Theoretical concepts are brought to fruition by our dedicated staff of research scientists with a broad range of backgrounds and skills. Innovative peptide constructs are tested in validated rat and dog models to determine pharmacokinetic profiles and therapeutic efficacy. Closely linked to our manufacturing facility, recombinant expression and purification is rapidly achieved in our in house laboratories, which also include the capacity for immunoassay development.
Currently, we are concentrating our peptide development expertise on advancing the Company’s oral formulation of a recombinantly produced parathyroid hormone (PTH) analog for the treatment of osteoporosis in postmenopausal women, the development of our lead proprietary preclinical metabolic program, UGP281 for obesity and the advancement of UGP302 for the treatment of Type 2 diabetes.
Oral PTH (UGP131) for Postmenopausal Osteoporosis
Shortly after the arrival of Mr. Palmer as CEO, Unigene entered into an amended and restated exclusive worldwide license agreement with GlaxoSmithKline (GSK) to develop and commercialize an oral formulation of a recombinantly produced PTH analog for the treatment of osteoporosis in postmenopausal women. PTH is unique among osteoporosis treatments in that is has an anabolic effect on bone. The Company received an upfront payment of $4 million in December 2010 to cover costs associated with the Phase 2 study, and also received an additional $4 million payment in May 2011 upon completion of Phase 2 patient enrollment. Subsequently, the agreement was terminated in December, 2011 following notification by GSK of its decision not to proceed with the development of oral PTH based on its internal evaluation criteria. As a result, Unigene regained the exclusive worldwide rights to its oral PTH program with no financial obligations to GSK and is actively seeking a new partner.
We commenced patient dosing for the Phase 2 oral PTH study in March 2011 and announced that the study achieved its primary endpoint with statistical significance in November, 2011. The primary objective of the study was to assess the change in bone mineral density (BMD) at the lumbar spine, a clinically validated predictor of fracture risk. This multicenter, double blind, randomized, repeat dose, placebo controlled study included an open label Forteo® comparator arm and a placebo arm and evaluated 97 postmenopausal osteoporotic women for a period of 24 weeks. The study demonstrated once-daily treatment with 5mg of orally delivered PTH resulted in a statistically significant mean increase in BMD at the lumbar spine of 2.2 percent (p<0.001) at week 24 as compared to baseline. The full study results were published online in BONE, the Official Journal of the International Bone and Mineral Society in December, 2012.
UGP281 for Obesity:
In February 2011, we announced our plans to accelerate the development of our lead proprietary anorexigenic peptide, UGP281, a peptide that selectively targets the amylin receptor. An anorexigenic peptide is one that diminishes or controls appetite and offers potential therapeutic benefit to morbidly obese patients. Additionally, the Company is developed a this analog for potential early stage licensing to a veterinary partner for companion animal obesity to help subsidize a portion of the human proof of concept development costs of UGP281.
In multiple-dose pharmacology studies in rats and beagle dogs completed in May 2012, UGP281, administered subcutaneously, produced a dose-related decrease in body weight of 10-15% over a 7-day treatment period. The reduction in food intake was acute and dramatic, falling close to zero at relatively low doses, and was consistent with the targeted pharmacology. Changes in body weight throughout the studies were tightly aligned with decreases in food consumption. UGP281 was well tolerated with no overt adverse findings in the studies conducted to date, and its therapeutic window appeared to be substantial.
These data compare favorably to what has been described preclinically with other weight loss compounds currently, or previously, under development. Additionally, since UGP281 does not bind to serotonin receptors, the risk of unwanted cardiovascular effects is expected to be significantly less as compared to other obesity product candidates. Furthermore, as successfully demonstrated in previous preclinical studies, UGP281 has the potential to be dosed orally and manufactured recombinantly by way of Unigene’s Peptelligence™ technology platform.
UGP302 for Type 2 Diabetes
In October 2011, Unigene and Nordic Bioscience announced the signing of a Joint Development Agreement to progress up to three of Unigene’s internally developed proprietary metabolic peptide analogs through Phase 2 proof-of-concept in humans. Nordic Bioscience discovers and develops innovative medical treatments for serious diseases such as osteoporosis and osteoarthritis, as well as metabolic disorders such as Type 2 diabetes.
Based on the studies to date, Unigene and Nordic have designated UGP302 as the lead compound for further study in the treatment of Type 2 diabetes. Several in vitro assays evaluated the potency of binding of the peptide to various relevant receptors, and additionally, in vivo assays demonstrated the efficacy of UGP302 in preclinical models of diabetes. In all of these studies, UGP302 has demonstrated significantly greater potency than the natural parent peptide from which it was derived. Further development of this peptide is actively ongoing.
Oral Calcitonin for Postmenopausal Osteoporosis
In 2009, we licensed our late advanced clinical-stage proprietary oral calcitonin formulation to Tarsa, a venture capital -financed company founded exclusively to conduct complete Phase 3 clinical testing and prepare our proprietary oral calcitonin formulation for commercialization. We currently own an approximately 16% of Tarsa on a fully-diluted basis. In March 2011, Tarsa announced positive top-line Phase 3 study top-line results for its multinational, randomized, double-blind, placebo-controlled Phase 3 ORACAL trial in postmenopausal women with osteoporosis. The study design and endpoints were agreed with the FDA through a formalized Special Protocol Assessment (SPA) process. Tarsa is also the sponsor of a Phase 2, 48-week, oral calcitonin trial for prevention of bone loss in postmenopausal women with low bone mass. The July, 2012, EMA announced the curtailment of calcitonin product usage in Europe. An FDA Advisory Committee Meeting was held on March 5th, 2013 and the Advisory Committee concluded via a 12-9 vote that the benefits of calcitonin products do not outweigh the potential risks associated with their use. Additionally, the Advisory Committee recommended that fracture prevention data should be required for the approval of new oral calcitonin products in development for osteoporosis prevention and treatment. It is our understanding that the FDA will now take the Advisory Committee’s recommendations under consideration.