18 June 2020

Let’s Do More With Less

mul·ti·plex (mŭl’tə-plĕks) adj.

  1. many, multiple
  2. being or relating to a system of transmitting several messages or signals simultaneously on the same circuit or channel

It hardly needs to be said that time is of the essence in the fight against the COVID-19 pandemic. Faster diagnostics can facilitate more accurate population-level insights, faster drug development can drive reduced hospital stays for critically-ill patients, and faster vaccine development could enable an earlier re-opening of society. However, decades of neglect in translational research for infectious diseases—including existential threats such as pandemic preparedness—have left the global healthcare infrastructure struggling to keep up. Couple this with basic failures in supply chains for fundamental commodities like surgical masks and diagnostic reagents and you have a recipe for the perfect storm of social and economic damage we are currently experiencing.

In a resource-limited system, that perfect storm is a hurricane, and the only way to increase output is to increase efficiency: to get more bang from the same amount of buck. In the world of testing and diagnostics, this means we need to find ways to glean more data from a single channel—known as multiplexing. Multiplexing is hardly a groundbreaking concept, but we believe that application to the appropriate bottlenecks has the potential to dramatically accelerate the global response to this pandemic and better prepare us for the next one. Here’s how two of Adjuvant’s portfolio companies, ChromaCode and InDevR, are using multiplexing to help diagnostic centers and vaccine developers keep pace in these trying times.

ChromaCode—the most-recent addition to the Adjuvant portfolio—is a San Diego-based biotechnology company that’s working to improve the global capacity to test for infectious diseases such as COVID-19 by polymerase chain reaction (PCR). Remember PCR is the test that can detect if patients have active virus in their system, regardless of symptoms (i.e. they’re actively infected and potentially contagious) and is responsible for all of those barbaric nasal swab cartoons you’ve seen on twitter (!!!!). PCR is a technology that’s been widely used to detect infectious diseases for decades, and while its healthcare system value has driven global uptake (there are around 80,000 instruments currently installed around the globe), PCR instruments remain relatively expensive and have a number of practical limitations preventing them from realizing their full potential at scale.

Enter ChromaCode’s HDPCR platform—which couples bioinformatics and novel reagents to enable up to 4x multiplexing of PCR diagnostics. Unlike other multiplex technologies that require dedicated instruments, ChromaCode’s technology enables a multi-fold increase in PCR capacity through plug-and-play compatibility with existing systems and no changes in standard workflow or additional technician training. ChromaCode recently received Emergency Use Authorization from the US FDA for its SARS-CoV-2 test kit, which typically requires 3 of a typical PCR machine’s 96 “slots” to run a sample. ChromaCode’s technology enables this test to be run in a single slot, thus easily tripling the capacity of PCR machines in labs working around the clock to process an unprecedented backlog of samples. Later this year, ChromaCode intends to leverage its multiplexing technology to launch a panel that combines multiple respiratory viruses into a single test in anticipation of the upcoming flu season.  Multiplexing, whether it be to increase sample throughput or test for multiple targets at the same time, is especially important in the developing world, where installed PCR capacity is lower and population density is often higher.

Moving on to one of our earlier investments from 2019, this week marked the official launch of InDevR’s VaxArray Coronavirus SeroAssay, a rapid quantitative test that can simultaneously screen clinical trial subjects for antibody responses to SARS-CoV-2, SARS-CoV-1, MERS, and all four endemic coronaviruses. While ChromaCode’s technology relates to viral testing of patients and populations, InDevR’s test technically falls into the category now commonly known as “antibody tests” that detect antibodies in a person’s blood to determine whether they have been infected with the virus. While the antibody tests discussed in the media and available to consumers are typically for epidemiological surveillance (i.e. determining what percentage of the population has been infected), InDevR’s test is different in a few critical respects: 1) it actually quantifies the strength of the antibodies in a subject rather than just providing a yes/no answer, 2) it can simultaneously quantify antibodies against eight different coronaviruses from a single sample (i.e. multiplexing!!), and 3) it has robust utility in vaccine clinical trials in addition to epidemiological surveillance.

We expect these points of differentiation will make InDevR’s SeroAssay immensely valuable for vaccine developers as it provides a standardized measurement of pre- and post-immunization antibody levels of clinical trial participants, and can illuminate any potential induced cross-protection against other coronaviruses such as SARS or MERS. In other words, InDevR’s test can generate multiples more insights for vaccine developers to work with as they seek to refine their vaccine formulations and illuminate new connections in the complex immune responses induced by SARS-CoV-2. The test is faster, offers 8x more data, and uses ~200x less antigen than traditional methods, which is critical during a time when supplies of antigens are limited.

ChromaCode and InDevR represent just two examples of our portfolio’s contributions to the fight against COVID-19 (we’re also supporting novel vaccine constructs and genomic testing and research), but they highlight one of our core investment theses at Adjuvant: even incremental improvements in infectious disease research and testing can drive much larger global health impact when one considers the population-level benefits. Infectious disease is a global problem and the solutions are often constrained by limited resources, but when innovative efficiencies are applied (like multiplexing!), a little can often go a long way.