Medicinova, Inc. H.C. Wainwright 28th Annual Global Investment Conference

David, all yours. Thank you, Lander, for the kind introduction, and we thank our viewers for joining us today.

As Lander said, my name is David Crean, Chief Business Officer for MediciNova. Dr. Yuichi Iwaki will also be joining us today, and also in New York next month. I want to start with the investment case on MediciNova. It is a biopharmaceutical company, as Lander mentioned. We are approaching two clinical readouts this year in 2026, with a balance sheet to reach those catalysts, and additional programs being advanced substantially through outside funding. Before we get started, would like to draw your attention that we will be making some forward-looking statements. Please refer to our SEC filings for any risks and uncertainties. We operate with a relatively lean senior team. Dr. Iwaki founded MediciNova and serves as our President and CEO.

Dr. Matsuda is our Chief Medical Officer, Jason Kruger, our CFO, and I lead business development, IR, public relations, and communications. That operating structure is very important when we start getting later on in our discussion about the amount of clinical activity that we have ongoing in support relative to our cash burn. You can see here our board then adds on finance, investment, legal, and medical experience. Let me move directly to the investment case. The investment case for MediciNova really comes down to four points. First, MN-166, or ibudilast, which is our core program. It is our core value driver in ALS. Enrollment, importantly, is complete in the 234-patient registrational trial called COMBAT-ALS. It is a phase IIb/III clinical study, and importantly, top line is expected by the end of this year.

Secondly, we have another clinical catalyst ahead of that, MN-001, and that is in a phase II study in patients with hypertriglyceridemia, type 2 diabetes, and NAFLD, or fatty liver disease. Enrollment is importantly also complete in that, and top line is expected in the third quarter of this year, so September. Third is our balance sheet. We reported $25.4 million on the balance sheet at the end of Q2. Historically, we have been operating our burn at approximately $12 million to $13 million annually. We have no debt, no warrants, and our expectation is that the current cash reaches the key clinical data milestones this year. Fourth, we have additional clinical programs being funded externally through government and academic collaborations, which really creates some optionality. Bottom line, our investors do not have to underwrite the entire pipeline. The near-term story is much simpler. You have two clinical readouts.

You have cash intended to get us through those readouts, and externally funded optionality behind them. Let's get to our unique model, and this is really how we deploy capital. As I mentioned, ALS is our core focus. It is internally funded, and it is our principal value driver and has the clearest near-term regulatory and commercial pathway. Outside of that core, we have programs in dyslipidemia, NAFLD or MASH, oncology, acute lung injury, where development is partner funded or grant driven. I want to be precise about the phrase that we are using, operationally de-risk, because we are talking about and operating in a financing model. We are not suggesting that clinical risk has disappeared. COMBAT-ALS still remains a binary clinical event until we have the data. So what we have done is to reduce the amount of shareholder capital required to maintain exposure to multiple programs.

You can see here our pipeline. There are multiple programs on this slide, but for the current investment horizon, let's just really focus on two. The upper one, which is COMBAT-ALS, as I mentioned, enrollment is complete, and top line is expected in the fourth quarter of this year. At the bottom is MN-001, and that is the cardiometabolic program with top line expected in the third quarter. Behind those are the ALS Expanded Access Program, or EAP. You also have degenerative cervical myelopathy, chemotherapy-induced peripheral neuropathy, and glioblastoma neural oncology. Those programs really create additional shots on goal, but the immediate valuation discussion should be driven primarily by the two upcoming readouts, as I mentioned. This is an important part of our capital deployment, our capitally efficient argument.

These partner programs are funded by government agencies and conducted by academic investigators in the U.S., in the U.K., Australia, and Canada. The deck that you see here today really reflects MediciNova retaining the regulatory pathway, very importantly, and it has retained exclusive commercialization rights upon any trial completion. So I would really treat these programs as upside optionality rather than something investors need to be putting into the base valuation today. Let's just really move on to what we consider the most important part of the company's presentation, that is MN-166 in ALS. You can see, as I mentioned, MN-166 or ibudilast is importantly a CNS penetrant, small molecule. The molecule has both oral and intravenous formulations, but what I would tell you that in the COMBAT-ALS trial, we are studying the oral formulation.

It acts through several mechanisms relevant to neural inflammation, including inhibition of MIF, multiple phosphodiesterases, you can see there, and TLR4. The intended clinical effects are reduction of neuroinflammation and neuroprotection. That is a multi-targeted profile that really matters because ALS is not a single pathway disease. That brings us to really the biological rationale for using MN-166 in ALS. You can see here the rationale has really three components. As I mentioned, neuroinflammation reduction, you have MIF, PDE, and TLR4 inhibition, and that can reduce pro-inflammatory signaling and attenuate glial cell activation. Secondly, you have that neuroprotection. By reducing the inflammation-supporting protein clearance, the objective is to protect motor neuron function. Then third is really, excuse me. Sorry. Third is autophagy, and the work that is supporting our MN-166 suggests an effect on the clearance of TDP-43 protein aggregates, which are tightly and highly relevant to ALS pathology.

We are not relying upon one receptor or one molecular pathway. We have a multi-targeted mechanism addressing several components of ALS biology. Our mechanism alone does not create value. What matters is whether it is going to translate into a clinical effect for the benefit of patients. Our first ALS study gave us a signal to pursue that question in a larger trial, and you can see here in our phase IIa responder signal in our first trial, this was our first clinical efficacy signal that we saw. It was a phase IIa study enrolling 51 patients.

They were relatively long duration ALS patients with ALS history of approximately five years, and they were also on riluzole, standard of care. Patients received 60 milligrams per day of MN-166 or given placebo for six months, followed by an open label extension. What interested us as well as clinicians was the responder pattern. On the ALSFRS, defined here as stable or improved from baseline, the responder rate was 21.2% on MN-166 versus 12.5% on placebo. For the quality of life, it was 51% versus 25%. Manual muscle testing was 33% versus 25% on placebo. I want to be careful about these data. This was a 51-patient trial, phase IIa study. It was not designed to really establish definitive efficacy. What we saw, though, was a directional responder signal across function, across quality of life, and muscle strength.

That signal, together with the biological rationale and the support of our investigators, really supported us moving into the larger registrational COMBAT-ALS study. You can see here that the commercial opportunity is relatively straightforward. There is approximately 30,000 people with ALS in the U.S., and average life expectancy remaining roughly two to five years from diagnosis. Treatment options, however, remain limited, and with the withdrawal of Amylyx's drug, RELYVRIO, it reinforces really the standard that matters here, a new therapy that has to demonstrate meaningful clinical benefit. You can see very large global market estimated at more than $2 billion. For us, market size is really secondary. If COMBAT-ALS demonstrate meaningful benefit on function and survival in a broad sporadic ALS population, then the commercial opportunity really follows from the data. Here is our ongoing COMBAT phase II/IIIb ALS study called COMBAT.

It is the pivotal study in this presentation. It is a randomized, placebo-controlled, double-blind phase IIb/III study conducted across multiple centers in the U.S. and Canada. Patients were randomized one-to-one to MN-166 or placebo. The dose was 100 milligrams per day. The double-blind treatment was 12 months, followed by a six-month open label extension. The plan size going into it was 234, but we ultimately randomized 234, and enrollment was completed in September of last year in 2025. Importantly, these are early-stage ALS patients. The protocol requires disease onset within 18 months. The primary endpoint is the combined assessment of functionality and survival. It combines a change in ALSFRS at month 12 with survival time through a global rank analysis. This is an important endpoint in ALS because it does not look just at functionality in isolation, it incorporates both functional progression and mortality.

The secondary measures include muscle strength, also quality of life, responder analysis, survival, safety and tolerability. Compared with the original phase IIa study that I showed you prior to this COMBAT study, it is much larger, uses the 100 milligram dose, and enrolls patients earlier in the disease course of ALS and evaluates them through a full year of double-blind treatment, so very important. Recruitment risk is now behind us, which is great. The issue is no longer whether we can enroll the study. The issue is what the data is going to show at the end of the year. Top line, as I mentioned, is expected by the end of this year. You can see here, this slide gives you some context on who we actually enrolled. Mean age is approximately 61 years of age.