Roche and Lonza Sign Global Exclusive License Agreement for RNAi Therapy
The race to develop RNA therapies targeting adipose tissue continues to heat up, with global pharmaceutical giants lining up to secure exclusive rights to promising candidates. Following GSK's recent move, Roche has now joined the fray, entering into a global exclusive license agreement with Lonza for its RNA interference (RNAi) therapeutic candidate targeting ALK7. Olikss (226950) is independently developing a similar obesity treatment program, 'OLX501A', aiming to regulate lipid storage and breakdown pathways to induce fat loss.
Targeting Adipose Tissue with RNA Therapeutics
The potential of RNA therapies to directly target adipose tissue has caught the attention of the industry, with major players recognizing the untapped potential in this field. Lonza's RNAi candidate, utilizing its innovative platform for extrahepatic tissue delivery, has attracted the interest of Roche, which aims to expand its portfolio in metabolic disorders and obesity.
Olikss' Independent Development Efforts
Olikss, a South Korean biotechnology company, is making significant strides in this domain. Its 'OLX501A' program, which targets the same ALK7 pathway as Lonza's candidate, is designed to tackle obesity by regulating lipid metabolism. The company's approach, which involves directly targeting adipose tissue, holds promise for a novel treatment strategy.
Future Outlook and Clinical Milestones
With Roche's entry into the RNAi space, the competition to bring these innovative therapies to market intensifies. Olikss, with its independent development efforts, aims to submit an investigational new drug (IND) application for its 'OLX501A' program by the first half of 2027. The company's focus on commercialization and its progress in preclinical studies with obese non-human primates position it as a key player in this emerging field.
Potential Deal Size and Structure
The potential contract, excluding royalties, could reach up to $1.16 billion. With an upfront payment and short-term milestones totaling up to $100 million, the remaining $1.06 billion is contingent upon meeting specific conditions during the development, approval, and commercialization stages. Post-commercialization, royalties will be received based on worldwide net sales, with yield rates varying across different stages.
Previous Industry Interest
This is not the first time a major pharmaceutical company has shown interest in ALK7-targeted therapies. In May, GSK entered into an exclusive global license agreement with Siranbio for their ALK7-targeted siRNA candidate, SA030, excluding the Chinese market. At the time of the contract announcement, SA030 had already entered phase 1 clinical trials.
Therapeutic Mechanism and Potential
These candidate therapies utilize RNA interference technology to reduce the expression of ALK7 in adipocytes (fat cells). ALK7 is a receptor involved in regulating signals that control the storage and breakdown of fats. By modulating these signals, the aim is to induce changes in lipid metabolism. The direct action on adipocytes makes these therapies a potential companion to existing obesity medications.
Developing a Novel Approach to Targeting Fat Reduction and Muscle Preservation
The focus is on developing a treatment strategy that aims to reduce fat while maintaining lean mass, including muscle. Unlike incretin-based drugs such as GLP-1 analogs, which regulate appetite and energy intake, this approach offers a different mechanism of action, providing hope for a complementary therapeutic strategy. The potential benefits of this combination therapy, particularly in terms of fat reduction and lean mass preservation, are yet to be fully realized and will require further clinical validation.
Target Selection: Unlocking Genetic Insights
Research published in the prestigious journal 'Diabetes' has identified a genetic basis for targeting ALK7. Certain variants in the ACVR1C gene, which encodes for ALK7, were associated with reduced abdominal fat and a lower risk of type 2 diabetes. This provides a strong rationale for exploring this pathway as a therapeutic target, distinct from the individual candidate compounds that have been clinically tested.
Olrix Advances with Proprietary Delivery Platform
Olrix is leading the charge with its independently developed ALK7-targeting siRNA program, OLX501A. The company has announced ongoing research in non-human primate models of obesity, leveraging its proprietary delivery platform.
OLX501A: A Promising Fat-Tissue Delivery Platform
OLX501A, developed by Olix, is based on the company's innovative fat-tissue delivery platform, 'OASIS-Adipose'. The firm has optimized its technology to efficiently deliver candidate substances to adipose tissue and maintain sustained suppression of target genes. While Olix and Lonowa utilize distinct delivery platforms, they share a common development direction, both targeting the ALK7 in adipocytes.
In Olix's recent announcement on July 30th, the results of their obesity primate trial revealed a remarkable 29.2% reduction in visceral fat volume in the OLX501A treatment group. In contrast, the comparison group, which received a different substance, experienced a 10.0% reduction, while the control group saw an 11.1% increase. These figures were adjusted based on baseline measurements and dietary intake, and were measured using magnetic resonance imaging (MRI) 49 days post-treatment.
During the trial, OLX501A and the comparison substance were administered at a dose of 3 mg/kg, with a one-month interval between doses. As these results are based on animal trials, the efficacy and safety for human use will need to be verified through future clinical trials. Olix has set its sights on submitting an investigational new drug application in the first half of 2027 as part of its subsequent development timeline.
