Our goal is to deliver safe and effective treatments for inflammatory diseases.
Xalud’s lead product candidate, XT-150, harnesses the power of the body’s potent natural anti-inflammatory protein, IL-10, to treat inflammatory diseases of the central nervous system (CNS) and joints. It is the outgrowth of work initiated in Dr Watkins’ laboratory. Her publications over the past 15 years have documented a steady progression of approaches to deliver IL-10 protein where it can best provide relief from pain. The greatest leaps in this progression began when Dr. Watkins and her colleagues Drs Raymond Chavez and John Forsayeth, also cofounders of Xalud Therapeutics, began investigating the use of gene therapy as means of delivering of IL-10 for prolonged periods and creating an effective, durable treatment for neuropathic pain.
XT-150 is the culmination of those efforts. It is a synergistic combination of plasmid DNA expressing a proprietary IL-10 protein and a simple compound that improves the uptake of the plasmid into cells. In years of testing the tools that make up XT-150 in animals, this therapeutic approach is safe, efficient, and produces profound and remarkably long lasting suppression of chronic pain. Importantly, XT-150 abolishes only pathological pain, returning aberrant pain responses to normal. It does not affect the animals’ ability to feel other pain. In gold-standard animal models of neuropathic pain, a single dose of XT-150 reliably and completely reverses neuropathic pain for up to three months with no signs of sedation, numbness, weight loss, tolerance, addiction or other adverse effects which are typically seen with the drugs used as treatment; the animals are healthy, a finding observed consistently throughout the development of Xalud’s gene therapies. XT-150 is a non-opioid, non-addictive therapy. The efficacy studies of XT-150 therapy in a wide range of rat models of neuropathic pain – chronic constriction injury, Chung, chemotherapy-induced, experimental autoimmune encephalomyelitis – have demonstrated an unrivaled duration of effect and a superior potency of this therapy when compared with currently available pain treatments tested in the same models.
XT-150 is revolutionary because it treats chronic pain by reversing glial activation through the actions of our proprietary transgene on each of the major pro-inflammatory cytokines responsible for the development and maintenance of neuropathic pain, rebalancing the natural communication between neurons and glial cells. XT-150 uses a proprietary variant of IL-10 that has demonstrated increased efficacy and duration of action in animal models as compared to wild-type IL-10. XT-150 is delivered by a single injection into the fluid surrounding the spinal cord in a simple procedure ensuring that the therapy reaches its target in spinal cord. By means of this targeted delivery, and taking advantage of the highly specific ligand/receptor interaction, XT-150 provides relief from chronic neuropathic pain without significant side effects. Unlike small molecules with complex and often unknown mechanisms of action, XT-150 exerts its effects solely through a single receptor that activates the same thoroughly understood intracellular signaling cascade in humans as well as laboratory animals.
In leading rodent models of neuropathic pain, XT-150 has been shown to be highly efficacious. For example, in the mechanical allodynia chronic constriction injury (CCI) model – generally considered to be the gold standard model for neuropathic pain – a single administration of XT-150 completely eliminates neuropathic pain for up to 12 weeks. XT-150’s efficacy has also been demonstrated in the thermal analgesia CCI model, the Chung model and the chemotherapy-induced neuropathic pain model. Importantly, animals receiving XT-150 do not become numb — they continue to perceive new pain stimulus in a normal manner — it is just their pathological pain that is eliminated.
This therapy has also been administered to pet dogs suffering from neuropathic pain — that is, actual animal patients with naturally occurring disease, not model animals. These animals have shown greatly reduced signs of pain and substantially increased activity levels as the result of treatment — with the effects lasting beyond 12 weeks. These remarkable results have been featured in an ABC 7 News Denver special report.
Inflammatory joint diseases, including osteoarthritis and rheumatoid arthritis, are marked by patterns of inflammation, macrophage activation, and immune system involvement that are similar to the patterns seen in the neuro-inflammatory diseases that were Xalud’s initial focus.
Xalud is also developing XT-150 for the treatment of osteoarthritis. XT-150 has been administered to the elbows of pet dogs suffering from osteoarthritis. These dogs showed long-term (beyond 12 weeks) significant normalization of gait, greatly increased activity levels, and reduced signs of pain as the result of XT-150 treatment.
Safety of XT-150
In animal studies, XT-150 has been very well-tolerated. There have been no signs of illness, weight loss, sedation, dizziness, addiction, or tolerance in any of the hundreds of animals treated with XT-150 or earlier versions during development. In a 30 day pharmacology/toxicology study, this therapy produced a dose-dependent response and was determined to be safe as administered. Because XT-150’s method of action is a natural rebalancing of the nervous system, the likelihood of side effects is greatly diminished. The targeted delivery of XT-150 directly to the fluid surrounding the spinal cord further restricts the potential for unwelcome side effects. Lastly, because pain neurons in the spinal column do not have IL-10 receptors, adverse effects on the CNS are particularly unlikely.
Additional Product Candidates
Building on Dr. Watkins’ insights into neuropathic pain and glial biology, Xalud is developing additional products to treat glia mediated diseases. These include products based on different vectors designed to reach areas of the CNS that are not readily accessible by XT-150 and small molecule treatments for drug addiction and opioid tolerance.