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Thursday, April 6, 2017

MabVax Posters Highlight Why I Like This Story

Earlier this week, MabVax Therapeutics, Inc. (NASDAQ: MBVX) presented two posters on MVT-1075 at the American Association for Cancer Research (AACR) annual meeting. MVT-1075 is the companies fully human antibody-based radioimmunotherapy (RIT) currently ready for Phase 1 clinical development, initially being evaluated for the treatment of pancreatic cancer and other CA19-9 malignancies. The posters highlight the excellent preclinical proof-of-concept and manufacturing / scale-up commercial viability of MVT-1075.

I'm a big fan of MabVax and MVT-1075. The preclinical data, which I cover below, look outstanding. I'm also encouraged by the initial clinical data with MVT-5873 (the cold antibody) and MVT-2163 (the PET imaging agent). Finally, there looks to be a number of catalysts on the horizon that should help the stock trend higher. These include presented additional data on MVT-5873 and MVT-2162 and closing a financing transaction to fund operations well into 2018.

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 CA19-9 positive tumors.

The initial focus is on pancreatic cancer, a logical approach because CA19-9 is the most frequently utilized and only validated serum market for assessment of pancreatic cancers. The CA19-9 antigen facilitates tumor proliferation, invasion, and metastatic spread (1). High serum levels correlate with poor prognosis (2). Importantly, it is found in up to 92% of pancreatic ductal adenocarcinomas (3) and is present in high copy number on cancer cells (4), thus making it an attractive molecular target.

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.


I have covered the Phase 1 data with MVT-5873 and MVT-2163 in a previous article so I will not rehash that here. Instead, I'd like to focus on MVT-1075. In January 2017, the U.S. FDA authorized the initiation of a Phase 1 clinical trial with MVT-1075 as a therapeutic treatment for pancreatic cancer. I am tremendously excited about the potential for MVT-1075. This is because the preclinical data looks excellent, the reproducibility and manufacturing process are commercially viable, and the market opportunity is tremendous.

AACR Poster # 1: CMC & Stability

MabVax' first poster at AACR summarizes the chemistry, manufacturing, and controls (CMC) conducted during IND-enabling investigations by the company to support the manufacture of clinical grade MVT-1075 drug product. The poster also includes details of the manufacturing process and characterization studies including product stability. This data confirms that MVT-1075 has commercial usability and applicability in the real-world setting.


AACR Poster #2: Preclinical Data


The second poster, "Preclinical development of MVT-1075 as radioimmunotherapy for pancreatic cancer and other CA19-9 positive malignancies," is a bit sexier. The poster summarizes the preclinical pharmacology, efficacy, and safety studies of MVT-1075 that supported starting dose determination and includes a synopsis of the Phase 1 clinical trial design.

- MVT-1075 Biodistribution -

Biodistribution data support the company's hypothesis that MVT-1075 targets CA19-9 on the tumor cells with minimal off-target (off-organ) binding. The graphs below show MVT-1075 biodistribution in normal mice compared to BxPc3 tumor-bearing mice. Notice the significantly higher concentration of drug in the tumor cells compared to the blood, lungs, liver, and spleen. Initial data from the MVT-2163 PET-imaging studies in humans confirm these findings. Quite simply, HuMab-5B1's has high specificity and minimal off-target binding, thus making it an ideal therapeutic approach for difficult to treat, non-resectable cancer.


- MVT-1075 Safety & Efficacy -

Escalating doses of MVT-1075 given as a single administration to athymic nude mice with established BxPc3 xenografts show the drug to be well tolerated with effective and sustained tumor growth inhibition throughout the observed period (Day 1 through 57). The graph below shows the normalized tumor volume for increasing doses of MVT-1075 (75, 150, 300, and 450 μCi) compared to MVT-5873 (naked antibody) and a saline control. Not only is there outstanding linear dose-response, but the highest dose of MVT-1075 (450 μCi) looks to have completely obliterated the tumor!

 

Additional data from athymic nude mice with established orthotopic BxPc3-Luc tumors show that MVT-1075 significantly inhibited tumor growth compared to a saline control. MVT-1075 treated group regressed to approximately 50% of the pre-treatment volume by day 20 vs. a mean tumor volume increase of approximately 300% for the saline control.


For the planned Phase 1 clinical trial, MabVax will administer MVT-1075 on a fractionated dose schedule. This may permit delivery of a higher total dose of MVT-1075 while maintaining acceptable tolerability levels.

What Did We Learn?

MabVax preclinical program with MVT-1075 confirms the following:

1) MVT-1075 is highly specific in targeting CA19-9. Biodistribution data shows significant accumulation around the tumor with minimal off-target binding. These data have been confirmed in Phase 1 human clinical testing with the PET-imaging agent, MVT-2163.

2) MVT-1075 provides rapid and dose-proportionate tumor inhibition.

3) Fractionated doses of MVT-1075 may allow for higher concentrations of MVT-1075 that ultimately lead to tumor cell death.

4) Manufacturing and product stability have been confirmed that provide efficient commercialization potential.

The Phase 1 Study

All of the above will need to be confirmed in a Phase 1 clinical study. In this initial Phase 1 trial, MabVax plans to evaluate the safety, dosimetry, and pharmacokinetics of MVT-1075 in an open-label, non-randomized, dose-escalation design. Patients enrolled in the study will have been diagnosed with recurrent locally advanced or metastatic (ECOG 0 or 1) 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. MabVax will use a blocking dose of MVT-5873 to reduce circulating levels of CA19-9 in the blood and increase the concentration of MVT-1075 on the tumor site.


The first investigative site has been announced at Memorial Sloan Kettering Cancer Center in New York City. IRB approval is currently being sought and enrollment is expected to begin in the second quarter 2017. 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.

Financing Overhang

MabVax exited December 2016 with $4.0 million in cash and investments. The burn rate for the fourth quarter 2016 was $2.7 million so management will need to raise cash in the near future. The company filed a Form S/1 on March 29, 2017, noting plans to issue up to 6.6 million shares. At the current stock price, this would equate to $13 million. For the record, I do not believe the company will see to raise this full amount in the near-term. I suspect management would like to raise enough cash to comfortably initiate the Phase 1 MVT-1075 clinical study and offer data later in the year.

Investors are often hesitant to buy biopharma companies around a financing transaction. I fully understand this concern; however, in the case of MabVax, the preclinical data are so powerful that I believe the only thing hold back the stock today is the financing overhang. I'm hoping that once the company closes the transaction investors will be more amenable to the story and realize: 1) just how exciting a drug MVT-1075 has the potential to be, and 2) just how ridiculously under-valued this story is today at $2.05 per share.

Conclusion

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.

6 comments:

  1. Incredible potential. What is the size of the market they will be looking at? You say the preclinical data is very compelling how good is data from a mouse model? It certainly looks amazing hopefully they can translate that efffectiveness to a human trial

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    1. From my previous article:

      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.

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  2. Tom @ cloefkapperApril 9, 2017 at 8:10 AM

    Not added value to your story, though so weird CEO and director are Selling shares at almost all time Low values. That's scaring. At the other hand, Arno therapeutics had great insider buyings and know they are going dark and requested delisting at the SEC ...

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  3. Why was there no therapuetic effect with MVT- 5873 in the trial for MVT-1075. I thought it is being evaluated in its own right as a cancer treatment

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    Replies
    1. Good question. That was only a "loading dose" administered one time at the start of the trial. It wasn't a therapeutic level and wasn't redosed like the current P1 trial they are doing.

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  4. It is amazing that there is zero interest in this company, trading 2 to 3000 shares a day. Why don't the insiders show some interest?

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