Isabel’s rapid whole genome analysis opens up the cancer treatment playbook –

Every cancer is unique because every person is unique, and one of the most important weapons in any cancer battle is information. Isabel offers that in abundance through rapid sequencing of the entire genome of cancer cells, potentially revealing within days which therapies will and will not be effective. The company has received a groundbreaking designation from the FDA and has raised $3 million to market its approach.

The past ten years have brought many medical advances thanks to the commoditization of genomic processes, from sequencing to analysis, and cancer treatment is no exception. In fact, because cancer (although it’s a simplification) is a genetic mutation that got out of hand, understanding those genes is a particularly promising line of research.

Panel tests look in the DNA of cancer cells for mutations in a selection of several hundred genes known to influence prognosis and clinical strategy. For example, a cancer may have certain mutations that make it susceptible to radiation but resistant to chemo, or vice versa — it’s incredibly helpful to know which ones.

Isabl co-founder and CEO Elli Papaemmanuil explains that as useful as panel tests are, they are only the beginning.

“These tests have been very carefully designed to look for the most common mutations, and they have revolutionized cancer diagnosis for patients with common cancers,” she said. “But patients with rare cancers — and what we define as a rare cancer is still a third of patients — don’t benefit from it.”

Even many with common cancers may find that their condition does not involve mutations of these most predictive genes. The relevant genes are somewhere between the other two billion base pairs — current tests look at only about 1 percent of the genome.

While the technology exists to look at that other 99 percent, it was historically expensive and slow compared to panels, and analysis of the resulting large amount of data was likewise difficult and time-consuming. But Isabel’s tests show that it is definitely worth it.

Diagram showing information (groups, individuals, cells) going into an analysis.

Image Credits: Isabel

“It turns out that whole genome sequencing can detect many more clinically relevant findings — results that we can respond to.” Today† And what we’ve done is develop a platform that allows us to summarize it in a way that doctors can read and use it in a day,” Papaemmanuil said. They call it a “clinically useful whole genome and transcriptome assay,” or cWGTS.

The company grew out of research Papaemmanuil did at Memorial Sloan Kettering, a New York-based cancer care and science partnership. “You could see all these successes in panel trials, and then all these patients who weren’t benefiting from it. But in my lab, we had the technology and the know-how,” she recalls. They collected and combined three different data sets: the germline genomes (ie from the patient); the genome of the tumor, and also the transcriptome, essentially what the body produces by transcribing the DNA.

“This gives a very complete picture of the profile of the tumor,” she said. “Instead of having a classifier or a model that annotates the mutations [i.e. an automated panel test]we have analyzes integrating those three layers to interpret the role of the mutation and its relevance to each tumor type.”

While Isabel owns the entire process from sampling to reporting, Isabel’s key advancement is data-based and therefore “there is no technical obstacle to making this solution available today. And we’ve shown that we can do it on a large scale,” Papaemanuil said. But in the medical world, just because it’s possible doesn’t mean it’s allowed. The FDA has granted the technology “breakthrough” status, which is a fast track, but even the fast track is slow in the federal government.

While full clinical approval is likely 3-5 years away, that is much faster than the 5-10 years estimated by the industry for these types of applications. But research, both for validation and other purposes, is underway, having just published the lead article proving the process. today in Nature Communications† (While this study focuses on childhood and young adult cancers, the technique is not limited to those demographics.)

“The seed round is mainly about letting us do the roadmap – it’s a good starting point for getting the necessary evidence and approvals,” Papaemmanuil said. “We’re already working with cancer centers to do studies, and especially to hear from oncologists what they need and how they want the data.”

From left to right, the co-founders of Isabl Andrew Kung, Elli Papaemmanuil and Juan Santiago Medina.

The $3 million round was led by Two Sigma Ventures, with participation from Y Combinator, Box 1 and other companies. The co-founders of Papaemanuil are CTO Juan Santiago Medina and Andrew Kung.

She also made it clear that Isabel’s research would be conducted openly – “We have a very strong scientific base and will be active in publishing the work. The data should be both published and made accessible in a form that allows for further research,” she said. The self-reinforcing game of producing and identifying predictive data could be an incredibly valuable resource across many disciplines.

Isabel exemplifies the power of a more or less pure data game in an industry more often associated with lab progress – although, of course, it took a lot of lab work to produce in the first place. But when automation of key processes, in this case DNA transcription, enables a massive increase in data capture, there is always value to be found. In this case, that value could save many lives.