Sutro Aims to Deliver Anti-Tumor “Warheads” More Precisely

10/1/13Follow @tanseyverse

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fine-tuning the genetic engineering of a different living cell to produce each new protein that might be of interest as a drug candidate. Sutro, by contrast, can produce any kind of protein using one of its standard cell extracts taken from 70 different strains of bioengineered bacteria, Hallam says. The DNA that codes for the desired protein is added to the reaction vessel, and cell extract components transcribe it into RNA, which the ribosome then uses as a manufacturing template. This means Sutro can rapidly produce an array of many different proteins, and screen them all to find the ones most likely to be effective against a particular illness.

In a demonstration project that took about five weeks, Sutro made 400 variations of trastuzumab—each linked to a toxin at different selected spots—through a genetic engineering maneuver that would have been deadly to a living cell, Hallam says. The tactic involves the use of artificial amino acids that don’t occur naturally in cells, and a non-natural way of reading part of the DNA code. Based on lab tests, Sutro predicts that the best candidate among its 400 experimental antibody-drug conjugates would have the same clinical impact as ado-trastuzumab emtansine, but with a fifth of the toxic warhead load. If a pharmaceutical company conducted a similar study using living cells to manufacture hundreds of such drug candidates, it might take six to nine months, Hallam says.

“This is not just a manufacturing platform,” says Sutro’s CEO William Newell of the company’s cell-free method. “It’s a manufacturing and (drug) discovery platform.”

Both capabilities were tapped last year by Summit, NJ-based Celgene (NASDAQ: CELG) , which is collaborating with Sutro to design antibody-drug conjugates and another new type of double-threat drug called a bispecific antibody, which has two different ways of recognizing a cancer cell or other particular cell type. Celgene, which has not disclosed its disease targets, has also assigned Sutro to manufacture one of its own antibodies.

Since 2011, Sutro has been collaborating with Pfizer on peptide drug candidates, and early this year it signed an agreement with Sanofi Pasteur to develop vaccines. The disease targets of these joint projects have not been revealed.

The deals come with “robust economics’’ such as upfront payments and potential milestone payments and royalties, Newell says. Sutro has raised more than $60 million from investors, and has about 60 employees.

Government agencies and global charities are getting interested in Sutro’s technology as a resource for rapid vaccine development and production in the face of emerging infectious diseases and pandemics, Newell says. The company has developed a method to freeze-dry its cell extracts, which could then be shipped throughout the world and cheaply assembled into manufacturing “pods” as small as a mobile home, he says.

Sutro is also in discussions about the use of its technology to manufacture “biosimilars”—versions of expensive biologic drugs that are losing patent protection.

However, Newell says, the company can’t pursue every avenue at once. He sees the “sweet spot” for Sutro’s current growth in the development of its own antibody-drug conjugates and bispecific antibodies as drug candidates in oncology. Sutro is focusing on an intriguing group of cancer drug targets called immune checkpoints, which can signal the immune system to bypass tumor cells that it might otherwise destroy. Big pharmaceutical companies are also hot on the trail for inhibitors of immune checkpoints, and Bristol-Myers Squibb already markets such a drug, the melanoma therapy ipilimumab (Yervoy). Sutro is aiming to seek FDA permission to start clinical trials for its own drug candidate for targeted tumor therapy by mid-2014.

“Sutro has two ways of delivering a one-two punch: bispecifics and combination warheads,” Newell says.

Bernadette Tansey is a freelance journalist based in Berkeley, CA. Follow @tanseyverse

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  • Jerry Jeff

    My understanding is that full-length antibodies are hard to produce, even in mammalian cells, because the post-translational processing (glycosylation and disulfide bond formation) has to be perfect every time. It’s not hard to imagine how Sutro can deal with the disulfides in vitro, but what about glycosylation?