Velox Q1 2019 Newsletter

We are having a great start to 2019! Here we will highlight our recent big win at the UC Systemwide Pitch Competition and the progress we are making on several R&D projects in our pipeline, particularly in cancer liquid biopsy and further expansion of the detection capability of our IC3D droplet digital detection platform.

UC Entrepreneur Pitch Competition

Dr. Byron Shen, a UC Berkeley PhD graduate and CEO of Velox Biosystems, was selected as one of the 12 finalists across the entire UC system to present at the 3rd Annual UC Entrepreneur Pitch Competition in conjunction with the Global Corporate Venturing & Innovation (GCVI) Summit on Jan. 31, 2019. Dr. Shen was the winner in the early-stage track, and he highlighted the breakthrough capability of Velox’s technology to combat the rapid rise of antimicrobial resistance at the point-of-care for urinary tract infections (UTI), a high prevalence medical problem (second only to respiratory infections). Dr. Shen also knows the win goes beyond the award and monetary prize: “having worked at a great Fortune Global 100 company myself and having worked with the former CEO of Medtronic directly for many years, I feel this win is especially meaningful. It shows that our idea is recognized by seasoned business leaders who understand how a real business is run and how it can be successful.” For details, please see the following press releases:

• University of California: “Two UC entrepreneurs take home top prizes at the Global Corporate Venturing & Innovation Summit”
• UCI Applied Innovation: “Velox Biosystems Wins Big at UC Entrepreneur Pitch Competition”

Cancer Liquid Biopsy

We recently published a high-profile paper with Prof. Weian Zhao’s Lab at UC Irvine demonstrating the superior sensitivity of IC3D in liquid biopsy applications. In the publication, “An Ultrasensitive Test for Profiling Circulating Tumor DNA using Integrated Comprehensive Droplet Digital Detection” (Lab Chip, 2019), we demonstrated that the IC3D system can detect oncogenic KRAS G12D mutant alleles against a high background of genomic DNA at a sensitivity of 0.00125 - 0.005%, or 50 to 1,000x more sensitive than leading liquid biopsy ddPCR and qPCR platforms, respectively. So, what does this extra sensitivity mean?

• The superior sensitivity of IC3D greatly improves the likelihood of finding those rare mutation targets during early stages of cancer or early onset of cancer recurrence. In a serial study with colon cancer patient samples, IC3D is able to detect minimal residue disease (MRD) and the onset of cancer recurrence much earlier than the current gold standard assessment tools (data to be published later). 
• IC3D is also able to analyze total tumor DNAs (CTC DNA, cfDNA, etc.) isolated from whole blood while existing techniques cannot do so due to the high interference of wild-type genomic DNA; so instead they analyze only partial components of blood such as plasma – but these fail to capture the complete picture and may also lose those rare targets during sample processing.
• And if the clinical specimen is limited and target loss during DNA extraction/purification process is a big concern, IC3D also has the unique ability to detect tumor DNA in unprocessed clinical specimens directly without sample pre-processing. 
• Lastly, in contrast with the limitation of current technologies, we have now shown IC3D is able to detect circulating tumor cells (CTCs) using their genetic markers without a pre-enrichment step. Not only does this offer its own clinical utility, but this approach may also be used to pre-amplify CTC DNA for downstream NGS analysis.

We are currently in discussion with other groups to leverage the IC3D technology in partnership projects. In collaboration with UCI Medical School, we also submitted a grant proposal to leverage this unprecedented sensitivity for a large colon cancer clinical study to monitor and treat MRD with the potential for earlier intervention. (For additional cancer liquid biopsy discussion, also see the micro-story in this newsletter: “A Very Brief History of Cancer Liquid Biopsy”.)

Additional Multiplexing Capability of IC3D Droplet Digital Detection

We also recently published a joint paper with Laboratory of Fluorescence Dynamics and the Zhao Lab at UC Irvine, “Fluorescence Lifetime Detection with Particle Counting Devices” (Biomedical Optics Express, March 2019). Most fluorescence detection methods rely on assessing signal intensity and wavelength (i.e., color) in multiple color channels for assay multiplexing. But simply increasing the number of color channels isn’t always possible and can be constrained by practical limitations. This paper demonstrated that by adapting the 3D rapid scan particle counter for fluorescence lifetime detection, we can achieve multiplexing capabilities even on a single-color channel/detector. This opens the door for higher multiplexing, i.e., identifying a broader panel of targets in the same assay (especially important when dealing with limited clinical specimen), and new fluorescence chemistry detection on a relatively simple optical system by using fluorescence lifetime analysis.

Velox Resources Update

We have updated our 2-page Executive Summary with a very clear and succinct description of our Company Overview, Target Markets, Innovation and Competitive Differentiation, and Key Millstones achieved. In combination with our recent Velox R&D poster, they should provide a very good overview to who we are and what we do.

And to wrap up with a micro-story (“A Very Brief History of Cancer Liquid Biopsy”) ...

Nothing in science really comes out of a vacuum or black hole. And it is always interesting to observe how ideas and approaches evolve in science. Given the challenges with tissue biopsy, the idea of detecting cancer biomarkers in blood draws (i.e., liquid biopsy) has certainly been very attractive for many years. But the evolution of the “how” has taken a more circuitous road. To date, the field of cancer liquid biopsy has evolved around the following areas: (a) rare but metastasis-competent CTCs shed from primary tumors, (b) cell-free tumor DNA (cfDNA) from tumor cell apoptosis and necrosis, and (c) microvesicles and exosomes secreted off tumor cells containing miRNA and DNA fragments. Each of them reflects a different aspect of the complex cancer biology and each comes with its own challenges and limitations.

Cristofanilli’s seminal work on CTC detection in early 2000 ushered in huge excitement for cancer liquid biopsy. However, several large clinical studies in the following decade showed the early methods of CTC detection failed to provide clinical benefit due to the challenges of capturing and enumerating CTCs. With that, the majority of cancer liquid biopsy work has since shifted to interrogating cfDNA, either by allele-specific PCR, digital PCR (including ddPCR), and/or NGS. But due to the inability/impracticality of current technologies in coping with a large amount of background genomic DNA, research and clinical tools have further confined themselves to extracting and finding cfDNA in plasma. While the cfDNA from plasma approach is working reasonably well in companion diagnostic tools for late stage cancer diagnosis and treatment, applications for early stage cancer detection in various clinical studies have proved to be less fruitful and lack clinical significance.

So, with IC3D’s ability to detect CTCs/CTC DNA without need for pre-enrichment and its ability to analyze total tumor DNA (CTC DNA, cfDNA, etc.) present in whole blood and combine all the cancer puzzle pieces together, perhaps we can now bring this evolution back full circle?

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