NEW YORK (GenomeWeb) – Seeking to fill an unmet need, newly launched firm Pairnomix will begin offering a commercial service this January consisting of comprehensive follow-up in vitro modeling and scientific research for individuals who have an identified, but ill-understood genetic variant in the context of genetically mediated rare disorders, starting with epilepsy.
The company hopes that such services can help pinpoint alternative treatment strategies for its customers, or at least advance the understanding of how more of these variants detected via genome sequencing actually mediate or influence the clinical manifestation and symptoms of patients.
Such investigations are already part of the rare disease genomics research field, but are not always accessible to every patient or family for whom sequencing identifies a putative causal variant, Pairnomix CEO Matt Fox told GenomeWeb this week.
In recent years, genomic sequencing has increasingly yielded case studies in which a patient’s previously inexplicable symptoms have been linked to a particular stretch of altered DNA. In some cases, advocacy and the expanding opportunities of social media have also led to the discovery of multiple cases with the same novel and extremely rare mutation. And in some, families have been able to work together to raise necessary large sums and develop relationships with academic researchers supporting exhaustive follow-up pathway and drug research in a search for an effective treatment.
However, for most rare variants, identification marks the end, rather than the beginning of a journey, Fox said, due to a lack access, resources, or influence to drive further research. It is this gap that Pairnomix hopes to be able to fill, Fox said.
“When a patient gets sequenced … and the report has come back and there is a mutation … you may be able to get to the point where you know that it is causing the issues the physician is seeing, but then there is nothing to do about it from that point forward,” he said.
“We take the mutation, our team looks at it, and we believe we can build a replica model to evaluate in a laboratory setting and test compounds against and report [the results] back to a patient’s treating physician,” Fox added.
The idea for the company came out of a relationships that Fox — who had been working for privately owned pharmaceutical company Upsher-Smith — developed with researchers in the epilepsy field, most prominently David Goldstein, currently professor of genetics at Columbia University.
“David said that in the academic setting, sometimes very wealthy families can pay extreme amounts of money to the alumni foundation to be reviewed by a lab [in these ways.] But it’s only available at a few centers — and academia is just not set up to do this — at least not with a focus on the individuals,” Fox said.
“So we think there is a value to having an independent company there to help individuals do this kind of work, starting with looking at the potential repurposing of drugs and then moving eventually to novel compounds.”
As part of its planned services, Fox said Pairnomix will first start with a concerted vetting process to make sure that it is only taking cases that have a change of benefiting from this process. The company’s advisory board includes Goldstein, as well as NYU neurologist Orrin Devinsky, and the University of Melbourne’s Slavé Petrovski and Steven Petrou. This group will review each case to make sure that the variant in question originates in genomic analysis from a reputable lab or company and also that there is secondary research that the gene in question is active in epilepsy and actually affects the phenotype before going forward.
After the initial vetting process, Pairnomix will build a cell line representing an individual customer’s genetic alteration, and use it to do basic research on the function of the variant, as well as to test a variety of available, and potentially also experimental drugs.
According to Fox, this process offers several layers of value. First, he said, “we believe we know what these mutations are doing but [we don’t] until we actually work in an in vit r o setting and characterize the mutation. So there is a real value to the physician and the family in understanding exactly how something is a gain of function or loss of function and how it is relevant to the overall system.”
The second tier of the company’s offering will focus on facilitating testing of patients’ in vit r o models against the 13 current US Food and Drug Administration-approved compounds that make up more than 98 percent of prescriptions in the epilepsy setting.
Beyond these drugs, the company will also seek to test FDA-approved drugs that might have an effect but are outside the epilepsy setting — compounds for which there are case studies in the literature with positive results. Finally, the company is also prepared to connect with pharmaceutical or biotech companies to test compounds that are in development as a way of advancing novel therapies.
“In the majority of cases we are not going to find a new drug that works for patients. We know we are not going to have that many easy wins,” Fox said. However, Pairnomix’s leaders believe that even just in fostering further understanding of mutations and developing connections between families and various resources will provide tremendous value.
This is something that has been reiterated, Fox said, by another member of the company’s board, Matt Might, a University of Utah professor whose family became known widely last year for their own experience identifying and seeking to further research the NGLY1 mutations responsible for their son’s complex condition.
According to Fox, Pairnomix will also try to find ways to make it as easy and inexpensive as possible to potentially share patient cell lines and research with other groups, and connect families with relevant work being done by other researchers in the field that may be able to impact their individual case.
Though he could not discuss a precise cost for the company’s research services, Fox admitted that the endeavor Pairnomix proposes could be vastly expensive depending on the particular individual.
“The biggest challenge to the business model … is that from that perspective it is very costly,” he said. “I’m not going to put a number on it, but just to build cell lines and do characterization on our end can cost $75,000 to $100,000 in some cases.”
While this might seem like a significant barrier to potential customers, Fox said that the company believes that there are families who would fit the profile of both being in a position to benefit from the company’s service, and being able to come up with the money to fund it.
Leading up to opening its doors to commercial customers in January, the company has also collected several pro bono cases that it is working with to build up evidence for the utility of its service.
For one of these cases, Pairnomix will be splitting the costs associated with its activities with the KCNQ2 Cure Alliance, an advocacy organization promoting education and research that could lead to treatments or a cure for patients living with disorders linked to alterations in the gene KCNQ2.
Eventually, Fox said, he hopes that Pairnomix will be able to collect enough case results to be able to make a case to payors for insurance coverage of its services.
Fox was clear that Pairnomix has strict guidelines for communication of results only to the individual patient’s physician. The company is not working with any kind of a direct-to-consumer model.
However, as it builds its client base, the resulting information may also come to benefit others who carry the same alteration. Collaboration among families with a rare disease genetic diagnosis has been one the rise with the opportunities enabled by the internet and social media, as evidenced by the path taken by Parinomix board member Matt Might and his family.
For its first year, the company hopes to engage with up to 50 clients, focusing mainly on epilepsy. After that it will work to expand to additional areas of the rare disease space.