Virios Therapeutics (Nasdaq: VIRI) is a development-stage biotechnology company focused on advancing novel antiviral therapies to treat debilitating chronic diseases, such as fibromyalgia (“FM”). Immune responses related to the activation of tissue resident herpes have been postulated as a potential root cause triggering and/or sustaining chronic illnesses such as FM, irritable bowel disease, chronic fatigue syndrome and other functional somatic syndromes, all of which are characterized by waxing and waning symptoms with no obvious etiology. Our lead development candidate (“IMC-1”) is a novel, proprietary, fixed dose combination of famciclovir and celecoxib designed to synergistically suppress herpes virus replication, with the end goal of reducing virally promoted disease symptoms. IMC-1 has been granted fast track designation by the FDA.
The Company is pursuing a second development candidate, IMC-2 (valacyclovir and celecoxib), as a potential treatment for managing the fatigue, sleep, attention, pain, autonomic function and anxiety associated with Long-COVID, otherwise known as Post-Acute Sequelae of COVID-19 (PASC). The Company has provided Bateman Horne Center (“BHC”) with an unrestricted investigational grant to conduct this study. BHC is a non-profit, interdisciplinary Center of Excellence advancing the diagnosis and treatment of chronic fatigue disorders, FM, post-viral syndromes, and related comorbidities.
About IMC-1: Evidence of IMC-1’s efficacy on a broad spectrum of FM outcome measures was previously demonstrated in a Phase 2a clinical trial. In this trial, IMC-1 delivered statistically significant reduction in FM related pain, fatigue, anxiety and depressive symptoms and improved overall patient health and functioning. IMC-1 was better tolerated placebo, as evidenced by a lower drop-out rate due to adverse events on IMC-1 as compared to placebo.
Virios’ novel FM development candidate, IMC-1, demonstrated exemplary safety and tolerability in the FORTRESS study (a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial of over 400 FM patients), but did not achieve statistical significance on the pre-specified primary efficacy endpoint of change from baseline in daily self-reported average pain severity scores compared to placebo. However, analysis of the top-line data revealed a bifurcation of response based on the timing of patient enrollment in the FORTRESS study that the Company believes is unlikely related to chance. Based on these results, the Company performed a deeper analysis of the FORTRESS data to determine factors driving these results to determine whether, and if so, how, to continue the development of IMC-1.
Post-hoc analysis of the FORTRESS (Fibromyalgia Outcome Research Trial Evaluating Synergistic Suppression of Herpes Simplex Virus-1) study results indicated that FM patients who were generally more naïve to prior clinical studies and prior FM drug treatment (“new” patients), demonstrated clinically and statistically significant reductions in pain, fatigue, FM symptoms and both anxiety and depression symptoms. In contrast, FM patients who were prior FM trial participants and/or study site database patients (“experienced” patients) did not exhibit a statistically significant treatment benefit in this study.
The Company believes targeting new FM patients for IMC-1 development is the optimal approach and plans to meet with the U.S. Food & Drug Administration (“FDA”) with the goal to progress IMC-1 into Phase 3 development.
Our Novel Approach to Treating Virally Mediated Fibromyalgia (FM)
Patients with FM have a problem with central pain processing. The exact causality of the heightened pain sensitivity in FM is poorly understood. What is generally agreed is that the central sensitization seen in FM is secondary to a combination of genetic and environmental factors that render the patient susceptible to developing the widespread chronic pain and related symptoms seen in FM. We believe that, when FM patients are exposed to significant life stressors, be they physical or emotional, it results in an abnormal stress which activates herpes virus mediated-immune response. Herpes viruses are unique in that they remain in a dormant state (latency) in neuronal nuclei as nonintegrated, circular DNA associated with nucleosomes, with recurrent reactivations for the life of the host (as seen here). We believe it is likely that nerve resident viral herpetic reactivation is necessary for the waxing and waning nociceptive manifestation of FM. This cyclical process of virus reactivation and lytic infection of herpes viruses is postulated to perpetuate FM symptoms in these patients. IMC-1 is proprietary, fixed dose, orally administered tablet combination of famciclovir and celecoxib designed to synergistically suppress herpes activation and replication, with the end goal of reducing viral mediated disease burden.
Unmet Medical Need
Despite a very high disease burden, just
over one in two (56%) patients currently diagnosed with FM are actively being treated with prescription medication. Furthermore, the three medicines approved to treat FM can give rise to a side-effect burden which limits their use. Even presently treated patients often have to manage the sub-optimal outcomes associated with using unapproved and/or potentially harmful medications to manage their FM disease.
For example, almost 40% of FM patients
are treated with opioids, despite well-established addictive properties, as well
as published references highlighting worse treatment outcomes for opioid-treated patients.
Our novel therapeutic is directed at interrupting the ongoing immune response by suppressing herpes viruses, which suppresses the abnormal stress response, thereby alleviating the central pain processing abnormality and other FM symptoms. Studies have shown that neither antivirals nor COX-2/nonsteroidal anti-inflammatory drugs (“NSAIDS”) taken alone result in a meaningful clinical benefit. However, when administered in combination, a synergistic response has been observed in preliminary clinical studies. The IMC-1 Phase 2a study generated proof-of-concept evidence of clinically significant pain reduction and
symptom alleviation through the coaction of the proprietary, fixed-dose combination of celecoxib and famciclovir.
Failed antiviral monotherapy - Kendall et al.
Failed NSAID monotherapy - Derry et al.
IMC-1’s antiviral mechanism represents an approach that can be directed at FM, IBS and CFS patents, as well as Somatic Symptom Disorder (SSD). These additional chronic conditions represent
a substantially larger market opportunity. The below listed SSD conditions are all chronic pain-related conditions that may be responsive to treatment with IMC-1.
2. Irritable Bowel Syndrome
3. Chronic Pelvic Pain
4. Chronic Neck and Back Pain
5. Temporomandibular Joint Dysfunction (TMJ)
6. Long COVID