The Biotechnology Innovations Organization (BIO) report, The State of Innovation in Vaccines and Prophylactic Antibodies for Infectious Diseases, on January 25, 2024, found that while the current vaccine development pipeline has great breadth, it lacks depth.
On February 26, during BIO’s CEO and Investor Conference in New York City, industry leaders discussed the real-world implications of the vaccine pipeline report. David Thomas, BIO’s Senior Vice President of Industry Research, began the session by reviewing the report’s findings, while Phyllis Arthur, BIO’s Senior Vice President of Infectious Disease & Emerging Science Policy, moderated the panel.
“Vaccines have led to a 100% reduction in the risk of death for a host of devastating diseases,” she said back in January. “Yet many common infections don’t have any vaccines in clinical development. That needs to change. We need to pursue both scientific and policy changes that can help spur investment in these vital products.”
The challenges and opportunities for antibodies
Rajeev Venkayya, CEO of Aerium Therapeutics, addressed the issue from a largely antibody-based perspective.
“In the antibody space, there isn’t a general awareness of what exciting things are happening in vaccines,” said Venkayya. Recently, “the timelines to bring the first COVID antibodies to the market were substantially reduced relative to what we’ve seen during peacetime.”
This is an important point, as regulatory pathways to getting new vaccines to market can struggle outside of pandemic or endemic eras. This is especially true for small and mid-sized companies. This struggle needs to be addressed if the depth of the vaccine pipeline is to be mined more successfully.
“There are a few technological advances that have really enabled rapid antibody development. The first is manufacturing,” Venkayya continued. “There’s a lot of global experience and antibody development and manufacturing, but I would say that this was really honed and optimized in the context of COVID, particularly amongst certain [contract development and manufacturing organizations], as well as in some large companies that redeployed their internal platforms toward the specific target.”
Yet, Venkayya also noted that in the antibody space, there is a high degree of changeability in the viruses themselves by their very nature. Each season, humans create a degree of immunity to different versions of viruses like COVID, and each season the virus changes to evade those immunities. Thus, each season a new vaccine needs to be produced to meet the challenge.
mRNA and cancer
Comparatively, Andrew Allen, Co-founder, President and CEO of Gritstone, discussed the vaccine pipeline from a more mRNA perspective, especially in the realm of cancer vaccines. He observed Gritstone’s internal research on cancer cells lends itself quite well to viruses. There are many good T cell targets within viruses, yet these T cell targets are often understudied.
“Novel approaches to identifying good T cell targets within viral pathogens have been of great interest to us,” said Allen. “And we have a deep learning tool that we’ve built using human data that really helps us in this endeavor to identify relevant targets in new pathogens.”
Addressing AMR
Finally, James Wassil, COO at Vaxcyte, approached the conversation from the point of view of antimicrobial resistance (AMR), especially in the pneumococcal vaccine space. He called AMR “a very slow-moving pandemic that people aren’t really paying the appropriate attention to.”
Vaxcyte’s platform technology, called Cell-free Protein Synthesis Technology, drew Wassil to work for the company after he worked on the issue for other companies.
“Cell-free protein synthesis (CFPS) is a platform technology that provides new opportunities for protein expression, metabolic engineering, therapeutic development, education, and more,” explains a paper published by the National Institutes of Health (NIH). “The advantages of CFPS over in vivo protein expression include its open system, the elimination of reliance on living cells, and the ability to focus all system energy on production of the protein of interest.”
Regulatory partners in the vaccine pipeline
The topic of regulatory partners was visited repeatedly throughout the session, highlighting the differences between vaccine development during pandemic and endemic eras versus so-called “peacetime” eras. The difference, the panelists observed, can be a make or break when it comes to the success of small vaccine innovation companies from year to year.
One of the regulatory areas of special interest was the area of platform technology, whose benefit can reach far into the future but can also be a tall barrier in the short term, especially for small and mid-sized companies.
“When we talk about platform technologies, what we’re saying is regulators impose on us a set of tasks or challenges,” explained Allen. “And once you’ve met all of those, then you’re given that coveted title of being a platform technology, then you can develop novel vaccines against novel pathogens with relative ease, and the bar is low. But the problem is that the initial wall you’ve got to get over to enjoy those green pastures has just gotten higher and more expensive.”
“In a world where you don’t have much capital, the wall you’ve got to get over is just not working,” he continued.
“I’ve seen this before, whether in an epidemic or pandemic, the regulator will move mountains for you to get through [development and to market],” said Wassil. “And six months later, we come with our next antigen, it takes 15 months. So, the level of willingness of a regulator to move things along and take justified risks to move through the regulatory process once the dust settles becomes much more difficult after an emergency is over.”
“The platform concept is very appealing because we would like to think that once a certain platform has proven itself against the target, that you can just repurpose that for other targets without having to worry as much about safety,” added Venkayya. “The reality is that every immunity is different, and you can’t predict what is going to perform partially in certain trials and what might have some cross-reactivity with a native antigen.”
The outlook for the vaccine pipeline
While the current pipeline for vaccines has its own challenges, there is still overall optimism in the industry.
A number of new technologies and platforms could help accelerate vaccine development in the coming years, and the biotech industry is not losing any momentum as they learn from their successes in the past, especially around COVID and streamlining regulatory processes going forward.
“I think there are some green shoots in this otherwise bleak landscape,” said Allen, who explained that companies in the later stages of clinical trials are more on track for success now than before. Additionally, Allen noted the growing interest in therapeutic vaccines, which can solve a host of issues previously underserved both in oncology as well as secondary auto-immune spaces.
“If you build it, they will come,” Wassil reminded the panel, observing that the industry has long been the vanguard for healthcare development and that that dynamic is not going to change any time soon.
