Biotech Values

[Biowatch]

GTCB (Tom Newberry) excerpt from TWST

http://archive.twst.com/notes/articles/abz603.html

TWST: We would like to begin with a brief historical sketch of the company and a picture of the things you are doing at the present time.

Mr. Newberry: GTC Biotherapeutics was originally spun out of Genzyme Corporation back in 1991, and we went public in 1993 as Genzyme Transgenics Corporation. We've been developing transgenic technology as a production platform for the development and commercialization of proteins that are either difficult to express in traditional bioreactor- based production or are required in very large volume where you can use the economics of transgenics to your advantage. In 2002, we changed the name to GTC Biotherapeutics, a recognition of our growing independence. The lead program is a recombinant form of human antithrombin. Antithrombin is a blood protein that is normally in the bloodstream to help balance the coagulation system so that you get clots when you want them, but not when you don't. And it can be used therapeutically both as an anticoagulant and as an anti-inflammatory agent. This compound has been trade-named ATryn, and it is now in for review and hopefully approval in Europe. We've just begun establishing our Phase III clinical trial here in the United States.

TWST: What is the value of transgenic technology?

Mr. Newberry: What transgenic technology is involved in, at least the way we apply it, is taking the DNA for a therapeutic protein of interest; in the case of our lead program, it happens to be a piece of human DNA for human antithrombin. We link that DNA to a milk-promoting gene, a protein that's dominant in the milk ' beta casein. We take that entire construct, and we insert it into the genome of an embryonic animal; in our case, it's typically a goat. That DNA is incorporated everywhere in the animal, but since it's linked to the milk promoting gene, it's only switched on during lactation. So the animal gestates, is born and matures. When it becomes sufficiently mature, we get it pregnant, and when it delivers its kid, it starts producing milk. In the milk is the therapeutic protein of interest. You simply then milk the animal and purify the milk to get to the therapeutic protein and then administer it as you would any other biologic drug, which is typically by injection.

Now, we happened to choose goats for a couple of reasons. One is that they are actually reasonably fast in gestation. They are born in about five to six months from conception. Then they reach sexual maturity at about another six to seven months. So every year, you have a new adult animal, so after 18 months a particular animal is producing product for you. And the goat will also produce relatively high volumes of milk, about 2 to 2.5 liters a day. That's not as much as a cow, which does 20 liters a day; we do actually use cattle as well. But the downside to cattle is they can take a lengthy period of time; they could take on the order of three years and more to produce the first milk versus 18 months. And they are not quite as fast as mice and rabbits, but on the other hand you produce a lot more milk. So the goats represent a very interesting optimum balance between speed and volume.

The way we apply this is not to go head-to-head with the traditional technology. Traditional technology is primarily represented through Chinese hamster ovary cell production where you have a cellular organism of some type, typically mammalian, that you put into a bioreactor. You culture it up, very similar to what we do with the animals; you transfect some DNA into it; you are coaxing it to try to express out into the surrounding biomedia. You dump the bioreactor, and you purify to get to your protein of interest. That process is well proven. It performs very well in a wide number of situations, but there are classes of products that don't express well in them. They are too complex or they become membrane bound or they don't express well on that type of a bioreactor setting.

The blood proteins in particular fit into that category ' antithrombin. We are also doing a program in alpha-1 antitrypsin, a recombinant form of that blood protein. Albumin ' we have a program there. There is a whole number of blood proteins that just don't express well in traditional bioreactor technology, which is why there is a blood industry that exists today, many decades after its inception.

By applying this technology to these known products to make recombinant forms, we think we can deliver two values. One is in releasing the supply constraints. One of the issues around a blood product is that you can only make as much of it as the blood supply that exists, regardless of how effective your fractionation process is. There are only a certain number of people who donate the blood, and that's all the product you can make. Many of these blood products have actually very high therapeutic value that's underdeveloped simply because there isn't enough of a supply. The second element that we think we can bring to this is that by developing through this technology, we are establishing a well-characterized single recombinant source of the material.

Compared to the challenges that exist in the blood supply today, such as collecting donor blood from a wide number of people who have been all over the world and may not even be aware of things they have been exposed to. So we think we can get to a source that's well characterized and that has an assured level of safety to it.