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Avaxia Biologic's Barbara Fox Stays on the Run at BIO 2013

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By Marie Powers
Staff Writer

CHICAGO – For Avaxia Biologics Inc., the decision to attend BIO 2013 was a no-brainer. The Lexington, Mass.-based company is in the middle of a Phase Ib study of lead compound AVX-470, an orally administered anti-TNF polyclonal antibody, in ulcerative colitis (UC). Results are expected in November, and if all goes well the company plans to report data in January 2014 at the J.P. Morgan Healthcare Conference in San Francisco.

Based on preclinical safety and efficacy findings, founder and CEO Barbara Fox said she is confident the company will move quickly into Phase IIa, and she's in the hunt for a partner to move with her.

Fox and Mike Rivard, Avaxia's vice president of corporate development, scheduled three full days of one-on-one meetings at BIO. Fox allowed BioWorld Today to tag along during their meetings on Monday.

7:30 a.m. We met at the BIO registration desk and headed to the first partnering booth to chat for a few minutes before the meetings began. On a typical workday, Fox rises by 5:30 a.m. and spends about an hour responding to emails and scanning stories in the New York Times, Wall Street Journal and Boston Globe. When she's in town, she's at the office by 8 a.m., where she devotes much of her time to reviewing FDA regulatory filings, writing scientific papers, updating company presentations and dealing with patent office actions. Fox also holds a weekly staff meeting that involves all 13 Avaxia employees, and she's always ready to "fill in the gaps" to maintain the small biotech's momentum.

"I'm the founder of the company, so part of my role is to keep the vision and the mission of the company on track," she said.

Fox spends about half her time on the road – mostly raising money, and occasionally traveling the better part of day for a single meeting.

"A lot of my responsibility is making sure we're capitalized," she explained. Avaxia is funded primarily by angel investors, which insulates the company from the vagaries of the venture market but requires more hand-holding. The company has raised more than $12 million from local and national angel groups and individuals since its founding in 2005, supplemented by $6 million in nondilutive grants and government contracts. Fox's goal is to have at least six months of funding in the bank. "It's a fairly time-intensive way to raise money," she admitted, "but we have a very loyal investor base." (See BioWorld Today, Nov. 11, 2011.)

Fox and Rivard packed much of their partnering schedule with companies outside the U.S. Most were established contacts seeking an update about the trial, others were initial introductions and some were third parties that contacted Avaxia about collaborative opportunities.

"A lot of this is about building relationships and establishing credibility," Fox told BioWorld Today. "We said we were going to accomplish certain goals, and companies want to see that we actually meet them." She cited FDA clearance of the company's investigational new drug application in November 2012 as a key milestone "that opened a lot of doors for us. Ideally, we would like to get companies teed up and as far along the diligence path as possible so we can engage them when the clinical data come in."

8:00 a.m. The director of business development at a Japanese specialty pharma first contacted Avaxia at BIO 2012, and the companies talked often in the ensuing months. He's also read previous partnering stories in BioWorld Today. "I hope you'll describe me as a young, handsome Japanese business executive," he joked.

As Rivard queued up the slideshow, Fox offered an update on the status of Avaxia's randomized, placebo-controlled, ascending-dose Phase Ib trial. Eight patients have been enrolled at the lowest dose at sites in the U.S. and Canada, and two have completed dosing. No discontinuations were reported, and the data monitoring committee is scheduled to take a look in mid-May. In the meantime, the company received regulatory approval for additional sites in Belgium and Hungary and a third European country is pending for the trial, which plans to enroll 24 patients, each dosed for 28 days. Plus, "we're doing some additional nonclinical work on pharmacokinetics and immunogenicity," Fox said, and the company is working on commercial manufacturing process development.

Because the Phase Ib trial – which the FDA approved as a first-in-human study – is blinded, the company won't get an interim look, she added. "But the data monitoring committee will review safety after every cohort so we know we can safely escalate the doses," she said.

The pharma contact liked what he heard, indicating he hoped to present his recommendations "to a wider audience" by June. "Keep me updated," he added, ending the meeting on a high note in just 15 minutes.

8:30 a.m. Fox greeted a long-time acquaintance who's now director of business development for a European biopharma with a significant U.S. operation. The company recently shuffled its internal priorities and has renewed interest in Avaxia, whose technology is designed around antibodies isolated from the early milk of immunized cows, known as bovine colostral antibodies, which are naturally resistant to digestion. By designing oral drugs that act locally in the GI tract, Avaxia is seeking to address both known and novel targets in inflammatory bowel disease with improved safety and efficacy.

Moreover, bovine milk antibodies have a predictable regulatory path through the FDA's Center for Biologics Evaluation and Research (CBER) Blood Products Group. The technology is scalable, since cows produce approximately 1 kg of immunoglobulin in three days, and millions of cows are available in the U.S. alone. Avaxia also has three issued U.S. patents, pending applications in all global markets and the ability to bypass most of the intellectual property issued around monoclonal antibodies.

"We're in line with where much of the field is going, which is trying to make suppression of the disease more specific to the particular tissue," Fox said. "And we think we're doing this in a really novel and more powerful way because we can use the same target, an anti-TNF, as currently marketed drugs and focus on the delivery of those antibodies into the GI tract. To our knowledge, we are the only ones doing direct delivery of antibodies to the gut."

Fox explained the company's plans to begin working on supply chain issues and to set up standard operating procedures to handle the animals – a sensitive issue in Europe and the UK. Avaxia recently hired a specialist to oversee its animal welfare plan.

"The fact that you've even thought about these issues this far ahead is a big deal," was the response. "This was a great presentation."

The obvious next question: What are Avaxia's thoughts on partnering? The company wants to finish the Phase Ib and go straight into a deal with up-front fees, milestones and royalties, Rivard responded.

But Avaxia is flexible, Fox added. Although she expects to partner after completing proof-of-concept studies, "we have room to look at a lot of different opportunities," she said, ranging from global deals with a pharma or big biotech to regional collaborations in Europe and Japan – even licenses with manufacturing and supply agreements.

"We have our ideas about the type of deal structure we would like, but all sorts of interesting things can come out of these discussions," Fox said.

9:00 a.m. Another Japanese firm, this time a large conglomerate with a pharmaceutical operation. The company was especially interested in the commercial process development and supply chain issues, asking about animal issues in Europe and cost models. The representatives also inquired about other formulations and whether Avaxia had considered Crohn's disease instead of UC as its first indication. "Yes," Fox said, but the diseases are different enough in nature, including tissue penetration, that UC looked superior from a patient management perspective in the clinical trials.

"Safety is our strongest seller," she added. "It's milk, and it's oral dosing."

Fox was heartened by the company's questions. "This company has been interested at a distance, but they're starting to circle in," she said. "They were much more engaged than I expected."

9:30 a.m. The fourth meeting almost ended before it began when the representative from a U.S. big pharma spotted the "media" sticker on my badge and prepared to walk away. Instead, I did.

9:55 a.m. We reconvened at the next partnering booth, where Fox graded the morning so far as "four for four" in terms of interest level. "What's not to like about an oral anti-TNF?" Rivard responded.

10:00 a.m. Using the BIO Partnering website, a U.S. academic medical center contacted Avaxia about a potential gut-targeted therapeutic in-licensing opportunity. Fox did a quick rewind on the company's technology and Phase Ib study, seeking to move on to the organization's investigational program.

"You're focused on your Phase Ib," the associate said.

"Well, yes," Fox responded. "We're a little company, and if you drop the ball on your lead program, you're dead. But we're opportunistic, so we're eager to take a look at something interesting."

As it happens, the technology appeared only distantly related, and Fox was mildly concerned over the prospect of an epithelial signal. She and Rivard asked about the organization's patent strategy and partnering approach and offered advice on alternative indications, such as necrotizing enterocolitis – which is off Avaxia's radar for now.

10:30 a.m. The managing director of an ex-U.S. company that specializes in biopharmaceutical imaging services sought this meeting with Avaxia, which currently relies on ELISA testing and biopsies to study pharmacokinetic antibody circulation and tissue penetration, respectively. Fox wants the ability to demonstrate where AVX-470 goes, how it interacts with other compounds and how it's cleared from the body – answers that could be provided by selecting the appropriate radioisotope.

The imaging technology also could help Avaxia advance a second application, in acute radiation syndrome, under a contract from the Biomedical Advanced Research and Development Authority. And, potentially, it could be used to stratify patients or to conduct a preclinical biodistribution study. "We're able to play with ratios of chelators and antibodies and to change coupling chemistries," the imaging rep pointed out.

Although potential implementation hurdles loom, Fox was clearly intrigued. "A lot of outstanding scientific questions could be answered with imaging studies," she said.

"We haven't done gut imaging, so we'd be learning, too," came the reply, suggesting co-development potential.

2 p.m. Following two private meetings and a quick lunch in the ever-crowded Plate Room Lunch Court at McCormick Place, we met back in the partnering hall with a large European specialty pharma. The company does development and commercialization but no early stage discovery, typically seeking to license an asset, commercialize it in Europe and partner elsewhere.

"What caught your attention about Avaxia?" Rivard asked.

"We're looking for products we can in-license to build our pipeline," the rep replied.

"Let's go through this and see if there's a fit," Fox added, spending the next 10 minutes on the company's presentation and citing another huge potential market that is up the pharma's alley: oncology patient-supportive care. Avaxia is developing a polyclonal anti-TNF antibody to block the inflammatory cascade that is central to the development and worsening of oral mucositis.

"Is this the sort of program you'd bring in after a Phase Ib?" Fox asked.

"Absolutely," was the reply, and both sides agreed to move discussions to the next level.

2:30 p.m. Fox and Rivard met with the business development manager at an ex-U.S. biotech seeking to out-license its inflammatory platform. The company was recently acquired, and the new owner wants to divest programs that fall outside its core expertise. Although the preclinical program has some nice data, the technology is a small-molecule inhibitor.

Fox is not averse to adding other technologies with attractive synergies, provided they don't distract from the company's primary mission. "I can't really see us going into a small molecule, especially at this stage," she said.

3 p.m. In one of Avaxia's most highly anticipated meetings of the day, we headed to the front of the business forum section where global big pharma booths are marked by company logos rather than nondescript alphanumeric designators. The senior official, a partnering lead, listened attentively as Fox made her pitch, interrupting with pointed questions. He asked about the use of immunized cows, jotting careful notes about the answer. He also made note of the CBER regulatory pathway and Phase Ib trial design. "Can I see any of your efficacy data?" he asked. "What is it about the antibody that causes it to be effective in the digestive system? Will it target multiple sites on TNF? Can you give me an idea of the cost of goods? How big of a herd is needed for commercial scale-up? Do you have competitors in the space? What's your IP? What are you looking for from a partner? What else is in your pipeline?"

He smiled politely as we left, telling Fox, "I look forward to seeing your data."

Gathering her thoughts outside, she shrugged her shoulders. "A typical first meeting," Fox noted. "He was completely inscrutable."

Rivard stayed a few minutes to chat with the pharma exec and emerged more optimistic. "He liked it," he said.

3:30 p.m. Another Japanese pharma meeting, this time with the associate director of licensing and alliances, who's already familiar with AVX-470 and the Phase Ib trial. Fox offered a quick update while he took copious notes before moving almost immediately into questions about the company's partnering strategy.

"We're flexible," Rivard responded. "It could be one global partner or multiple deals, but we want to find someone that will invest in development and commercialization and sell a lot of product.

"If the Phase Ib data look good, we want to move fast," he added, making a note to forward the company's presentation.

4 p.m. Two meetings were left on the schedule, and everyone was dragging. A patent attorney from the tech transfer office at a European university requested this meeting, and Fox's antenna went up when she heard that a researcher at the institution developed antibodies that appear to show an anti-inflammatory effect in UC. In fact, the antibodies seem to target lesions in the colon.

"What's the IP?" Fox asked. "This is potentially a very nice fit for us."

"The university is open to any collaborative research or licensing approach," the attorney responded. In fact, the investigator plans to attend Digestive Disease Week in Orlando next month, which Fox and her clinical staff also will visit. Meeting there "would be a great next step," Rivard suggested.

4:30 p.m. Last meeting of the day, and one of the most important. Rivard has been talking regularly with the senior manager of business development and licensing at the European division of this Japanese specialty pharma since they met at BIO 2012 in Boston. Recently, the two companies held "a very productive" conference call. This was the first meeting to involve a senior licensing official from the Tokyo office.

The show was all Fox's, with nary an interruption from the rapt audience. As she concluded, Rivard neatly transitioned into the partnering pitch.

"We're trying to address any questions about contract manufacturing, animal welfare or other concerns up front so we can partner as quickly as possible once we have Phase Ib data," he said. "We want to have partner input into the design of the Phase II study."

Almost as an aside, he added, "We've hired a regulatory consultant in Japan, and we've been assured there are no outside issues."

"We're really interested," the manager responded. "I guess we just need to see Phase Ib data."

With the sound of the last partnering chimes of the day, we navigated through the quickly darkening exhibition hall. Rivard headed for his hotel as Fox and I moved on to the Women in Bio reception. She was energized by the positive feedback, which she called "a great way to start the week."

Many small biotechs overestimate their ability to execute, which hurts their credibility, Fox observed. That's a misstep she's taken great pains to avoid at Avaxia.

"We haven't had any scientific setbacks, although financings sometimes take longer to get done than we anticipated," she said. "But you have to prepare for setbacks and know how to handle them.

"You have to be nimble in this industry," Fox added. "You can carve out a strategy, but you've got to be able to move on the opportunities that come your way."