BioWorld Today Columnist

When I first met Dr. Ed Amento in the early 1990s, he was building an unusual biotech company, one focused on the broad goal of deciphering the underlying biology of connective tissue, the balance between formation and degradation that supports proper function of every organ in the body.

The eventual goal was to create effective treatments for serious disorders including the kidney and lung fibrosis that kills patients with a range of diseases.

Amento came from a high-flying academic background (Stanford, Harvard) and an equally snazzy biotech pedigree (Genentech). He and his cofounders, Dr. Eugene Bauer and Brian Seed, created the scientific and medical backbone of Connective Therapeutics Inc.

Amento learned firsthand the challenges of doing early stage basic research in a venture-backed environment. Not surprisingly, his investors wanted to see product sales in the near future. And also not surprisingly, the basic biology research was not showing signs of generating product sales any time soon.

Connective Therapeutics morphed into Connetics, which in-licensed products for scalp psoriasis and other dermatology uses, spun out its interferon programs into Intermune in 1999, and out-licensed its relaxin technology to BAS Medical Inc. in 2002.

While the company he helped found had to evolve away from the initial research, Amento still loved that translational work, trying to move basic projects like understanding molecular mechanisms of fibrosis from the bench into patients.

He became convinced that it didn’t make sense to put venture money into understanding a basic process. "The risks are so high at the target ID stage that no reasonable person would invest," he said. After trying it in academia and in for-profit settings, he decided to give the nonprofit approach a try in 1996.

Not For Profit

The nonprofit independent research institute turns out to be a popular model in the U.S. Some are very large and well-known: Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center and Scripps Research Institute. There are 89 biomedical members in the Association of Independent Research Institutes (

Amento started the Molecular Medicine Research Institute (MMRI) in 1996 with help from Connetics. "We started in a small building in Mountain View, [Calif.], brought in some folks with their own grants, and used a version of NIH overhead rates to charge them for using our space," he said. "We moved to a building in Sunnyvale, then added a second building."

MMRI’s financing comes from competitive research grants, donations of cash or equipment and sponsored research. While Amento dreams of an endowment that throws off income, federal and foundation grants are likely to stay the key source of funding. The sponsored research grants are part of a unique aspect of MMRI - synergistic sharing of resources with start-up groups.

In-House Programs

The MMRI programs reflect Amento’s continuing interest in the interface between immunology and connective tissue biology, where he looks for the key mechanisms that control connective tissue turnover in tissue repair and in fibrosis. His team is trying to understand regulation of turnover in functional organs - how the body keeps the balance and what happens when things go awry.

One of Amento’s favorite regulators of extracellular matrix turnover is relaxin. Scientists thought relaxin was important only during pregnancy, helping connective tissue loosen so that the growing baby could fit. But experiments with knockout mice deficient in relaxin showed slow, progressive age-related fibrosis throughout the body. Somehow loss of one protein tipped the balance to accumulating fibrosis.

Working With Affiliates

The MMRI also provides up-and-running lab space to groups looking for a temporary home. "It simply evolved into a working model as people asked me about space. About 30 companies have hatched here."

One of the very first groups to work at MMRI, Protigen, is still there. Other affiliates include ChemoCentryx, Threshold Pharmaceuticals, Raven Biotech, and current tenants Applied Genomics, Juvaris and Pharmadyne.

Typically, the affiliates aren’t ready for prime time upon arrival. There is some crucial proof-of-concept work to do before they can raise venture dollars. MMRI provides a setting, unlike incubators, in which companies can walk in the door and do experiments that day - they don’t even have to order pipettes! In-house staff with special expertise can be "rented" by affiliates, avoiding the need to hire.

Dr. Jennie Mather, founder and president of Raven Biotechnologies, appreciated the "plug and play" aspect of MMRI. "This allowed us to start with the idea of a new company in December, incorporate the company the first week of January 1999, move into the MMRI space Jan. 15 and do our first experiment by the 18th. MMRI had a working animal facility, tissue culture space and wet lab space. We could get started on a very small amount of seed money and actually be doing experiments while we were raising the Series A round of financing."

The best part of the affiliates program, from Amento’s perspective, is filling the halls at MMRI with bright, entrepreneurial, dedicated folks. It creates a great environment for him and the other MMRI staff. "We help them at a critical stage of their development, and they bring novel ideas related to our mission," he said.

Scientifically, it’s a great way to be exposed to cutting-edge science in many different fields over the years - almost like a university setting without teaching or academic politics.

A critical component of the MMRI-affiliate relationship is Amento’s insistence on keeping intellectual property out of the equation. The incoming researchers retain all of their own IP. Amento said that he is not looking for a downstream financial benefit from the affiliates at this point - no stock options, no royalty stream. "It’s easier to collaborate because they don’t need to worry about keeping things proprietary," he said.

As the financing environment continues to resist investing in anything earlier than Phase II, incubating your concept in an independent research institute like MMRI to generate that needed proof of concept could be a cost- and time-efficient approach.

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