Thoughtleader: Martin Mattingly, Ambrx - Pharmaceutical Executive


Thoughtleader: Martin Mattingly, Ambrx

Pharmaceutical Executive

With our first two products, we're attaching PEG (polyethylene glycol) molecules, which are standard in the industry to lengthen the time-activity of proteins. But our technology allows us to attach the PEG molecule exactly where we want it—whereas other companies are using technology that limits them to the natural amino acids that are already chemically reactive, because that's the only place that the PEG molecule will go.

We can insert that amino acid wherever we like—usually in multiple places—and then we test the molecules. We can play with it, attach it in multiple places, and see which one's the best in animals before we put it into humans.

How will this technology change the way biologics are developed?

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It enables companies to develop protein drugs the way they've always developed small molecules, and that is simply a capability they do not have today. And with this technology, they can make 50 different versions of a protein that are different only in a single site of substitution. And then they can test those molecules with lab assays and in animals and then pick the best molecule to go into humans. That's what everybody does with small molecules and nobody can do with proteins.

We are in active discussions with a number of the major pharmaceutical companies that are committed to proteins, and I think it's safe to say there's a tremendous amount of interest and enthusiasm in the technology.

How might ReCODE improve existing products?

Take a really exciting area right now: antibody fragments. The antibody market has really become huge, with a lot of successful cancer antibodies and arthritis antibodies that are on the market.

Researchers are now looking at using antibody fragments, which are a part of the full antibody but smaller, less expensive to manufacture, and might penetrate tissues more easily, for instance, in treating diseases like cancer.

The problem with them is they don't last very long in the body. They get chewed up very quickly, before they can really have an effect.

That's an area that we're working on. We have two programs right now with pegylated antibody fragments. Using our Ambrx glue, we can attach a molecule to the fragment that will allow it to last longer and protect it so that it has enough time to be active in the body.

Separately, we also have a lead project that is a weekly version of human growth hormone. All of the current products are daily, so we're applying our technology to growth hormone so it only has to be given on a weekly basis. We'll start clinical trials within the next six-to-nine months with that program.

At what stage of a drug's clinical life will you begin to look for partners?

Generally speaking, if you have the ability and the finances, it's better to carry a clinical asset as far as you can before you partner it. The value keeps going up. If you partner your own products very early, you simply do not get the same amount of value for it. So if you believe in your product, which we do, it's better to take on some risk and hopefully reap greater rewards.

Now, other types of partnerships happen much, much earlier. If a company is working on its own existing proteins, we can then work with them early in the development process to take their products and optimize them with our technology. And those are some deals that we're looking at right now.

How many partnerships have you done so far?

So far, Roche is our only partnership. We're a very young company. We're less than three years old at this point. We anticipate in the next six to nine months signing several additional partnerships. We're in very active discussions right now with multiple companies.

It's been a very rapid rise. One of the things that we are most proud of is that two years after we started lab work here at Ambrx, we were manufacturing our first modified protein, which is the growth hormone, at a scale that could be commercialized. And we will put our first modified protein in the clinic almost three years after we started.

In a short period of time, we did something that is very difficult to do in the pharmaceutical industry, and that is take a core technology platform that has never been used before and apply it rapidly to products.

Nobody wants to wait 10 to 15 years for you to prove that your exciting technology can actually make a better product. And so that's why we started from the get-go and focused on products and, again, we'll put one in a clinic very quickly.


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