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Genentech Partners with Xenon to Discover, Develop Genetically Targeted Pain Drugs, Companion Tests

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By Turna Ray

Roche subsidiary Genentech is working with genetics-focused drug development company Xenon to advance personalized medicines for pain.

According to an announcement this week, the Burnaby, British Columbia-based drug firm will work with Genentech to discover and develop novel treatments and companion tests for pain treatment targeting specific gene markers.

Under the terms of the collaboration, Xenon will receive from Genentech an undisclosed upfront payment and research funding, and is eligible to receive research, development, and commercialization milestone payments, totaling up to $646 million. Xenon may also receive royalties on sales of products resulting from the collaboration.

A company spokesperson told PGx Reporter that Genentech will be responsible for the development and commercialization of drug candidates that are discovered through the collaboration with Xenon. Additionally, Genentech will be in charge of the development and commercialization of companion diagnostics that may be needed to pick out best responders to drugs that are discovered and advanced through the partnership.

Xenon CEO Simon Pimstone said in a statement that the collaboration will allow Xenon to expand its pipeline of novel pain medicines. The pain market may be a profitable one for genetically targeted personalized medicines, since industry observers estimate that the global analgesics market will be valued at $34.6 billion by 2015.

Currently, Xenon is studying several analgesics that target pathways associated with the absence of pain. According to Xenon's website, the company has used its global clinical network to identify "rare individuals with a congenital form of human analgesia known as congenital insensitivity to pain" who lack the ability to feel pain.

"We discovered CIP patients have mutations in the SCN9A gene resulting in absence of the NaV1.7 sodium channel, thereby validating this drug target as essential for human pain sensation," the company states on its website. Xenon believes that inhibition of NaV1.7 "should be a highly effective and safe mechanism to treat a broad spectrum of painful conditions."

Xenon has conducted proof-of-concept trials with its lead candidate, XEN402, in the setting of inflammatory pain for dental extraction as well as in erythoromelalgia, an inherited disorder characterized by spontaneous pain and caused by mutations that activate the NaV1.7 channel. The company has also conducted a Phase II trial investigating topical XEN402 as a treatment for alleviating the pain of post herpetic neuralgia, and found that patients treated with the investigational agent reported greater reductions in pain than those treated with placebo. Additionally, Xenon is investigating XEN403, a follow-on oral product, in Phase I trials.

The company has partnered with Takeda to develop and commercialize these agents in Japan and other Asian countries.

Genentech will focus on developing new genetically targeted pain drugs beyond XEN402 and XEN403. "These molecules are not part of our collaboration," the Genentech spokesperson said.

It is unclear whether the partners will pursue additional gene targets tied to the NaV1.7 channel. Xenon did not respond to questions for this article, and Genentech declined to disclose the gene targets of interest for this collaboration.

Xenon said that the collaboration with Genentech represents its sixth partnership with a major pharma company involving genetics-focused drug development. Xenon's drug discovery efforts are focused on studying small, isolated populations to identify the underlying genetic causes associated with disease phenotypes. The company then inks partnerships with pharmas to develop treatments targeting specific gene markers or associated pathways.

Outside of the pain market, Xenon is developing drugs for iron overload, anemia, heart conditions, and metabolic disease.

Xenon is working with Isis in the anemia space to develop antisense therapeutics targeting loss-of-function mutations in hemojuvelin and hepcidin linked to juvenile hemochromatosis. The company is working with Merck to develop drugs for atherosclerosis that hone in on certain gene markers. Xenon and Roche, meanwhile, have a partnership around anemia research efforts.

Finally, Xenon is collaborating with Novartis to develop drugs that inhibit SCD1. Xenon has shown in clinical and genetic studies that decreased SCD1 enzymes in humans may be associated with reduced obesity, improved insulin sensitivity, and lower cardiovascular risk.


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