Perfecting Detecting

Adjuvant joins Domain Associates, New Enterprise Associates, and Northpond Ventures in ChromaCode’s Series C financing
ChromaCode had developed novel chemistries and signal processing software to massively increase the throughput and capacity of polymerase chain reaction (PCR) analytical equipment
Proceeds will support the launch of ChromaCode’s multi-drug resistant bacteria panel, tick-borne pathogen panel, SARS-CoV-2 panel, and upper-respiratory-tract infection panel

Characters and Characterization

In 1983, a colorful biochemist named Kary Mullis was working at Cetus Corporation on oligonucleotide synthesis. Cetus, one of the first “biotech” companies, was in the midst of an epic race against Genentech to synthesize interleukin 2, an important immune modulator. Mullis had just been dumped by his girlfriend and fellow Cetus Corporation scientist, Jennifer, and was feeling down in the dumps. (Mullis spent a portion of his 1993 Nobel Prize on the topic of Jennifer, whom he had left his previous wife for in 1981: “I was sagging as I walked out to my little silver Honda Civic. Neither [his assistant] Fred, empty Beck’s bottles, nor the sweet smell of the dawn of the age of PCR could replace Jenny. I was lonesome.”)

At the time, Mullis was manually synthesizing oligonucleotide probes to help detect a sickle cell anemia mutation. He had grown tired of the laborious, error-prone manual approaches required to amplify and detect target genes and was contemplating ways to ease the mundanity of his work. In what has been described as an “ah ha!” moment in his silver Honda Civic, Mullis conceived of a method that relied on a cascading biochemical reaction that split (denatured) target DNA segments, which would then be combined (annealed) with complementary primers and then enzymatically processed by a DNA polymerase to create new DNA templates (this cascading reaction resulting in polymerized target DNA become known as a “Polymerase Chain Reaction” or “PCR”).

When Mullis presented his invention at the 1984 Cetus Corporation annual meeting, it received little interest from his colleagues. The meeting ended with a physical altercation between Mullis and a colleague, and Mullis was removed as head of Cetus’ oligonucleotide lab.

Terrific & Specific

While PCR can be used for a number of research and clinical applications, perhaps its greatest impact has been on clinical diagnostics for infectious disease. PCR machines have made molecular testing for infectious disease nearly ubiquitous, enabling highly specific diagnosis of the world’s highest burden pathogens in settings as different as university hospitals in the United States and rural TB clinics in the Philippines.

Each step of the PCR process requires precise reaction timing and thermal regulation, which was originally accomplished manually but has since become the basis for automated PCR machines. These machines come in a variety of formats, ranging from high-end customizable instruments for large labs, to easy-to-use cartridge-based systems that can evaluate an unprepared blood sample collected by a community health worker in a rural clinic and output a diagnostic result in an hour.

Faster, Better, Stronger (Cheaper)

A number of innovations, including the development of improved polymerase enzymes and lower-cost reagents, have dramatically lower the cost of PCR and increased the number of PCR instruments installed around the world. Still, PCR instruments are expensive and have a number of throughput and other practical limitations.

This is why we are so excited to partner with ChromaCode, a San Diego-based biotechnology company developing novel chemistries and signal processing technology to make molecular PCR testing better and cost less. ChromaCode’s technology enables existing owners of PCR equipment to run more complex tests – for example, a test that can detect all of the most common tick-borne pathogens. Why is this important? Instead of using clinical signals and process of elimination to reach a diagnosis over weeks or months, a single ChromaCode panel can help healthcare providers identify the cause disease in a single test and put the patient on the proper course of treatment in a matter of days.

In addition to enabling novel multi-target panels, ChromaCode’s technology can be used to increase the throughput of existing PCR machines by applying the same technology it uses to test for multiple targets and instead using it to increase the volume of samples that can be run at a time. A salient example of this is the PCR test for the novel coronavirus, SARS-CoV-2, developed by the US CDC, which requires 3 of a typical PCR machines’ 96 “slots” to run. ChromaCode’s technology enables this test to be run in a single slot, tripling the capacity of many PCR machines in labs working around the clock to process an unprecedented backlog of samples.

Working With What We’ve got

Thanks to programs like PEPFAR, which has helped strengthen global HIV testing capacity, and efforts by the Bill & Melinda Gates Foundation (and others) to expand TB testing capacity, there is now an installed base of tens of thousands of PCR instruments in low and middle-income countries around the world. These instruments have been critical to the fight against HIV/AIDS, antimicrobial resistance, and emergent pathogens like SARS-CoV-2 and Ebola.

This installed base represents a huge public health opportunity to develop new ways to use existing instruments to perform more tests, better, faster and cheaper. With extremely limited local budgets to consistently buy and upgrade new diagnostics equipment (as is often the case for new diagnostics), finding ways to leverage these installed machines is a low-cost way to improve the diagnosis and treatment of infectious diseases globally.

ChromaCode’s technology represents a unique opportunity to leverage this global installed base. Perhaps more importantly, ChromaCode’s products can be deployed into the existing global reagent supply chain, and its software can be accessed via the cloud or run locally on inexpensive PCs.

We’re thrilled to partner with ChromaCode to bring this important and exciting technology to bear across Adjuvant’s focus geographies and disease areas.