Advancing novel NLRP3
inflammasome therapeutics
The Halia Therapeutics Story:
Pioneering Therapies to Combat Chronic Disease
FAMILY TREE
Halia Therapeutics was founded in 2017 after a groundbreaking scientific discovery by our co-founder and renowned geneticist, Dr. John “Keoni” Kauwe. He identified a family with a genetic risk for Alzheimer’s disease, yet none developed the illness. His investigation revealed a protective gene mutation, which sparked a mission: translate this discovery into a therapy safeguarding others from Alzheimer’s.3,4
COMBINED DATABASE
Utah’s foresight in merging genealogical data with public health records created the Utah Population Database, a powerful tool for genetic research. This unique access fueled our journey, allowing us to identify families with specific diseases and those predisposed due to genetics.
INFLAMMATION’S LINK TO DISEASES
Our initial focus was transforming the protective gene mutation into a novel Alzheimer’s treatment. However, a remarkable discovery unfolded. The mutation not only offered resilience to Alzheimer’s but also uniquely blocked chronic inflammation. This discovery challenged the prevailing theory that Alzheimer’s is solely caused by brain plaques. We learned inflammation is a key driver of the disease, leading to neuronal degeneration. While plaques are common with age, only some develop dementia. This crucial finding—inflammation, not just plaques, is a hallmark of Alzheimer’s and became a cornerstone of Halia’s mission.3,4
OUR EXPANDED APPROACH
Our vision expanded, recognizing the link between inflammation and numerous chronic diseases. Our immune systems play a significant role in many age-related illnesses, from Alzheimer’s and cardiovascular disease to cancer and skin, intestinal, and liver disorders. This realization transformed our approach.5
INFLAMMATION SUPPRESSION
We are pioneering a method to disrupt this chronic inflammatory pathway, potentially treating many chronic diseases. Pre-clinical studies have shown our approach can suppress inflammatory signals across various organs, from the brain to the skin. While the journey continues, in the early stages of clinical trials in patients, we are evaluating our approach’s safety and preliminary activity.
Obesity
Almost half of US adults are obese or severely obese. Lack of physical activity, unhealthy eating behavior, and, in some cases, genetics contribute to obesity. Halia is developing investigational treatments to combat obesity.
Pain and Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is an autoimmune condition where the immune system—normally the body's defender against infection and disease—attacks its own tissues. This results in pain, swelling, stiffness, and loss of joint function. Halia is developing an investigational treatment for both RA and post-surgical pain.
Alzheimer's Disease
Alzheimer’s disease involves parts of the brain that control memory, language, problem-solving, and other thinking abilities. It can seriously affect a person’s ability to carry out daily activities. Halia is developing a potentially relevant pathway and investigational treatment for Alzheimer’s.
Parkinson's Disease
Parkinson’s disease is a progressive disorder that affects the nervous system and the parts of the body controlled by the nerves. Tremors, stiffness, or slowing of movement are typical symptoms. Halia is developing a potential brain-penetrant compound to treat the disease.
Cancer
The landscape of Chronic Inflammation
Inflammation is an essential biological response of the human immune system that protects against disease. However, when dysregulated, inflammation can become a driver of disease by promoting a persistent, systemic immune response that fuels the development of many chronic diseases.
NLRP3 Inflammasome:
A key validated drug target
Over the past decade, many scientific discoveries have revealed the NLRP3 inflammasome as a central upstream activator of the pro-inflammatory cytokines IL-1β and IL-18. NLRP3 has been validated as a viable therapeutic target that may overcome the limitations of many therapeutic strategies researched as treatments for chronic diseases.6 Halia’s scientists have made important insights into NLRP3 biology, providing a potential new path for developing novel treatments for chronic inflammatory disease.
NEK7
We applied our extensive experience to design and advance multiple drug candidates as potential treatments for neurodegenerative and inflammatory diseases. Halia’s science focuses on clinically validated novel protein targets that drive the pathogenesis of numerous serious diseases. Our lead clinical program targets the assembly of the NLRP3 inflammasome through a novel mechanism of NEK7 allosteric inhibition. By blocking the interaction of NEK7 and NLRP3 in pre-clinical models, we prevent the formation of the inflammasome and the downstream signaling that drives immune-inflammatory diseases, hematologic malignancies, and cancer development. (View NEK7 PowerPoint)
LRRK2
We combined library screening and CADD to understand key structural features required to design potent and selective inhibitors of LRRK2, a large kinase that directly phosphorylates and activates RAB10. LRRK2 gene mutations have been identified as the most common genetic cause of familial Parkinson’s, Alzheimer’s, and other neurodegenerative disorders. The LRRK2-RAB10 signaling pathway is linked to the body’s inflammation response — this can lead to more brain cell damage and worsening neurodegenerative disorders. RAB10 inhibition represents a promising set of therapeutic targets for Alzheimer’s Disease, Parkinson’s Disease, and neurodegenerative disease intervention. (View LRRK2 Powerpoint)
