NEW YORK (GenomeWeb) – NovellusDx will work with Centre Léon-Bérard (CLB) to gauge the accuracy of its functional annotation for cancer treatment (FACT) assay to predict treatment response in cancer patients.
The Israeli biotechnology firm hopes that a successful outcome of the study will raise its profile among oncologists, though work with pharmaceutical companies continues to be its main source of revenue.
"Sequencing has become quite routine, but it's still a new technology," said NovellusDx CCO Michael Vidne. "The more you show scientifically that doing a functional characterization of the tumors, mutations, and drugs is beneficial, the more physicians want to use that to help their patients."
Founded in Jerusalem in 2011, privately held NovellusDx opened its clinical laboratory in 2016. The company uses its flagship FACT assay to test the response of variants of unknown significance (VUS) to various cancer treatments to predict clinical outcomes.
Rather than relying on biopsy tissue from patients, the firm works with next-generation sequencing data, synthesizes the mutations of interest, and transfects them into cells for wet lab analysis. For the price of $600 per gene, NovellusDx provides a functional characterization of these VUS, giving clinicians another tool for tailoring treatment.
"Generally speaking, most mutations found in an NGS report are unknown by the community," said Vidne. Clinicians "send us data about the mutation, we synthesize it, see what it does in the live cell, then the report tells the physician if the mutation was activating, and if it was activating, what pathway was it activating," Vidne said.
At the American Society of Clinical Oncology meeting in Chicago last year NovellusDx connected with Olivier Tredan, co-chair of the department of medical oncology at Lyon, France-based CLB.
The partners agreed to embark on a retrospective analysis of two arms of the My Own Specific Treatment (MOST) trial, a phase II trial carried out by CLB that includes 560 participants. The aim of MOST is to determine whether three months of treatment with a targeted therapy based on alterations detected in the tumor is sufficient to stabilize the disease compared to longer treatments. It targets all patients presenting with the alteration, regardless of cancer type or site.
Clinical follow up on two of the MOST trial's study arms has been completed. One arm focused on using the drug everolimus, marketed by Novartis as Afinitor, to target alterations in the PI3K/AKT/mTOR pathway. The other arm focused on using the compound sorafenib, co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar, to target multiple kinase proteins. NovellusDx will now analyze the sequencing data of patients from those two arms of the MOST trial to predict the clinical outcomes of patients retrospectively.
"The idea is for them to run the assay and decide or predict in vitro if the patients will be responders or nonresponders to these therapies," said Gwénaëlle Garin, clinical project manager at CLB. "We already have the clinical data for these patients, because they were already treated," Garin said. "At the end, we will see if there is a correlation between the NovellusDx assay and the data."
According to Garin, CLB has already provided NovellusDx with sequencing data for 63 patients enrolled in MOST, 43 from the sorafenib arm, 20 from the everolimus arm. She said that assessing the correlation between NovellusDx's results and the clinical data collected in the MOST trial will be a "preliminary and first step" for CLB, which might later consider using the assay more widely in the treatment of patients.
"The idea of Dr. Tredan for this collaboration is that such an assay could help … physicians to better identify biologically relevant molecular alterations to better guide treatment decisions for cancer patients," she said.
"For each patient, we receive NGS data and what drug was used on that patient, and we are blinded to the clinical outcome," Vidne noted. "We synthesize the mutations of the patient, we test the drug that was used on the patients on our cells, and for each of the patients we characterize them, we predict whether they were responsive or nonresponsive to the drug that was given," he said. "That allows us to go and see if we were correct in our predictions or not."
Garin said that it is likely this part of the study with NovellusDx will take a few months, and confirmed their intentions to describe it in a publication. "There will be a paper, and if it is really impressive, maybe we can start to include their test in real life," Garin said. "This will be additional information for clinicians to guide treatment," she said.
Garin added that the study with NovellusDx could be expanded to additional centers in France. While discussions in that direction continue, she said no other partnerships had been inked yet.
Vidne said that NovellusDx has been experiencing "strong traction" in France. He noted the company already carried out a retrospective analysis of 12 patients who were enrolled in the SHIVA01 trial in collaboration with Christophe Le Tourneau, a senior medical oncologist at Institut Curie. The work was described in a recent paper in Molecular Oncology.
"In that work, the analysis was limited to a dozen patients, and in the MOST trial we have the opportunity to analyze a much larger cohort of patients," said Vidne. "We and Dr. Tredan realize that repeating the powerful results of the SHIVA reanalysis on a larger cohort will lead to a paradigm change in the field of oncology," he said.
SHIVA01 was a prospective, randomized precision medicine trial that compared targeted therapy based on tumor molecular profiles and aimed to demonstrate that using molecular profiling such as NGS data to guide therapy improves patient outcome. However, as Vidne noted, the trial was negative for its endpoint, as researchers did not find a statistically significance difference outcome for those who had their tumors profiled using sequencing and those were given the conventional standard of care.
"One of the main reasons for the negative results is that classification of somatic variants is not straightforward, rendering treatment decisions based on variants with unknown significance hard to implement," Vidne said. "Mutational data by itself is not sufficient."
NovellusDx is now starting to spread that message via collaborations such as the one with CLB.
"This trial, as well as many others we are participating in, brings the issue of variants of unknown significance to the attention of physicians as well as the solution we provide," Vidne said. "We believe that in near future every cancer patient will be sequenced, but this is only a first step," he said. "Once sequenced, the [variants] must be investigated in order to optimize treatment and make the best use of the NGS capabilities and the given arsenal of drugs."
NovellusDx therefore envisions itself as the "next stop after sequencing," Vidne continued.
"Patients will go through Foundation Medicine or LabCorp, it doesn't matter, and once they find that they have mutations that are unknown in the literature, they have them characterized by us," he said.
Currently, all testing on the FACT platform is paid for by patients. While NovellusDx's lab is CLIA compliant and accepts samples internationally, Vidne said it has the capacity to process about 10,000 tests per year, a "drop in the bucket" in terms of a large market like the US.
"We are not concerned about reimbursement at this point," said Vidne. "Once we reach 100,000 tests a year, at a full commercial scale, that is when reimbursement becomes important," he said. "It isn't worth it yet for us to go through the hurdles of reimbursement when our patients are willing to pay out of pocket."
He noted however that most of NovellusDx's customers are not yet patients. "Most of our clients are pharma because of limited capacity and bandwith," Vidne said. "The work we are doing with oncologists and medical centers is to generate traction and some recognition," he said. "The revenue is actually generated in the pharma field," Vidne added. "Pharma understands the technology, understands the unmet need, understands the value you are bringing them," he went on. "We are getting good traction there."
In addition to its work with CLB and pharma customers, NovellusDx is engaged in other activities. In July, Christina Care's Gene Editing Institute licensed gene-editing technology to the company. Vidne said the collaboration is going "extremely well" and that the partners three weeks ago submitted a joint patent on performing CRISPR in vitro.
"All other CRISPR is done in live cells, our technique is the only one doing it in vitro," said Vidne. "This makes our process much faster and robust and can also be used for many other synthetic biology applications," he said. A paper discussing the approach is also in progress.
The company also announced last summer that it had raised $12.5 million in a private financing round that included investors OrbiMed, IntraCure, and Pontifax. Vidne said the company is in the process of forming a new round with participating from all existing investors, as well as some new ones.