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Potential First-In-Class Migraine Medication

Migraine is the 2nd-most disabling disorder worldwide, due in large part to suboptimal treatment with current medications.  While there are a number of recently-approved migraine therapeutics, all of these new drugs target CGRP, a peptide that contributes to migraine in many, but not all patients.  Targeting PAR2 is a completely distinct approach from inhibiting CGRP signaling, and may provide efficacy in patients who are non-responsive to current agents.
Emerging evidence supports a role for the immune system in migraine pathology but current drugs (including triptans and CGRP inhibitors) do not effectively block neuroimmune interactions that can contribute to migraine pain.  PAR2 is activated by proteases released by several distinct types of immune cells, it is expressed on pain-sensing neurons that innervate the cranial meninges (neurons that are essential for headache), and our preclinical modeling shows that our PAR2 antagonists can block headache behavior induced by multiple proteases associated with the immune system.  Importantly, these models show that our PAR2 antagonists have efficacy without the need to access the central nervous system and they have efficacy even after behavioral responses have developed. These are critical factors as many current medications have CNS side effects and most need to be taken before or very early into an attack to be efficacious.

Migraines

Stop migraines before they develop

All of the current migraine medications target mechanisms that are likely to be far downstream of the initiation of the pain phase of migraine.  Our small molecule antagonists can effectively stop the immune/inflammatory response caused by PAR2 before headaches fully develop, thus preventing further progression into a migraine attack.

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A New Approach to Chronic Pain Treatment

Chronic pain impacts one in every five adults and is linked to several other health conditions such as restricted mobility, opioid dependence, and depression. Chronic pain is primarily due to a heightened sensitivity to a stimulus that wouldn’t usually cause pain — a condition known as hyperalgesia. Our novel small molecule approach addresses both the cause and symptoms of migraines.
Primary treatments for chronic pain include over-the-counter nonsteroidal anti-inflammatory drugs and opioids. Both manage acute pain but are less effective in addressing the long-term effects of chronic pain. Also, opioids come with numerous intolerable side effects and a quick rate of tolerance, which leads to a need for higher dosage and risk of dependence.

Chronic Pain

A promising alternative to pain medication

PARMedics small molecule treatment is a promising alternative to current chronic pain medication. PAR2 can amplify pain signals by increasing excitatory neurotransmitters’ release and promoting inflammatory mediators’ release. Our small molecule treatment inhibits and prevents the sensitization of pain receptors that underlie chronic pain. By blocking PAR2, we can treat both the cause and the symptoms of chronic pain.

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Meeting an Unmet Need for Alternative Asthma Treatment

Asthma is primarily treated by inhaled steroids that reduce overall inflammation, and by long-acting beta-2-adrenergic receptor agonists (LABAs), that decrease acute bronchoconstriction events. While steroids do treat underlying inflammation, they are not tolerated well for long-term treatment and patients can eventually become less responsive to the benefits of LABAs for acute asthma attacks. In recent years, a number of antibody medications have emerged that reduce specific inflammatory molecules known as cytokines, reducing inflammation; however, these treatments often have widespread immunosuppressive effects, require regular injections, and do not adequately control patients with moderate to severe asthma Thus, there is a need for an alternative asthma treatment that can effectively be used long-term for moderate to severe asthmatics.
Common household pathogens that are associated with moderate to severe asthma can activate PAR2 on the lining of the airway and on inflammatory cells, leading to production of inflammatory cytokines, eosinophil and neutrophil influx and production of mucus. These responses ultimately cause airway obstruction and bronchoconstriction. By targeting PAR2, we are blocking a response to environmental allergens rather than suppressing a systemic immune response, which reduces the chance of adverse side effects. Our specific approach to targeting PAR2 also takes advantage of the fact that we can tailor our antagonists to specific signaling pathways.

Treating Asthma

A better treatment for asthma

PAR2 also promotes the release of molecules that dilate the bronchioles, counteracting some of its inflammatory responses. At the molecular level, these two responses are the result of distinct signaling pathways, a pro-inflammatory beta-arrestin pathway and a protective G-protein one. Our approach is to develop PAR2 antagonists that specifically target the inflammatory beta-arrestin pathway to effectively to effectively treat moderate to severe asthma in patients who are unresponsive to current standard-of-care.

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Our treatments can be life-changing.

PARMedic’s small molecule design addresses chronic pain and inflammatory disease at its source, providing viable long-term treatment of chronic illnesses such as migraine and asthma without diminishing effectiveness or debilitating side effects. Our treatment can have life-changing implications for patients with chronic disease, and we are looking for investors to help bring our small molecule treatment to the market.