Vaxxas President and CEO David L. Hoey discusses HD-MAP with GEN in a recent Zoom interview.

Fear of needles has long been a driver of resistance to vaccines, no matter a patient’s age: A 2012 study found 24% of adults and 63% of children expressing that fear, while a 2018 meta-analysis of 35 studies showed that among grown-ups, avoidance of influenza vaccination because of needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of workers at long‐term care facilities, and 8% of healthcare workers at hospitals.

Those and other needle-avoiding patients may be more likely to accept and receive vaccines through an alternative approach developed over nearly a decade by Vaxxas, an Australian company with commercial operations in Cambridge, MA.

Earlier this month, Vaxxas won $22 million from the Biomedical Advanced Research and Development Authority (BARDA) toward advancing clinical development of its proprietary High Density Micro-Array Patch (HD-MAP) non-invasive vaccination platform in response to pandemic threats to public health.

The contract from BARDA (75A50120C00180) will fund an upcoming Phase I clinical validation study designed to evaluate HD-MAP for pandemic influenza in 420 people, using both unadjuvanted and adjuvanted vaccine formulations.

BARDA is footing most of the trial’s $24.1 million cost, with Vaxxas contributing the remaining 8.5% or $2.1 million. Vaxxas said pandemic influenza vaccine was selected for the validation study in order to generate a comprehensive baseline of immune responses and safety data for HD-MAP when used for pandemic preparedness and response.

However, Vaxxas adds that it is actively investigating opportunities to apply HD-MAP toward improving the performance of vaccines for other pandemics—including against COVID-19.

HD-MAP uses an ultra-high density 9x9mm array consisting of thousands of projections that are approximately ~250µm and thus invisible to the naked human eye, coated with vaccine. That vaccine is applied to the skin for rapid delivery to the immune cells immediately below the skin surface.

“A Smarter Way”

“It’s just a smarter way to deliver vaccines,” Vaxxas President and CEO David L. Hoey told GEN. “There aren’t too many people that like a needle. So if you’re a patient, you’ll enjoy the fact that it’s a patch.”

Vaxxas’ HD-MAP packaging

Hoey said HD-MAP can enhance the efficiency and effectiveness of immune response. HD-MAP requires smaller concentrations of vaccine than the traditional needle and syringe, which can save vaccine developers on production costs and time needed to distribute doses.

Also, the dry vaccine formulation contained in the patches does not need refrigeration, allowing for rapid distribution using commercial shipping carriers such as the U.S. Postal Service, UPS, or FedEx.

“What we’re trying to do is essentially put the vaccine antigen right amongst those populations of immune cells. In contrast, by needle and syringe, when you are putting it into the muscle, essentially, the vaccine is wandering around. It will get picked up systemically, and sooner or later it’ll bump into an immune cell that will bring it to a lymph node for processing,” Hoey explained. “What we do is we started trying to almost target lymphatic delivery. So by putting the vaccine just under the surface of the skin the vaccine antigen is picked up by the dendritic cells and taken very efficiently and effectively to lymph nodes.”

Vaxxas says it has developed a prototype of a compact manufacturing system designed to deliver more than 250 million vaccine doses per year. Hoey said the company expects its first HD-MAP vaccine to reach the market within five or six years, with plans to build a portfolio of vaccine products afterward.

“This can be a technology in the tool belt that has the potential to be used across a whole range of different vaccines, that just fundamentally improves every aspect of response,” Hoey said. “I’d like to think that in 20 years, the leading vaccine in every disease category is going to be delivered by this technology because it’s just a fundamentally more sensible way to deliver a vaccine.”

Emerging Technologies

Vaxxas is among developers of patch-based delivery of drugs and vaccines to emerge in recent years:

  • 3M has developed microneedle drug delivery systems consisting of both solid microneedle technology for delivering vaccines and biologics of up to 300 mcg capacity, as well as hollow microeedle technology designed to deliver liquid biologic formulations of 0.5 mL to 2 mL over a variety of viscosities. Last year, 3M spun out its drug delivery business for $650 million to Altaris Capital Partners, which renamed the business Kindreva Drug Delivery and plans to establish a headquarters in the Minneapolis suburb of Woodbury, MN.
  • Corium has applied its MicroCor® microneedle system to administer Eli Lilly’s osteoporosis Forteo® (teriparatide [rDNA origin] injection), a parathyroid hormone analog, (PTH 1-34), which is indicated for three forms of osteoporosis.
  • CosMED Pharmaceutical has developed a dissolving MAP (D MAP) called MicroHyalaTM, made of hyaluronic acid, and intended for cosmetic products like those designed to combat acne or age spots.
  • Emory University researchers led by Nadine Rouphael, MD, published a study in The Lancet on June 27 detailing their 100-participant Phase I trial (NCT02438423) which showed that a microneedle patch system was safe and just as effective as intramuscular injection in generating immunity against influenza.
  • Zosano Pharma uses a transdermal intracutaneous microneedle system to deliver its acute migraine candidate Qtrypta™ (zolmitriptan). In August, Zosano launched a collaboration of undisclosed value with Mitsubishi Tanabe Pharma to study the feasibility of formulating an undisclosed drug being developed by the Japanese pharma for administration in humans using Zosano’s microneedle patch.

Vaxxas has evaluated HD-MAP in the largest microarray patch clinical vaccination study ever performed, involving 210 participants as well as researchers from the company and clinical partners including the University of Queensland and University of Melbourne. The study was designed to measure the safety and tolerability of A/Singapore/GP1908/2015 H1N1 (A/Sing) monovalent vaccine delivered by HD-MAP, compared to an uncoated Vaxxas HD-MAP and IM injection of a quadrivalent seasonal influenza vaccine (QIV) delivering approximately the same dose of A/Sing HA protein.

Dose-Sparing Potential

In that Phase I trial (Australian New Zealand Clinical Trials Registry No. ACTRN12618000112268), detailed in a study published March 17 in PLoS Medicine, the use of HD-MAP to deliver a 2.5 μg dose of vaccine—one-sixth of the standard dose—induced haemagglutination inhibition (HAI) and microneutralization (MN) titers that were similar to those induced by a standard dose of 15 μg injected IM. That result validated the dose-sparing potential of Vaxxas platform, according to Vaxxas.

At two higher doses, 10 and 15 µg, HD-MAP was shown to produce significantly high titers and faster onset kinetics than 15 µg injected IM. HD-MAP was also shown to be stable when stored at 40°C (104°F) for at least 12 months.

HD-MAPs are prefabricated by injection-moulding of polymer, which will make them less expensive for commercial manufacture than Vaxxas’ original Nanopatch™ system formed from dry-etched monocrystalline silicon.

Earlier studies of the Nanopatch showed it to be safe, well tolerated, preferred by recipients to needle and syringe delivery, and able to induce immune responses at least as potent as IM injection. Last year, for example, investigators from Vaxxas and other research partners published a study in the journal Vaccine: X that found the use of the Nanopatch to have induced immune response similar to that of the Mantoux technique for intradermal injection in delivering a dried formulation of unadjuvanted Gardasil™ 9, Merck & Co.’s vaccine for human papillomavirus (HPV), into rhesus macaques.

Overall, Hoey said, Vaxxas has published studies assessing its patch platforms in some two dozen different vaccine types. That number will increase in January, when Vaxxas launches a first-in-human clinical trial evaluating HD-MAP’s delivery of measles and rubella vaccines now administered by needle and syringe, using funding from the Bill and Melinda Gates Foundation. The measles and rubella vaccine formulation being used to coat the HD-MAP has been engineered for greater stability at higher temperatures than needed for needle/syringe vaccination.

The Gates Foundation in March awarded Vaxxas $5 million toward IND-enabling studies and the first-in-human clinical study, building upon an earlier grant by the foundation of $4.5 million focused on preclinical development.

World Exclusive

Vaxxas was established in 2011. A year later, it inked a collaboration agreement with Merck granting the pharma giant an option to use HD-MAP. On May 28, Vaxxas announced that Merck had exercised that option, gaining exclusive worldwide rights to develop and commercialize a vaccine using HD-MAP technology.

Merck has not disclosed what that vaccine will be, though Hoey said it is expected to enter the clinic in about two years. Vaxxas is carrying out preclinical development designed to provide them with some materials to be used in future clinical studies Merck will conduct.

As a result of exercising its option, Merck will pay Vaxxas $12 million consisting of equity funding and option fees associated with the agreement. Vaxxas is also eligible to receive undisclosed future option, development, and commercial milestone payments. Merck has also agreed to oversee clinical development, and fund any requested additional research activities conducted by Vaxxas.

Privately-held Vaxxas is based in Brisbane with commercial operations in Cambridge, MA. The company employs about 55 people, and is hiring another 20 now—mostly for manufacturing positions to be created in Brisbane as the company builds out a pilot line for late stage clinical material and early commercial production set to be up and running in about 18 months to two years. Some of the new hires will fill business development positions in Cambridge.

“We’re scaling up a bit, so that we will grow to about 75 folks by the end of this year, and probably add something like another 50 during the course of next year,” Hoey said.

Since its founding, Vaxxas has raised about A$66 million ($47 million) in financing, plus another A$40 million (nearly $29 million) in non-dilutive funding.

“We know we’re in a good position, but we’re about to proceed to build our first manufacturing pilot line, which is an expensive exercise,” Hoey said.  “We need to have that in place to start producing the material that we’ll need for our late-stage clinical studies. And even though those are a couple of years away, it takes about 18 months to build your pilot line. It takes about a year to validate it, and then you’ve got to produce it.”

That pilot line is the initial effort of an alliance Vaxxas announced in May with Harro Höfliger, a German pharmaceutical process engineering and sterile manufacturing concern. Through their partnership, whose value was not disclosed, Vaxxas and Harro Höfliger committed to develop the world’s first high-throughput aseptic line for vaccine-HD-MAP production, with a capacity of compact modular lines targeted at 5 million units per week.

Vaxxas also plans to build a manufacturing facility in the US, Hoey said, adding: “But that’s still a couple of years out.”

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