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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.

Pipeline Update: MVT-5873 (Updated March 2017)

MabVax initiated a Phase 1 clinical study with MVT-5873 in February 2016. This is a two-part clinical program, with the first part examining MVT-5873 as a monotherapy in patients with relapsed or refractory locally advanced or metastatic (stage 3 and 4) pancreatic cancer. The primary analysis of this program is safety - seeking a maximum tolerated dose (MTD) and pharmacokinetics (pk). Tumor response is also be evaluated based on RECIST 1.1 criteria.

MabVax recently presented interim data from this program. According to an 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. Patient enrollment continues as of today. Management has noted that they are very close to closing out this part of the study and establishing both the MTD and the planned dose for Phase 2.

Importantly, biomarker data demonstrate that doses of 1 mg/kg MVT-5873 appear to normalize elevated levels of circulating CA19-9 in approximately 50% of patients. CA19-9 is an antibody typically raised in response to sLeA shed into the bloodstream from tumor cells. Doses of 2 mg/kg appear to completely normalize levels of CA19-9.

As of March 2017, 25 patients have been treated with increasing doses of MVT-5873. The data show five patients remain on drug today, with three patients achieving stable disease at six months.


Based on the encouraging results from the first part of this program, MabVax has progressed into the second part of the study in which newly diagnosed patients with unresectable or metastatic pancreatic cancer will be treated with a combination of MVT-5873 plus standard of care chemotherapy, gemcitabine + nab-paclitaxel (Abraxane®). The dose has been scaled back from the monotherapy cohort and management anticipates early clinical data will be available around the middle of the year.

I am optimistic on this program because preclinical xenograft data demonstrate a synergistic effect between MabVax's MVT-5873 and chemotherapy. The figure below on the left shows the relative growth of BxPC3 human pancreatic cancer cells treated with increasing doses of MVT-5873 on top of chemotherapy. The figure on the right shows DMS79 small cell lung cancer tumor volume growth untreated (control) or treated with increasing doses of MVT-5873, paclitaxel, or the combination of MVT-5873 plus paclitaxel.


The effects of MVT-5873 as both a monotherapy and when combined with chemotherapy are impressive. Given the strong data, MabVax has the potential to develop MVT-5873 along multiple pathways: 1) As an adjuvant (maintenance) therapy post chemo or post surgery to prevent recurrence, 2) In patients with poor performance status unable to tolerate chemotherapy, and 3) In patients with refractory disease that are failing standard of care chemotherapy, and 4) In combination with other targeted anti-cancer agents.

- Speaking of combination therapy - 

On February 13, 2017, MabVax announced preclinical results evaluating MVT-5873 with Halozyme Therapeutic's (HALO) PEGPH20. PEGPH20 is a recombinant human hyaluronidase enzyme, which temporarily degrades hyaluronan (HA), a glycosaminoglycan or chain of natural sugars that accumulate around certain tumors. Data show that the removal of HA from tumors reduced pressure inside the tumor and improves the ability of chemotherapies or immunotherapies to penetrate the tumor, inhibiting its growth. Halozyme is currently studying PEGPH20 in a Phase 3 trial combined with gemcitabine + nab-paclitaxel in patients with pancreatic cancer.

MabVax preclinical data demonstrate an improvement in the accumulation of MVT-5873 on tumors in an animal model of pancreatic cancer when administered in sequence with PEGPH20. This data is quite intriguing and warrants exploring further this synergistic effect. It also suggests a potential benefit to combining both MVT-2163, the company's immuno-PET imaging agent, with PEGPH20, as well as MVT-1075 with PEGPH20 in future studies. As of now, MabVax has no formal collaboration with Halozyme, but the potential certainly exists should the preclinical data continue to look encouraging.

- Speaking of MVT-2163 -

Work with MVT-2163 continues on plan. Management is conducting a Phase 1 trial designed to establish the safety, pk, and optimal doses to be used during PET imaging. Recall, MabVax recently found that dosing MVT-5873 as a blocking agent prior to MVT-2163 improves the outcome of the scan. Dosing MVT-5873 prior to MVT-2163 is designed to normalize any circulating CA19.9 antigen and allow MVT-2163 to increase biodistribution on the tumor cells. This is a validated blocking approach used by diagnostic market leaders, such as Roche.

I see a sizable market opportunity for MVT-2163. Initial data from the Phase 1 trial show MVT-2163 images highly specific targeting on the tumor sites. This not only validates the concept for MabVax but provides a strong rationale for advancing MVT-1075 into clinical studies. Data so far show a high correlation with FDG-PET standard, with MVT-2163 potentially able to identify smaller nodes that a CT scan might miss. This could prove important when staging patients for surgery or assessing the effectiveness of various treatment options. Given the increased sensitivity of MVT-2163, MabVax believes the imaging agent might hold utility in other difficult to diagnose and monitor visceral cancers like stomach cancer, colon cancer, and small cell lung cancer. This is particularly interesting for the Asian market where stomach cancer rates far exceed that in the U.S.

Why This Update Is So Important?

Safety and PK data from a Phase 1 interim update in only 25 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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