In May, GSK plc brought in SironBio's ALK7-targeted obesity drug candidate (SA030) for up to $1 billion (about 1.5 trillion won) including upfront and milestone payments. Betting that much on a compound that has not even completed phase 1 signals that global big pharma sees strong potential in the ALK7 mechanism.
In Korea, OliX Pharmaceuticals is developing an RNA interference (RNAi) therapy with the same mechanism, OLX501A. It recently completed optimization of the lead and finalized the candidate. Additional data to be released in July will likely be the first test to gauge out-licensing potential.
◇ Next-generation obesity target to complement GLP-1 limits, ALK7
GLP-1 class obesity drugs reduce weight by suppressing appetite signals in the brain and slowing gastric emptying to lower caloric intake. They are powerful but have limits. Fat loss is accompanied by muscle loss, and weight often rebounds when the drug is stopped. In Wegovy's long-term trial (104 weeks), an analysis found that 32% of patients lost less than 5% or even gained weight.
Not all obesity starts with an appetite problem. Therefore, in patient groups where visceral fat accumulation, insulin resistance, and impaired adipocyte metabolic function are the main causes, appetite suppression alone is unlikely to be sufficiently effective. ALK7 targets precisely this point.
ALK7 is a receptor involved in signaling pathways that suppress lipolysis in adipocytes and maintain fat storage. Inhibiting it with siRNA (small interfering RNA) can induce adipocytes to break down stored fat on their own. It intervenes directly in adipose tissue rather than appetite.
However, ALK7 drug development faces high barriers in delivery technology. Most RNAi therapies have been commercialized via liver delivery. Adipose tissue has low blood accessibility and cellular uptake efficiency, making it a difficult organ for drugs to reach. This is why, despite ALK7 being seen as a promising target, there are not many actual developers.
◇ OLX501A shows potential to reduce fat and preserve lean mass in preclinical studies
OliX Pharmaceuticals released early preclinical data for OLX501A in Mar. In a nonhuman primate model, a single dose of the early lead reduced ALK7 gene expression in adipose tissue by up to 84% at week 2, with about 70% suppression maintained at week 4. The industry is responding positively to achieving this level of gene knockdown in adipose tissue.
In rodent models, improvements in body composition were observed. With 28 days of OLX501A monotherapy, body weight decreased 10.7% and body fat decreased 32.6%. Lean mass did not decrease and instead tended to increase. However, because lean mass includes body water and other components besides muscle, it is premature to conclude a muscle-gain effect.
The combination results with the GLP-1 class drug zepbound (domestic name Mounjaro) are even more striking. When OLX501A was combined with a low dose of zepbound (one-tenth of the high dose), body fat reduction was similar to zepbound high-dose monotherapy. After stopping treatment, the rate of body fat increase in the combination group was 25.2%, lower than the high-dose monotherapy group (54.8%). In other words, it used less zepbound while maintaining efficacy and reducing rebound.
The results suggest that ALK7 agents may be used as combination partners to complement, rather than replace, GLP-1. The company said, "We have secured positive data for both monotherapy and combination therapy," and noted, "Based on this, we are reviewing our clinical development strategy."
◇ Out-licensing talks to accelerate; July data will be a watershed
OliX Pharmaceuticals plans to release additional efficacy data from a nonhuman primate model next month and file an Investigational New Drug (IND) application in the United States in the first quarter of next year.
On the 8th, it finalized the candidate based on interim data obtained from the nonhuman primate model. After the announcement, CEO Lee Dong-gi said, "We plan to proceed with full-fledged business development (BD) discussions with global partners on major pipelines, including OLX501A."
The market environment is seen as favorable. With GSK securing SironBio's SA030, big pharma demand for ALK7 has been confirmed, and U.S.-based Arrowhead, the leader in this field, is maintaining an independent development strategy, creating a dynamic where supply is limited relative to partnering demand. OliX Pharmaceuticals said, "We intend to pursue a global out-licensing even at the preclinical stage."
OliX Pharmaceuticals also has experience closing a deal with Eli Lilly and Company. OLX702A, a MASH (metabolic dysfunction-associated steatohepatitis) and obesity therapy out-licensed to Lilly, targets a different gene (MARC1) but was derived from the same platform as OLX501A. It means Lilly has directly vetted the OliX platform.
It also has financial flexibility. After securing more than 130 billion won last year through its deal with Lilly and a paid-in capital increase, OliX Pharmaceuticals raised about 110 billion won more in early June with participation from L'Oréal Group's venture fund BOLD and U.S. asset manager Weiss Asset Management.
However, the fact remains that OLX501A is still in the preclinical stage. Confirming target gene suppression in a nonhuman primate model and proving weight and body fat reduction and safety in people are entirely different matters.
The company said, "The early nonhuman primate data released in Mar. were verified to be on par with Arrowhead. We expect the additional data to be released soon to come out even better," and added, "Our platform has demonstrated safety and efficacy in the clinic, and our technology has been validated by global big pharma."
Regarding whether there will be further talks with existing partners, it said the matter was "confidential," declining to elaborate.