Why Fibrosis is a Hot Area for Pharmaceutical Research

By Peter G. Traber, M.D. on October 21, 2015

Bristol-Myers Squibb ($BMS) recently paid $150 million for the exclusive right to acquire Promedior, a clinical-stage biotechnology company in the midst of a Phase 2 trial on the treatment of idiopathic pulmonary fibrosis (IPF) and myelofibrosis (MF). If clinical trials are successful, the deal could be worth as much as $1.25 billion. This is just one of a number of fibrosis-related acquisitions for BMS over the past few years, and BMS is not the only company active in this market. Fibrosis is a hot area right now. But why so?

The scientific community has known for a long time that fibrosis is a common final pathway for many different diseases. An investigator at the NIH suggested in 2004 that as many as 45 percent of the deaths in the United States are related to fibrosis (1). That would include, in addition to liver fibrosis, heart, kidney, lung, skin, and arterial fibrosis – all organs that can be scarred as the result of a chronic disease, which then leads to organ failure and death.

While we can certainly work on curing each individual chronic disease that causes fibrosis, another approach would be to inhibit the fibrotic process. This approach could potentially be applied to a lot of other diseases as well — it’s been something of a Holy Grail in medicine for decades.

It’s a great idea. Unfortunately, there hasn’t been very much progress in the development of anti-fibrotic agents, until now.

Recently, there has been promising work in agents that appear to inhibit fibrosis — for example, our own GR-MD-02, which in our preclinical studies has shown to not only prevent fibrotic damage, but even reverse it. I think these breakthroughs are happening now because the medical community is coming to understand that fibrotic diseases, such as NASH, are complex conditions that require agents that affect multiple pathways in the fibrogenic process.

Let me give an example. There are many important cytokines in the inflammatory process, so it might make sense to inhibit one of them and see how that changes the inflammatory or the fibrotic process. However, by doing that, you are ignoring dozens of other cytokines that are also involved in the inflammatory process. Even if you inhibit the one, you’re not having any impact on the other cytokines involved.

Therefore, agents that address a number of different cell types in the liver that express a wide range of cytokines and fibrotic mediators may be more effective than a pinpoint attack on a particular cytokine or mediator. GR-MD-02 appears to affect macrophages as well as activated myofibroblasts in the liver, which inhibits a wide range of different fibrotic processes. It may be that affecting master regulatory cells involved in inflammation and fibrosis is going to be more effective than affecting any individual mediators.

But as I pointed out, fibrosis is a problem in many other organs than the liver. My sense of it is, if you’re going to have a drug that is robust for a particular organ fibrosis, it’s more than likely going to work for other fibrotic diseases. That’s one of the reasons why we have done pre-clinical studies of GR-MD-02 in lung, kidney and heart, and it’s shown an effect in those as well. That is also, I suspect, part of BMS’ calculations in acquiring Promedior. IPF and lung fibrosis is an indication that creates a large enough market on its own, but the potential to address a disease process involved in 45 percent of the deaths in the U.S. can be found in the background of any fibrosis drug.

That is one of the things that makes GR-MD-02 different than many of the other drugs being developed to address NASH and fatty liver disease. Most of the dozen or so compounds don’t address the core fibrotic process, so even if they work in NASH, they’re not likely to work elsewhere in the body. Only the truly anti-fibrotic drugs like GR-MD-02 have the potential to address fibrosis in other organs.

These “CEO Perspectives” will be a regular feature of our communication activities and may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events and use words such as “may”, “could”, “expect” and others. These statements include those regarding the hope that Galectin’s development program for GR-MD-02 will lead to the first therapy for the treatment of fatty liver disease with advanced fibrosis and cirrhosis. For a discussion of additional factors impacting Galectin’s business, see the Company’s Annual Report on Form 10-K for the year ended December 31, 2014, and subsequent filings with the SEC. You should not place undue reliance on forward-looking statements. Although subsequent events may cause its views to change, management disclaims any obligation to update forward-looking statements

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