AbbVie, Maker of World's No. 1 Drug, Bets on Synthetic Biology Startup

[neversickanymore]

AbbVie, Maker of World's No. 1 Drug, Bets on Synthetic Biology Startup
Luke Timmerman
FEB 10, 2016

AbbVie has the top-selling drug in the world, a hit for inflammatory diseases. But as its patents age, it’s placing a bet on an edgy little MIT spinout that could, at least conceptually, do an even better job of treating inflammatory diseases of the gut.

Cambridge, Mass.-based Synlogic, a synthetic biology company built on research from the labs of James Collins and Tim Lu at MIT, is announcing today it has struck a multi-year R&D collaboration with AbbVie ABBV +2.84%. Financial terms aren’t being disclosed, but AbbVie is getting worldwide rights to Synlogic’s technology for treating inflammatory bowel disease, and the research teams will focus on Crohn’s disease and ulcerative colitis.

The idea is a wild one. Synlogic essentially wants to take a live bacterium, like a probiotic, and program in some specific genetic circuitry that no other drug on the market contains today. With the genetic circuits programmed just so, the bacterium can sense the ever-changing conditions it encounters in the body, and adjust the dose of a drug based on what’s needed in the moment. (For more details on the science, subscribers can see “Why a Pfizer R&D Exec Joined Synlogic to Make Therapeutic Synthetic Life” in Timmerman Report.)

Real-time dose adjustment in the body is especially tantalizing for the treatment of autoimmune diseases, in which the immune system goes haywire and attacks healthy tissues. These inflammatory diseases like the ones treated by AbbVie’s blockbuster adalimumab (Humira) tend to wax and wane, with unpredictable flares that can be painful and disabling. Instead of bluntly suppressing the immune system all the time to prevent that from happening, Synlogic’s drug could stay in the gut for a day or two, and do nothing when nothing is needed. It would release the business part of the anti-inflammatory drug when the body needs to counteract a flare.

“You could take a synthetic biotic every day, like a probiotic,” said Jose-Carlos Gutierrez-Ramos, CEO of Synlogic, and a former Pfizer executive. “Before you have a flare, the synbiotic senses you’re having a flare, and it’s activated.”

Jim Sullivan, AbbVie’s vice president of pharmaceutical discovery, said in a statement: “AbbVie is committed to collaborating with scientific leaders with new technologies and therapeutic advances that complement AbbVie’s internal expertise.”

AbbVie, because of its long experience with Humira, knows much more about the Crohn’s and ulcerative colitis market that any little company possibly could. Nuances in the patient populations, connections to the expert physicians, understanding of what it takes to win regulatory approval and win reimbursement from payers are all there at AbbVie, Gutierrez-Ramos said.

That knowledge helps AbbVie see where the field is headed. Today, it’s OK for AbbVie to have a biologic drug targeted at the TNF inflammatory protein that delivers a 15-20 percentage point advantage in remission rates compared with placebo. But by 2025, when Synlogic’s products could reasonably be expected to reach the market, the bar will be higher for patients and payers. A successful drug will need to beat a placebo by 40 to 50 percentage points on remission rates, Gutierrez-Ramos said. That’s the goal.

continued here http://www.forbes.com/sites/luketim...ogy-startup-can-keep-it-going/2/#7283130bf3dd

 

[aced126]

Neat idea. Is there any more detailed information on this idea? Like what proteins the genetic circuitry will code for?

The picture I have in my brain right now is as follows: when the internal environment of the human changes such that the drug is required, the bacteria will also start transcripting a gene necessary to cope with the environmental changes. In doing so it also transcripts the engineered gene which might code for an enzyme to break down the drug (maybe this gene could come from Fungi which feed saprotrophically). How then is the enzyme supposed to leave the bacterial cell? I cannot think of any examples where hydrolytic enzymes are secreted by bacteria, but maybe I'm wrong. Or maybe the drug could be contained within the bacteria itself.

 

[serotonin2A]

Neat idea. Is there any more detailed information on this idea? Like what proteins the genetic circuitry will code for?

The picture I have in my brain right now is as follows: when the internal environment of the human changes such that the drug is required, the bacteria will also start transcripting a gene necessary to cope with the environmental changes. In doing so it also transcripts the engineered gene which might code for an enzyme to break down the drug (maybe this gene could come from Fungi which feed saprotrophically). How then is the enzyme supposed to leave the bacterial cell? I cannot think of any examples where hydrolytic enzymes are secreted by bacteria, but maybe I'm wrong. Or maybe the drug could be contained within the bacteria itself.

A better example of how this would work would be to think about how a bacteria that secretes insulin could be used to treat diabetes. You could design the level of insulin secretion to be regulated by glucose concentration in the environment. They are thinking along those lines, but for inflammatory diseases.

 

[aced126]

A better example of how this would work would be to think about how a bacteria that secretes insulin could be used to treat diabetes. You could design the level of insulin secretion to be regulated by glucose concentration in the environment. They are thinking along those lines, but for inflammatory diseases.

How does insulin from GM-bacteria leave the cell?

 

[serotonin2A]

How does insulin from GM-bacteria leave the cell?

Easiest way would be for it to hitch a ride on the mechanisms that bacteria use to excrete other proteins.

http://iai.asm.org/content/80/6/1948.full

 

[Kittycat5]

I think the two diseases they are tackling currently, PKU and UCD, work more on a model of engineered bacteria that take up the substances into their cells and replace the body's organs as places where these can be metabolized. That seems even simpler than releasing an enzyme or drug from within.

However, I imagine serotonin2a idea is similar to what needs to occur with the Abbvie partnership as they undoubtedly will be looking to utilize their drugs and expertise on UC patients.