In March 2022, HDT Bio announced that they had dosed the first healthy patient in a Phase I clinical trial for their next-generation Covid-19 RNA vaccine, HDT-301. The aim of the study was to evaluate HDT-301’s efficacy as both a booster and a primary vaccine. But as the company approaches the tail-end of the study, the ever-changing Covid-19 vaccine space means the Seattle-based biopharmaceutical company is now formulating different strategies.
The Phase I study (NCT05132907) corroborates the prominent safety profile of the vaccine established abroad and additionally strengthens the depth of demonstration of cellular immune response to new heights, COO Christopher Pirie told Pharmaceutical Technology. Now the company is deliberating whether to proceed to Phase II for a single indication or broaden the vaccine’s scope.
While Pirie did not share specific indications the company could potentially be targeting, he disclosed that it would be amongst the slate of what other developers are incorporating into their multivalent strategies.
Multivalent vaccines advance
At the 41st annual J P Morgan Healthcare Conference earlier this year, combination vaccines were a hot topic. Companies aimed to combine Covid-19 vaccines with vaccines for other respiratory viruses such as influenza and respiratory syncytial virus (RSV).
In December 2022, Pfizer and BioNTech received fast track designation from the US Food and Drug Administration (FDA) for their Phase I-stage Covid-19/influenza mRNA-based vaccine candidate. Another Seattle-based biotech, Icosavax, also gained an FDA fast track designation for an RSV/human metapneumovirus vaccine candidate, IVX-A12, in February 2023.
With the successful approval of GSK’s RSV vaccine Arexvy RSV, companies are exploring the possibility of individual protection against Covid-19, influenza, and RSV to provide a defence against a trifecta of respiratory disorders.
“I think we, as an industry, and as a patient population generally, of which I count myself as one, want for an annual vaccine that is as broadly protective as possible,” said Pirie. The nature of HDT-Bio’s repRNA/LION platform, as per Pirie, will allow for an even broader multivalent potential than what other companies are striving for and therefore will respond to market demand.
“We want for incorporation of even more antigens from diverse viruses. The more antigens and more immunity you can induce with a multivalent vaccine, the more effective that product can be. And thus the more difficult a development trajectory it may face. I think our platform’s significant advantages in multivalent potential, lend itself to such a product thesis,” says Pirie.
The company will likely decide direction, towards a single Covid-19 vaccine or a multivalent vaccine targeting more diseases, towards the end of this year.
At the same time, while heavy-hitting companies such as Pfizer experience Covid-19-related losses, HDT-Bio will continue its Covid-19 vaccine programme and take advantage of the product market opportunity surrounding Covid-19, says Pirie.
In animal models, the company has vaccinated dozens of different antigens across many disease types simultaneously, without loss of single-agent immunogenicity. In addition to addressing long-term prophylactic interventions with HDT-301, the company aims to also address the demand for short-term therapeutic interventions through the intranasal, antiviral spray, HDT-201.
HDT-201, a thermo-stable, broad-spectrum, repRNA/LION-using intranasal small RIG-I agonist antiviral candidate, is being evaluated both as a high-risk pre-exposure prophylactic and a post-exposure therapeutic to treat a spectrum of deadly human viruses.
The drug candidate, which recently received $1m in funding from Blue Knight, is being developed as a part of Project NextGen, a $5bn Covid-19 vaccine development initiative launched by the US Government. Preclinical data points to efficacy in inducing a SARS-CoV-2 antiviral response that inhibits viral replication, thereby blocking viral transmission and infection. The company hopes to begin clinical trials for HDT-201 in 2025.
