BlueWillow Biologics CEO Dave Peralta

BlueWillow Biologics this month plans to vaccinate its first patients with a next-generation anthrax vaccine candidate. The BW-1010 vaccine—developed in partnership with Porton Biopharma Ltd. (PBL)—is designed to outlast the anthrax vaccine currently stockpiled by the federal government.

BW-1010 is an intranasal vaccine that combines BlueWillow’s novel intranasal NanoVax™ platform with PBL’s recombinant protective antigen (rPA) for anthrax. BW-1010 will be studied in a Phase I trial (NCT04148118) to evaluate the vaccine candidate’s safety and immunogenicity in 84 healthy adult volunteers. BlueWillow announced FDA clearance of its IND application for BW-1010 in October.

“The subjects were screened in December 2019, and the first subjects will be vaccinated later this month,” BlueWillow CEO Dave Peralta told GEN Edge. “We’re actually off to the races.”

BlueWillow’s NanoVax platform uses a proprietary oil-in-water nanoemulsion adjuvant designed to enable intranasal vaccines for respiratory and sexually transmitted diseases. The technology incorporates nano-scale droplets manufactured at an average size of 400–500 nanometers to deliver and adjuvant a broad spectrum of vaccines. Through either a dropper or a sprayer device, droplets from the nanoemulsion readily permeate the nasal tissue, which is rich in immune-presenting cells.

According to BlueWillow, dendritic cells sample the vaccine at the nasal mucosa and carry the antigen back to the immune system, eliciting both mucosal and systemic immunity. According to the company, this uniquely enables stronger protection against anthrax and other respiratory infections.

The intranasal vaccine program is supported by an up-to-eight-year contract from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), the value of which could reach $24 million if all options are exercised. PBL was established in 2015 to commercialize pharmaceutical development and manufacturing capabilities at the Porton Down site in Wiltshire, U.K., previously carried out by Public Health England.

“The NIAID contract that we received is just to develop BW-1010 to our first study in humans. If we’re successful, we will be pursuing further support to progress to Phase II and Phase III studies,” Peralta said.

Extending shelf life

Importantly, Peralta added, the goal of the NIAID contract is to add at least another year of stability to the current three-year shelf life of BioThrax® (anthrax vaccine adsorbed), the anthrax vaccine stockpiled by the Biomedical Advanced Research and Development Authority (BARDA) in the U.S. Strategic National Stockpile (SNS).

“Thus far, informally with our stability studies, we’ve shown five years of stability using multiple batches of the product,” Peralta said. “We’re going to test it again at the six-year mark.”

By expanding the vaccine’s shelf life to five years, he added, “we could save the government probably north of $100 million per year, just by using a NanoVax anthrax vaccine.”

BioThrax’s developer, Emergent BioSolutions, has already begun rolling out a successor vaccine. Last year, Emergent introduced into SNS the next-gen anthrax vaccine candidate AV7909 [anthrax vaccine adsorbed (AVA), adjuvant]—a combination of BioThrax and the novel immunostimulatory compound CPG 7909 adjuvant, designed to be faster and offer greater immune response than BioThrax.

According to Emergent, 13 million doses of AV7909 are in process for FY 2019-20—including the exercise by BARDA of the first one-year, $261-million option for 10 million doses of the vaccine, part of an up-to-$1.5 billion contract signed in 2016.

In March 2019, the Gaithersburg, MD-based company launched a Phase III trial (NCT03877926) of AV7909 designed to evaluate the lot consistency, immunogenicity, and safety of AV7909 following a two-dose schedule administered intramuscularly in healthy adults. Emergent plans to study 3,850 adults across 35 sites within the United States, with an estimated primary completion date of November 2020.

Addressing analysts at its Investor Day last November, publicly-traded Emergent said it plans to file a BLA for AV7909 in the fourth quarter of 2021.

Aiming for safer vaccine

In addition to BW-1010, BlueWillow’s lead product candidates include intranasal vaccines for RSV, pertussis, HSV-2, chlamydia, and peanut allergy. [BlueWillow Biologics]

In developing BW-1010, Peralta said, BlueWillow and PBL aim to produce a vaccine with fewer adverse events than generated by BioThrax. Animal studies have shown BW-1010 to be safe and to elicit protection against anthrax after one or two vaccinations.

BlueWillow has also cited BioThrax’s FDA label, which warns in part: “BioThrax can cause fetal harm when administered to a pregnant woman.” According to that label, the most common local (injection-site) adverse reactions seen in clinical studies of BioThrax were tenderness, pain, erythema, edema, and arm motion limitation. The most common systemic adverse reactions were muscle aches, headache, and fatigue. And in a study of 1,564 healthy adults also referenced by the FDA, the percent of serious adverse events was similar between groups randomized to BioThrax and a placebo group.

“One of the desires in awarding Blue Willow and our partner this contract was to use an antigen that’s just a single protein,” Peralta said. “It’s essentially a much cleaner antigen that presumably will lead to a safer vaccine.”

In addition to BW-1010, BlueWillow’s lead product candidates include intranasal vaccines for RSV, pertussis, HSV-2chlamydia, and peanut allergy. An influenza vaccine was rapidly progressed to Phase I. But without rights to an influenza antigen to combine with NanoVax, the company instead pursued other programs where it could secure an antigen, partner for antigen, or connect with partners via the NIH.

Headquartered in Ann Arbor, MI, BlueWillow employs 14 full-time employees and five part-time consultants. BlueWillow has won a $10-million Series A financing and $70 million in contracts, mostly from NIH but also including the U.S. Department of Defense and the Bill and Melinda Gates Foundation.

Strategic pivot

BlueWillow was founded as NanoBio Corp., a spinout from the Center for Biologic Nanotechnology at the University of Michigan (U-M). The Center expanded in 2005 into the current Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), whose director is NanoBio’s founder James R. Baker Jr., MD, the Ruth Dow Doan professor of biologic nanotechnology and chief of the division of allergy.

When Baker left in 2012 to join Merck & Co. as SVP, head global vaccine franchise, Peralta was promoted from COO to CEO, after joining NanoBio in 2006 as CFO.

NanoBio initially focused on using nanotechnology to treat topical infections and potentially deliver other molecules across the skin. In 2017, NanoBio strategically pivoted its operations to refocus its nanotechnology platform on the development of intranasal vaccines for infectious and allergic diseases, as well as topical anti-infective treatments for wounds.

A year later, the company announced its name change to BlueWillow, in conjunction with the Series A financing, which was led by North Coast Technology Investors, Line Moon Ventures, and U-M through its Michigan Invests in New Technology Startups (MINTS) initiative. MINTS invests up to $1 million in Series A capital in qualified U-M startups upon the recommendation of U-M’s Tech Transfer office and a qualified venture fund partner.

“The tech transfer office of the University of Michigan has been a phenomenal supporter of the companies that have been spun out from the university,” Peralta said. The company also has received funding from the state of Michigan, which is trying to support companies with exciting technologies. “I think we’re in a very good spot geographically, where we can tap into a lot of resources with the University of Michigan. But it’s not hard for us to travel back and forth to Washington to meet with NIH or with pharma companies on the East Coast.”

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