Zacks Small Cap Analysis – MNOV: Part 3 ALS Readout in 2025… – Go Well being Professional

By David Bautz, PhD

NASDAQ:MNOV

READ THE FULL MNOV RESEARCH REPORT

Enterprise Replace

Part 3 ALS Trial Ongoing

MediciNova, Inc. (NASDAQ:MNOV) is at the moment evaluating MN-166 (ibudilast) in a Part 3 scientific trial for amyotrophic lateral sclerosis (ALS). The trial initiated in 2019 and, if profitable, outcomes from this trial are anticipated to assist a New Drug Software (NDA) for MN-166 in ALS. A knowledge readout is anticipated in 2025.

The Part 2b/3 scientific trial is a multi-center, two-arm, randomized, double blind, placebo managed trial that’s evaluating MN-166 to placebo in roughly 230 sufferers with ALS (NCT04057898). Individuals within the trial will probably be randomized 1:1 between placebo and 100 mg/day of MN-166 for 12 months of remedy. The first endpoint of the trial is the imply change in ALS practical ranking scale-revised (ALSFRS-R) (Cedarbaum et al., 1999). The ALSFRS-R consists of a collection of 12 questions on primary duties (speech, salivation, swallowing, handwriting, reducing meals, dressing and hygiene, handing over mattress, strolling, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency) which can be rated on a five-point scale the place 0 = can’t do and 4 = regular means. The person objects are summed to provide a rating of between 0 = demise and 48 = finest. The ALSFRS-R rating is utilized to maintain observe of the well being of all ALS sufferers, and is a standard consequence measure in ALS scientific trials in addition to a longtime FDA-approvable endpoint. Secondary endpoints within the trial embrace the imply change from baseline in muscle power and high quality of life, time to survival, and security and tolerability.

Necessary inclusion standards embrace onset of ALS not more than 18 months previous to screening, the usage of riluzole for at the least 30 days previous to initiation of the research drug, gradual important capability at the least 70% of predicted, and an ALSFRS-R rating of at the least 35 at screening.

Optimistic Outcomes from Part 2 Trial of MN-166 in ALS

MediciNova beforehand studied MN-166 in a Part 2 trial in ALS. This was a single middle, double blind, placebo managed six-month research with sufferers randomized 2:1 to obtain riluzole (100 mg/day) plus both MN-166 (60 mg/day) or placebo. The six-month double blind portion was adopted by a six-month open label extension section throughout which all sufferers obtained MN-166. The intent-to-treat (ITT) inhabitants consisted of 51 sufferers who had been randomized to placebo (n=17) or MN-166 (n=34) for the double-blind portion of the research. The per protocol (PP) inhabitants consisted of 44 sufferers that accomplished the double-blind portion of the research (n=15 for placebo; n=29 for MN-166) and 35 sufferers that accomplished the open label extension (n=12 for placebo; n= 23 for MN-166).

Since this was the primary time MN-166 was examined in ALS sufferers the first consequence of the research was security and tolerability of the drug when administered together with riluzole (100 mg/day), the usual of take care of ALS sufferers. The research achieved the first consequence with no severe or life-threatening treatment-related hostile occasions (TRAEs). There have been six topics that had a complete of seven severe hostile occasions (5 for MN-166 group and one for placebo group), nevertheless none of them had been associated to remedy.

Along with the first endpoint of security and tolerability, the research additionally evaluated secondary efficacy endpoints. These secondary endpoints, which included an evaluation of ALSFRS-R, weren’t powered for statistical significance however had been evaluated to search for constructive traits that might assist information the design of future scientific trials. For this research, a responder was outlined as somebody who had a ≤1-point decline within the ALSFRS-R in the course of the six-month double blind interval whereas a non-responder was outlined as somebody who had >1-point decline in ASLFRS-R. For the ITT inhabitants, the outcomes confirmed that 29.4% (10/34) of MN-166-treated sufferers had been responders, in comparison with 17.6% (3/17) of placebo-treated sufferers. Within the open-label six-month extension section, 35.3% (6/17) of the sufferers who had obtained placebo in the course of the double blind portion of the research had been responders when taking MN-166. This compares fairly favorably with the 29.4% of sufferers who had been responders with MN-166 in the course of the double blind portion of the research.

Part 2 Trial of MN-001 in MASLD, Sort 2 Diabetes, and Hypertriglyceridemia Ongoing

MediciNova is at the moment conducting a Part 2 scientific trial of MN-001 (tipelukast) in sufferers with metabolic dysfunction-associated steatotic liver illness (MASLD; previously NAFLD), Sort 2 diabetes mellitus (T2DM), and hypertriglyceridemia. It’s a multi-center, two-arm, double-blind, placebo-controlled trial in roughly 40 sufferers within the U.S. Sufferers will probably be randomized 1:1 to obtain 500 mg/day of MN-001 or placebo for a complete of 24 weeks. The co-primary endpoints will probably be 1) change from baseline in liver fats content material as measured by MRI-PDFF; and a pair of) change from baseline in fasting serum triglycerides (TGs) at Week 24. Secondary endpoints will embrace adjustments in liver profiles, security, and tolerability. Earlier this yr, the corporate reported that 33 sufferers have been enrolled within the research, with 19 sufferers at the moment randomized and 14 sufferers having accomplished the research. So far, three topics have reported severe hostile occasions, nevertheless they had been all thought of “unlikely associated” or “unrelated” to check drug.

The Part 2 trial builds upon a number of earlier research inspecting the impact of MN-001 on TGs in MASH/MASLD (previously NASH/NAFLD) sufferers, preclinical research in mice, and in vitro research inspecting the mechanism of motion of MN-001 in reducing TGs.

• MediciNova beforehand reported constructive outcomes from a Part 2 scientific trial of MN-001 in sufferers with NASH and NAFLD with hypertriglyceridemia. A complete of 15 sufferers accomplished eight weeks of remedy with MN-001 (4 weeks at 250 mg/day and 4 weeks at 500 mg/day), with MN-001 decreasing serum TG ranges in 14/15 topics. The common pre-treatment serum TG degree was 328.6 mg/dL, which was decreased to a median 192.9 mg/dL following eight weeks of remedy (-41.3%, P=0.02). The corporate additionally analyzed the information excluding an outlier topic that had a particularly excessive serum TG degree of 1288 mg/dL previous to remedy that was decreased to 300 mg/dL after remedy. That evaluation confirmed that 13 out of 14 topics had a discount in serum TGs, from a median 260.1 mg/dL previous to remedy to a median 185.2 mg/dL following remedy (-28.8%, P=0.00006). Importantly, there have been no clinically vital security or tolerability points in the course of the research.

• In November 2021, MediciNova introduced the presentation of outcomes from a research investigating the mechanism by which MN-001 (tipelukast) alters TG metabolism in hepatocytes at The Liver Assembly 2021. The research concerned the remedy of HepG2 cells with arachidonic acid (AA), LXR agonist T0901317, and MN-001 both alone or in varied mixtures. In comparison with car, T0901317 elevated TG synthesis by 3.8-fold, AA alone elevated TG synthesis by 15.3-fold, and the mixture of T0901317 + AA elevated TG synthesis by 24.3-fold. The addition of MN-001 decreased TG synthesis when added together with T0901317 or AA. In comparison with MN-001 alone, MN-001 + T0901317 elevated TG synthesis by 1.7-fold, AA + MN-001 elevated TG synthesis by 3.7-fold, and the mixture of T0901317 + AA + MN-001 elevated TG synthesis by 3.7-fold. The mechanism by which MN-001 decreases TG synthesis seems to be resulting from a lower in CD36 expression. CD36 is among the receptors accountable for fatty acid uptake into hepatocytes, thus the inhibition of CD36 expression might clarify its means to decrease TG ranges.

• Two separate research in mouse fashions of NASH have proven MN-001 to have each anti-NASH and anti-fibrotic exercise:

o Research #1: MN-001 was administered orally as soon as each day (10, 30, or 100 mg/kg) for 3 weeks within the STAM (NASH-HCC) mouse mannequin of NASH. The mannequin is created by a mix of chemical and dietary interventions in a regular laboratory mouse pressure. Therapy with MN-001 resulted in a dose-dependent discount in liver fibrosis as demonstrated by a discount in liver hydroxyproline content material (P<0.01). As well as, there was a big enchancment (P<0.01) within the NAFLD exercise rating (NAS), which is a summation of the separate scores for steatosis (0–3), hepatocellular ballooning (0–2) and lobular irritation (0–3). Concurrently, MN-001 was proven to considerably down-regulate (P<0.01) the expression of MCP-1, CCR2, collagen type-1, and TIMP-1; all of that are genes related to the formation of fibrosis.

o Research #2: In a second research, the identical STAM (NASH-HCC) mouse mannequin of NASH was utilized, nevertheless the mice had been at a extra superior stage of NASH. MN-001 was administered orally as soon as each day (10, 30, or 100 mg/kg) for 4 weeks. As soon as once more, remedy with MN-001 resulted in a statistically vital lower in NAS rating (P<0.001), owing largely to a lower in hepatocyte ballooning rating and lobular irritation rating. Fibrosis space was additionally considerably decreased within the MN-001 handled group (P<0.01). MN-001 was as soon as once more proven to lower expression ranges of the beforehand examined genes together with LOXL2, a gene proven to be upregulated in fibrotic livers (Barry-Hamilton et al., 2010). Importantly, remedy with MN-001 had no impact on physique weight or common situation of the mice in comparison with placebo.

New Patent for MN-166 in Lengthy Covid

On August 29, 2024, MediciNova introduced it obtained a Discover of Allowance from the U.S. Patent and Trademark Workplace for a pending patent utility that covers MN-166 for post-COVID circumstances. The patent covers administering ibudilast to alleviate a spread of post-COVID circumstances together with nervousness, fatigue, melancholy, shortness of breath, post-traumatic stress dysfunction, chest tightness, palpitations, odor or style dysfunction, sleep difficulties, hair loss, and rash. As soon as issued, the patent is predicted to run out no sooner than November 2042.

Monetary Replace

On August 8, 2024, MediciNova filed Type 10-Q with monetary outcomes for the second quarter of 2024. As anticipated, the corporate didn’t report any revenues within the second quarter of 2024. R&D bills within the second quarter of 2024 had been $1.6 million in comparison with $1.7 million within the second quarter of 2023. The lower was primarily resulting from a lower in performance-based inventory possibility expense and product legal responsibility insurance coverage. G&A bills within the second quarter of 2024 had been $1.4 million in comparison with $1.6 million within the second quarter of 2023. The lower was primarily resulting from a lower in performance-based inventory possibility expense and payroll prices.

MediciNova exited the second quarter of 2024 with roughly $44.3 million in money and money equivalents. We estimate the corporate has enough capital to fund operations at the least via the top of 2025. As of August 5, 2024, the corporate had roughly 49.0 million shares excellent and when factoring in inventory choices a completely diluted share rely of roughly 57.5 million.

Conclusion

We stay up for information readouts from the Part 3 ALS trial and the Part 2 trial of MN-001. After having discussions with administration, it has grow to be obvious that the corporate will be unable to maneuver MN-166 ahead in growth in progressive a number of sclerosis (MS) however will as a substitute require a associate to assist fund the Part 3 trial and commercialization, if profitable. Because of this we now have drastically decreased the contribution of the MS indication in our mannequin, which has decreased our valuation to $10 per share.

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