Lonar-Roche deal valued at up to $1.16 billion; focus on RNA therapeutics targeting adipose tissue.
Olicx conducts follow-up studies in obese primates, targeting clinical trial application by the first half of 2027.
Global pharmaceutical giants are aggressively securing ALK7-targeted RNA therapies capable of directly accessing adipose tissue. Following GSK, Roche has now entered the fray to acquire promising drug candidates in this space, while the Korean biotech firm Olicx (226950) continues the independent development of its obesity therapeutic program, "OLX501A." This approach aims to induce body fat loss by regulating the pathways involved in fat storage and lipolysis.
Roche Strikes Exclusive Global Licensing Deal with Lona
Lona Therapeutics announced on the 13th (local time) that it has signed a deal granting Roche an exclusive worldwide license for its ALK7-targeted RNA interference (RNAi) drug candidates. The agreement covers obesity and metabolic disease candidates utilizing Lona’s proprietary platform for delivery to extra-hepatic tissues.
The deal is valued at up to $1.16 billion, excluding royalties. This includes an upfront payment and short-term milestone payments totaling up to $100 million, with an additional $1.06 billion contingent upon the achievement of development, regulatory, and commercialization milestones. Post-commercialization, Lona will receive tiered royalties based on global net sales.
This is not the first instance of a major pharmaceutical company investing in ALK7-targeted therapies. In May, GSK entered into an exclusive global licensing agreement (excluding Greater China) with Siran Bio for their ALK7-targeted siRNA candidate, "SA030," which had already entered Phase 1 clinical trials at the time of the announcement.
Direct Action on Adipocytes: Potential for Combination Therapy
The fundamental mechanism for these candidates involves using RNA interference to downregulate the expression of ALK7 in fat cells. ALK7 is a receptor involved in signaling pathways that govern fat storage and breakdown. By modulating these signals, developers aim to shift fat metabolism.
Lona has set a development goal of reducing fat while preserving lean body mass, including muscle. Because this mechanism differs from incretin-based drugs—such as those in the GLP-1 class that regulate appetite and energy intake—there is significant anticipation regarding potential combination treatment strategies. The benefits of fat reduction coupled with lean mass preservation remain key hypotheses to be confirmed in clinical trials.
The rationale for targeting ALK7 is supported by human genetic research. A study published in the international journal Diabetes revealed that certain variants of the ACVR1C gene, which encodes the ALK7 protein, are associated with a lower ratio of abdominal fat and a reduced risk of type 2 diabetes. While these findings provide a scientific basis for exploring this pathway, they remain distinct from the clinical results required to prove the efficacy of individual drug candidates.
Olicx Advances Primate Studies with Proprietary Delivery Platform
Olicx stated that it is independently developing "OLX501A," a fat-tissue-targeting siRNA program aimed at ALK7, and is currently conducting follow-up studies in obese primate models.
OLX501A is based on Olicx’s proprietary adipose tissue delivery platform, "OASIS-Adipose." The company has optimized its technology to deliver candidates to fat tissue and sustain the suppression of target genes. While Olicx utilizes a different delivery platform than Lona, both share the development strategy of targeting ALK7 in adipocytes.
In obesity primate trial results released on July 30, Olicx reported that the visceral fat volume in the group treated with OLX501A decreased by 29.2%. In contrast, the comparison group showed a reduction of 10.0%, while the control group saw an 11.1% increase. These figures were measured via MRI 49 days after administration, adjusted for baseline and dietary intake.
The study involved two doses of 3 mg/kg of OLX501A and the comparison substance, administered at one-month intervals. As these results are derived from animal studies, the efficacy and safety in humans must be rigorously validated in future clinical trials. Olicx has set a target to submit its Investigational New Drug (IND) application in the first half of 2027.
