Surprise: INGAP Moves Ahead!

Remember INGAP? Well, the quick overview is that INGAP stands for Islet Neogenesis Associated Protein. I noted it in a posting back in January when I reported that researchers at the University of Florida had announced findings from a study involving the use of proteins as a potential therapy for type 1 diabetes which accomplished something remarkably similar to INGAP -- in their case, the protein Pdx1 or simply PDX stimulated new islet growth. INGAP appears to incent Pdx1 production. More details on the INGAP story is chronicled here for reference:

Spring 2002
Winter 2002
Summer 2003
Spring 2004
Fall 2006
The SPIRIT Research Program
Update on the SPIRIT Research Program

INGAP has something of a checkered history. Although it appears promising, the rights to commercialize it have traded hands a number of times, having once been owned by Procter & Gamble, but P&G dropped it. After perhaps a year or so, the rights were then acquired by GMP Companies. However, things had kind of gone silent for a while, which prompted some of us to speculate what INGAP's future might be. Apparently, Kinexum Metabolics, Inc. has since sublicensed INGAP Peptide from GMP Companies for further clinical trials. Kinexum has continued development under the guidance of Dr. G. Alexander Fleming, a well-known authority on metabolic drug development, who headed diabetes drug review at the FDA for over a decade.

If you recall, the Strelitz Diabetes Research Institute of Eastern Virginia Medical School's Research Director, Dr. Aaron I. Vinik discovered INGAP along with a former colleague, Dr. Lawrence Rosenberg who happens to now work at McGill University in Montreal, Canada.

Well, last week, researchers at McGill University Health Centre (MUHC) reported some further progress on INGAP. They announced a significant donation from John and Pattie Cleghorn to the MUHC Foundation in support of the MUHC's Best Care for Life campaign which will be used to advance research on INGAP. John and Pattie Cleghorn's interest in supporting diabetes research at the MUHC has a personal connection. Pattie herself is a diabetic, as is their young grandson.

"We are thankful to the Cleghorns for this important donation. It represents substantial support for continued basic research and clinical development of INGAP, and eventually for advancing this exciting therapy toward regulatory approval," stated Dr. Rosenberg. "We are very encouraged by on-going research and collaboration with Kinexum Metabolics to advance INGAP into a Phase 2 human study."

Dr. Rosenberg most recently found that INGAP can induce normal human pancreatic duct cells to differentiate into insulin-producing endocrine cells. This discovery will accelerate the understanding of islet biology and the development of additional islet regeneration therapies. Dr. Rosenberg's findings will be presented at an important Keystone conference in April.

Results from the first Phase 2 clinical trials evaluating INGAP in patients with diabetes were presented as late-breaking abstracts at the American Diabetes Association meeting in 2005 by Dr. Robert Ratner.

Dr. Ratner commented in his report, "In these Phase 2 trials for safety of INGAP, clear trends for efficacy have been found and suggest that with appropriate dosage, site of administration and duration of therapy, this approach holds clear promise to evolve into a new therapeutic approach to Type 1 and Type 2 diabetes." He also reported that both people with Type 1 and Type 2 diabetes showed an increase in C-peptide levels indicating that new islets were being formed.

More recently, Kinexum's Dr. Fleming added "INGAP Peptide probably does not affect the underlying immunologic cause of Type 1, but it may by itself overcome the ongoing immune destruction of insulin secreting cells. As safe and effective immunotherapies become available, they are likely to work synergistically with INGAP Peptide to return perhaps close to normal insulin secretion."

On the immunotherapy front, there are several enticing possibilities. One, of course, is Denise Faustman's research, but since clinical trials are only now recruiting, it will be some time before we know if that works. But the JDRF-Eli Lilly announcement from October 2007, in which Lilly announced they had partnered with MacroGenics, Inc. and the two companies have entered into a global strategic alliance to develop and commercialize teplizumab, a humanized anti-CD3 monoclonal antibody, as well as other potential next generation anti-CD3 molecules for use in the treatment of autoimmune diseases, including type 1 diabetes looks promising as a potential option here. As part of that deal, Lilly will acquire the exclusive rights to the molecule. I noted too often, these therapies target mainly the newly diagnosed, but I surmised that the Lilly partnership might push into testing on longstanding patients. Theoretically, its possible that treatment with teplizumab could be used to arrest the immune system's attack on the pancreatic beta cells, combined with INGAP to regenerate beta cells, which suggests an exciting cure possibility could be in the works.

Looks exciting -- stay tuned for more details!