Replies to post #185181 on Biotech Values

[DewDiligence]

[Piper Jaffray 2015 prediction]: Gene therapy cures blindness…

[biowatch]: Not all types of blindness.

Good point.

[poorgradstudent]

Re: heart failure / gene therapy success

2. Heart failure explodes on the biopharma scene with gene therapy success

Who is working on it? What projects are in the works? What are they targeting?

I know that BMY and Myokardia are in this area, and Merck is also looking into it.

The primary interest is in sarcomeric proteins like myosin, myosin binding protein-C, actin, etc... They're focusing on the mutations in these proteins found in some hypertrophic and dilated cardiomyopathies. The thinking is that the mutations allow them to streamline the clinical trial process, running smaller and more focused trials with a relatively homogenous patient population to increase chances of success.

However, none of these programs are anywhere near showing clinical gene therapy success next year. The companies are throwing around various sorts of strategies to target these mutations, most of which I'm rather unexcited about. In addition, some of their targets are junk (see: myosin binding protein-C) and I've indicated as such to some people involved.

Time will tell which direction they go, but nothing is close right now.

[Biowatch]

Dosing & economics of CARTs:

See #msg-106927477

THE DOSAGE DILEMMA

Design is only one piece of making an immunotherapy work. Researchers also must decide how many reprogrammed cells are needed to elicit a safe and strong response against cancer...

...Novartis and its collaborators at Penn have established a dose-ranging system that they expect to describe at the annual meeting of the American Society of Hematology in December. And because doctors now anticipate the side effects, they can try to mitigate serious damage to patients, Azam notes.

Two companies have responded to the dosing dilemma by embedding a gene in the CART that will be activated only in the event of a health crisis. The French biotech firm Cellectis has incorporated a cell-surface marker that, when turned on by the cancer drug Rituxan, causes the number of engineered T cells to plummet. Cellectis hopes to begin human tests of its first treatment a year from now.

Bellicum Pharmaceuticals has added a cell death switch to its CARTs that is activated by an otherwise inert small molecule. The company has shown in animal studies that it can eliminate the majority of the engineered T cells in as little as half an hour, according to Chief Executive Officer Thomas J. Farrell. Bellicum aims to put its first CART with the safety switch into clinical trials by the end of next year.

http://cen.acs.org/articles/92/i40/Immune-System-Fights-Back.html

COMMERCIAL REALITIES

CARTs are proving in clinical studies to be effective killers of blood cancer, but it’s not clear yet if they can be turned into successful commercial products. Currently, most CARTs are made from scratch using a patient’s own T cells, putting the technology at the frontier of personalized medicine. [Personalized medicine might be the ultimate silver bullet, but it is expensive.]

“This doesn’t fall into the kind of paradigm that big pharma uses as they try to develop drugs,” says Steven A. Rosenberg, chief of the National Cancer Institute’s surgery branch, who in 2010 published the first report of a patient responding to CART therapy. “They want vials on a shelf that are stable and can be widely distributed for treatment. And they don’t really care if it costs half a billion dollars to make the first vial, as long as they can make the second vial for a dollar.”
[Years ago, I worked on this in Steve Rosenberg's lab. It is nice to see it work in patients.]

Companies are working diligently to understand how to translate what has primarily been an academic endeavor into an industrial process. Manufacturing CARTs for a wide audience will mean figuring out how to make individualized therapies quickly, consistently, and affordably.

“The thing that has kept many players away from this space is fear of manufacturing,” Novartis’s Azam says. But Novartis believes the challenge is surmountable. Soon after forging its pact with Penn, the company bought a manufacturing plant in Morris Plains, N.J., from Dendreon, a Seattle-based company that developed an approved, but commercially unsuccessful, personalized treatment for prostate cancer. Novartis has since been working diligently on how to ease the complexity and cost of CARTs.

Bringing down the cost of personalized immunotherapies will require improvements at every point in the process. Companies hope that properly designing CARTs will improve potency and cut down on the number of T cells needed to elicit a response. They are also honing the manufacturing process to ensure patients can be treated swiftly and safely.

Etc.