02-12-FINAL.pdf

 

Market Outlook and Competition:

This market looks like it will continue to grow higher in the foreseeable future.  Driven mainly by alcohol and tobacco abuse, it is expected that the global head and neck cancer market will grow at an astounding CAGR of 22.6% from 2018 to 2023.  This would push the market to reach $2.3 billion by the end of that growth period.  The World Health Organization estimates that there are more than 550,000 cases and nearly 300,000 deaths worldwide each year.  Roughly 90% of head and neck cancers are squamous cell carcinomas, creating the sixth leading cancer by occurrence.  An estimated 63,000 Americans developing head and neck cancer annually, and 13,000 dying of this disease. In Europe, there were approximately 250,000 cases of cancer registered and 63,500 deaths in 2012.  Looking back at our numbers earlier, roughly 5% of these cases are due to HRAS mutations, the precise market that Kura is targeting and has no current, successful treatment option.

Drugs approved for head and neck cancer include Abitrexate (Methotrexate), Blenoxane (Bleomycin), Bleomycin, Cetuximab, Docetaxel, Erbitux (Cetuximab), Folex (Methotrexate), Folex PFS (Methotrexate), Hydrea (Hydroxyurea), Hydroxyurea, Keytruda (Pembrolizumab), Methotrexate, Methotrexate LPF (Methotrexate), Mexate (Methotrexate), Mexate-AQ (Methotrexate), Nivolumab, Opdivo (Nivolumab), Pembrolizumab, Taxotere (Docetaxel). Drug combinations used in head and neck cancer include TPF – Docetaxel (Taxotere), Cisplatin (Platinol), and Fluorouracil. Drugs in the phase III clinical pipeline for SCCHN include Avelumab, Durvalumab, Gilotrif/Giotrif (afatinib), Multikine (leukocyte interleukin), Tremelimumab, and Yervoy (ipilimumab). The immune checkpoint inhibitors (durvalumab, tremelimumab, ipilimumab and avelumab) are expected to obtain approval by 2021.  However, none of these products are specifically targeting HRAS mutations.

 

Finances:

The company recently underwent a public offering of common stock on July 2, 2018 in which the company sold an aggregate of 4,600,000 shares of common stock at a price of $16.75 per share. Net proceeds from the public offering, after deducting underwriting discounts, commissions and offering expenses, were approximately $74.5 million.  This Q2 2018, the company posted R&D expenses of $11.5 million, more than double that of Q2 2017 and a 50% increase in administrative expenses.  The net los for the quarter was $14.7 million, or $0.45 per share, again more than double the loss of last year, but only a $0.05 loss per share due mostly to the dilution which occurred this past July. 

Kura does have cash and cash equivalents which total $200.4 million due to the raise in capital form the offering, which will allow the company to have enough cash to fund current operations through 2021.  Thankfully for investors, this means that they do not plan on diluting any time soon.  I would however likely expect a dilution in about a year, around the same time they did this year just to keep the cash on hand at a high level.

 

Review:

This company looks promising.  This product has a decently sized market that is expected to grow at over 20% for the next 5 years.  That is an astounding number that provides a great opportunity for Kura to fill an unmet need.  The stock has been trading between $14 and $24 through 2018, and is settled right now at a good support level of $16.75.  It has traded down this past month after posting an earnings loss and following the dilution, however I see a turn around coming. 

With the high amount of cash on hand and updated data coming out as they present at the ESMO as well as initiating a Phase III study in coming weeks/months, you will see a pop in price here. This company might be a great long-term hold, as they are producing a product that will fill an unmet need, however success at the end of the road is not guaranteed.  Oncology drugs that pass Phase I have only shown a likelihood of approval of 5%, compared to an average of 12% for all other indications outside of oncology.

Short term, Phase II data is really showing safety.  I see that survival rates for HNSCC are low, incident rates are high, and this drug is well tolerable.  I think Phase II will see success and going into Phase III you will see a price increase.  Results from Phase III however is a different story.  My play here would be a short to medium term investment for now.  Their flagship drug has 4 indications that seem to have high potential as well as two other candidates in their pipeline.  There will be activity over the next year and with the volatility and price range that this stock sees, I think anything around $16 would be a good buy as we will likely see $22 before the start of 2019.

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