Genentech Seeks Partners For Biomarker-Driven Drug Development Beyond Oncology
Executive Summary
Roche subsidiary hopes recent deals with 23andMe and Human Longevity for whole genome sequencing will help identify targets and biomarkers for Parkinson's disease and other non-cancer conditions. Firm also is taking a personalized medicine approach to development of treatments for pain, macular degeneration and asthma.
Genentech Inc. is looking for business development deals and licensing opportunities that will continue the biotech giant's expansion of its biomarker-based approach to drug development beyond the oncology setting.
"We like to let the world know that we're open for business," Genentech Senior Director-Business Development Tom Zioncheck said. "We're looking and seeking collaborations and good science all over the world. We recognize that there are a lot of great, different approaches and discoveries being made every day."
During a recent interview at the Biotechnology Industry Organization's annual convention in Philadelphia, Zioncheck talked about key candidates in the company's non-oncology pipeline and recent collaborations the Roche subsidiary hopes will lead to a personalized medicine approach in the treatment of such conditions as neurodegenerative diseases and pain.
Genentech's approach to developing drugs with companion diagnostics outside of cancer has been a long-time ambition (Also see "Personalized Medicine Takes Aim At Common Diseases" - In Vivo, 16 Jul, 2013.). Genentech sees this approach as a way of bringing greater efficiency to late-stage drug development, and the company is hoping the fruits of these labors will pay off in the form of regulatory filings over the next few years. Business development can help accelerate that process.
"We are very fond of … taking a deep understanding of not only the biology, but trying to identify biomarkers and companion diagnostics as we go through development because we think those are critically important to helping us de-risk some of these late-stage Phase III clinical trials," Zioncheck said.
Taking Aim At Parkinson's Disease …
Genentech's partnering group is separate from that of parent company Roche; it focuses on discovery through clinical proof of concept and supports Genentech's Research and Early Development team (Also see "Roche’s pRED Team Reviews R&D Wish List As Firm Continues Push To Diversify" - Pink Sheet, 9 Feb, 2015.).
Zioncheck's business development responsibilities are largely focused on neuroscience, ophthalmology, metabolic disease, technology innovation and companion diagnostics, including whole genome sequencing collaborations.
The 27-year Genentech veteran's job is to find partners and assets that enable the company to do what it does so well in oncology – identify a biomarker that can guide drug development and treatment in a targeted patient population – into the non-cancer setting.
Genentech has entered several deals in the past year that it hopes will enable it to accomplish this goal in various therapeutic areas.
In January, Genentech and 23andMe Inc. announced an agreement to generate whole genome sequencing data for 3,000 patients in the consumer genetics company's Parkinson's disease community.
Zioncheck said access to the cohort was extremely attractive to Genentech because the company has preclinical research programs ongoing in Parkinson's disease.
Genentech will use the genomic data from the 23andMe collaboration in a number of ways.
"The first and most basic is to have a better understanding of the pathophysiology of the disease," Zioncheck said. "By understanding the genetic mutations and SNPs [single nucleotide polymorphisms] that are associated with the disease, we hope to get more insights into the basic pathways and targets that are involved."
"Ultimately, the goal is to have a companion diagnostic so we'll really be able to know in advance which patients are most likely to benefit from our therapies," Genentech's Zioncheck said.
"We also expect to have this sequence information shed light on new targets for Parkinson's disease and give us insights into companion diagnostics and biomarkers to really help us through the R&D process, not only to be able to select and enrich the appropriate patients in our trials," he said. "Ultimately, the goal is to have a companion diagnostic so we'll really be able to know in advance which patients are most likely to benefit from our therapies."
Also in January, Genentech and Human Longevity Inc.announced a deal for whole genome sequencing and analysis of de-identified samples from clinical trial patients. A genomics and cell therapy-based diagnostics and therapeutics company, Human Longevity was founded by former Celera Corp. CEO and human genome pioneer Craig Venter.
"Because these patients are coming from our clinical trials, one big advantage [is] we'll be able to get some insights into are there genetic signatures that can predict what patients are responding and those that aren't," Zioncheck said.
"This we see as being incredibly valuable information for us to be able to not only further refine our later-stage clinical trials, but ultimately … end up with companion diagnostics that will allow us to take this personalized health care approach, which we're very excited about for essentially all of our portfolio."
Unlike the 23andMe deal, the Human Longevity partnership is not specific to a particular therapeutic area.
"We have some flexibility to choose what clinical trial samples we would like to use. We actually have some flexibility to also use patient samples coming in from academia and other research collaborations as well," Zioncheck said.
... And Alzheimer's …
Parkinson's is not the only neurodegenerative disease where Genentech believes whole genome sequencing could unlock the door to scientific advances and effective treatments.
Crenezumab, which was discovered by AC Immune SA and is being co-developed by Genentech, is a humanized monoclonal antibody designed to bind to amyloid beta that is being studied in a prevention trial in cognitively healthy individuals who are likely to develop Alzheimer's disease due to their genetic history.
The study, undertaken in collaboration with the Banner Alzheimer's Institute and the National Institutes of Health, is being conducted in Colombia with participants from local families that can be traced to a common descendant. The participants share a rare genetic mutation that typically triggers Alzheimer's symptoms around age 45.
"We feel like the science is really breaking open in so many areas, whether it be on the whole genome sequencing aspect … or just more insights into the biology of disease, that we're very excited about the possibility of being able to make an impact in this space in the coming years," Zioncheck said of Alzheimer's disease.
Nevertheless, Genentech has already faced some development challenges with crenezumab in the treatment (as opposed to prevention) of Alzheimer's; the drug missed cognitive improvement endpoints in two Phase II trials in patients with mild-to-moderate disease, although there were some positive data points (Also see "Alzheimer’s R&D In Brief: Roche’s Crenezumab Misses Endpoints, Novartis Plans Large New Genetic Study" - Pink Sheet, 21 Jul, 2014.).
… And Pain
Pain is another area where Genentech believes a biomarker/companion diagnostic approach to drug development may bear fruit.
The company's efforts in the pain space grew out of a 2011 partnership with Xenon Pharmaceuticals Inc. to discover and develop compounds and companion diagnostics for the treatment of pain.
Through basic research and genomic sequencing, Xenon has identified Nav1.7, a sodium-gated voltage channel, as a potentially critical target for pain.
"We very much liked their approach, and it was a genetics approach to identifying targets," Zioncheck said. "They had spent a lot of time and effort identifying families with extreme phenotypes, so families with either a hypersensitivity to pain or families that weren't feeling any pain sensation at all."
The 2011 collaboration is focused on developing selective oral Nav1.7 inhibitors, and Genentech has a small molecule clinical program under way.
However, the validity of Nav1.7 as a target has been called into question by drug development failures in this space, including most recently Xenon and Teva Pharmaceutical Industries Ltd.'s TV-45070, an ointment that targets a number of different sodium channels, including Nav1.7. The drug failed a Phase IIb study in osteoarthritis; a Phase IIb study in post-herpetic neuralgia is ongoing (Also see "Teva/Xenon’s Pain Ointment Failure Leaves Sparser Nav1.7 Pipeline" - Pink Sheet, 1 Jul, 2015.).
However, Genentech is not putting all its money in the future of Nav1.7. In March 2014, the companies established a new collaboration that leverages Xenon's Extreme Genetics platform to discover and validate therapeutic targets beyond Nav1.7.
"We feel more than anything that focusing on the human genetics as a guide to target selection is an incredible advantage in improving our probability of technical success, particularly in areas where preclinical animal models haven't necessarily been predictive," Zioncheck said of the collaboration.
Regulatory Filings On The Horizon
Genentech's biomarker-focused strategy in the non-oncology arena is expected to produce regulatory filings over the next few years in ophthalmology and asthma.
In ophthalmology, Genentech already markets the VEGF-inhibitor Lucentis (ranibizumab) for a host of indications, including neovascular (wet) age-related macular degeneration (AMD).
Lampalizumab, an anti-Factor D antigen-binding fragment, is in Phase III development for geographic atrophy, an advanced form of dry AMD for which there are no approved treatments. The Phase II MAHALO study showed a doubling of treatment effect in patient groups differentiated by a biomarker (Also see "Roche Considers Moving Two Drugs Into Phase III, Drops Early-Stage Alzheimer’s Compound In Strong 3rd Quarter" - Pink Sheet, 17 Oct, 2013.).
In asthma, the company has identified a biomarker – levels of the protein periostin – that appears to be predictive of robust response to its anti-interleukin-13 cytokine lebrikizumab, which is in Phase III development (Also see "Roche Believes Biomarker Could Position Antibody For Severe Asthma For Success" - Pink Sheet, 7 Nov, 2011.).
"You're seeing a couple of examples outside of oncology where we have biomarker strategies and positive Phase II studies that are giving us a fair degree of confidence going into Phase III in these non-oncology areas," Zioncheck said.
A recent Phase III success for ocrelizumab, an anti-CD20 antibody in development for multiple sclerosis, has further boosted Genentech/Roche's non-oncology pipeline (Also see "Ocrelizumab May Represent Roche’s Rebound In Neuroscience" - Pink Sheet, 30 Jun, 2015.).