Understanding Tumor Microenvironments With Cofactor Genomics
Managing Editor, Carl Smith sat down with Director of Scientific Projects and Market Development at Cofactor Genomics, Dr. Natalie LaFranzo…
A year ago, you were excited with the release of Pinnacle. Now we have the impressive Paragon assay to look forward to. Could you talk us through the new assay?
Paragon represents the next step in the evolution of Cofactor’s RNA-based technologies, which are aimed at advancing cancer care through molecular profiling and diagnostics. Current statistics from the US, Canada, and the UK estimate as much as 50% of the current population will be diagnosed with cancer, with 25% ultimately succumbing to the disease. Those are sobering statistics that Cofactor aims to change.
In a sentence, Pinnacle profiles the tumor, while Paragon profiles the tumor microenvironment.
With the field of immuno-oncology exploding, there’s an increased focus on the idea that characterizing the tumor alone does not provide sufficient context for making impactful treatment decisions. Rather, understanding and accounting for the tumor microenvironment, the composition of the infiltrating immune cells, and the neoantigenicity of the tumor can enable improved therapeutic outcomes. This part of the solid tumor story, immune-profiling, has previously been accessible primarily via technologies such as flow cytometry (flow) or immunohistochemistry (IHC). But, with flow, you’re restricted to using only fresh tissue and with IHC, it’s difficult to screen multiple markers and quantify these markers effectively. Current technologies are not compatible with the vast majority of clinical samples, and are very limited in the scope of microenvironment characterization.
So, our goal was to develop an assay, using our expertise in RNA, that enabled high-throughput, quantitative immune profiling of clinically-relevant solid tumor samples. Paragon represents something really powerful – it opens up tumor microenvironment profiling to all current tumors being biopsied, as well as a rich pool of clinical FFPE archives with outcomes and phenotype data.
The assay is built on a few key computational features:
- Immune escape and expression characterization: reports on the expression levels of key IO genes.
- Immune phenotyping: quantifies immune infiltrates, including major and minor subtypes, using immune cell expression fingerprints and deconvolution software.
- Mutational Burden: without requiring a matched normal sample, the software provides a measure of neoantigen load in mut/Mb, useful in understanding immune response.
Requiring only a few FFPE curls, we extract RNA and use Cofactor’s molecular technologies paired with next generation sequencing (NGS) to generate the data which feeds into Paragon’s analysis software. It’s both high-throughput and quantitative, and capitalizes on the immense biological information represented by Cofactor’s algorithms and database of RNA profiles.
How are you using the experience of Pinnacle to influence the roll out of Paragon?
Pinnacle was our first CAP-accredited assay, so we built quite a bit of infrastructure and established rigorous validation checkpoints for our development process. While Paragon itself will be more translational (not clinically-approved), the technology may be tailored to build more focused custom clinical assays, which is certainly where this will go in the future. And, our experience with building a validated assay is definitely helping shape the path for this product – to ensure we are confident in the results that we produce.
Who are your Beta users? How are they helping you get it ready for the next phase?
As we continue to develop Paragon, we’re partnering with clinical researchers at some of the most progressive research hospitals and institutions who have previously run, or are currently running, clinical trials focused on immune-oncology. We may not always find that Paragon gives us a smoking gun – a clear immune signature which explains a therapeutic response. But, it’s important for us to benchmark the performance of our assay against existing technologies, and demonstrate opportunities where our assay can provide information and context that was not achievable before. Furthermore, evaluating the performance of the assay on as many cancer types as possible will help us to ensure the assay is robust.
When the company started, you were more focused on offering full end to end sequencing as a service. It looks like you’re pivoting to prioritise R&D for tech development now?
That’s right. We’re still serving the need that exists for high quality RNA-seq and comparative expression analysis – we have a suite of Discovery/RUO assays that accommodate nearly every sample type out there – and we’re happy to continue to offer these. We’ve never shied away from challenging samples – from low-input, to low-quality, or both!
But, realistically, to apply RNA-seq to more challenging questions in human health, we need assays that move far beyond what is achievable with comparative RNA-seq alone. It’s not enough to just report on single gene expression differences. This requires both novel RNA-specific software algorithms and complementary molecular tools. Developing these technologies is exactly in Cofactor’s wheelhouse, and as you mentioned, we’re really focusing our efforts on this. What’s exciting is that the underlying technology behind Paragon has so many follow-on applications in other immune-relevant diseases. So, once we’ve delivered on our plans for a robust IO assay, there’s plenty more that we can contribute to.
How are you approaching educating clinicians around the potential utility of RNA?
The collaborations we’ve put in place with our Beta and Early Access users have been strategic – these are leaders in the field that have biological samples which will help us to interpret and demonstrate the power that RNA-based technologies, such as Paragon, provide. We want to prove not only that we’ve built a technically-sound assay, but that it has the capacity to expedite the drug development process, select an ideal therapeutic regimen, or better understand a patient’s cancer progression.
But, we can’t do this alone – we need these experts in the field who understand the immunological responses we’re characterizing and the downstream clinical applications of having this information in hand. So, we see collaborations as an investment not only in our technology, but in demonstrating the utility of RNA as a whole.
Recently, we saw the good news of your Series–A Round. It looks like you have a good investment team supporting you. How are they helping you grow Cofactor?
Team is definitely the operative word here. We were extremely fortunate to have more individuals offer to join Cofactor on our mission than we realistically could accommodate. So we were in both a rare and fortunate position to build our dream team. Cofactor’s CEO has made it clear that this capital raise was about dollars and sense. A deep tech organization like ours needs money to build this new generation of technologies, but possibly even more important has been bringing on leaders in data-science, biotech, innovation, intellectual property, organizational scaling, and healthcare. For those that don’t know – Cofactor is supported by funding from Menlo Ventures, Data Collective, Y Combinator, Stanford University, iSelect, Silicon Valley Bank, Wilson-Sonsini-Goodrich-Rosati, and Ascension Ventures. All of these world-class leaders, working together with Cofactor to make an impact in precision medicine, is nothing short of inspiring.
I think one of the most exciting partnerships that has evolved through this funding round is the relationship we’re building with 15 healthcare networks — through the support of Ascension Ventures. With almost 500 hospitals in 40 states nationwide, these partners have a clear focus on bringing the most powerful precision medicine tools to their patients. Having the opportunity to engage clinicians who will ultimately be the downstream users of our technology enables us to receive valuable insight into what’s needed in the field. This is an immense advantage for us, and we’re grateful for their willingness to invest in Cofactor and the future of precision medicine.
You’re going to be at the Festival of Genomics Boston in October. What are you going to be sharing with the Festival goers?
Both myself and our COO, David Messina, will be at the Festival in Boston. I’ll be providing a lightning introduction to the Paragon technology, and data from some of our validation experiments.
For those that want more information than I can provide in my short talk, David and I are setting up meetings over email, as well as making ourselves available in the Launch Pad zone at the conference. Our contact info is on our Cofactor Genomics website. Reach out and connect with us. I look forward to catching up with our partners, clients, and friends face-to-face!
Is there anything else you’d like to mention to our readers?
It’s an exciting time to be a part of the evolution of precision medicine. We know that by creating better technologies for analyzing RNA, what we’re really doing is helping to better understand how our bodies fight disease and which individuals will respond to a given therapy. I invite you to partner with us to put these tools into practice!