MediciNova(MNOV) - 2021 Q4 - Annual Report

Drug Development and Clinical Trials - The company is focused on developing MN-166 (ibudilast) for various neurological disorders, including progressive multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) [18] - In the SPRINT-MS Phase 2b clinical trial, MN-166 (ibudilast) demonstrated a statistically significant 48% reduction in the rate of progression of whole brain atrophy compared to placebo (p=0.04) [21] - The same trial showed a 26% reduction in the risk of confirmed disability progression compared to placebo (hazard ratio = 0.74) [21] - The company has initiated a Phase 2b/3 clinical trial of MN-166 (ibudilast) in ALS, following positive results from earlier trials [24] - The company is conducting ongoing clinical trials for MN-166 (ibudilast) in chemotherapy-induced peripheral neuropathy and degenerative cervical myelopathy [30][31] - Positive preclinical findings for MN-166 (ibudilast) as an adjunctive treatment for glioblastoma were published, with ongoing clinical trials [32] - MN-166 (ibudilast) achieved the primary endpoint of safety and tolerability in a clinical trial for ALS, with a higher rate of responders on the ALSFRS-R total score compared to placebo [56] - The trial evaluating MN-166 (ibudilast) for degenerative cervical myelopathy is funded by a grant from the National Institute for Health Research (NIHR) in the UK [67] - The Phase 2 clinical trial for MN-166 (ibudilast) for ARDS caused by COVID-19 has completed 75% of planned enrollment as of August 2021 [70] - The ongoing clinical trial for MN-166 (ibudilast) for ARDS has received FDA acceptance and is currently in progress [70] - The company is aware of multiple competitors in the clinical development space for both NASH and IPF, indicating a competitive market [143][144] - The clinical development program may not lead to commercial products due to various risks, including failure to demonstrate safety and efficacy in clinical trials [186] Regulatory Designations and Approvals - The FDA has granted Fast Track designation for MN-166 (ibudilast) for both progressive MS and ALS, providing expedited development and review [22][25] - MN-001 (tipelukast) has received Fast Track designation from the FDA for the treatment of nonalcoholic steatohepatitis (NASH) with fibrosis [37] - MN-166 (ibudilast) has received Fast Track designation from the FDA for three indications: progressive MS, ALS, and methamphetamine dependence, facilitating expedited development [46] - The FDA granted Orphan-Drug designation to MN-166 (ibudilast) for ALS, providing seven years of marketing exclusivity if approved [58] - MN-001 (tipelukast) received Orphan-Drug designation from the FDA for Idiopathic Pulmonary Fibrosis (IPF), providing seven years of marketing exclusivity upon approval [38] - The FDA granted orphan-drug designation to MN-166 (ibudilast) as adjunctive therapy to temozolomide for the treatment of glioblastoma [69] - The FDA has granted Fast Track designation to MN-001 (tipelukast) for the treatment of patients with NASH with fibrosis [85] - The company has obtained regulatory authorization to conduct clinical trials for its product development programs, with INDs approved by the FDA [191] Financial Performance and Projections - For the year ended December 31, 2021, the company reported a net loss of $10.1 million, with an accumulated deficit of $393.1 million since inception [176] - As of December 31, 2021, the company had available cash and cash equivalents of $71.4 million and working capital of $69.2 million [176] - The company expects to incur significant operating losses for the foreseeable future as it continues to develop its product candidates MN-166 (ibudilast) and MN-001 (tipelukast) [179] - The company anticipates an increase in research and development expenses in 2022 compared to 2021 due to ongoing development activities [179] - The company may apply for patent term restoration for its currently owned or licensed patents, potentially extending patent life beyond current expiration dates [160] - The company anticipates that out-licensing upfront and milestone payments will be its primary source of revenue prior to commercialization [183] Market Opportunities and Competition - The economic burden of methamphetamine use in the United States is approximately $23.4 billion [60] - There are approximately 1.5 million people aged 12 or older with methamphetamine use disorder in the United States [60] - The prevalence of chemotherapy-induced peripheral neuropathy (CIPN) was 68% in the first month after chemotherapy, 60% at 3 months, and 30% at 6 months or more [66] - Approximately 28.3 million people aged 12 or older in the United States have alcohol use disorder [64] - There are no approved pharmaceuticals for chemotherapy-induced peripheral neuropathy or degenerative cervical myelopathy, highlighting a market opportunity for MN-166 [137][138] - Current treatments for opioid dependence include generic methadone and Suboxone Film, with additional products like Vivitrol and Zubsolv approved [135] - Competitors may develop more effective products, posing a risk to the company's market opportunities and potentially rendering its product candidates obsolete [214] - The company faces competition from pharmaceutical and biotechnology companies with greater resources and advanced development products targeting the same diseases [131] Safety and Efficacy Findings - An interim analysis of a clinical trial for MN-001 (tipelukast) showed a significant reduction in mean serum triglycerides, a primary endpoint [37] - In a Phase 2 clinical trial for MN-001 (tipelukast), there were no worsening IPF events in the treatment group compared to one event in the placebo group, indicating a favorable safety profile [38] - MN-001 (tipelukast) significantly reduced mean serum triglycerides by 135.7 mg/dL, resulting in a 41.3% reduction (p=0.02) in a Phase 2 clinical trial for NASH [85] - MN-001 (tipelukast) demonstrated significant anti-fibrotic effects in preclinical studies, reducing fibrosis area compared to placebo (p<0.01) and improving NAFLD activity score (p<0.01) [83] - MN-166 (ibudilast) significantly decreased basal, daily alcohol craving over the course of a study (p<0.05) [64] - In a study, 33% of subjects with recurrent glioblastoma were progression-free at six months after treatment with MN-166 (ibudilast) in combination with temozolomide [69] Strategic Partnerships and Collaborations - The company has partnered with BARDA to develop MN-166 (ibudilast) as a potential medical countermeasure against chlorine gas-induced lung injury [34] - The company is pursuing strategic partnerships with leading pharmaceutical companies to support the development and commercialization of its product candidates [42] - The company relies on strategic collaborations and third-party manufacturers for the development and commercialization of its product candidates [176] - The company relies on third-party manufacturers for the production of active pharmaceutical ingredients and finished products for clinical trials and future commercial needs [101] Risks and Challenges - The company faces risks related to regulatory compliance, including potential fines and withdrawal of approvals if foreign regulatory requirements are not met [168] - The company currently has no products approved for commercial sale and does not expect to generate any revenues from product sales in the foreseeable future [183] - The company is largely dependent on the success of its MN-166 (ibudilast) and MN-001 (tipelukast) product candidates, which have not completed the clinical development process [185] - Delays in clinical trials could result in increased costs and limit the ability to obtain regulatory approval for product candidates [205] - The inability to secure adequate funding could require the company to delay or scale back clinical or regulatory activities [182] - The company may face significant setbacks in advanced clinical trials, even after earlier trials show promising results [188] - The loss of rights to develop and market product candidates could significantly harm the company's business [209]