Metabolex, Inc., a privately held biotechnology company, has entered into a comprehensive global strategic agreement with Ortho-McNeil, Inc., a Johnson & Johnson company, and will collaborate on the development and commercialization of multiple programmes addressing metabolic diseases, including type 2 diabetes, obesity and dyslipidemia.
The agreement includes Metabolex's two clinical compounds, metaglidasen and MBX-2044, and additional follow-on compounds for which Ortho-McNeil has received an exclusive license for worldwide development and commercialization.
The transaction will provide Metabolex with $40 million in equity and convertible financing. Metabolex is eligible to receive up to $508 million for achievement of specified development and sales milestones.
As part of the agreement, Metabolex will conduct the ongoing phase 2/3 study of metaglidasen and the phase 1 trial of MBX-2044 with clinical, regulatory and technical support from Ortho-McNeil. Metabolex will pay the development costs for metaglidasen through the end of the phase 2/3 study, and Ortho-McNeil will pay the other costs of development, marketing and sales thereafter. Ortho-McNeil will pay the development and marketing costs related to MBX-2044.
Metabolex retains co-promotion rights for all compounds in the United States and is eligible to receive double-digit, tiered royalties on all product sales up to 21 per cent.
In addition, as part of the transaction, Metabolex gains exclusive license to a PPAR-delta agonist program, including RWJ-800025, which has completed Phase 1b clinical testing, and a cannabinoid receptor-1 inverse agonist clinical programme, which targets obesity. This agreement also includes a target collaboration in which Ortho-McNeil and Metabolex will work together to screen metabolic disease targets identified by Metabolex.
Completion of the transaction is subject to expiration of the applicable waiting period under the Hart-Scott-Rodino Act.
"This agreement enables Metabolex to build a significant franchise in metabolic disease. Not only does the agreement include development and commercialization of our lead best-in-class type 2 diabetes products, but it also enhances and broadens our mid-stage clinical programmes and advances our pipeline with the screening collaboration on novel targets capable of producing future, first-in-class therapies," said Harold E. Van Wart, Ph.D., president and CEO of Metabolex. "Our agreement with Ortho-McNeil provides us with financial resources and clinical development and commercial expertise, while allowing us to lead clinical development of our two lead product candidates."
"Diabetes and obesity affect hundreds of millions of people worldwide and are growing in incidence," said Garry Neil, M.D., group president of Johnson & Johnson Pharmaceutical Research and Development, LLC. "We are committed to developing improved treatments for metabolic diseases, and Metabolex's expertise and portfolio of potential high-value product candidates for metabolic diseases make it an ideal fit for our strategy of collaborating with best-in-class companies."
]Metaglidasen and MBX-2044 represent a novel class of insulin sensitizers that has the potential to markedly improve the standard of care for the treatment of patients with type 2 diabetes. Earlier this quarter, Metabolex initiated a Phase 2/3 study of metaglidasen. Metabolex plans to initiate a clinical proof-of-concept study of MBX-2044 later this year.
Phase 1b clinical testing of RWJ-800025 demonstrated that the compound may have a favorable safety profile and changes in efficacy parameters that suggests utility in dyslipidemia and type 2 diabetes. Metabolex plans to begin Phase 2 trials next year after completing toxicology studies.
Insulin resistance is an underlying cause of type 2 diabetes, and insulin sensitizers can both treat and delay the progression of the disease. The currently marketed insulin sensitizers, which are from the thiazolidinedione (TZD) chemical class and are full PPAR-gamma agonists, have worldwide sales of nearly $4 billion. They represent an attractive treatment option for type 2 diabetes because they target insulin resistance, and may preserve the function of pancreatic beta-cells (the source of insulin). However, these drugs exhibit the dose-limiting side effects of weight gain and edema, compromising patient compliance. Furthermore, currently marketed insulin sensitizers carry a warning of increased risk of congestive heart failure due to fluid retention.
Metaglidasen and MBX-2044, selective PPAR-gamma modulators (SPPARMs), have a different chemical structure and method of action from the TZD insulin sensitizers. As a result, they may be able to treat insulin resistance with a side effect profile that is superior to that of the TZDs. Results presented at the American Diabetes Association's 65th Scientific Sessions in June 2005 showed that metaglidasen was well tolerated without an increase in weight gain or edema. Phase 1 clinical trials of MBX-2044 have shown that it is well tolerated and has favourable pharmacokinetics.