The COVID-19 pandemic looked like a turning point for vaccines, but while R&D has made tremendous strides with ground-breaking platform technologies and mRNA, vaccines continue to attract fewer investments than areas such as oncology. As panel members at the “Reviewing Vaccine Pipeline Breakthroughs and Barriers” session during BIO’s recent CEO and Investor event pointed out, the small biotechs developing 62% of the vaccines and prophylactic antibodies in the pipeline continue to struggle with lengthy timelines, funding and regulatory hurdles.
The industry is going after 51 pathogens, 31 of those have never been addressed by a vaccine before
David Thomas, senior VP, Industry Research, BIO
Vaccine Innovation
The session focused on vaccines, “Reviewing Vaccine Pipeline Breakthroughs and Barriers” at the recent conference came on the back of a new study published by the Biotechnology Innovation Organization (BIO), reviewing the history of vaccines and the tremendous advances they have made, as well as current clinical pipelines and the investment environment around vaccine development.
As the report demonstrates, vaccines have not only irradicated a number of diseases, they have drastically reduced mortality from others. COVID-19 is a vivid recent example and during the pandemic, vaccines were suddenly in the spotlight. However, vaccines have a long and impressive research legacy of tackling infectious diseases, one that continues today.
“The industry is going after 51 pathogens, 31 of those have never been addressed by a vaccine before,” said David Thomas, senior VP, Industry Research at BIO, reviewing the results of the study.
There is no shortage of clinical phase vaccines, Thomas noted. “249 vaccines are between phase I and phase III, plus 3 are in the submission phase,” he asserted, while marking a shift in focus. “Most of these are in the protein space, 87. In second place is the mRNA space, that is what has changed in the last 5 years.”
While Thomas maintained that the company-sponsored clinical pipeline for infectious diseases holds immense promise, he lamented that “the industry has a depth problem, it is broad but not very deep when you look at individual indications.” In fact, the report finds that just 10 percent of infectious disease threats addressed in the vaccine pipeline have 10 or more programmes dedicated to them.
And due to the complexity of bringing a vaccine forward, Thomas further regretted, “when we look at success rates, you have little better than a one in ten chance of making it.” But, he did add that “compared to small molecules, vaccines have had a much higher success rate.”
Lengthy timelines
With vaccines the average pay back is about 25 years
James Wassil, COO, Vaxcyte
It goes without saying that drug discovery is a lengthy process, but when it comes to vaccines there are added difficulties. “With vaccines the average pay back is about 25 years,” said James Wassil, COO of clinical stage vaccine company, Vaxcyte, whose lead candidate, a pneumococcal conjugate vaccine (PCV) has been granted FDA Breakthrough Therapy designation for the prevention of invasive pneumococcal disease in adults.
“The timelines are long,” Rajeev Venkayya, CEO of novel monoclonal antibodies-focused Aerium Therapeutics agreed. Formerly president of the Global Vaccine unit at Takeda, Venkayya used the company’s dengue vaccine as an example. “The dengue vaccine we [Takeda] brought to market was about 12 years after we acquired the company with the phase II asset.”
“It is very difficult to conduct a large-scale efficacy study because you are reliant on the epidemiology,” Venkayya pointed out, another factor that drags out vaccine development.
“The big challenge now is to get to the big scale randomized phase II data from hundreds of patients and that’s expensive,” said Andrew Allen, co-founder, president and CEO Gritstone Bio, a company focused on T cell immunity.
Funding hurdles
Often public money is not there and private money is leary
Andrew Allen, CEO, Gritstone Bio
Thomas regretted the lack of investment interest in vaccines, something that has not changed, even after they proved their inestimable worth during the COVID-19 pandemic. “Most investments from venture capital went into oncology [during the period from 2013-2022], and even in 2021 when vaccines saved the world, only 2.2 percent went into vaccine companies.”
With small emerging biotechnology companies developing 62% of the vaccines and prophylactic antibodies described in the BIO report, Wassil argued that due to a lack of investment assurance many vaccines do not progress. “A lot of the vaccine dropouts are because of a lack of confidence in funding.”
“We have raised 2 billion dollars and we have had to ask investors to pony up 2 billion dollars without a revenue or a product,” he added, referring to his own company. Vaxcyte, Wassil explained, got around the funding hurdle by focusing on an established path where it is not alone. “Coming into the market against an incumbent is a lot quicker and easier, so we will be able to quickly get on to the market where the winner can take it all.”
For Andrew Allen, the role of public funding and non-profit organisations is key. “The pandemic was transformative for our industry. It enabled us to do some initial work in mRNA that was funded by public money and that took some of the risk from the platform,” he said. “Because there was a commercial opportunity, investors could see and there was public money going into that commercial opportunity.”
In the CEO of Gritstone’s view, that era is sadly over and for a company such as his, working in an area like T cell immunity where there is no established path forward, funding is even more challenging. “Often public money is not there and private money is leary, [because] it is not clear what the commercialization path is, especially as a small company” he complained.
Venkayya stressed the risk alleviating capacity of partnerships with organisations such as BARDA or the Gates Foundation. “It’s essential to have de-risking from public and philanthropical organisations.”
Regulatory obstacles
Vaccines face regulatory impediments as well. Before reaching the market, they have an additional hurdle that other kinds of drugs do not face: government advisory recommendations for use. Once approved, vaccines are evaluated for specific recommendations by National Immunization Technical Advisory Groups (NITAGs) that define where each vaccine will have the most public health, societal and individual benefit. “If the national recommending body does not recommend the vaccine, the uptake will be very low,” said Venkayya. Thus, innovation in vaccines is partly driven by vaccine developers’ and investors’ confidence and understanding of how a novel vaccine might be recommended.
On another regulatory front, US legislation has created a formal “Platform Technology Designation,” a programme within the FDA designed to enable faster, more predictable product development. However, Allen argued that it has made it even harder for vaccine companies. “Regulators impose a set of challenges and once you’ve met all of those and are given the coveted title of being a platform technology, then you can develop novel vaccines against novel pathogens with relative ease,” he said. “The initial wall you’ve got to get over to enjoy those green pastures has just got higher and more expensive. Investors are not excited about vaccine companies, so that is not great.”
The exceptions regulators were willing to make during the COVID-19 crisis have also not been carried over post-pandemic according to Wassil who contended that the willingness of regulators to move things forward “is there for emergencies, but then the dust settles.”
Venkayya conceded that the challenge of demonstrating safety is real, making a platform’s approval more difficult. “The process is the product,” he said, “which means that a critical part of showing equivalence between products is the chemistry manufacturing package which shows that the process is the same in facility A and facility B.”
