Additionally, mRNA, as a relatively simple medium that can encode any number of diverse proteins by adjusting the sequence of four nucleotide building blocks, can be co-opted and scaled efficiently. This enables rapid development and manufacture of new vaccines in response to emerging viruses or variants of established infectious diseases, or even other indications involving immune modulation, including cancer. Furthermore, as a new frontier in vaccinology, mRNA technology has ample room for innovation and optimisation. Tolerability, for example, is a pain point for many mRNA vaccine recipients. Even inherent strengths can be improved upon: speed and cost of scale-up can always be refined. Unknowns also remain, including the durability of the vaccines’ effect – ie, how long the immune responses to the vaccine will offer protection against infection, transmission, severe illness, or death after dosing the subject.
As a broader consideration, vaccines against infectious disease confer benefit not only by protecting individuals’ health, but also the collective; by protecting communities from the consequences of outbreaks such as hospital system overload or economic instability. Thus, a vaccine’s accessibility to the entire demographic of people who are at risk for a given infection is critical to fulfill its therapeutic potential. Unfortunately, the COVID-19 pandemic exposed a widespread lack of resilience to outbreaks of infectious disease at several levels, including equitable vaccine distribution worldwide.
There remains a need for vaccines that are regionally produced and distributed, particularly in low- to middle-income countries. Vaccine developers now find themselves with a chance to address several opportunities in the vaccine lifecycle: exploring the potential of mRNA technology, identifying indications whose existing vaccine or therapy landscape can be improved with an mRNA vaccine option, and ensuring accessibility to their products. As CEO and co-founder of mRNA vaccine developer Providence Therapeutics, I would like to share my team’s approach to addressing each of these opportunities.
The following are some key achievements in this area:
- Development of a platform that we continuously seek to optimise.
- Identifying infectious diseases and cancers where new mRNA vaccines stand to improve patients’ outlook.
- Potential to partner with other companies and governments in regions of the world that most need our vaccines so that we can distribute mRNA vaccines widely at accessible costs.
Thoughtful mRNA platform design
Our approach to developing a truly innovative, differentiated mRNA vaccine platform begins with designing each mRNA construct with optimised codons – the triplets of consecutive nucleotide ‘letters’ in the mRNA sequence that encode individual amino acids. A given amino acid can often be encoded by several different ‘spellings’ of codons without any difference in the resulting protein. However, the different codons are not entirely interchangeable and certain codon sequences can cause an mRNA strand to stick to itself and form loop structures that can affect how efficiently the mRNA is translated into protein. Providence’s mRNA platform maximises the efficient production of protein – eg, a COVID-19 spike protein, a tumour antigen, etc – from the vaccine’s mRNA. We have also designed formulation and purification processes that result in a substantially purer mRNA product, which promotes superior tolerability to other mRNA products. As many other mRNA vaccine developers do, Providence uses lipid nanoparticles (LNPs) to package the mRNA and deliver it intracellularly to specific tissues upon injection. However, Providence has its own LNP platform that enables the selection of safe and scalable lipids, which stand to improve the specific immune response of our vaccine products. It was also important for us to build a proprietary in-house manufacturing process that enables rapid, cost-efficient commercial-scale yields.
Clinical validation in emerging infectious disease
Providence’s approach to vaccine design has thus far been validated in the setting of COVID-19, as the company’s monovalent COVID-19 candidate was the first vaccine product in the world to have demonstrated non-inferiority to an approved mRNA COVID-19 vaccine, per the results of a recent immunobridging Phase II clinical study measuring neutralising antibody titers.1 Going forward, we hope to find that our approach can yield a safe and effective vaccine option for regions of the world that lack access to the already approved mRNA COVID-19 vaccines, such as India and Brazil. At a market size of about $51 billion globally, there is ample room for a mRNA vaccine option that can be produced accessibly and within a given country’s own borders to promote resilience against the ongoing pandemic. Towards the aim of ensuring accessibility, Providence has partnered with China-based Everest Medicines to help distribute a vaccine option, if approved, in China, as well as other parts of Southeast Asia.
Filling gaps in global public health
Outside the context of emerging infectious diseases, the rabies virus serves as a prime example of an established, well-known infectious disease whose at-risk populations could benefit from an mRNA vaccine. Despite two rabies vaccines being commercially available, rabies remains a public health threat in areas of Asia and Africa, where 95 percent of cases occur. In Asia alone, where the cost of post-exposure prophylaxis measures is the world’s highest at $1.3–1.5 billion annually, rabies kills over 35,000 people each year. Furthermore, China accounts for approximately 70 percent of the global market for rabies. Rabies, transmitted through the bite of an infected animal, is almost always lethal without early post-exposure intervention. However, the available vaccines involve several barriers to the utility of existing rabies vaccines: they carry significant side effects, are prohibitively priced, and require several doses administered through painful injections into the stomach. There remains a need, therefore, for an accessibly priced vaccine option that requires fewer doses and is better tolerated. At Providence, we saw this need and again partnered with Everest Medicines to use our mRNA technology to develop and distribute a highly potent vaccine candidate that can provide post-exposure protection with fewer doses and fewer side effects.
Beyond infectious disease
When I co-founded Providence in 2015, I envisioned a company focused on cancer vaccines. However, as much of the biotech industry did at the onset of the COVID-19 pandemic, our team pivoted to focus on infectious disease. Having established powerful clinical validation of our mRNA technology in the setting of COVID-19, we believe it is important to continue to explore what mRNA vaccines can contribute to oncology. In the context of cancer, vaccines serve as a therapeutic rather than a prophylactic by delivering harmless cancer antigens that match the type of cancer a patient has. Those antigens stimulate the immune system to mount a more robust, cancer‑specific attack against the patient’s cancer than the patient’s body could have done on its own. Given that mRNA vaccines can be designed to encode several cancer antigens into a single mRNA strand, that their immunogenicity can be finely regulated, and that they demonstrate high potency with the right LNP, they represent a promising modality with which to target several cancer types with high unmet need.
To date, most mRNA-based cancer vaccine candidates – including Providence’s – are in pre-clinical development, with immense market opportunity ahead and room for multiple players. Our team looks forward to returning to our foundations in oncology with a clinically validated platform technology in our arsenal.
Brad Sorenson, MBA. Brad is the founder and CEO of Providence Therapeutics. He achieved an MBA from University of Rochester and was co-founder of Arcturus Therapeutics. In 2013, a stage four cancer diagnosis for Brad’s teenage son set a course for Sorenson to dedicate his time and research towards eradicating then word “terminal” from any cancer diagnosis. Brad is a staunch advocate for brain cancer research.
Reference
- Providence Announces Positive Top-Line Data from Phase 2 Primary Immunization Trial of its mRNA Vaccine Candidate PTX-COVID19-B in Adults – Providence Therapeutics
[Internet]. providencetherapeutics.com. [cited 2023 Mar 10]. Available from: https://providencetherapeutics.com/pressdetails/providence-announces-positive-top-line-data-fromphase-2-primary-immunization-trial-of-its-mrna-vaccinecandidate-ptx-covid19-b-in-adults.html
