To Fellow Shareholders,

We continue to advance our key programs to create viable treatments for both metabolic disease and amyotrophic lateral sclerosis (ALS). Recently, we announced topline results of our Phase 2 clinical trial (MN-001-NATG-202) evaluating MN-001 (tipelukast) in patients with nonalcoholic fatty liver disease (NAFLD) and hypertriglyceridemia associated with type 2 diabetes mellitus. This randomized, double-blind, placebo-controlled study enrolled 40 patients over a 24-week treatment period and was designed as an exploratory, proof-of-concept trial.

We observed encouraging signals, although the trial did not achieve statistical significance on its primary endpoints. There were statistically significant improvements in high-density lipoprotein cholesterol (HDL-C) and HDL particle concentration (HDL-P) compared with placebo, as well as an early, statistically significant reduction in serum triglycerides. At the end of the 24-week treatment period, serum triglycerides, liver fat, and body weight were also reduced in the MN-001 group compared with placebo, although these differences did not reach statistical significance. These observations were consistent with findings from previous clinical trials and preclinical studies evaluating the mechanisms of action of MN-001 and with the directional signals anticipated from an exploratory study of this size.

We are conducting further analyses of the full dataset to better understand the observed outcomes, including the potential influence of concomitant medications and baseline severity of lipid abnormalities. MN-001 was well tolerated in this study, with no drug-related serious adverse events reported, consistent with the favorable safety profile observed among more than 650 subjects exposed to MN-001 in prior clinical studies, including studies that evaluated substantially higher doses than the dose used in the current trial.

We believe the observed changes are clinically relevant and that we have met our overarching goal of demonstrating proof of concept of MN-001 in this treatment context. The findings support continued evaluation of MN-001. Once our analyses are sufficiently advanced, we will use the results to assess potential next steps for this indication, including how the program may proceed, and will provide updates as appropriate.

We are also approaching a significant milestone for our lead asset, MN-166 (ibudilast), for ALS. In September, we announced completion of the last patient, last visit in the double-blind portion of COMBAT-ALS, our Phase 2b/3 trial evaluating MN-166 in 234 patients with ALS. The trial's primary endpoint is the Combined Assessment of Function and Survival (CAFS), and we remain on track to report topline results by year-end. MN-166 has received Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration for ALS, as well as orphan designation in Europe. ALS remains a devastating disease with limited treatment options.

We look forward to continued communication around our development of MN-001 in metabolic disease. We believe MN-001 remains a worthwhile pursuit and are encouraged by signals observed to date. We also look forward to sharing topline results from COMBAT-ALS and advancing MN-166 as a potential treatment for people living with ALS. We are grateful for our shareholders’ ongoing support and remain committed to creating long-term value for our shareholders.

Sincerely,

Yuichi Iwaki, M.D., Ph.D.

Founder, Chairman, CEO, and President

MediciNova, Inc.