BVXV: Immunogenicity Results From Phase 2b Trial of M-001 Expected Soon…
Zacks Small Cap ResearchJune 2, 2017
By David Bautz, PhD
Financial Update
On May 30, 2017, BiondVax announced financial results for the first quarter of 2017. As expected, the company did not report any revenues during the quarter. The company reported a net loss of $3.2 million for the first quarter of 2017, which was comprised of $0.5 million in R&D expenses and $0.3 million in G&A expenses. Total cash burn for the first quarter of 2017 was approximately $0.65 million.
As of March 31, 2017, BiondVax had cash, cash equivalents, and marketable securities of $9.6 million. On January 2, 2017, BiondVax announced that Angels High Tech Investments Ltd., which is owned by Marius Nacht (co-founder of Check Point Software Technologies Ltd. [Nasdaq: CHKP]), had agreed to invest approximately $2.83 million in the company in exchange for 844,000 Nasdaq listed ADS. Following the transaction, Angels Investments holds 19.99% of all issued and outstanding shares of the company. An investment such as this is important as it shows a level of confidence in both M-001 and the BiondVax management team as well as providing the company with much needed capital to continue development of M-001 into Phase 3 clinical trials. Lastly, the added financial stability provided by the investment could make it easier for the company to pursue grants and other non-dilutive funding sources.
BiondVax Publishes Regulatory Approval Strategy for Universal Influenza Vaccines
On March 13, 2017, BiondVax Pharmaceuticals Ltd. ( BVXV) announced the publication of an article written by BiondVax-affiliated authors titled, “Strategy for approving a universal flu vaccine” in the journal Future Virology (Ben-Yedidia et al., 2017). The authors discuss the strategy to get M-001 through the regulatory process by using a stepwise approach that first utilizes an existing regulatory marker before using newly defined markers.
Currently, the efficacy of all seasonal influenza vaccines is tested based on induction of hemagglutination inhibition (HAI) antibodies that target the outer variable regions of the viral hemagglutinin protein. Since M-001 is targeted against conserved regions of the influenza virus, it does not elicit HAI antibodies but instead induces a cellular response. Thus far, BiondVax has taken the conservative approach of using M-001 as a primer to be given ahead of the seasonal influenza vaccine. This has allowed the HAI antibody response to continue to be used to verify the efficacy of M-001. When given has a primer, M-001 enhances and broadens the HAI antibody response induced by the seasonal influenza vaccine.
One possible path forward that the company is considering is to conduct two Phase 3 clinical trials to support approval of M-001 as a primer vaccine. One Phase 3 study would likely focus on the use of M-001 as a primer for seasonal vaccination in the elderly, while another Phase 3 study would focus on the use of M-001 as a primer for pandemic immunization for approval to be stored in the national stockpile. According to the article by Ben-Yedidia et al., regulatory agencies have suggested 3,000 participants in the experimental group and 1,500 in the placebo group. Assuming a 10% drop out rate leads to a total of approximately 5,000 individuals in total for those studies.
The primer vaccine trials will continue to employ the serum HAI titer as an efficacy outcome, which will be measured on Day 0 and 42. Success will be measured as a seroconversion response of ≥10% to at least two of the trivalent influenza vaccine (TIV) strains and noninferiority to the third TIV strain. This outcome was accepted by the FDA for the Sanofi Fluzone High Dose vaccine marketing authorization.
If BiondVax were to seek approval as a primer vaccine in the elderly first, it would likely be followed up by Phase IV clinical trials being conducted with M-001 as an independent, stand alone influenza vaccine. These trials will need to include tens of thousands of participants with an efficacy endpoint of reduction of influenza illness rate and severity with M-001 compared to those immunized with the seasonal vaccine.
BiondVax is planning to apply for an FDA-accelerated approval pathway that could lead to approval based on a limited-size Phase 3 clinical trial, such as the planned trial in the elderly to test M-001 as a primer to the seasonal vaccine.
We believe the plan as set forth in the article by Ben-Yedidia et al. for gaining regulatory approval for M-001 is a sound one. The plan is likely to prove successful as the company already has a large amount of data showing the ability of M-001 to induce a greater immune response in patients when used as a primer compared to those who are only given the seasonal influenza vaccine. In addition, it allows regulatory agencies the opportunity to get comfortable with a new type of influenza vaccine through its use as a primer, and to collect an abundance of real-world efficacy and safety data before considering it as a stand alone vaccine.
BiondVax Approved for Grant to Help Construct Manufacturing Facility
On March 30, 2017, BiondVax Pharmaceuticals Ltd. (BVXV) announced that the Israeli Ministry of Economy and Industry approved a grant to cover 20% of the NIS 20 million budget for construction of a manufacturing facility for M-001. The facility will be used to produce sufficient quantities of vaccine for Phase 3 clinical trials and commercialization. BiondVax is planning to construct a mid-sized facility in Jerusalem that could potentially one day produce tens of millions of doses of M-001.
Background on M-001
BiondVax is developing the M-001 vaccine, a synthetic peptide-based protein that targets both existing and future seasonal and pandemic strains of the influenza virus. The vaccine targets conserved regions of Type A and B influenza viruses such that M-001 could be considered a “universal” influenza vaccine, capable of offering immunological protection against all strains of the influenza virus.
The company is planning to seek regulatory approval through a two-part strategy:
1. As a “Universal Primer” to be used before any hemagglutinin-based flu vaccine. BiondVax targets two indications for its universal primer: i) seasonal primer for influenza vaccine in the elderly, and ii) pandemic primer for national stockpile.
2. As a stand-alone independent “universal” vaccine against influenza.
Many infectious diseases have been eradicated over the past century, for example polio and smallpox, thanks to vaccination. In order to eradicate an infectious disease, a community (or herd) immunity must be achieved. Three conditions are required to achieve community immunity:
1. An effective vaccine,
2. Broad coverage and unchanging vaccine formulation, and
3. Enough people to be vaccinated.
With a universal flu vaccine such as BiondVax’s M-001, it appears theoretically possible, for the first time in history, to achieve the goal of influenza eradication. In support of this, the company was recently invited to attend the “Eighth WHO meeting on the development of influenza vaccines that induce broadly protective and long-lasting immune responses”. The Global Vaccine Action Plan (GVAP) has a goal for at least one universal influenza vaccine to be on the market by 2020, and the World Health Organization (WHO) is supporting this initiative through constant interaction with leading experts in the field through events such as the one BiondVax will be attending. M-001 is a leading contender to be the first universal influenza vaccine due to its safety profile and strong immunogenicity along with currently being in Phase 2b clinical trials.
M-001 Composition
M-001 is composed of nine peptides that are believed to be common to most known influenza strains in existence, in part because these peptides seem to be critical for the virus’ ability to infect a host cell. They are derived from hemagglutinin (HA), matrix 1 (M1) and nucleoprotein (NP) viral proteins and are arranged as triplicates into a single recombinant protein easily manufactured in bacteria. As discussed above, HA is an antigenic glycoprotein found on the surface of influenza viruses and is also the main constituent for a number of seasonal influenza vaccines. However, the peptides from HA in M-001 are derived from the inner parts of the protein where little to no variability between strains exists. M1 is a matrix protein that forms a layer under the patches of the viral cell membrane that contain HA, NA, and M2 proteins, and is responsible for mediating the encapsulation of RNA-nucleoprotein complexes into the membrane envelope (Sha et al., 1997). NP is a structural protein that encapsidates the viral RNA inside the virus. The sequence of each of the peptides is shown below, along with the order in which the peptides are arranged in the full-length recombinant protein.
