Jeff Lin
Betting on a single new drug has always been extremely risky and such risk is normally significantly mitigated when Phase 1 clinical trial has yielded some promising results, or somehow proven the safety of the drug. Those startup companies with a technology platform that offers a strong pipeline of candidates or cancer targets are more investible as risk is lower as a collective portfolio. Drug candidates which may potentially be effective against a wide array of diseases such as multiple type of solid cancer tumors have higher potential and are less risky than others.
Recent advancement in the field of mRNA-based therapeutics, immunotherapy and application of computational biology and AI in CAR-T, TCR and lipid nanoparticles engineering has offered opportunities for starting companies to develop therapeutics for a range of diseases such as cancers or fast-evolving respiratory pandemics over a common base platform.
Fast-evolving pandemic requires fast time to market new vaccines to protect the people. The mRNA design and delivery platform invented by vaccine manufacturers can be utilized to quickly build boosters that can catch up with variants. Take Pfizer BioNTech as one example, its Omicron BA.4/5-adapted bivalent demonstrated substantially higher immune response in adults compared to the original Covid-19 vaccine. As this new booster share the same common platform as the original vaccine, it is considered reasonably safe with the huge amount of clinical data from the older vaccine of vaccines already used by billions of people and allows the regulator to make a relatively easy decision to approve without having to go through the conventional cycle of full clinical trials. mRNA-based therapeutics makes drug development as programmable as software configuration, users can easily configure on the same proven base version to cater for their current needs and expect a high chance that this new version can run smoothly on the human body.
“The mRNA design and delivery platform invented by vaccine manufacturers can be utilized to quickly build boosters that can catch up with variants.”
New technology will also enable on-demand quick small-scale production for such mRNA drugs. One year ago, Codex DNA and RNAImmune announced collaboration on the development of future mRNA Synthesis and Delivery Kits. One possible application is to use a single desktop instrument to print mRNA vaccine when needed somewhere near the patients (e.g. a CGMP lab in local hospitals). This will allow for personalized drug production in a decentralized manner and eradicate the need for costly long-haul cold chain logistics. Different cancer patients may be able to be administered mRNA cancer vaccine which is tailor-made to their specific cancer targets. Such a change in the therapeutics supply chain will be revolutionary if this vision comes true. Small CDMOs which traditionally are supporting drug products for clinical trials may play the role of ‘print’ for such on-demand requests too. It will eventually benefit the patients and the payers, as it allows the healthcare system to respond faster and avoid unnecessary waste caused by a mismatch of supply and demand, if you remember the UK government had to destroy their unused AstraZeneca Covid vaccine that has expired.
AI and in-silicon screening has played a big role in shortening the time to market and reduce waste in drug development too. Those startup companies with better in-house expertise in AI have competitive advantage in generating better design and achieving better epitope mapping. AI and bioinformatics also facilitate the discovery of new cancer targets too. Data from sequencing of RNA from hundreds of cancer tissues or proteomicscan provide information on immune system response too, which may lead to clues for cancer targets for certain type of cancer. Those startups with access to patient samples and AI capability may be able to secure such intellectual properties faster. Some of these startups may choose to focus on prediction and design of drug candidates, and outsource the validation and pre-clinical animal study to CROs. With that, they can be nimble and scale. Startups don’t have to see through the whole cycle of clinical trials. One way for them to monetize is to license the drug candidate to international pharmaceutical companies for sizeable upfront fee and subsequent milestone payment and royalty, just with the pre-clinical data obtained.
The paradigm shift driven by technological advancements and the convergence of disciplines has reshaped the market. Drug discovery used to be very brute force based, new generation of platform technologies makes such a discovery process more systemic and efficient. More than two decades ago, eCommerce platforms such as Amazon invented a new business model and apply this model from one category of products (books) to almost any categories of products needed by consumers, and dominate the market. Likewise, we believe there will be platform companies in the field of mRNA-based therapeutics and immuno oncology which can address a wide range of patient’s needs, be it to fight against next few variants of Covid virus or new types of flu or Ebola or all sorts of cancers. We believe such platform companies are most worth pursuing for VC investors.
