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Case Study: TG101348 Development - TargeGen, Inc.

The 2005 discovery of the V617F mutation of JAK-2 by several distinguished research groups including Dr. Gary Gilliland at Harvard created a surge of interest in commercial JAK-2 inhibitor development for the treatment of myeloproliferative diseases and a dramatic expansion of academic research interest in this field. As of this date, no approved drug exists for the treatment of polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis, which collectively constitute the major myeloproliferative diseases (MPD) affecting approximately 250,000 patients annually in the United States alone.

Shortly after the discovery of V617F, a small company San Diego based TargeGen, Inc. initiated a rational drug design program whose goal was the development of an oral, potent and highly specific JAK-2 inhibitor. This effort proved to be highly successful and led to the discovery and development of TG101348. The development path of TG101348 is unusual from the perspective of how quickly the drug advanced from raw discovery to human clinical trials and how this rapid advancement was facilitated by industry-academia cooperation and interaction.

The V617F mutation discovery was first published in mid 2005. By early 2006, TargeGen had internally developed several interesting drug candidates for pre-clinical testing. By late 2007 and IND had been submitted to FDA and by February, 2008 a specific drug candidate TG101348 was in human clinical trials at six major cancer centers in the United States. As of October, 2009 this compound had completed a 59 patient Phase I/II clinical trial the results of which are scheduled for presentation at the 2009 annual ASH Meeting in early December. Earlier preliminary clinical results pertaining to this compound were presented at the European

TargeGen’s first step in the development of TG101348 was to reach out to the academic thought leaders in this field to develop a specification which would describe the necessary characteristics of a drug that would be clinically useful in the intended field of use. In the process important relationship were formed with key clinician scientists at Harvard, the Mayo Clinic and with Dr. Catriona Jamieson at The UCSD Moores Cancer Center. Once the company had defined its design objectives and developed a drug candidate, the academic relationships were critical toward carrying out proof of concept studies with the TargeGen compound. The results of these studies then provided the necessary justification for advancing the compound human clinical trials.

The April 2008 Issue of Cancer Cell is unusual in that it contains two articles from two separate research groups located on opposite end of the country pertaining to the same compound TG101348. One of these was from the Gilliland led group at Harvard who looked at the compound in internally developed pre-clinical models of PV, the other was from the Catriona Jamieson led group at UCSD whose research with the compound focused more on stem cell related issues and the drug’s effect on hematopoesis. These two bodies of research laid the foundation for the ultimate clinical development of TG10348.

The close proximity of TargeGen to UCSD has led to easy, frequent, and highly productive collaboration with Dr. Jamieson and her Moores Cancer Center team. TargeGen was able to provide some research funding for these research efforts at UCSD but the project was greatly aided by additional funding to UCSD from CIRM as UCSD was one of the early recipients of CIRM funding.

The story of the clinical development of TG101348 remains a work in progress as the compound progresses towards approval for commercial sale however the story to date provides a unique example of how the goals of industry and academia can be complementary and synergistic and how this kind of cooperation can significantly reduce the typically long lead time required to make worthy drug candidates available to patients who need them.

The UCSD/TargeGen collaboration and a combination of TargeGen and CIRM research funding has led to more rapid advancement of TG101348 to human clinical trials. Patients with a life threatening disease have benefited through access to one of the first experimental specific therapies for their disease. UCSD has participated as one of TargeGen’s clinical trial sites. The success of the TargeGen collaboration with UCSD was used as one point of justification for additional CIRM funding which has been awarded to UCSD. A portion of the new CIRM funding will be used to test TG101348 for potential utility in the treatment of other hematological malignancies. All of this was not an accident but rather the product of rational goal oriented cooperation designed to benefit all involved.

Peter G. Ulrich
President, CEO and Co-Founder
TargeGen, Inc.