From The Editor | January 2, 2020

How BlueWillow Biologics Is Pioneering Mucosal Vaccine Tech

Matt Pillar

By Matthew Pillar, Editor, BioProcess Online

nasal spray

How a CPA-wielding business and finance executive leads a pioneering intranasal nano vaccine developer through the advent of next-generation of immunotherapies.

Dave Peralta isn’t the stereotypical CEO of a promising emerging biopharma firm. He grew up near Detroit, received a bachelor’s degree from the University of Michigan, earned his CPA license, then, according to plan, cut his accounting teeth at global auditing and consulting firm Coopers & Lybrand. He moved on to spend over ten years as CFO at two global enterprise software companies. His career trajectory was marked by success, albeit pretty standard fare for a well-trained business and finance guy.

That trajectory changed significantly in 2006 when Peralta got bit by the bio bug. At the behest of a board member, he took a CFO position with a venture-backed biotechnology company called NanoBio. By 2013 he was CEO there, and leader of a corporate restructuring that included a rebrand to BlueWillow Biologics, the company’s current moniker.

We caught up with Peralta for a conversation on the business side of running a small biopharma company and to get an update on the work BlueWillow is doing.

Matt Pillar: You made an interesting transition from managing the finances of tech firms to running a biopharma company. Was that a difficult move?

David Peralta, CEO,
BlueWillow Biologics
Dave Peralta: I found that a lot of the fundamentals associated with building, growing, and achieving value inflection points at technology companies are highly leverageable to biotech companies. The fundamentals—a desire to work with cool technologies, the need to hire top people and raise money and focus on things that can build value and secure potential partner or investor interest—those all apply.

Pillar: What’s the backstory on NanoBio/BlueWillow?

Peralta: NanoBio Corporation was focused on using nanotechnology for various dermatology applications. Over time, we started realizing that we could use other nano formulations for intranasal vaccines. That’s when we started winning some significant grants to support those vaccination projects. When I was promoted to CEO, I made the decision to refocus the company on our intranasal NanoVax vaccine platform. We've maintained the topical applications, which are still produced under the NanoBio brand and mainly pursued through partnerships. BlueWillow is the umbrella holding both brands — NanoBio and NanoVax. 

Pillar: Where is BlueWillow on the drug development and marketing continuum?

Peralta: We've done nearly 250 animal studies of our NanoVax platform in more than a dozen diseases, and in several of those studies we've progressed all the way up and through the primary animal models. The theory behind intranasal vaccinations is to elicit both a systemic and a mucosal immune response. Injectable vaccines typically elicit a systemic immune response involving antibodies in the blood only. Nasal vaccinations elicit both antibodies in the blood and antibodies in mucosal tissues, which provide protection from pathogens at the point of entry.

We're now entering an NIH-funded phase one study in humans for an intranasal anthrax vaccine. We’ll also begin a phase one human study for a pandemic flu vaccine in 2020. We’ve secured nearly $80 million in funding, largely from NIH and DoD grants, but also from the Gates foundation. We've shown that the technology works very effectively in a wide range of animal models, so we're taking the step toward studies in man. If we see success with a couple of vaccines over the next three or four years, we may try to take the company public to accelerate the commercialization of some of our key targets.

Pillar: Is there a developing market for mucosal vaccines or is this a novel idea?

Peralta: Mucosal immunity is often considered the next key frontier in the field of immunology, yet there are very few, if any, companies that have technology focused on it. That’s because most new vaccines being developed use adjuvants, which are solutions designed to boost, enhance, and modulate the immunity elicited by a vaccine. Most of the adjuvants that are in development will cause some sort of inflammatory response, so you can't use them intranasally.

Our technology is unique in that it doesn’t induce inflammation. Nano droplets carry the vaccine into the nasal mucosa, and basically load immune presenting cells that are naturally there. We don't have to elicit inflammation to draw those cells to a site. This is something we stumbled on through a chance finding, but we were smart enough to pursue it extensively and we’ve won a lot of grant funding to support our efforts.

We think we have a unique platform that could enable intranasal vaccination across a number of diseases. In the case of diseases where pathogens are entered in the body across a mucosal surface, like respiratory infections and sexually transmitted infections or allergens (both respiratory and gut), intranasal vaccination that elicits mucosal immunity can be key to enabling an effective vaccine.

Pillar: Was the pursuit of an anthrax vaccine and the government’s interest therein a tactical decision to support your funding strategy?

Peralta: NIH has a list of pathogens that they categorize based upon priority in terms of risk to national health. Anthrax is a Category A pathogen. It's one of the highest priorities because it could be aerosolized in a biological terror attack. The federal government stockpiles anthrax vaccine for use in a future emergency, and it spends up to $300 million annually on injectable anthrax vaccine to maintain its stockpiles. Our project was awarded $25 million by the US government to try and develop the next generation anthrax vaccine that’s safer, has a longer shelf life, and that results in better immunity.

Pillar: In your role as CEO at BlueWillow, what is it that you're most concerned with?

Peralta: I'm surrounded by people with very deep science and medical backgrounds. In a biotech company, the CEO is often an MD or a PhD. I'm not. As a result, I lead the financing and business development efforts, and I oversee, along with our senior VP of vaccine research, all of our vaccine programs. We have a very capable team of scientists and physicians to support those programs, but I spend significant time working with them to ensure our studies are designed to build program and company value. In addition, I spend a lot of my time with potential pharma partners to discuss collaboration opportunities, as well as potential investors regarding the company’s financing plans. Here in the Midwest (BlueWillow is headquartered in Ann Arbor, MI), we don't have the access to many venture capitalists that could lead a significant round for a vaccine company, so that means a reasonable amount of travel is required for meetings on both coasts.

Pillar: I would think you’d have to exhibit an unnatural amount of trust in the scientists who are working on your product, not being a scientist yourself?

Peralta: With some level of research and experience in the space, it's not too hard to get up to speed in terms of what sort of endpoints you're looking for from studies, and what’s truly indicative of a response that's real as opposed to noise or something purely theoretical. When you start to talk about the underlying science or maybe specific elements of the mechanism of action, a lot of times that hasn't been fleshed out and maybe never gets fleshed out completely. At times, people that come from a deep science background might get wrapped up in that and really lose sight of what we're trying to achieve for patients. That’s when a business focus is most helpful — thinking about the patients and the unmet medical need.

We have to make sure our vaccines are safe and make sure they work, and over time we can start to tease out specifics of the mechanism. But the key is that we are doing things that are safe and efficacious in animals, and have a high likelihood of translating in terms of efficacy to man.

Pillar: Jumping back to that finance challenge and your geographic position, what's your solution to that?

Peralta: We've been very fortunate, but it's not by chance. It takes a lot of effort to be positioned to receive significant support from the NIH, DoD, the Gates Foundation, and other not for profit and government agencies. We run a very active business development program to work with partners that have an interest in our vaccine candidates or in diseases that we're not actively pursuing. Those are sources for us to get further validation of our technology and potentially additional funding.

I spend a decent amount of time developing relationships with individual investors, family wealth officers and VCs well in advance of pursuing an investment. This way, the potential investor has time to really get comfortable with BlueWillow and to understand and confirm that we're doing what we've said we're going to do in terms of operating the business.

It’s also important that your strategy includes multiple shots on goal. I think that’s been critical for us. If we were focused on one indication, with one molecule, it would place a lot more risk on that program’s success. Sometimes you can have a negative result, but it's not indicative of a failed program, it’s just indicative of something you need to look at differently or further pursue. The fact that we have five vaccine programs that we're actively working towards, as well as some other programs that we're involved in collaborations with partners, gives us multiple shots on goal. And they don't all need to hit the mark in order for us to be successful.

Pillar: Do you find that your non-traditional approach to vaccines creates additional challenges to securing funding?

Peralta: In some cases, yes. But being different can also be helpful. It's a bit of a double-edged sword. It’s probably easier for us to differentiate ourselves, but there are no benchmarks that help assign a value to the company, or to confirm that the path we're on is one that will unfold as we expect it to unfold.

Pillar: So, a Silicon Valley finance guy steps into the chief role at a biopharmaceutical firm. To some, it might sound like the lead into a silly joke. As a business guy who's coming into a new space where science is king, how do you establish credibility and set the cultural tone for your team?

Peralta: I started asking questions when I first joined the company, and I haven’t stopped. Why are we doing this study in this model? Have we looked at what other companies running similar programs have done? Are they using the same model? Are they using mice before they move into ferrets? What are the endpoints that we're trying to reach in the study? Is our approach consistent with some of the leaders in this space? If not, why is it better? What sort of result is meaningful? Is that result associated with systemic immunity? Do our results illustrate the induction of  a mucosal immune response? What are the different ways we could detect that?

The longer I've been part of the business, the more questions I have and the more insightful my questions have become. I spent a decent amount of time reading about what other companies that are pursuing similar vaccines are doing, albeit largely on the intramuscular side. I think challenging our employees to anticipate and proactively consider these kinds of questions prepares them to design the best study possible.

When I first started in this industry, someone told me there are a lot of exceptional scientists and there are a lot of exceptional business people, but there are very few people that are good at both. If you’re leading a biopharma business and you don't come at it from the science angle, you have to make sure you're surrounded by people who do. Then you have to listen to them, and then you have to challenge them to be their best.

Pillar: That begs a question about what characteristics you hire for.

Peralta: I want to work with people who refuse to fail, people who are going to embrace a challenge and demonstrate the resolve and work effort to figure it out. We don't have the option that Pfizer or J&J have to simply shut down a lagging program. Our programs have to work, and we have to work through the challenges that come with them.

There’s a point in the movie Apollo 13 that I often use as an example, where the aircraft is up in space and the control team in Houston becomes alarmed that the CO2 levels in the cabin are increasing. They soon realize they did the calculations based on two astronauts in the ship as opposed to three. Someone walks into the conference room in Houston, throws down a box of stuff representative of everything they have on the aircraft, and sets a deadline for a solution to the problem. We talk about that scene in interviews with prospective employees, and I look for an eager reaction to that kind of challenge because we want to hire people that do not accept failure as an option.  

Pillar: What’s the most significant challenge you’ve had to overcome in your leadership of BlueWillow?

Peralta: As I mentioned, the company originally developed nano technology for dermatology applications. We had some successes in that area and we had some disappointments. We believe the technology works for dermatology and other topical applications, and we've been able to advance those applications through grants and partnerships, as I mentioned. But pivoting the company from a dermatology focus to an intranasal vaccine focus, reestablishing our purpose and our brands created a fair share of challenges, and it didn't happen overnight. I think we've come out the other end of that effort in a much stronger position, and I think the opportunities are pretty significant at this point.

Pillar: What are you most excited or optimistic about?

Peralta: The basic premise of our intranasal NanoVax platform and the importance of mucosal immunity is intuitive, and the data that we've generated in animals supports it. Pathogens like influenza, pertussis, RSV (respiratory syncytial virus), and pneumococcus enter the body through the respiratory tract. The concept of using an adjuvant—which both delivers the vaccine and modulates or enhances the immune response—to elicit protection at the mucosal surface where these pathogens are entering the body could be revolutionary for the vaccine field over the next 10 to 20 years.

It’s exciting to be at the forefront of that, and over the past three or four years, some of the studies that we've performed in infectious disease have demonstrated that the technology can also be applied to allergens. In animal studies, we've demonstrated that when we vaccinate intranasally with a peanut extract, or a set of peanut proteins, for instance, we're able to shift the immune response from an inflammatory allergic response to a more desirable cellular immune response. The potential use of the NanoVax platform to enable vaccines that permanently suppress allergic reaction is quite exciting. It’s a step-change away from current immunotherapies that require people to either consume allergens daily, or wear patches that have the allergen in them in an attempt to desensitize the patient to that allergen. Those therapies don’t create a shift in the immune response. They require daily maintenance in order to see a benefit, and as soon as the person stops therapy, the benefits stops. We're quite a bit different than that because we're trying to actually reprogram the immune system via a vaccine.

Learn more about Peralta and BlueWillow Biologics at www.bluewillow.com