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Tuesday, November 15, 2016

MabVax Reports Highly Encouraging Phase 1 Data In Pancreatic Cancer

Interim Data Shows Safety & Target Specificity

MabVax Therapeutics, Inc. (NASDAQ: MBVX) is an incredibly intriguing and undervalued biopharma company developing proprietary monoclonal antibody (mAb) products for the treatment of cancer. Management is currently examining MVT-5873 and MVT-2163 in a Phase 1 clinical study for the treatment and detection of metastatic pancreatic cancer, one of the most lethal forms of cancer in the U.S. On November 14, 2016, the company provided an update to investors on the status of that very important program.

Quick Background

MabVax’s novel platform technology involves a unique twist on the generation of fully human monoclonal antibodies derived from patients vaccinated with an anti-cancer vaccine. This technology is in contrast to antibodies produced in mice or in vitro. MabVax's cancer vaccines are designed to elicit an immune response to a highly specific antigen found almost exclusively on cancer cells. For example, the company’s lead antibody candidate, HuMab-5B1, was derived from a patient immunized with a cancer vaccine targeting sialyl LewisA (sLeA), a carbohydrate antigen found almost exclusively on cancer cells.

The initial focus is on pancreatic cancer, a logical approach because sLeA is found in up to 92% of pancreatic cancers and its expression is correlated with more aggressive phenotypes (1). The company is taking advantage of HuMab-5B1's high specificity and minimal off-target binding to develop the drug via multiple pathways: as a therapeutic (MVT-5873), a PET-imaging agent (MVT-2163), and a radioimmunotherapy (MVT-1075) for patients with pancreatic cancer.


The Phase 1 Trial

MabVax is currently conducting a Phase 1 trial with MVT-5873 in subjects with advanced (stage 3 or 4) pancreatic cancer. It's an open-label, multicenter, dose escalation trial designed to evaluate the safety and determine the maximum tolerated dose (MTD) of MVT-5873 as monotherapy (Part 1) and in combination with a standard of care chemotherapy (Part 2) in subjects with advanced pancreatic cancer. Secondary measures include pharmacokinetics (PK) and biodistribution data, as well as the relationship between circulating CA19.9 (sLeA) levels and tumor response.

According to the interim update announced on November 14, 2016, the safety of MVT-7853 has been established at three increasing dose levels by treating 16 patients at three concurrent clinical sites. This is important because moving into Part 2 of the study is contingent upon establishing safe doses for MVT-7853 as a monotherapy in patients with relapsed/refractory disease. Patient enrollment continues as of today. The company reports that seven patients (44%) achieved stable disease using the RECIST 1.1 criteria to evaluate tumor response rate and duration of response. Response rates lasted from three to eight months.

To date, the MTD has not yet been established; however, the company has established safety when used in conjunction with MVT-2163, the company's companion PET imaging product. In fact, dose levels already achieved in Part 1 of the MVT-5873 safety study now exceed the highest dose levels management expects to administer in the concurrent Phase 1 trial of MVT-2163 and the expected dose level for MVT-1075, the company's radioimmunotherapy candidate that combines MVT-5873 and the low-energy radionuclide 177Lu.

Previous biomarker data released in September 2016 show CA19.9 has decreased in all patients (n=12, at the time), including measuring in the normal range for three patients with stable disease. The data also show a pharmacokinetic profile for MVT-5873 that is similar to other monoclonal antibody therapeutics. These early results are promising. Management intends to provide a more comprehensive data analysis in early 2017.

The next step for MabVax is to begin Part 2 of the Phase 1 program. This includes dosing MVT-5873 in combination with standard of care chemotherapy for advanced pancreatic cancer, nab-paclitaxel plus gemcitabine. Management also plans to enroll previously untreated patients with newly diagnosed disease. This presents the opportunity for MVT-5873 to move to front-line therapy - no doubt a potentially huge opportunity for MabVax. Preclinical data with MVT-5873 shows the drug to have strong antitumor activity, as well as synergy with the standard of care chemotherapeutic agents.

With respect to the MVT-2163 Phase 1 trial, the company has demonstrated safety, pharmacokinetics, and biodistribution by completing two cohorts of patients: first dosing MVT-2163 alone and second in combination with MVT-5873. Recall, management is pre-administering MVT-5873 (the cold antibody) along with MVT-2163 to "soak-up" circulating CA19.9 levels in the plasma and increase the sensitivity (true positives) and specificity (true negatives) of the test. Initial biodistribution data supports this validated blocking approach used by diagnostic market leaders, such as Roche.

The company reports that the initial PET images demonstrated target specificity by correlation with lesions identified by conventional computerized tomography (CT) scans. The trial is taking place at Memorial Sloan Kettering Cancer Center, along with two sites within the Sara Cannon Research Institute network in Tennessee and Florida. MSKCC provided us with a glimpse at the data back in August 2016. Results show MVT-2163 has high specificity and "is successfully going where it is supposed to go."


The company is actively recruiting patients and expects to establish the optimal co-administration dose of MVT-5873 early in 2017. Future studies with MVT-2163 include using the imaging agent to diagnose, monitor, and even assist with pancreatic cancer treatment. This is clearly an exciting opportunity.

Why This Update Is So Important?

Safety and PK data from a Phase 1 interim update in only 16 patients would normally not be considered market moving material. However, what investors need to understand is the expected progression in MabVax' pipeline over the next year. MBT-5873 is the "naked" or "cold" antibody. It is the highly specific and targeted delivery vehicle for the PET imaging agent or anti-cancer payload, which includes both radionuclide and cytotoxic agents. By demonstrating that MVT-5873 is safe, well tolerated, highly specific, and has therapeutic-like pharmacokinetics, MabVax now has now derisked progressing MVT-2163 and MVT-1075, which I believe have tremendous commercial potential. 


I also think investors need to understand what management is doing with the MVT-2163 Phase 1 trial. Yes, there is clear potential and medical need for a pancreatic cancer diagnostic. I discuss this below; but, there's another very interesting angle to the MVT-2163 program. By doing the PET imaging, MabVax management can prove that HuMab-5B1 is not only hitting CA19.9, but also hitting it on the tumor in the pancreas! That's exactly the kind of stuff potential development partners want to see. Is it safe and does it hit the target? The answer to both these questions is a resounding, yes. Now it makes sense to move forward with MVT-1075 knowing this information. It's a very astute strategy being well executed by management.

A Huge Market Opportunity

Pancreatic cancer is notoriously difficult to detect and even harder to treat, making it one of the most deadly forms of cancer. This is because pancreatic cancer typically has few if any symptoms early on, and it is not until it metastasizes to other parts of the body that patients begin to experience noticeable symptoms. There are no cost-effective screening strategies for early detection, like mammography or MRI for breast cancer or colonoscopy for colorectal cancer. Due to the fact it is rarely found before metastasizing, the five-year survival rate for patients with stage 3 or 4 pancreatic cancer is only 1-3% (2). MVT-2163 may be able to improve those abysmal numbers.

The American Cancer Society estimates just over 53,000 adults will develop pancreatic cancer in the U.S. each year; nearly 42,000 will die from the disease in 2016 (3). Standard of care treatment for metastatic pancreatic cancer is the chemotherapeutic agent gemcitabine either as a monotherapy or in combination with nab-paclitaxel (Abraxane®). Abraxane® combined with gemcitabine resulted in an improvement in overall survival from 6.7 months to 8.5 months in patients with metastatic pancreatic cancer (4). However, given that overall survival rate is still well below a year, it is clear that more efficacious therapeutic options are desperately needed. MVT-5873 and MVT-1075 may be able to improve these statistics.

Conclusion

I believe HuMab-5B1 has the potential to make a real impact due to its high specificity and efficacy in preclinical models, particularly as a radioimmunotherapy or antibody-drug conjugate product. MabVax currently has a market cap of only $24 million! The company just recently closed on a financing and since a successful pancreatic cancer treatment would easily produce >$500 million in peak revenues, the risk/reward profile for MabVax is quite compelling at its current valuation.

MabVax fits many of the parameters I've experienced lead to tremendous upside in a biopharma stock. HuMab-5B1 is a novel drug candidate that targets a large market opportunity where there is a significant unmet medical need. The IP is solid. The company's pipeline offers multiple shots on goal and synergistic products built off a novel platform. The relationship with MSKCC is solid. The shares are extremely undervalued and there are near-term catalysts. Potential acquirers of MabVax (should) include Celgene, Pfizer, Bristol-Myers, and Novartis.

The company will likely be announcing (presenting) additional data from the two ongoing Phase 1 clinical trials for MVT-5873 and MVT-2163 in early 2017. Management plans to file an Investigation New Drug (IND) application on MVT-1075 in the coming weeks. A Phase 1 study with MVT-1075 is expected to begin during the first half of 2017. Recall, if MVT-5873 is successful, then MVT-5873 linked to the radionuclide 177Lu should be even more powerful. PET-imaging data with MVT-2163 proves the drug ends up where it is supposed to end up. This is an exciting story for 2017.

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