Waging war on chronic inflammation

Halia Therapeutics CEO on moving into multiple Phase 2 trials for chronic inflammation and whether the company may have created a ‘longevity drug.’
Fresh from announcing positive Phase 1 trial results for its inflammation-targeting drug candidate, Utah-based biotech Halia Therapeutics is now pursuing Phase 2 studies in a range of indications. The Salt Lake City company’s lead compound is an inhibitor of the NLRP3 inflammasome, a known driver of systemic chronic inflammation, which is linked to conditions including fibrotic disease, Alzheimer’s, Parkinson’s and many others.

Halia is taking a unique approach to the NLRP3 inflammasome by targeting the protein NEK7, which plays a key role in gene’s activity. In preclinical models, the company has shown its approach disrupts the formation of the NLRP3 inflammasome and promotes its disassembly once activated, reducing the overall inflammatory response. In its recent Phase 1 trial, in addition to showing positive safety and tolerability data, Halia’s drug demonstrated positive effects in blood samples taken from healthy volunteers, showing “over 90% suppression of multiple NLRP3-mediated cytokines and chemokines.”
Longevity.Technology: Chronic inflammation is a frequent topic of discussion in longevity circles. The term “inflammaging” refers to the increase of inflammatory cytokines in our bodies as we age, which is linked to chronic morbidity, disability, frailty and premature death. While there is no doubt that Halia believes that its approach can potentially impact many diseases, does the company have aging itself in its sights? We caught up with CEO Dr David Bearss to find out.

Interestingly, the core scientific breakthrough on which Halia was founded is very much rooted in longevity science. Earlier in his career, the company’s scientific co-founder, renowned geneticist Dr John “Keoni” Kauwe, was involved in research at Washington University linking the APOE4 gene with increased risk of Alzheimer’s disease. APOE4 hit the headlines in 2022 when the actor Chris Hemsworth learned he had two copies of the gene.

“Keoni moved from WashU back to Utah, which is a great place to study human genetics, because public health records are merged with the genealogical records of the LDS Church,” says Bearss. “We can ask questions here that you can’t do in other places, like finding families that have Alzheimer’s in every generation, for example.”

Protection against inflammation
While looking for data on families at high risk for Alzheimer’s, Kauwe was surprised to find a family that had the APOE4 gene, but no one in that family appeared to get the disease. This led him to explore if there was something else in their genetics that was protecting them from developing Alzheimer’s and he discovered that they all had a polymorphism in a gene called RAB10.

“We started the company to see if we could somehow target that pathway to treat Alzheimer’s,” says Bearss. “We initially thought we might be targeting the mechanism of depositing beta-amyloid in the brain as we age, but our big discovery was that stem cells created from people with this polymorphism were resistant to inflammation, thanks to its effect on this big protein complex called the NRLP3 inflammasome.”

Waging war on chronic inflammation