MediciNova(MNOV) - 2018 Q4 - Annual Report

Clinical Trials and Efficacy - MN-166 (ibudilast) demonstrated a statistically significant 48% reduction in the rate of progression of whole brain atrophy compared to placebo in progressive MS patients[17]. - The Phase 2b clinical trial of MN-166 (ibudilast) in progressive MS achieved both primary endpoints of whole brain atrophy and safety and tolerability[17]. - The SPRINT-MS trial completed randomization of 255 subjects, exceeding the planned goal of 250 participants[17]. - MN-166 (ibudilast) demonstrated a statistically significant 48% reduction in the rate of progression of whole brain atrophy in progressive MS compared to placebo (p=0.04) in the SPRINT-MS Phase 2b trial[37]. - The same trial showed a 26% reduction in the risk of confirmed disability progression compared to placebo (hazard ratio = 0.74) as measured by EDSS[37]. - The ALS trial at Carolinas Neuromuscular/ALS-MDA Center achieved the primary endpoint of safety and tolerability, with a higher rate of responders on the ALSFRS-R total score in the MN-166 group compared to placebo[40]. - The ongoing ALS/Biomarker study aims to evaluate the effects of MN-166 (ibudilast) on reducing brain microglial activation in ALS subjects[19]. - The ongoing clinical trial for chemotherapy-induced peripheral neuropathy is assessing the effects of MN-166 (ibudilast) in patients receiving oxaliplatin[47]. - MN-166 (ibudilast) has shown promise in reducing alcohol craving and is currently being evaluated in a Phase 2b clinical trial for alcohol dependence[46]. - The clinical trial for MN-166 (ibudilast) in DCM is funded by a grant from the National Institute for Health Research (NIHR) in the UK, aiming to evaluate its effectiveness as an adjuvant treatment post-spinal surgery[48]. - The FDA accepted the Investigational New Drug Application (IND) for MN-166 (ibudilast) for glioblastoma treatment, allowing clinical investigation to proceed[50]. - A Phase 2b clinical trial of MN-221 (bedoradrine) showed significant improvements in Dyspnea Index scores, with a treatment failure rate of 43% in the MN-221 group compared to 74% in the placebo group[54]. - In a Phase 2 clinical trial for NASH, MN-001 (tipelukast) significantly reduced mean serum triglycerides by 135.7 mg/dL, resulting in a 41.3% reduction (p=0.02)[61]. - MN-001 (tipelukast) is currently undergoing a Phase 2 clinical trial for IPF at Penn State, with significant anti-fibrogenic effects observed in preclinical studies[63]. - In the first Phase 1 trial, stable disease was observed in 12 out of 34 patients, indicating some anti-tumor activity[67]. - The second Phase 1 study showed one patient had a partial response lasting 74 days, with stable disease in seven out of 20 subjects[68]. Regulatory Designations and Approvals - The FDA has granted Fast Track designation to MN-166 (ibudilast) for the treatment of progressive MS, ALS, and methamphetamine dependence[32]. - MN-001 (tipelukast) received Fast Track designation for the treatment of patients with NASH with fibrosis and is currently in a Phase 2 clinical trial for IPF[27]. - MN-166 (ibudilast) received Orphan-Drug designation from the FDA for ALS, providing seven years of marketing exclusivity upon approval in the U.S.[33]. - The European Commission granted Orphan Medicinal Product Designation for MN-166 (ibudilast) for ALS, offering potential 10 years of marketing exclusivity if approved in Europe[33]. - The FDA has granted Orphan-Drug designation and Fast Track designation to MN-001 (tipelukast) for the treatment of idiopathic pulmonary fibrosis (IPF)[62]. - The FDA requires extensive data supporting safety and efficacy for drug approval, and none of the product candidates have been approved yet[117]. - The IND process involves several stages, including preclinical tests, submission of an IND, and completion of human clinical trials[120]. - The FDA's Fast Track program aims to expedite the review process for drugs addressing serious conditions and unmet medical needs[126]. - The FDA may grant priority review for drugs that offer significant improvements over existing therapies, which can facilitate the approval process[129]. - Patent term restoration under the Hatch-Waxman Amendments can extend patent life by up to five years, but cannot exceed a total of 14 years from the product's approval date[130]. - The FDCA provides a five-year period of non-patent marketing exclusivity for the first applicant to obtain NDA approval for a new chemical entity[131]. Financial Performance and Projections - For the year ended December 31, 2018, the company reported a net loss of $14.7 million, with an accumulated deficit of $356.1 million since inception[143]. - As of December 31, 2018, the company had available cash and cash equivalents of $62.3 million and working capital of $60.6 million[143]. - The company expects research and development expenses to increase in 2019 compared to 2018, focusing on the development of MN-166 (ibudilast) and MN-001 (tipelukast)[147]. - The company does not expect to generate any revenues from product sales for at least the next several years, relying on out-licensing upfront and milestone payments as primary revenue sources[151]. - The success of the company is largely dependent on the regulatory approval and commercialization of MN-166 (ibudilast) and MN-001 (tipelukast), which have not yet completed the clinical development process[152]. - The company has incurred significant operating losses and expects to continue doing so for the foreseeable future, with no guarantee of adequate future financing[143][150]. Strategic Partnerships and Licensing - The company is pursuing strategic partnerships with leading pharmaceutical companies to support late-stage product development and commercialization[28]. - The company has acquired licenses for MN-166 (ibudilast), MN-001 (tipelukast), MN-221 (bedoradrine), and MN-029 (denibulin) for various therapeutic indications[24]. - The license agreement with Kissei for MN-221 (bedoradrine) includes exclusive rights for commercial supply, contingent on FDA approval[75]. - The company has entered into multiple license agreements covering its product candidates, holding 24 issued U.S. patents and 36 issued foreign patents[76]. - The company has paid Kyorin $700,000 to date under the license agreement for MN-166 (ibudilast) and is obligated to pay up to $5.0 million based on clinical milestones[81]. - The company has paid Kissei $1.0 million to date and is obligated to make payments of up to $17.0 million based on achieving certain clinical and regulatory milestones[89]. - The company has paid Kyorin $4.0 million to date and is obligated to make payments of up to $5.0 million based on achieving clinical and regulatory milestones[93]. - The company has paid Angiogene $1.4 million to date and is obligated to make payments of up to $16.5 million based on achieving clinical and regulatory milestones[97]. Market and Competitive Landscape - Approximately 20,000 ALS patients are in the U.S., with 5,000 new diagnoses each year, highlighting a significant medical need for effective treatments[38]. - There are approximately 964,000 individuals in the U.S. with methamphetamine use disorder, with an economic burden estimated at $23.4 billion[43]. - The company faces competition from pharmaceutical and biotechnology companies with greater resources and advanced products targeting the same diseases[103][104]. - Competitors may develop more effective products, posing a risk to the company's market opportunities[180]. Manufacturing and Supply Chain - The company relies on third-party manufacturers for active pharmaceutical ingredients (API) and finished products for clinical trials and future commercial production[73]. - The company relies on third-party manufacturers for production, which may result in delays and increased costs for clinical trials and commercialization[192]. - The company may struggle to manufacture product candidates in commercial quantities, which is essential for successful commercialization[197]. - Availability of materials necessary for manufacturing may not be guaranteed, potentially delaying development and commercialization of product candidates[198]. - Compliance with FDA-mandated current good manufacturing practices (cGMPs) is critical; failure to adhere could result in significant delays in clinical trials and product launches[195]. - The company may face challenges in establishing commercial manufacturing and supply arrangements, which could lead to interruptions in supply and adversely affect business operations[194]. Risks and Challenges - The company is subject to extensive regulation by the FDA and other authorities, which could delay the development and commercialization of its product candidates[161]. - The company faces risks related to the clinical development of its product candidates, including potential failure to demonstrate safety and efficacy in trials[153][155]. - The company has not yet received FDA approval for any of its product candidates, and the approval process is lengthy and costly[161]. - The company may need to perform additional testing or amend clinical trial protocols due to changes in regulatory requirements, which could increase costs and delay approvals[161]. - The company faces potential regulatory difficulties even after obtaining U.S. FDA approval, which may include significant restrictions on product use and marketing[167]. - Approved products are subject to ongoing FDA requirements, including labeling, packaging, and post-market safety information submissions[168]. - The company may incur increased costs and delays in clinical trials due to undesirable side effects of product candidates, which could limit commercial potential[170]. - Regulatory authorities may impose restrictions or withdraw approval if unknown problems with a product are discovered, potentially leading to product recalls[173]. - The company may face significant dilution of stockholder ownership if additional equity or debt financing is raised[187]. - The company is obligated to comply with license agreements, and any breach could lead to termination of rights to develop and market product candidates[178]. - The company relies on CROs and other third parties for clinical trials, and any failure on their part could adversely affect the development timeline[188]. - The company's operating results are expected to fluctuate, making it difficult to predict future performance due to various factors including clinical trial dynamics and market demand[215]. Product Development Focus - The company is developing MN-166 (ibudilast) for multiple indications, including progressive MS, ALS, and substance dependence, with no current approved treatments for some of these conditions[105][106][107]. - MN-001 (tipelukast) is being developed for the treatment of Nonalcoholic Steatohepatitis (NASH), with no current approved therapies available for this condition[112]. - MN-001 (tipelukast) is also under development for Idiopathic Pulmonary Fibrosis (IPF), with existing approved treatments including Roche's Esbriet and Boehringer Ingelheim's OFEV[113]. - MN-029 (denibulin) is being developed for solid tumor cancers, with approved treatments including Roche's Kadcyla and Bayer's Stivarga[114]. - The company has initiated clinical development of MN-166 (ibudilast) for glioblastoma, with current standard treatments including surgery and chemotherapy[110]. - The company has been granted 14 U.S. patents covering various uses of MN-001 (tipelukast), including indications for nonalcoholic fatty liver disease and ulcerative colitis[90].