Lohocla Development Pipeline
Preclinical
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Lead
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Efficacy
in vitro
in vivo
Pharmacokinetics
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in vivo
Safety
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in vivo
IND
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Phase II
Kindolor: the network approach to treating chronic pain
Network models suggest that partial inhibition of a surprisingly small number of targets can be more efficient than the complete inhibition of a single target.
—Csermely et al., 2005
Lohocla Research Corporation rationally designed a novel small molecule that we named Kindolor for
treatment of chronic pain syndromes. The molecule reduces the over-activity of the nociceptive
(pain-sensing) peripheral neural network that generates chronic pain. Kindolor has negligible penetrance
into the brain, thus reducing deleterious CNS side effects. Accordingly, Kindolor’s actions are confined to
the peripheral nervous system, where Kindolor has been shown to produce significant anti-hyperalgesic
effects in five animal models of chronic pain. No genotoxic effects of Kindolor have been noted. Acute
dosing levels 20 to 30 times higher than doses producing therapeutic effects produced no overt signs of
toxicity, and we estimate the therapeutic index for Kindolor to be greater than 30.

Illustrates the peripheral nociceptive transmission pathway.
Kindolor selectively modulates
the activity of key nodes in this nociceptive pathway, attenuating over-activity.
Background
Over 100 million adults in the U.S. suffer from intermittent or constant chronic pain, and chronic pain
affects at least 10 percent of the world’s population. The primary pharmaceuticals for treatment of chronic
pain have been natural or synthetic opioids. However, the use of opioids for pain treatment has resulted in
an “epidemic” of opioid
abuse, addiction, and lethal overdoses. Through a process of rational drug design, Lohocla Research has
generated a new chemical entity (NCE) called Kindolor. Kindolor is a non-opiate, non-addicting molecule that
was developed specifically to target the aberrant over-activity of the peripheral sensory system that is
integral in the initiation and propagation of chronic pain. Kindolor dampens the over-activity of the
signaling network that conducts and magnifies pain signals (Fig. A), but leaves the normal response to acute
painful stimuli intact. Lohocla Research has developed a process to synthesize Kindolor at 99 percent
purity. Pre-clinical studies have demonstrated the efficacy of Kindolor to reduce or eliminate chronic pain
generated in five animal models at doses compatible with use of Kindolor in humans. Initial evidence
demonstrates the safety (high TI) of Kindolor as well as its uneventful metabolism. Additional attractive
features of Kindolor are that it can prevent the development of chronic pain if given soon after tissue
injury. Additionally, if combined with low doses of opiates, Kindolor produces a substantial “opiate
sparing” effect through synergistic actions with the opiates. Lohocla Research is working to bring
Kindolor to the public. An IND application is in process, and Phase 1 trials are planned for early 2023,
followed by Phase 2 trials for efficacy in treating diabetic neuropathy. In all, our goal is to license to
or partner with a Pharma company willing and able to bring this innovative medication to the chronic pain
sufferer.
Public Health Relevance Statement
The U.S. and other countries around the world are facing “dual crises of pain and opioid addiction.”
Lohocla Research Corporation has responded to the opioid crisis and medication development challenge by
designing, synthesizing, and demonstrating, in pre-clinical studies, the efficacy and safety of a
non-opiate, non-addictive new chemical entity (NCE) for treatment of chronic pain. This NCE, called
Kindolor, has significant additional benefits of being able to prevent the development of chronic pain if
administered soon after tissue injury, including post-operative conditions. Kindolor also has a highly
significant “opiate sparing” effect in conditions that may require the use of opiates, since
Kindolor demonstrates a strong synergistic effect with morphine. Given the FDA approval of our IND status,
we will complete first-in-human, Phase I clinical studies for safety and Phase 2a studies of efficacy to
bring our medication to chronic pain sufferers.