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Tuesday, February 28, 2017

MabVax MVT-1075 Cleared For Phase 1

MabVax Therapeutics Holdings, Inc. (NASDAQ: MBVX) announced last week that the U.S. FDA authorized the initiation of a Phase 1 clinical trial with MVT-1075 as a therapeutic treatment for pancreatic cancer. This is an important step for the company. Preclinical data on MVT-1075 look very impressive and position MVT-1075 as a potential breakthrough targeted radioimmunotherapy for recurrent locally advanced or metastatic pancreatic cancer. This is the company's third IND approval in the past 14 months off the HuMab-5B1 platform targeting CA19-9 positive cancers.

Below is a quick review of the MabVax pipeline, including a look at recent news and what's in store for 2017.

Quick Background

MabVax's proprietary monoclonal antibody (mAb) product candidates are designed to elicit an immune response to highly specific antigens found almost exclusively on cancer cells. The company’s lead antibody candidate, HuMab-5B1, targets 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.


Pipeline Update: MVT-5873

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.

At BioCEO held in February 2017, management presented the clinical results as of January 5, 2017. Twenty-two patients have been treated with increasing doses of MVT-5873. The data show five patients remain on drug today, with three patients making it at least six cycles of treatment. Nearly half the patients (10/22) achieved stable disease.


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 approach for many PET imaging agents.

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, color 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.

MVT-1075 Enters The Clinic

Last week that the U.S. FDA authorized the initiation of a Phase 1 clinical trial with MVT-1075 as a therapeutic treatment for pancreatic cancer. Even with as much promise as MVT-5873 plus chemotherapy holds, I am even more excited about the potential for MVT-1075. This is because the preclinical data looks excellent.

Below are results from a preclinical study conducted at Memorial Sloan-Kettering Cancer Center (Lewis, Ph.D.) demonstrating substantial tumor growth suppression and tumor regression following a single administration of increasing concentrations of MVT-1075. The data show tumor regression for doses of MVT-1075 in excess of 150 ╬╝Ci (left) with minimal off-target biodistribution to non-target locations (right).

 

In this initial Phase 1 trial, MabVax plans to evaluate the safety, dosimetry, and pharmacokinetics of MVT-1075. Patients enrolled in the study will have been diagnosed with recurrent locally advanced or metastatic (stage 3 and 4) pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies. Patient disease status will be evaluated based on tumor measurements using RECIST 1.1 criteria. The first investigative site has been announced at Memorial Sloan Kettering Cancer Center in New York City. IRB approval is currently being saught and enrollment is expected to begin around the middle of the year. I'm hopeful we see initial data before the end of 2017. The company has separately secured a third party cGMP manufacturer for MVT-1075 for clinical studies.

Conclusion

MabVax’s unique antibody discovery platform differentiates it from other companies developing antibody therapeutics as it allows for the generation of fully human antibodies while also taking advantage of the capabilities of the human immune system to generate products that are highly specific and efficacious. The company’s unique platform also allows for the use of lead antibody products in a number of different modalities, as exemplified by the development of HuMab-5B1 as a therapeutic agent (MVT-5873), an imaging agent (MVT-2163), a radioimmunotherapy (MVT-1075), and an antibody drug conjugate.

The company will likely be announcing additional data from the ongoing Phase 1 clinical trials for MVT-5873 and MVT-2163 in the next few months. I will post an update with an analysis of the data after it is released. As noted above, these data are important because confirmed safety and therapeutic effect de-risks the story and could potentially lead to a potential partnership for the HuMab-5B1 platform. At BioCEO, management noted being in, "Active discussions with potential partners under CDA." Noteworthy opportunities over the near term include out-licensing rights for the Asian market, combination therapy, or third parties potentially interested in using HuMab-5B1 as a vehicle for cytotoxic agents.

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 approximately $19 million. This seems absurdly low considering the market opportunity for a successful pancreatic cancer treatment would easily produce >$500 million in peak revenues. I intend to explore the market opportunity future in my next article.

The final slide below - taken from the company's presentation at BioCEO - shows the relative valuation of MabVax compared to its peers. There are three key points I want to leave investors with. Firstly, $19 million is absurdly low for a company with three Phase 1 programs and preclinical data that looks excellent in one of the most difficult to treat cancers. Secondly, HuMab-5B1 is a platform for targeting multiple solid tumor cancers where sLeA is overexpress. This presents the opportunity for many different types of partnerships for the company in the near future. The company's stated goal is to complete at least one transaction in 2017. Finally, organizations like Opko and Frost Gamma have been supportive of the story in the past and continue to invest in the name today.


I think MabVax shares offer investors an incredible opportunity. I really like the platform and the data so far look very good (Charisma). There are numerous data read-outs and updates expected over the next several months (Catalysts) and MSKCC continues to be an excellent clinical investigator for the company (Credibility). Cash is perhaps the only missing piece to the story, which I expect management to address in the near future.

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BioNap expects to add to a position in MBVX in the near future.

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