A decade after it began developing a patch-based vaccination platform, Vaxxas is positioning itself for clinical trials later this year by licensing a vaccine to be applied through the technology—a next-generation SARS-CoV-2 spike subunit vaccine developed at The University of Texas (UT) at Austin.
Vaxxas has in-licensed UT Austin’s HexaPro vaccine, as well as a companion background technology the company is licensing from the NIH. Vaxxas says the licenses—whose values have not been disclosed—will enable the company to create the first needle-free, room-temperature stable COVID-19 vaccine patch for clinical studies that are expected to begin in the coming months.
HexaPro would be distributed into patients through Vaxxas’ proprietary high-density microarray patch (HD-MAP), a non-invasive vaccination platform designed for response to pandemic threats to public health.
“We’re wrapping up the final preclinical studies. It’s going to be the first candidate for us in what I would call the in-licensing of the Vaxxas product pipeline,” Vaxxas President and CEO David L. Hoey told GEN Edge. “We will see data out of that before the end of this year.”
Should the Phase I trial prove successful, Vaxxas will advance HexaPro plus HD-MAP into later-phase studies, though the company said it is not projecting any timing or duration of those studies, let alone how soon it would file for approvals or launch its product.
HexaPro applies the most advanced spike protein developed by UT Austin’s vaccine development team led by Jason McLellan, the Robert A. Welch Chair in Chemistry and an associate professor of molecular biosciences.
In early 2020, weeks after COVID-19 began wreaking havoc, McLellan and colleagues partnered with collaborating researchers at the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center to design a version of the SARS-CoV-2 spike protein that was genetically altered by swapping in two amino acids called prolines.
The resulting prefusion-stabilized two-proline mutation “S-2P” spike is intended to stabilize the spike protein and allow the immune system to better fight off SARS-CoV-2 infection, since the spike protein of SARS-CoV-2 naturally changes shape, making it more difficult for the body to recognize. That spike is used in all COVID-19 vaccines approved or emergency-authorized for distribution in the U.S.
Six of the Best
HexaPro improves upon the S-2P construct through genetic alteration with six beneficial substitutions of prolines, with the aim of better training the human immune system to recognize and fight SARS-CoV-2 infection.
HexaPro also has two key advantages over S-2P. One is an approximately 10-fold higher expression yield of protein compared with the spike protein found in current COVID-19 vaccines. The other is an improved ability to withstand heat stress, storage at room temperature, and multiple freeze-thaws—making the vaccine more suitable for distribution worldwide, especially in developing countries.
“We started working a bit more than a year ago with Jason’s next iteration, which confers additional stability,” Hoey said. “From a manufacturing sense it’s much, much easier to produce very large quantities.”
Last year, a team of Australian researchers published preclinical research—first as a preprint posted in bioRxiv, later as a peer-reviewed study in Science Advances—showing that HexaPro delivered through Vaxxas’ HD-MAP offered enhanced virus neutralizing antibody and T-cell responses against all variants of concern—including Omicron as well as the early-discovered alpha, beta, gamma, and delta variants—compared with HexaPro administered via traditional needle and syringe vaccination.
“These findings represent a substantial improvement in many areas of SARS-CoV-2 vaccination and offer a promising alternative to currently available vaccines that warrants further investigation in the context of human SARS-CoV-2 infection,” concluded the Australian research team, led by principal investigator David A. Muller, PhD, of the University of Queensland.
Hoey said the positive preclinical results encouraged Vaxxas—an Australian company with commercial operations in Cambridge, MA—enough to initiate formal discussions with the University of Texas to license HexaPro as part of its move into the clinic.
HD-MAP uses an ultra-high-density 9x9mm array consisting of thousands of projections between ~250 µm and ~300 µm—all invisible to the naked human eye—that are applied to the skin for rapid delivery of vaccines to immune cells immediately below the skin surface. Vaxxas reasons its technology can enhance the efficiency and effectiveness of resulting immune responses of vaccines.
Vaxxas uses proprietary dry-coating technology to apply an active and stable vaccine onto the projections. That approach, according to the company, could eliminate the need for vaccine refrigeration during storage and transportation, addressing the “cold chain” challenges that have complicated the distribution of COVID-19 vaccines.
HD-MAP also enhances the efficiency and effectiveness of immune response, according to Vaxxas, since HD-MAP requires smaller concentrations of vaccine than the traditional needle and syringe. That difference can save vaccine developers on production costs and time needed to distribute doses, the company asserts.
By enhancing ease of vaccine use, Vaxxas adds, HD-MAP could enable more simplified administration, potentially including self-administration.
From Square to Round
While the patch initially used a square configuration, Vaxxas has since shifted to a round design following a change in the patch’s design wrought by advancing to industrial-scale production—the company changed the material used for the patch from monocrystalline silicon to plastic.
“We were no longer constrained by the requirements of the monocrystalline silicon, so we were able to move to geometries that actually fit much better with things like injection molding processes,” Hoey said.
He said Vaxxas has completed three human clinical studies of HD-MAP: “We’ve had more than 300 people now through clinical studies showing that the technology is safe and confers those benefits to humans as well.”
Vaxxas manufactures its HD-MAP vaccine administration device, including the integrated applicator and patch. The company can produce hundreds of patches a day for clinical use, as well as its own material for Phase I and Phase II studies.
Vaxxas is in the final stages of engineering design for its first commercial production line, capable of producing millions of devices per week in Brisbane, Australia, where the company is based.
“We’ll occupy that facility maybe by January of next year, and we’re hoping to have the physical line installed maybe in about 18 months from now, to start bringing it up for late stage clinical trial production,” Hoey said, adding that the facility would also be capable of carrying out early commercial-phase production.
“We want to have that pilot line operating in time for us to be able to produce the material for the Phase III study, so we’re on converging paths and working very hard on that,” Hoey added.
That pilot commercial manufacturing line is the initial effort of an alliance Vaxxas announced in 2020 with Harro Höfliger, a German pharmaceutical process engineering and sterile manufacturing concern. Through their partnership, whose value has not been disclosed, Vaxxas and Harro Höfliger have 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.
Patch Work
Vaxxas is not alone in pursuing patch-based delivery of drugs and vaccines.
Zosano Pharma delivers its lead candidate Qtrypta™ (zolmitriptan, also called M207), a treatment for acute migraine, through a transdermal intracutaneous microneedle system. Zosano’s patch consists of an array of approximately 2,000 drug-coated titanium microneedles mounted on an adhesive patch that is administered to the skin using a reusable applicator.
In November 2021, Zosano said it successfully formulated its own COVID-19 vaccine candidate onto its microneedle patch system. But last month, Zosano failed to convince the FDA that it had fully addressed concerns raised by the agency in a 2020 complete response letter (CRL) to Zosano’s NDA for Qtrypta. The company resubmitted the NDA in January 2022 with data from an additional pharmacokinetic study, only to be told the FDA will not begin substantive review of the application absent what it deems a complete response.
Also in January, Kindeva Drug Delivery agreed to combine its FDA-approved transdermal fentanyl patch (fentanyl transdermal system) with Nutriband’s abuse deterrent transdermal technology to develop Nutriband’s lead product, AVERSA™ Fentanyl, under a collaboration whose value was not disclosed. Kindeva is the renamed drug delivery business sold by 3M for $650 million in 2019 to Altaris Capital Partners.
In September 2021, a team of Chinese researchers reported in ACS Nano that they developed a separable microneedle patch (SMN) to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines designed to trigger immune response for blocking SARS-CoV-2 infection through the expression of S- and N-proteins in antigen-presenting cells.
“In vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses,” the researchers wrote. “This study may lay the foundation for developing a promising thermal stable and easy operating vaccines for combating COVID-19 pandemic.”
Also in September, researchers from Stanford University and the University of North Carolina at Chapel Hill published a study in Proceedings of the National Academy of Sciences (PNAS), showing that their 3D-printed microneedle vaccine patch generated an immune response in animals that was 10 times greater than vaccines delivered into an arm muscle with a conventional needle.
Beyond COVID-19
COVID-19 is among infectious diseases Vaxxas aims to help combat through HD-MAP. Another is pandemic influenza, for which HD-MAP will be evaluated in an upcoming Phase I clinical trial that Hoey said will recruit between 400 and 500 people. The study will be funded through the $22 million contract awarded last year to Vaxxas by the Biomedical Advanced Research and Development Authority (BARDA).
“The pandemic flu program is doing really well. We’re in preclinical development at the moment, and we’re on track to start that either late this year or early next year,” upon completion of demonstration work, Hoey said. “We’re excited about the progress and that would be obviously great to have a technology like as in place if a flu pandemic ever happened.”
Two other infectious diseases Vaxxas aims to deliver via HD-MAP are measles and rubella. Last year, the company launched a first-in-human clinical trial evaluating HD-MAP’s delivery of measles and rubella vaccines now administered by needle and syringe, using approximately $5 million in funding awarded in November 2019 by the Bill and Melinda Gates Foundation.
Vaxxas has completed a Phase I measles and rubella study, and plans to advance its studies into a Phase II trial set to start next year, Hoey said.
Within the next couple of months, he added, the company expects to announce funding from “a global philanthropy” toward studies of HD-MAP delivery of a travel vaccine for “an endemic disease” for use in developing countries, based on an existing vaccine used in the developed world.
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—an option the pharma giant exercised in 2020, gaining exclusive worldwide rights to develop and commercialize a vaccine using HD-MAP technology.
As a result, Merck paid Vaxxas $12 million consisting of equity funding and option fees. 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.
Merck has not disclosed development details of the planned HD-MAP vaccine, for which Vaxxas has been carrying out preclinical development designed to provide its partner with some materials to be used in future clinical studies Merck will conduct.
Hoey said Vaxxas cannot comment on Merck’s progress in the collaboration.