Alantos Pharmaceuticals Holding Inc. could receive at least $75 million for out-licensing to Les Laboratoires Servier overseas rights to its lead compound.
Specifically, the diabetes-focused deal provides the French firm exclusive rights outside the U.S. to the oral small molecule ALS 2-0426. In return, privately held Alantos, which will continue to own all rights stateside, stands to receive up-front and potential milestone payments of nearly $75 million, plus double-digit royalties down the road.
That funding stream, explained Alantos CEO Keith Dionne, "allows us to drive the rest of our programs forward without dilutive financing at this point of time." The company, of Cambridge, Mass., has raised about $50 million in two rounds of venture capital financing.
"There's short-term money, we're financing the program and we've got the long-term upside," Dionne told BioWorld Today,
That's because both companies will work together on a joint worldwide development plan through the end of Phase II on the Type II diabetes drug, with Servier shouldering all development costs through that point. After that, Alantos would bear responsibility for further U.S. development expenses and Paris-based Servier would assume costs abroad.
This structure allows Alantos to hold onto the drug's domestic value, Dionne said, which "we wanted to make sure that we maintained downstream" for further partnering plans. In addition, navigating an area of drug development that's "very competitive" in tandem with a partner at this point means that the program's path forward won't slow down. Rather, he said, ALS 2-0426 should advance at "full speed" in clinical and toxicology studies, in parallel with manufacturing and formulation efforts.
Phase II studies are scheduled to start at the beginning of next year.
The compound, which entered Phase I over the summer, inhibits an enzyme called dipeptidyl peptidase IV (DPP-IV). That in turn inactivates glucagon-like peptide-1 (GLP-1), a mediator of blood glucose levels following meals. Drugs of that class have been shown clinically to provide long-term improvement of glucose control, without the risk of hypoglycemia and weight gain. In addition, preclinical evidence suggests that DPP-IV inhibitors protect beta cells and lead to their regeneration, which could affect the progression of Type II diabetes.
Those multiple benefits, Dionne said, underscore the opinion of many who view the drug class as "being the most exciting thing to hit diabetes in a long time."
Just last week, the FDA approved the first DPP-IV inhibitor for the disease, Januvia (sitagliptin, from Merck & Co. Inc.). Another first-generation drug from that class, Galvus (vildagliptin, from Novartis AG), could be approved by the end of this year, Dionne said.
Alantos' drug, a second-generation DPP-IV inhibitor, has advanced quickly. It was first synthesized in April 2005, declared a clinical candidate two months later and entered the clinic this summer.
Dionne said preclinical comparisons between ALS 2-0246 and other DPP-IV inhibitors such as Januvia and Galvus "make us think that ours is the better molecule," both in terms of efficacy and safety, because of improved potency, prolonged duration of action, high selectivity and a distinctive distribution profile. "From what we've seen and what we can compare," he added, "we're very excited."
ALS 2-0426's initial clinical program is designed in two parts. First, a double-blind, placebo-controlled trial enrolled about 50 healthy male volunteers at one U.S. site to examine a single ascending oral dose through a sequential cohort design. It is being followed by a multiple-dose study in healthy volunteers to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics.
Dionne said the studies would serve as early indicators of efficacy, providing a "very good biomarker" of the extent and duration of DPP-4 inhibition. Phase II trials would reveal ALS 2-0426's effects on blood glucose levels.
Upon achieving human proof of concept, the company would look to partner with a large pharmaceutical firm that has a U.S. footprint to carry ALS 2-0426 to market in the U.S. at the same time as Servier does so abroad.
With the diabetes drug's development secured for the near term, Alantos will continue to advance its secondary program toward the clinic, led by an osteoarthritis therapeutic that targets the protease matrix metalloproteinase-13 (MMP-13). Designed to slow and prevent cartilage degradation, it remains in preclinical toxicology studies and should enter Phase I next year. The company owns all rights to that first-in-class program.
In addition, it has earlier-stage MMP-13 inhibitors that also could find use in diseases impacted by the same target.