THE LITTLE ENZYME THAT COULD:
INVESTORS BELIEVE IN CRYSTALS

By Jo McIntyre
Small Times Correspondent

Jan. 9, 2002 — Venture investors, pleased with the progress of research and product development at Altus Biologics Inc. in Cambridge, Mass., have contributed $50 million in two parts, the most recent a round of $15 million in December.

The company will use the new money to accelerate development of a drug that shows promise in treating pancreatic insufficiency, a condition that afflicts most sufferers of cystic fibrosis.

Proteins are nanodevices that carry out very specific jobs, said Peter L. Lanciano, Altus president and chief executive. The trick is to control and manage the proteins — a hard thing to do when they are in a solution phase, but as a solid they can be managed in a stable form.

“Our technology allows one to control that very precisely using the crystalline form that can make the molecules work in a wide range of applications. We want to prove it broadly across many industrial and medical sectors and make the technology accessible to corporate partners,” Lanciano said.

One of the product’s medical applications caught the attention of the Cystic Fibrosis Foundation (CFF) last year. In March 2001, Altus received $25 million from the Cystic Fibrosis Foundation Therapeutics Inc., the foundation’s drug development affiliate.

Pancreatic failure afflicts 90 percent of all CF patients. When the pancreas fails, patients cannot digest and absorb food nutrients properly unless they take enzymes orally to do the job, said Chris Penland, director of research at CFF.

When the pancreas doesn’t produce enough enzymes, in kids specifically, it also leads to poor growth and poor ability to thrive because the child doesn’t receive enough calories, added Alex Margolin, head research scientist at Altus.

“So far we have very exciting animal data, but it is always a big step forward to go from animals to humans. Our technology makes very pure and very active enzymes,” he said.

The technique puts a protein into a solid form in an ordered crystalline array, by crystallizing the target enzyme, then chemically cross-linking the molecules to form a CLEC (cross-linked enzyme crystal). The resulting material is insoluble, with good structural integrity. It’s also porous, so the substrate can access all the active enzyme sites.

The process makes a material that retains the catalytic activity of the enzyme while gaining the structural integrity needed to withstand extremes of temperature, pH, proteases and a range of solvents. Other patients who could benefit from this drug are people who suffer from chronic pancreatitis, Margolin said.

Bill Tanner, a biotechnology analyst and managing director at SG Cowen in Boston, said Altus “has no competitors in terms of this technology.” Just about any company in the $20 billion per year biotech market could find Altus’ technology useful.

The technology could be used in industrial manufacturing, where the company has agreements to stabilize proteins as enzymes, as well as in the medical field to improve therapeutic proteins. In fact, Tanner said, Altus can enhance desirable drug characteristics of many proteins.

“Altus’ blended business model combines short-term revenues from strategic technology collaborations with long-term potential revenues from the company’s internal pipeline. Together, these components make Altus a solid investment opportunity,” Denise Pollard-Knight, head of Healthcare Private Equity at Nomura, said in a statement.

Altus expects to launch a personal care product in partnership with an undisclosed European company by the end of next year. Lanciano said the cosmetic product “makes skin look younger and more youthful.”

Other organizations that have announced partnerships with Altus include current partners Triangle Pharmaceuticals Inc. and Abbott Laboratories.

Follow-on investors included CMEA Ventures and China Development Industrial Bank (CDIB), with additional participation from Hotung International Co. Ltd. and the Palladian Group. In the earlier $35 million funding portion announced in October, Nomura International and U.S. Venture Partners served as lead investors, with additional participation from BankInvest and Clariden Bank among others.

Other small tech research supported by the Cystic Fibrosis Foundation involves high throughput screening for drug discovery, which uses robotics, with Aurora Biosciences, a subsidiary of Vertex Pharmaceuticals (VRTX), in La Jolla, Calif.

The foundation is also currently exploring supporting a second phase of drug discovery research with Genzyme Corp., which also uses robotics.

“We also have a structural biology program under way to elucidate the structure of the nonfunctioniong protein in cystic fibrosis, called CFTR (CF transmembrane conductance regulator),” Penland said. The research, which uses robotics and microtiter dishes, is being done by Structural Genomix, a private company, also based in La Jolla.

“The foundation takes the perspective that we have projects peer-reviewed and pursue the high quality and goal oriented ones. We try to be proactive,” he said. “We are encouraged by the progress these companies are making and the advancements being made in the academic world for drug screening as well.”

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