Javelin Biotech partners with Pfizer to transform preclinical drug discovery via organ-on-a-chip based computational platform
Why is the current drug development process broken?
After over 9 months, 60 million cases, and 1.4 million deaths, we still don’t have a vaccine for COVID-19. This yet again calls our attention to just how long, arduous, and expensive a process pharma companies go through to get a single drug out to market — over $2.5 billion and 10–15 years that is. Why is this still the case? And what should be done to improve this?
The picture below shows the drug development process. Scientists first research the disease at the cellular/molecular level, in order to identify potential targets for the treatment. Then, they consider five to ten thousand or more natural or synthetic compounds that could act on this target. This is narrowed down to 1–5 compounds with the greatest potential, through a variety of iterative safety and efficacy testing via in-silico (computer simulation) and/or in-vitro (in a test-tube outside a living organism) models. The goal is to identify the compounds that might have the best chance of success in human clinical trials. The prioritized compounds then enter the preclinical phase, where they are tested on animal models, before 3 phases of human clinical trials with increasing number of patients. After successfully passing all 3 phases of the clinical trials, the candidate compound is approved by the FDA, manufactured at mass scale, marketed, and delivered to patients.
More specifically, animal testing is used at the pre-clinical stage to simulate the most human-like conditions for testing. One might assume that if a drug candidate works well in mice or monkeys, it should work well in humans. However, only 12% of candidates that enter human clinical testing are ultimately successful . That number is even lower (8%) for cancer drugs — terrible results considering the extensive time, cost, and the contributions of animals involved in this process (115 million animals are used for testing annually ).
While there are many drivers, one of the main problems here is that in-silico, in-vitro and animal testing are not able to accurately predict human reactions to the compounds. Human bodies are highly complex and diverse — hence the failure rate is so high even for compounds that have successfully completed preclinical testing.
This raises the question — is there a better way to do preclinical testing? Would it be possible to simulate a more human-like system for during or prior to pre-clinical testing? Simple cellular assays are currently used in high throughput toxicity screening, but they don’t reflect the complexity of full organ & body behaviors. In recent years, a few start-ups have developed organ-on-chip (OoC) technologies, which try to simulate complex human organs on a chip. However, they are mostly hardware-only companies that are failing to integrate their one-size-fits-all solution within the current highly complex process.
Meet Javelin
Javelin Biotech is solving this exact problem with the 1st ever comprehensive platform that combines complex in-vitro human models (ex: organ-on-chip) with computational intelligence to deliver the most accurate predictions of drug-human interactions as early as possible in the drug discovery process — specifically in the lead optimization phase right before animal testing. This could lead to an eventual move away from animal models altogether in the broader drug discovery & development process — resulting in lower cost, shorter time, and better success in human clinical trials.
More importantly, with their proprietary workflow that uses the OoC models for advanced in-vitro approximation of the human body, unique AI-powered virtual human software to translate in-vitro measurements to in-vivo, and ML algorithms to predict human clinical outcomes, Javelin is pioneering the computational intelligence-driven human clinical predictions in drug development.
Javelin spun out of MIT’s Translational Center for Tissue Chip Technologies (TC2T) to commercialize the work of the former director, Dr. Murat Cirit, and his teammates Kevin O’Handley and Emily Geishecker. While at MIT TC2T, Dr. Murat Cirit and the team received significant funding from DARPA, NIH, and NASA to build their technology, completed over 20 peer reviewed publications and 50 presentations at international conference on their work, and have established themselves as one of the main industry experts on this subject (the American Association of Pharmaceuticals Scientists recently presented Dr. Murat Cirit, CEO and cofounder of Javelin Biotech, with an AAPS Journal High Impact Article Award). This has also led to the team working closely with top pharma companies to test out their technology in an active drug discovery process.
Pfizer partnership
We are excited to share that Javelin has started on a 3-year collaboration with Pfizer to design and build what could be potentially an “industry-leading platform to evaluate ADME (absorption, distribution,, metabolism, and excretion) properties of small molecules” as the “first organ-on-a-chip-based [computational platform] on the market specifically designed for human pharmacokinetic (PK) predictions, a key measure in evaluating new drug candidates in preclinical research”.
As detailed in their announcement here, the “ADME platform will comprise an MPS system that contains chambers for the four most important human tissues involved in drug disposition (liver, kidney, intestine, and tissue distribution), as well as a microflow pumping system that circulates media among the compartments. The system will be coupled with [proprietary computational system] that will translate the data to a physiologically based model of human PK across sub-populations and will guide first-in-human dosing strategy for Phase I clinical trial design.”
As noted by Charlotte Allerton, Head of Medicine Design at Pfizer, this has the potential to lead to a “transformational change in how [Pfizer] evaluates human PK without dosing humans” — a significant step towards eventually eliminating animal testing.
Our team at Innospark has had the privilege of leading Javelin’s seed round in late-2019 to help accelerate their path to commercialization. We have loved being part of their journey over the last year as they continue to advance their technology towards a mission to provide earlier and better human clinical insights for compound selection and reduce the cost & length of drug development. We are excited about the importance & complexity of AI & computational intelligence in Javelin’s platform, as well as their potential for impact on society, which aligns perfectly with our quest to support #AIforGood. Please join us in congratulating them on their great accomplishments to date! Be on the lookout of their upcoming commercial launch of their 1st product & contact them for partnership if your company can benefit from their technology!
