Join the BioNap Email List:

Wednesday, May 18, 2016

BriaCell Selects CRO To Run Phase 1/2 BriaVax Clinical Trial

BriaCell Therapeutics Corp. (TSXV: BCT) (BCFXF) continues to make progress on the initiation of its Phase 1/2a clinical trial with BriaVax™. This morning, the company announced it has signed a definitive agreement with Cancer Insight, LLC, a cancer-vaccine focused clinical research organization (CRO) to provide clinical and regulatory affairs management services for the trial. BriaVax™ is the company's proprietary whole tumor cell vaccine for the treatment of late-stage cancer. The company announced in April 2016 that plans to initiate the trial in the coming months. The trial is expected to enroll up to 24 late-stage cancer patients, mostly with metastatic breast cancer. BriaCell is also working on a companion diagnostic based on identified biomarkers aimed at prospectively identifying patients likely to benefit from BriaVax™.

I continue to be intrigued by BriaCell and what the company is doing in immuno-oncology. The stock is largely unheard-of by retail investors and flying so-far-below the radar of institutions that I believe a significant opportunity exists at today's ground-floor valuation. My article below is a quick review of the story, with a highlight on recent progress.

About Cancer Insight, LLC.

Cancer Insight is a clinical research organization (CRO) dedicated to discovering, developing and testing emerging biotechnologies related to cancer immunotherapy. The company's website notes over a decade of scientific and clinical expertise in cancer immunotherapy, with previous work under the military's Cancer Vaccine Development program. Cancer Insight is led by Col. (ret) George E. Peoples, MD, a former U.S. Army surgeon and research scientist with over 30 years of active duty. A quick search of ClinicalTrials.gov shows Cancer Insight current recruiting a handful of cancer vaccine programs, with flagship clients including Genentech and Celgene.

Funding Secured 

On May 3, 2016, BriaCell closed on a CAD $1.275 million private placement. Management reported that a "leading U.S. biotechnology fund" invested a total of CAD $650,000 as part of the transaction. In total, the company issued approximately 3.42 million shares of common stock at CAD $0.19 per share. The investors also received 3.42 million warrants exercisable at any time over the next five years at CAD $0.30 per share. Management plans to use these proceeds to initiate a Phase 1/2 study with BriaVax™.

I'm expecting enrollment to begin in July 2016. The initial portion of the trial will likely involve enrollment of 8-10 patients with an interim analysis at 4-6 months. Based on what I have seen in the past, the Phase 1 portion of the trial will likely cost $0.5 million (best guess is $2 million for the full trial all-in), so the funding noted above looks sufficient to fund at least the first portion of the trial. With proof-of-concept 4-6 months later, additional funds should be relatively straightforward to secure - at likely significantly higher prices - thus allowing management to complete the entire program.

About BriaVax

BriaVax™ is a proprietary whole tumor cell vaccine isolated from a chest wall lesion of a 39-year-old woman with metastatic breast cancer. The irradiated cells are ER/PR negative and overexpress HER-2/neu, a clinically validated target of effective monoclonal antibody therapeutics. BriaVax™ has been genetically engineered to release sargramostim (granulocyte macrophage - colony-stimulating factor [GM-CSF]) for up-regulation of professional antigen-presenting cells. GM-CSF has been shown to be the most potent immunostimulatory secreted molecule for inducing tumor immunity (1) and is believed to provide an antitumor effect that prolongs survival and disease-free survival in subjects with stage III and IV melanoma (2) and metastatic non-small cell lung cancer (3). Also, part of the treatment regimen is the addition of low-dose cyclophosphamide (CY) 2-3 days prior to inoculation to down-regulate the activity of regulatory T cells and the use of interferon (IFN) alpha to boost differentiation of dendritic cells.

An investor recently asked me if the failure of ECLIPSE by Aduro Biotech, Inc. (ADRO) dampens my enthusiasm over BriaVax™. I think these are vastly different programs. I note the following key points:

- First off, Aduro was targeting third-line metastatic pancreatic cancer, a notoriously difficult population to treat. The control arm in the study reported a median overall survival of only 4.6 months. In contrast, peer-review suggests that third-line metastatic breast cancer patients have an overall survival ranging between 10 and 12 months (4). This suggests these patients are more apt to respond to treatment.

- Secondly, Aduro used low-dose CY prior to inoculation to down-regulate the activity of regulatory T cells but did not also use interferon (IFN) alpha to boost differentiation of dendritic cells. In previously articles, I've described BriaCell's approach to using CY as "foot off the brake" and IFN as "stepping on the gas". These may seem like minor protocol adjustments, but if you are going to fight cancer with immunotherapy, a prolonged and powerful immune response is necessary.

- Thirdly, BriaCell is targeting specific patients that they believe will have uber-response to BriaVax™ and is developing a companion diagnostic based on identified biomarkers aimed at prospectively identifying these patients. In fact, the company just presented findings on a gene signature potentially predictive of patient response to the vaccine at AACR in April 2016. I encourage investors to view the poster (AACR #2369) or read my article on the subject for a quick overview of the company's strategy.

Conclusion

What I find most interesting about BriaVax™ is the potential for a potent targeted approach to immunotherapy. BriaVax™ is a genetically engineered whole tumor cell vaccine that presents multiple tumor-specific antigens to the immune system, stimulating dendritic cells and inducing a humoral response. The biomarker and gene expression data presented at AACR-2016 significantly improves the likelihood of response based on the double matching of HLA alleles. BriaCell is working on a companion diagnostic, BriaDx™, to prospectively identify patients most likely to respond to BriaVax™ and, potentially, as a way to monitor patients response during clinical studies. This increases my confidence level on the program.

BriaCell Therapeutics remains one of my favorite under-the-radar immuno-oncology names. Therapeutic cancer vaccines have a lamentable history, but the science has come a long way since the failures of Dendreon's Provenge®. BriaVax™ is an allogeneic whole cell vaccine, and thus not hampered by the immune masking or the logistical commercial nightmares of previous autologous approaches. Instead, BriaVax™ seems to offer the ideal immunotherapy - powerful enough to induce both a broad-scale innate and adaptive immune reaction, targeted to reduce systemic side-effects, and selective based on genetic biomarkers to improve the odds of success. Plus, with a market capitalization (USD) of only $20 million, the upside looks tremendous if the Phase 1/2 trial succeeds.

----------

Please see our Disclaimer.

7 comments:

  1. Impressive that they were able to get Dr. Peoples involved. He's been researching cancer vaccines for over a decade. Great resume!

    ReplyDelete
    Replies
    1. I agree! I quick Google of Dr. Peoples and you can see his credentials.
      I particularly like these two stories, both relevant to BriaCell:
      https://vimeo.com/125639900
      http://www.vetsfightingbreastcancer.com/Vaccine_Research_2.html

      Thanks for reading!

      Delete
  2. You said "Thirdly, BriaCell is targeting specific patients that they believe will have uber-response to BriaVax™ "

    I understand that ultimately the companion diagnostic will be used to identify strong responders but it still seems like early days for that aspect of the science. From memory I dont remember Briacell ever confirming that pre-screening was going to be part of the clinical trial protocol. I realse it might have been possible, given the recent poster, and I also noticed that Cancer Insights have done this type of pre-screening on other trials. Are you now confirming that pre-screening is going to be part of the clinical trial? I guess it would make sense even if the data supporting the pre-screening approach is still somewhat limited.

    I would also agree Cancer Insight does look like a good fit.

    Thanks for the update.
    P

    ReplyDelete
    Replies
    1. Hi P,

      No, I'm not confirming that. Last time I spoke with BCT on the subject they said they were still deciding. There are obviously two routes: 1) Take all-comers and then screen post-hoc to see if there are any interesting findings or 2) Screen a priori enrolling only patients with the desired gene signature, hoping they got it right at the AACR presentation.

      PROS to 1: Enrollment will go faster if they take-all comers. Plus, they may still get a good response (maybe not "uber" but better than standard-of-care) in patients with the non-target gene signature.
      CONS to 1: The trial may "fail" to hit statistical significant if not enough patients with the target gene signature enroll. Cynical investors may also accuse them of data-mining if they go back and find patients that responded.

      PROS to 2: You increase the odds of success in the P1/2 trial.
      CONS to 2: You potentially take longer to enroll and you could miss patients that are "ok" responders, when "ok" may still be better than standard-of-care.

      I think the company will go with #2. Hopefully they let us know on this soon.

      Jason

      Delete
  3. Yes, sorry, I also had a follow up question. The poster never mentioned how big the "uber responder" population might be as a proportion of the general population. I started the process of trying to look at the frequency in the US population of the various HLA alleles in the vaccine and was getting fairly low numbers (admittedly I didnt check all of them). Do you know if there is yet any idea how many individuals would need to be pre-screened before they identified a potential uber-responder.

    Again thanks P

    ReplyDelete
    Replies
    1. P,

      Yes, I have a ton of data on this subject and will be doing an entire article highlighting my findings once the company's strategy is clear. Based on the peer-review literature I was able to find, it looks like 30-40% would be good targets based on HLA alleles and response from the AACR poster.

      Jason

      Delete
    2. Thanks for the quick response. That looks like excellent news. P

      Delete