Gene, cell therapy strides expose work still ahead

Print 28 September 2015
Randy Osborne / BioWorld

BOSTON – Concluding with sessions devoted to regenerative medicine, Biopharm America hosted a panel talk on the state of gene and cell therapy, "a new frontier for all of us," said Frank Borriello, head of search and evaluation for Baxalta Inc., the spinout from Baxter International Inc., of Deerfield, Ill.

The fields themselves aren't new, but the goal of finding an enduring therapy to provide lifelong health for patients with serious diseases has turned out to be "an onion with multiple layers," Borriello said. "You always think the problem looks so simple, until you start delving below the first layer, and then you find out there are interesting nuances. We're dealing with those nuances in clinical trials. We're learning in real time, making adjustments and partnerships to help us overcome problems as we confront them." All this while under the gun of competition. "I wouldn't say there's a race, but the same competition the pharma industry is used to already," he said.

How to control downstream biology and how to scale up manufacturing were named as key hurdles, though each company represented on the panel had, or required and was searching for, a slightly different solution. Robert Millman, CEO of Cambridge, Mass.-based Semma Therapeutics Inc., said his firm "need[s] delivery technology to access a very large patient population," and is working on the matter in-house while exploring outside possibilities. "If you have a 'not-if-it-wasn't-invented-here' attitude, you're not going to get very far very fast," he said. "You can get to the end game, but you're not going to get there probably as fast as [you would by] taking all comers."

Using a device invented by a separate firm "has a dilutive effect on your value," Millman acknowledged. "Cell plus device: Who gets what piece? That always is an interesting dynamic. However, the goal here, if you can keep the VCs at bay around your board, is treating patients. How do I get what I have to patients?"

In March, Semma, which is developing a stem cell-based therapy for type 1 diabetes that could reduce or eliminate some diabetics' reliance on daily insulin injections, closed a $44 million series A led by MPM Capital. Combined with a new partnership with Novartis AG, of Basel, Switzerland, the funds are expected to carry the program through clinical proof of concept. The round follows a seed financing and consists of equity and strategic funding. Fidelity Biosciences, Arch Venture Partners and Medtronic also took part. (SeeBioWorld Today, March 25, 2015.)

Also in the discussion was Stephen Potter, chief business officer of Gainesville, Fla.-based Applied Genetic Technologies Corp. (AGTC), which in July entered a potential $1 billion deal with Biogen Inc., of Cambridge, Mass. The arrangement brought $124 million up front for AGTC, with more later if milestones are met. Two main development programs stand at the forefront of the deal: a clinical candidate for X-linked retinoschisis and a preclinical prospect for the treatment of X-linked retinitis pigmentosa. Not part of the deal is an early research effort in achromatopsia, an inherited condition caused by mutations in any of several genes and associated with visual acuity loss, extreme light sensitivity resulting in daytime blindness, and reduced or complete loss of color discrimination. (See BioWorld Today, July 6, 2015.)

MAKING THE CASE FOR PAYERS

"I can remember 10 years ago, when we did our first gene therapy product at Genzyme," Potter said. "It was easy. You took a wild-type AV2, you had a gene, and you squirt it in the eye. Everybody's going to see. You changed the world. I would argue that was [version] 1.0. We're probably at 2.0 now." AGTC has "what we need today," a gene of interest, a vector and promoters, he said. "I think we all recognize that we're in the early days here," shooting for version 3.0. "A lot of us are going after things that we can leverage as the technology exists today, whether that's hemophilia [as with Baxalta] or ocular diseases," he said. "There's a whole range of other things that gene therapy should be good for," but a lot more research has to be done. AGTC deploys adeno-associated virus vectors.

With regard to manufacturing, moderator Brock Reeve, director of the Harvard Stem Cell Institute, asked whether it's "a beast," as some suggest, or "eminently controllable." Baxalta's Borriello said chemistry, manufacturing and controls (CMC) "is one of those things that, when it's working well, nobody thinks about it. But these new technologies have so many components that the problems are really formidable. The approach we take, and it's only our approach, is that we have all of our manufacturing in-house. And we do that because we know how integral the CMC package is to the approval of any drug. We also, though, have an eye toward outsourcing these things eventually, because the world is more specialized than it used to be. We don't have to have everything under one umbrella. Just like people used to make all their own antibodies, and now there are plenty of third-party manufacturers who make an excellent product. You just [need] the money to pay for it. I think that's probably where [Baxalta is] going to go," though the company will need a well put-together "package and the ability to transfer the manufacturing know-how that you've developed confidentially," he said.

The bar for success is "getting higher all the time," Borriello said, "because the existing therapies are really good, and their use improves with clinical practice." An economic case must be considered early. "We'd all like to go into a field where there's no competitor," he said, and cited the upcoming chimeric antigen receptor T-cell treatments that target "truly an unmet medical area" by way of a new avenue. "I know early stage companies don't like to think about [economics], but for those of us who work in companies where we have no exit strategy except to sell the product on the market, it's very much top of mind," he said. "There's nothing like being able to say, 'This person is alive because of this therapy.' I think that's something everybody can get behind – senators, representatives in Congress and patient groups."

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