Even though it recently decided to unload a gene therapy for hemophilia into a yet-to-be-named spin-out company, Biogen, one of biotech’s most risk-taking firms, is doubling down on gene therapy for other diseases. The Cambridge, MA-based company said today it is forming an alliance that could be worth $2 billion with two of the field’s pioneers at the University of Pennsylvania.
Jean Bennett and James Wilson have worked for decades of at UPenn on gene therapy, a method of ferrying genetic instructions into the body to produce what could become a long-lasting treatment for various diseases. Those effects are as yet hypothetical; no gene therapy has been approved in the U.S.
Bennett was one of the first to deliver a gene therapy into the eye, a program which Spark Therapeutics (NASDAQ: ONCE) of Philadelphia, which Bennett helped found, could carry forward to be the first ever gene therapy approval in the U.S. next year.
Wilson (pictured above), meanwhile, the director of UPenn’s gene therapy work, is a central figure in gene therapy’s three-decade-long rollercoaster ride. He co-led the infamous clinical trial that led to the death of teenager Jesse Gelsinger in 1999. He then became a key figure in advancing the gene therapy delivery tool known as an adeno-associated virus, or AAV, which has become a critical part of gene therapy’s renaissance. Wilson’s AAV work led to a company called RegenXBio (NASDAQ: RGNX), which has deals in place with a number of gene therapy players, among them Dimension Therapeutics (NASDAQ: DMTX) and Audentes Therapeutics.
Only now is gene therapy starting to inch towards the market. There are two approved gene therapies, both in Europe: Glybera, from Amsterdam’s UniQure (NASDAQ: QURE), for a rare metabolic disease; Strimvelis, from the British drugmaker GlaxoSmithKline (NYSE: GSK), for a rare immune system disorder.
Many questions remain about these treatments, like how long they will last and how much they should cost. Glybera, for instance, was launched with a $1 million price tag, and thus far, for a variety of reasons, as MIT Technology Review reported recently, has only been used on one patient. As Dimension CEO Annalisa Jenkins told Xconomy regarding Glybera earlier this year, the celebration over Glybera’s approval was short lived.
“The success of a therapeutic in a healthcare system is not the day it gets approved,” she said. “It’s the number of patients that it manages to impact and the value that it creates for shareholders.”
In other words, gene therapy is by no means a success yet. It won’t be until many patients on approved gene therapies are free of their disease for years, without complications. Potential treatments continue to advance, and new companies, such as the recent British startup Orchard Therapeutics, continue to launch. GSK won approval of Strimvelis in March. More data continues to accrue from Spark, UniQure, Bluebird Bio (NASDAQ: BLUE), BioMarin Pharmaceutical (NASDAQ: BMRN) and others in diseases like hemophilia, in which a person’s blood doesn’t clot properly and every cut or scratch could be life-threatening without treatment; cerebral adrenoleukodystrophy, when an abnormal immune response destroys myelin, the coating of the brain’s neurons; and Sanfilippo syndrome, an inherited metabolic disorder in which the body can’t break down certain types of sugar molecules. As Wilson told Xconomy in 2014: “I tell my wife that my career is starting at 60. That the field of gene therapy is now born. That it’s the beginning, it’s not the end.”
UPenn’s deal with Biogen (NASDAQ: BIIB) today is the latest example of significant investment in the field. Biogen will fund Wilson and Bennett’s work on seven different preclinical programs. Biogen will pay UPenn $20 million up front, and has committed another $62.5 million in research funding over the next three to five years in the alliance. UPenn could receive $2 billion total if all seven programs hit a variety of milestones, an extremely unlikely scenario (which is why future dollar figures attached to longterm biotech deals are often known as “biobucks”).
Separately, Biogen has also cut a deal with RegenXBio to use two types of AAV viruses—AAV8 and AAV9—for some of these programs.
The deal has both near-term and long-term implications for Biogen. According to Olivier Danos, who leads Biogen’s two-year-old gene therapy division, the programs for which Biogen will use AAV8 and AAV9 could be ready for clinical testing within two years. These programs will be gene therapies for rare forms of inherited blindness, achromatopsia and choroideremia. Danos says Biogen will also fund UPenn’s work on a gene therapy for spinal muscular atrophy. He didn’t provide details about the other four programs in the collaboration.
Biogen is already working on two gene therapies for two other rare forms of inherited blindness with Gainesville, FL-based AGTC (NASDAQ: AGTC). The company also formed a collaboration last year with two Italian entities on a gene therapy for hemophilia, but announced plans earlier this month to funnel that work into a new hemophilia spin-out.
In the UPenn deal, meanwhile, Biogen will also lean on Wilson and Bennett for what it calls in its announcement “next-generation gene transfer technology.” The two researchers are developing newer types of AAV viruses meant to be more efficient at delivering genes into patients’ cells than the AAV versions currently available. Biogen isn’t funding this work, and won’t get exclusive licenses to these AAVs—which, it should be noted, are not owned by RegenXBio either—just an option to use them in programs Biogen takes forward. Wilson, Danos says, is also collaborating with other Penn researchers on other delivery tools that aren’t viruses—things like phospholipids, which are molecules consisting of two fatty acids. Biogen is keeping an eye on the work. “This is how we get access,” Danos says.
This is all part of Biogen’s effort to possess improved gene therapy tools, like more efficient ways to deliver genes, or perhaps ways to, as Danos says, “control the amount of gene expression.” The gene therapies in clinical trials today are typically geared toward diseases characterized by a single genetic problem, like hemophilia, where one mutation prevents the production of a blood-clotting protein. Danos says developing better tools might help Biogen eventually go after more complex diseases of the brain or eye, such as multiple sclerosis, Parkinson’s, or age-related macular degeneration. That’s important for expanding the reach of gene therapy into more prevalent and complex diseases.
Biogen has other benefits in mind, too. The firm wants to get more involved in gene editing—a method of snipping out and replacing a defective gene.
Biogen already has a 2014 partnership with Sangamo Biosciences (NASDAQ: SGMO), which owns the rights to one method of gene editing known as zinc fingers. Biogen hasn’t yet cut a deal with any of the companies harnessing CRISPR-Cas9, a newer gene editing technology that has taken the scientific world by storm over the past few years. “This is obviously something we’re looking into,” Danos says, calling the UPenn alliance a “stepping stone” for a potential partnership with a CRISPR company, because it gives Biogen a deeper toolkit of delivery technologies that it and its partners can work with.
Likewise, Danos says, maybe smaller gene therapy developers might be able to benefit from Biogen’s help. Perhaps Solid Biosciences—a gene therapy startup that Biogen acquired a stake in last year—eventually needs some help moving forward a gene therapy it’s developing for Duchenne muscular dystrophy, Danos says.
“At some point if they’re gong to be successful in the clinic, they’re going to need to move to the next [step],” he says. “Who can do that? Probably not a small biotech.”