Blog | 4/23/2020

Rapid Responders: How Innovative Technologies are Accelerating Development of New Vaccines

By Joseph McInnes, PhD, Senior Analyst; Kristine Mechem, PhD, Vice President; Vivek Mittal, PhD, Partner

Key Takeaways

  • Within three months of the first cases of COVID-19 (SARS-CoV-2) appearing in China, there are already more than 40 novel drugs in the US pipeline to target COVID-19, and five novel vaccines in clinical trials worldwide
  • Newer technologies such as nucleic acid-based vaccines and single cell sequencing have enabled faster lead identification times than in previous pandemics
  • A diversified pipeline portfolio of fast-moving innovative products and long-term traditional vaccines with other containment strategies like shelter in place and social distancing, can provide a balanced short and long-term strategy to bring pandemics under control
  • Companies with platforms that can be more readily customized such as mRNA vaccines, antisense oligonucleotides (ASOs) and RNAi therapies can move through development faster, but they are often smaller biotech startups who will require more federal financial assistance in early pre-pandemic stages when risk is still high
  • Federal assistance programs need to be developed and tailored to provide R&D funding to companies at pre-pandemic stages to encourage rapid mobilization of resources to bring new products to clinical trial as quickly as possible

Innovative Technologies Driving Faster Development
As we approach the three-month mark since COVID-19 cases began spreading throughout China, it may feel like there's no hope in sight for getting new drugs and vaccines to the frontlines to bring the pandemic under control. In reality, biopharma companies are moving faster than in previous pandemics. As of early April, there are approximately sixty COVID-19 drugs in the US pipeline, with about 80% of those being novel vaccines and drugs specifically tailored to fighting the novel coronavirus.  Of the novel drugs in development, approximately half of those are vaccines, and a quarter are neutralizing antibody therapies that could be used as both prophylaxis or treatments. As of April 9th, there are already five vaccines of various technological modalities in clinical trials worldwide, two of which are in the US (see Table 1). Any of these candidates, if successful, could have a significant impact on bringing the COVID-19 outbreak under control and potentially could be a foundation for a potential future response if or when new coronaviruses surface.

Table 1: Vaccines in Clinical Trials for COVID-19 Worldwide as of April 9thpicture1-6.png

Source: Health Advances analysis, PharmaProjects, Le 2020 Nat Rev Drug Discov, company press releases.


Table 1: Health Advances set out to understand which US companies are moving quickly in developing novel coronavirus-targeting drugs and what factors are contributing to their development timelines. In our analysis, we focus on companies that we refer to as "Rapid Responders" – companies that quickly mobilized to initiate R&D programs of new COVID-19 vaccines and therapeutics, and are predicted to reach clinical trial by this summer. We performed an in-depth analysis of factors including platform technology, access to capital, federal assistance, and clinical development resources. Surprisingly, we found that the primary driving factor contributing to a rapid response was innovative  technology platforms. Below, we provide illustrative examples of US companies that are representative of larger trends in the global pipeline (see Table 2).

Table 2: Overview of Key Rapid Responders, Technologies and Development Timelinespicture2-6.png

Source: Health Advances analysis, PharmaProjects, Le 2020 Nat Rev Drug Discov, company press releases


Moderna gained notoriety with the first novel coronavirus vaccine to begin clinical trials. What enabled Moderna to progress so quickly? Compared to big pharma giants, it may not have had access to as large sources of capital or decades of experience in large, global clinical trials. What it did have, was a unique technology platform that enabled it to bypass traditional vaccine development bottlenecks. Moderna's vaccine platform is based on delivering mRNA to patients, rather than protein or viral antigens as in a traditional vaccine. The mRNA delivered to patients contains the genetic instructions for the host's cells to make the viral antigen themselves, which will trigger an immune response and confer immunogenicity. Compared to a traditional vaccine, this provided three major advantages:

  • Faster: Sequence design of the mRNA molecule is fast and done in silico and took only two days to generate a mRNA vaccine candidate sequence following the release of the novel coronavirus genome sequence.
  • Cheaper: mRNA manufacturing is cheaper and more streamlined than recombinant protein or viral production used for traditional vaccines since there is no need to optimize production for each new mRNA molecule, and production can be scaled rapidly on existing infrastructure.
  • Safety: The mRNA vaccine platform itself is already considered safe for use in humans since it has nine other mRNA-based prophylactic vaccine candidates in clinical trials. This allowed the rapid adaptation to the new sequence, without the long process of comprehensive preclinical safety profiling in rodents.

In comparison, a traditional protein antigen or adenoviral-based vaccine will generate a new protein or adenovirus antigen for each new product, and each new antigen will need to both have production optimized and scaled, and will also require safety and efficacy testing in animal studies. Moderna was able to bypass that long process due to its platform, which enabled the company to generate a lead in just 25 days and enter clinical trials thirty-eight days after that on March 16th.  This was only sixty-three days after the death of the first COVID-19 patient in Wuhan. If the eight-week trial shows signs of success, Moderna would be on track to start immunizing front-line healthcare workers in the fall of 2020.

Inovio also rapidly mobilized its DNA-based vaccine platform and made an early move in generating a vaccine against the novel coronavirus. Similar to Moderna, using a nucleic acid-based platform enabled a quick product design based on sequence, and a streamlined production process. In contrast to RNA vaccines that can be delivered with only the assistance of liposome-based agents, Inovio’s DNA vaccine must be delivered with a handheld device that injects the DNA and simultaneously electroporates the host cells to promote DNA uptake. This platform required efficacy studies in rodents, leading to a clinical trial start time three weeks later than Moderna.

Both Moderna and Inovio’s platforms rely on cost-effective and scalable synthesis of long synthetic nucleotides that can be used as a vaccine. The artificial synthesis of DNA and RNA fragments long enough to encode full antigen-encoding genes (i.e. ~1 kb and larger) was not readily possible or scalable until the last decade. Continued technological improvements in DNA and RNA de novo chemical synthesis, and RNA in vitro transcription, have allowed these fragments to be produced in a relatively cheap and scalable fashion that have enabled these vaccine modalities to be possible. Moreover, next generation sequencing technologies enabled the SARS-CoV-2 viral genome to be reported in a mere number of days once it was isolated in China, which allowed for rapid in silico sequence-based design of DNA and RNA vaccines. Together, these recent advances in nucleic acid synthesis and sequencing are major drivers of enabling these new fast-moving vaccine platforms.

In addition to nucleic acid-based vaccines, other players are bringing in newer technologies to speed up the development of more traditional antibody-based modalities. AbCellera, in collaboration with Lilly, is using a novel platform of single cell immune cell profiling and sequencing to screen a blood sample from a recovered COVID-19 patient to isolate and clone coronavirus-neutralizing antibodies. They were able to produce 500 candidate coronavirus neutralizing antibodies in only eleven days from receiving the blood sample. The strength of the AbCellera platform is that it allows the best 'developer' of virus neutralizing antibodies (the human immune system) to be the chosen platform. Using a single cell screening and sequencing platform allowed them to bypass a lengthy process of monoclonal antibody production in rodents and subsequent humanization engineering, a process that would have taken closer to eleven months rather than eleven days.  This approach effectively saved months in the development process. Additionally, their partnership with Lilly allows them to take advantage of Lilly's expertise in antibody manufacturing and potential manufacturing scale up capabilities.  Through the partnership, AbCellera hopes to be in clinical trials and enrolling patients to start testing its coronavirus neutralizing antibodies this summer.

Regeneron is also using innovative technologies to speed up the typically lengthy process of developing neutralizing antibody therapies. Regeneron's VelocImmune platform utilizes mice that have had significant regions of the genome encoding the building blocks of antibodies replaced with human counterparts, effectively creating mice with a 'humanized' immune system. This means that antibodies generated in these mice in response to a viral antigen are already 'human' antibodies by sequence, and compatible with the human immune system. While the process of isolating, culturing and screening mouse immune cells and the subsequent manufacturing scale-up is still a very lengthy and expensive one, this technology does enable bypassing the arduous step of needing to 'humanize' a mouse antibody by sequence engineering.  This removes one key bottleneck, saving precious time. Using their coronavirus-fighting mouse hybrids, Regeneron was able to identify lead antibodies 40 days after initiating R&D and anticipates beginning clinical trials this summer.

As a benchmark, Johnson & Johnson's Janssen, a global leader in vaccines, rapidly initiated a R&D vaccine program to tackle novel coronavirus in January, being one of the first responders when the number of cases worldwide was still less than 10,000. While Janssen's more traditional adenoviral-based vaccine program is tried and true, this traditional technology platform comes at a significant disadvantage – longer time to clinical trials.  Despite being one of the first rapid responders to initiate a COVID-19 program, they do not expect to reach clinical trials until September 2020.

At this point it is not clear, which technology will produce a prophylactic vaccine in time to address the significant clinical need. In order to ensure that the right product comes to market in the right timing, industry must have multiple shots on goal. Both traditional and more innovative technologies must be pursued in order to mitigate the impact of the COVID-19 and future pandemics. While newer innovative technologies may be able to respond faster in a crisis, they are also less proven on efficacy and safety in the long-term. At this point, we do not know whether the most efficacious and safe solution to ending COVID-19 may indeed be a traditional vaccine that takes one year to develop. However, even if faster-moving products would end up being only half as efficacious or have safety profiles that could limit their use, they may still be a viable solution in the near-term until other more efficacious or safer products become available.  Leveraging multiple traditional and innovative technologies due to their advantages simultaneously is the best way to balance these risks and the only way to ensure that the US is better prepared for the next coronavirus outbreak. 

As can be seen in Table 3, more innovative technologies are viewed as more attractive because of their lower R&D costs and shorter development times; while more traditional vaccine approaches are viewed as having greater proven efficacy. Pursuing multiple avenues simultaneously allows for balancing short- and long-term risks and needs and increases the probability of a response that could mitigate another crisis situation like that seen in New York from happening.

Table 3: Comparison of Advantages, Disadvantages and Relative Risks of Profiled Key Technologiespicture3-5.png


Source: Health Advances analysis, FiercePharma.


Getting the Timing Right: Mitigating R&D Risk Pre-Pandemic to Hasten Novel Vaccine and Therapy Development
During the SARS, Ebola, Swine Flu and Avian Flu outbreaks, the time from outbreak onset to clinical trials of candidate vaccines was one to two years on average (see Table 4). In the case of SARS, by the time a vaccine was available, the pandemic had largely died out and clinical trials could not be completed. Without sufficient patients and disease burden to test efficacy in a clinical trial, programs were abandoned. That left companies that invested in SARS with no return on their investment.  Since the vaccine was never tested, there was no vaccine that could be sold to national stockpiles, and the R&D costs were shouldered exclusively by their investors.   

Table 4: Comparative Examples of Time from Outbreak to Clinical Trial in Previous Pandemicspicture4-5.png

Source: Health Advances analysis, FiercePharma, Coalition for Epidemic Preparedness Innovations.


Being able to predict pandemics is an impossible feat, and poses a critical question to companies: When is the right time to start investing in expensive R&D on a product to help minimize the impact of a pandemic? Clearly, the answer is before it reaches the level of infection and mortality rates as seen with COVID-19. But how much earlier is the question. The transmission rate of COVID-19 would suggest that the investment needs to be made before the virus follows the business and personal travel patterns between the country of origin and the US.  The COVID-19 experience showed that it can be very short – only a few months.

How does industry turn on a dime and gear up to meet the challenge of a virus that can go pandemic in a matter of mere months? There are two major factors to consider:

  • Leveraging innovative technologies: Encourage companies with streamlined platforms that require relatively less time in development by using safe and established customizable platforms like mRNA vaccines, antisense oligonucleotide (ASO) therapies, or RNAi therapies to pursue vaccine development.
  • Resource companies with those technologies: Provide federal assistance to biotech companies with these technologies to help fund R&D efforts to offset the risk associated with missing the window of commercial opportunity (products that are approved after the pandemic is over) or a non-reoccurring pandemic (the virus is contained locally and vaccines are not needed) or the vaccine failing in clinical trials.

Moderna is a case study of how leveraging innovative technology and providing federal resources could enable a rapid response. Moderna did not have to assume as much financial risk as a traditional vaccine maker because comparatively, repurposing its existing mRNA vaccine platform and scaling nucleic acid synthesis is not as expensive as development of a vaccine based on recombinant proteins or viral vectors. Moderna also had a close collaboration with the National Institute of Allergy and Infectious Disease (NIAID), which provided assistance for both R&D and phase I clinical trials. Because of this, Moderna was the first of the rapid responders to announce the beginning of its program on January 11th, when there were fewer than 100 known cases in China, and only one death. If COVID-19 had not become a pandemic, Moderna would not be as financially impacted as a traditional vaccine maker was at the end of SARS. Just last week, BARDA committed $483 million in assistance to help Moderna fund phase II-III clinical trials and vaccine manufacturing scale-up.  With mitigated financial risk and federal assistance, Moderna made an early bet, and the NIAID partnership allowed senior management to make a shift in their R&D that has the potential to have a decisive impact on controlling this outbreak. 

Table 5 tracks the project start dates and the estimated clinical trial start date of the rapid responders that Health Advances analyzed.  Moderna took action before the disease had spread to the US. With the support of NIAID, their management may have felt more comfortable in redirecting valuable R&D resource to a virus which may or may not cross the Pacific Ocean. At that point, there were only sixty confirmed cases worldwide.  

Table 5: Timelines of Highlighted Rapid Responders Initiating Projects at Various Stages of the Novel Coronavirus Outbreakpicture5-3.png

Source: Health Advances analysis, OurWorldInData European Center for Disease Prevention and Control


If a rapidly deployable funding mechanism had been in place, other companies may not have waited to redirect their R&D resources to COVID 19 until the disease had passed tens or hundreds of thousands of cases worldwide and had been detected in the US.  Starting at a riskier time (before the disease has spread outside China) could potentially have resulted in their clinical trials starting three weeks earlier in May. With this type of funding mechanism, companies like AbCellera may have been in clinical trials as we write this blog. Presumably, there are numerous other companies with innovative potential solutions to tackle coronavirus that could have been encouraged to participate in R&D efforts but saw the risk as too high to become engaged, or could have started R&D weeks to months earlier.

Why is a funding mechanism like this so important?  Innovative technologies like mRNA vaccines, antisense oligonucleotide (ASO) therapies, and RNAi therapies that move through R&D faster are generally developed in smaller biotech companies that are more cash strapped than big pharma. As a point of comparison, Janssen also announced initiation of its coronavirus-targeting vaccine in January when the pandemic was still restricted to China with less than 10,000 cases reported. Given their cost-intensive, more traditional vaccine development platform, this was a large financial risk at a time where it was not clear that the vaccine would have a commercial market.  This is a risk that could only be taken by a large pharmaceutical company.

There are federal assistance programs that exist today to support the manufacturing of vaccines for pandemics.  Unfortunately, they do not address the core issue of offsetting R&D costs.  Currently, the US Department of Health and Human Service’s Biomedical Advanced Research and Development Authority (BARDA) will buy vaccine stockpiles left over at the end of a pandemic. This program has two major issues:

  • It does not provide research grants to offset the early R&D costs, which is critical to smaller biotech companies who often are cash strapped.
  • It only provides a revenue stream for commercialized products. Companies who take the risk but cannot bring a product to market have no way to recoup their investment. The possible risk of a product not panning out or a disease not becoming a pandemic makes the decision very difficult for companies to convince their stakeholders to initiate programs.

How can we ensure that the R&D efforts for the next potential pandemic start at day 0 rather than the first patient in the US? Companies need to be incentivized to initiate R&D early on in disease outbreaks before a pandemic is even called. US federal agencies such as BARDA should create accelerated federal grant programs that provide emergency grants to appropriate companies that initiate R&D at early signs of an epidemic. With such new initiatives in place, R&D could be started when the risk for the individual company is still high, but has the potential for greatest clinical impact. The potential consequences of not taking early action will continue to have a drastic impact on public health, healthcare costs, and the economy.  

As the number of confirmed COVID-19 cases surges towards 2 million worldwide, new vaccines and coronavirus-targeting therapies are urgently needed to get this pandemic under control. While the situation may seem bleak, pharma, and biotech companies alike are moving faster than ever before to develop new products. Among the fastest responders, newer innovative technology platforms like mRNA vaccines could proceed through a streamlined response, but these companies may also require federal funding to offset R&D costs in order for projects to be initiated early enough to meaningfully change mortality outcomes such as those we are seeing in this pandemic. Federal assistance to offset early R&D efforts, especially those with fast-moving technologies such as mRNA vaccines, ASOs or RNAi therapies, will assist in enabling a rapid response and allow a better response to the next coronavirus that may materialize into a pandemic.  The US has the ability and resources to enable industry to move on vaccine development earlier.  Now we need to ensure that federal programs are developed and put in place to encourage earlier participants to pivot their R&D efforts so that we can get into clinical trials earlier for the next virus that may become a pandemic. 


About the Authors

Joseph McInnes, PhD is a Senior Analyst in the Health Advances San Francisco office.

Kristine Mechem, PhD is a Vice President in the Health Advances San Francisco office.

Vivek Mittal, PhD is a Partner in the Health Advances San Francisco office.

To further discuss this topic or for more information, contact the Health Advances Biopharma Practice at

Company websites and press releases, PharmaProjects, European Center for Disease Prevention and Control, OurWorldInData (graphics), FiercePharma, Coalition for Epidemic Preparedness Innovations, Le et al Nat Rev Drug Discov 2020.

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