RESEARCH TRIANGLE PARK – Millions of Americans are at risk for anaphylaxis, a severe allergic reaction to medicines, foods, bee stings, insect bites, dust, latex or other substances. And up to 25% of those at risk have not been diagnosed.
People who have an anaphylactic reaction require a fast emergency treatment to reverse potentially life-threatening symptoms such as difficulty breathing, swelling of the throat and tongue, rash, nausea and shock.
The current recommended emergency treatment is an intramuscular shot of the hormone epinephrine, typically self-administered in the thigh with a pre-filled device called an auto-injector. Most consumers know the devices as an “EpiPen.” EpiPen, Adrenaclick, Auvi-Q and Symjepi are the top-selling brands.
Scott Lyman believes his small biopharmaceutical startup company in Raleigh has devised a more patient-friendly, rapid-acting and cost-effective way to ensure patients have access to epinephrine during emergencies.
“We’ve developed a more elegant solution,” said Lyman, co-founder, chief executive officer and board chairman of Belhaven Biopharma. “The long-term opportunity is we could potentially make many emergency-use intramuscular (IM) auto-injectors obsolete and provide first responders medications to treat patients earlier.”
Dry powder drug delivery through the nose
Belhaven has developed a dry powder formulation of epinephrine that can be administered into the nose with a simple, pre-filled nasal device. Lyman said the drug-device combination, called Nasdepi (an acronym for nasal dry powder epinephrine), promises several advantages over IM auto-injectors or a liquid nasal spray.
Nasdepi doesn’t require a painful needle injection, is easier to use and is about half the size of an auto-injector, easily fitting into a person’s pocket. The dry powder medicine it delivers has a longer shelf life, is less sensitive to extreme temperatures and gets into the bloodstream faster – in three to five minutes versus about 20 minutes for a liquid auto-injector. Because it is a powder and not a liquid, it provides more consistent dosing that can be administered to patients who may have rhinitis, a runny nose that is common during an allergic reaction, and it doesn’t depend on the patient’s position or level of consciousness.
“We want to fix all of the problems related to IM auto-injectors, not just a few of them that liquid nasal formulations may address,” Lyman said. “There’s no reason we should be using large, expensive auto-injectors when we have this dry powder nasal platform available to us.”
A growing market
The global market for epinephrine auto-injectors was valued at over $2 billion in 2022 and is projected to reach $3.2 billion by 2032, according to a report by Future Market Insights, a market intelligence and consulting firm based in Delaware.
“The increasing number of persons allergic to dust, insect bites and venom, food and food additives has propelled the demand for epinephrine auto-injectors,” the report says.
Belhaven aims for Nasdepi to disrupt the U.S. market for emergency-use epinephrine while expanding access to the drug globally, including the developing world.
But first it needs to gain federal regulatory approval of Nasdepi. The company is conducting clinical trials to confirm that the absorption of the dry powder formulation of epinephrine generates the same drug levels as the FDA-approved liquid delivered with an intramuscular shot. An initial pilot study, due to end in December, will evaluate different doses of Nasdepi to determine the dose for a larger clinical trial required for FDA approval.
Global licensing plans
Because Belhaven’s core expertise is in drug formulation and spray drying, not commercialization, the company plans to license Nasdepi to one or more pharmaceutical companies when the product is ready for launch, Lyman said.
“We’ve got a list of potential partners,” he said. “There is an opportunity for somebody to disrupt the market in the U.S. and abroad. The ideal scenario is we find a partner that says, I want worldwide rights.”
Belhaven is also open to having multiple licensees address various markets such as the United States, Europe, Japan and the rest of the world.
“Our goal is to expand access to epinephrine globally, even if we need to license the product out by regions,” Lyman said.
Longer term, he sees Belhaven’s dry-powder formulations expertise applying to other FDA-approved emergency-use drugs used for early treatment of life-threatening conditions and as medical countermeasures to chemical and biological agents.
“We look at this as a platform technology,” he said, “and we’d like to do more products. Nasdepi is the first of many emergency treatments that could use an upgrade to make decades-old treatments more accessible.”
Raising angel investment
Belhaven is currently raising a seed round of funding from angel investors to support further development of Nasdepi, Lyman said. The $3 million Bridge Round is expected to close in early January before the announcement of clinical trial results.
The company, founded in 2021, previously raised two seed rounds of angel investment along with two loans from the North Carolina Biotechnology Center.
A $250,000 Small Business Research Loan awarded in 2021 helped Belhaven fund pre-clinical lab studies of Nasdepi, and a $500,000 Strategic Growth Loan awarded in 2022 helped the company with its initial regulatory filing and clinical trial.
“NCBiotech’s funding has supported the company’s drug development and advancement toward the Investigational New Drug stage,” said Greta Brunet, senior director of investments for the Biotech Center.
“Over the last 10-plus years, the exorbitant price increases in brand and generic aqueous epinephrine auto-injectors have made it difficult for patients to carry one auto-injector, let alone the standard advised two-pack,” Brunet said. “Belhaven’s product has the potential to fill a significant need for millions of patients.”
Lyman expects Belhaven will need a “modest” Series A round beyond its current fundraising to position Nasdepi for commercialization. The company will likely begin raising a Series A round of venture capital in early 2024, he said.
Meantime, Belhaven is keeping expenses low by operating virtually with a core management team working remotely throughout the Research Triangle area. Additional support is provided by expert consultants working in toxicology, regulatory affairs, clinical operations, statistics, medical affairs and pharmacokinetics. External vendors support Belhaven’s program in areas such as human factors test, device reliability, device manufacturing, spray drying and secondary packaging, Lyman said.
New board members
Belhaven recently added to its board of directors three new members with expertise valuable to the company’s strategic direction, Lyman said.
- Eric Edwards, M.D., Ph.D., is co-founder and chief executive officer of Phlow Corp., a pharmaceutical manufacturer, and previously was co-founder of Kaléo Inc., a drug-device pharmaceutical company. He was co-inventor of the Auvi-Q epinephrine auto-injector.
- Wes Wheeler was most recently president of Global Healthcare at UPS and previously was chief executive officer and/or president of Marken, Patheon, Valeant Pharmaceuticals and DSM Pharmaceuticals.
- Derek Winstanly, MBChB, is board chair of two biopharmaceutical companies, Renovion of Durham and Huya of San Diego. Previously he held several senior executive roles at Quintiles (now IQVIA) and GlaxoWellcome (now GSK) over more than 30 years.
Belhaven’s other board members are Lyman, a chemical engineer with pharmaceutical spray-drying experience at Amgen who later held leadership roles at Grid Therapeutics, GlaxoSmithKline, BioCryst and Salix; and Dave Neal, Belhaven’s co-founder and chief financial officer, who is also an attorney, professor and venture capital partner.
Many of Belhaven’s executives, board members and scientific advisory board members have ties to the University of North Carolina at Chapel Hill. Some earned degrees at UNC, while others teach or conduct research there.
Many of the company’s angel investors are connected to the Research Triangle Park area, Lyman noted.
(C) N.C. Biotech Center