What You Need to Know About Metacrine

What You Need to Know About Metacrine
December 2, 2015
By Mark Terry, BioSpace.com Breaking News Staff

Metacrine is privately held and built on technology licensed from the laboratory of Ronald Evans at the Howard Hughes Medical Institute at the Salk Institute. The company has two distinct programs, both targeting diabetes, non-alcoholic steatohepatitis (NASH), as well as other metabolic and liver disorders.

Evans’ work involved the discovery of nuclear receptors and mechanisms of hormone signaling. Hormone receptors are involved in controlling sugar, salt, calcium and fat metabolism, as well as reproductive physiology. They are the primary targets in the treatment of breast cancer, prostate cancer, leukemia, osteoporosis, inflammation and asthma.

The company as founded by Evans, Rich Heyman, formerly the chief executive officer of Seragon Pharmaceuticals, and Michael Downes, a senior staff scientist in the Gene Expression Laboratory at Salk Institute for Biological Studies.

“One of our programs,” Metacrine Chief Executive Officer Neil McDonnell told BioSpace , “is based on some work that Evans’ lab did on a small molecule, FXR agonist. It’s a nuclear hormone receptor, which is what Ron Evans is well known for.”

The compound has shown interesting metabolic effects on mice, which lost weight and became sensitized to insulin. But of big interest is that the compound appears to function on gut hormones and signals to the liver. “From a drug safety development perspective,” McDonnell said, “a drug that isn’t actively circulating is nice from a safety standpoint.”

The other program involves fibroblast growth factor 1 (FGF1). Evans published a paper in Nature in 2014 about how FGF1 appears to help the body respond to insulin. “Through a lengthy process,” McDonnell said, “they proved that FGF1 was similar to drugs like Actos and Avandia and had a similar effect. What’s nice is it doesn’t seem to be the same mechanisms in which the toxicities of those drugs occur. So you don’t see weight gain, you don’t see fractures or bone loss, or edema.”

Company Leadership
Neil McDonnell—chief executive officer of Metacrine. McDonnell has more than 20 years of experience in top-level medical research, development and delivery companies. Prior to joining Metacrine, he was senior vice president and therapeutic area leader for cardiovascular and metabolic diseases at Takeda Pharmaceuticals . Before that, he held strategy and research-and-development positions in the Global Health Program at the Bill & Melinda Gates Foundation, the U.S. State Department, and at biotech companies ZymoGenetics and Immunex.

Trisha Millican—chief financial officer. Prior to Metacrine, she was the senior vice president of finance at Seragon Pharmaceuticals until it was sold to Genentech /Roche in August 2014. Before Seragon, she was the vice president of finance at Aragon Pharmaceuticals until it sold to Johnson & Johnson in 2013.

Nicholas Smith—senior vice president, chemistry. He was the vice president of chemistry at Seragon Pharmaceuticals, and before that, Aragon Pharmaceuticals.

Eric Bischoff—vice president, business operations. Before joining Metacrine, he was senior director of business operations and contracts at Seragon Pharmaceuticals. Before Seragon, he was director of operations at Aragon Pharmaceuticals.

Brandee Wagner—director, biology. Prior to joining Metacrine, she was a team leader of a group developing an anti-miR targeting microRNA-103/107 for nonalcoholic steatohepatitis (NASH) in patients with Type 2 diabetes at Regulus Therapeutics .

Company Financing
In August 2015, Metacrine raised $36 million in Series A financing. Participants included Arch Venture Partners, EcoR1 Capital, Polaris Partners and venBio. “The financing round,” said McDonnell, “is going to be used to develop these two programs and allow us to name development candidates.”

As described above, Metacrine is essentially working on two preclinical development programs. One is an FXR agonist. The other involves FGF1. “It’s up to us now to prove,” said McDonnell, “that we can see all the benefits that have been shown with other FXR compounds…. They have clinically validated activity in NASH, and that makes ours an interesting compound. We took it, replicated a lot of the Evans’ lab data, and are working on making a better compound into a drug.”

The second program, involving FGF1, would be a treatment for Type 2 diabetes. “It’s a therapeutic protein. You give it in an injection. It looks like it would be a once-a-week injection without having to do any modifications by way of how it works. Single-shot effects would last about a week. Both programs are in preclinical development. Evans’ lab did fantastic foundational work and we have a strong team here that will take that scientific work and turn them into drugs,” McDonnell said.

Market Competition
First glance would suggest that Metacrine is working in a well-marked out territory of insulin treatments, but McDonnell says he doesn’t view insulin as a competitor. “This is an insulin sensitizer,” he told BioSpace. “There are a lot of classes of drugs that you can use to treat diabetes, but only TZDs (thiazolidinediones) are true insulin sensitizers and most of the other drugs work on the other side of the problem—they work on insulin production.”

He said that what they’re working on is a new class of drugs and an important one, “which we think will fill a need around insulin sensitizers. In that respect, I would say it’s a largely open field.”

Dollars and Deals
Metacrine is a very young company, essentially launched in August 2015. McDonnell said there has been a lot of companies interested in their work, “but it’s early and mostly what we have is great data out of Evans’ lab. We’re starting to generate our own, but we’re working primarily on the science right now.”

What to Look For
The focus now is on identifying development candidates and generating proof-of-concept data. “Over the next couple years,” McDonnell told BioSpace, “that’s where we want to be and I’m convinced we can generate proof-of-concept pretty early in both programs and convince people that it will deliver on what’s come out of the research labs.”

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