Amarin Corp Plc (AMRN)

[dogn]

Sleven,

Interesting find. I was just myself looking a bit yesterday into status of the Matinas Biopharma (MTNB) omega-3 formulation, which - based on their lipid nanocrystal (LNC) platform in theory seems promising due to claimed greater bioavailability for use in something like a once per day treatment pill.
This study looks at on-treatment EPA plasma levels, which have been correlated in REDUCE-IT to CVD benefits. I don't believe MTNB has looked beyond triglyceride lowering into CVD benefits, which would require a large, expensive CVOT like REDUCE-IT or STRENGTH, but one could extrapolate that if it's all about the EPA levels, similar results may be obtained.

The link you post appears to be an automatic update to the ENHANCE-IT clinical trial data to reflect March 4 publication of results ("Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number)." The "Actual Study Completion Date : January 18, 2021" is nearly 14 months ago. A direct link to the published paper is given, from which I found and browsed the full text article at:
https://www.ahajournals.org/doi/full/10.1161/JAHA.121.024176

The trial compared MAT9001 (= "Lypdiso") and Vascepa.

MAT9001 is an omega-3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA-ethyl esters [EE]), EPA+DPA-FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega-3 levels following twice daily dosing, with meals, of EPA+DPA-FFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet.

What stands out to me is:

(1) only modestly lower triglyceride and non-HDL cholesterol levels with MAT9001 vs Vascepa:

Both EPA+DPA-FFA and EPA-EE reduced TC, LDL-C, HDL-C, VLDL-C, and non–HDL-C concentrations, but there were no statistically significant differences between treatments in their effects on these parameters in the pharmacodynamic population. However, in the per protocol population, EPA+DPA-FFA compared with EPA-EE produced significantly larger reductions in TC (5.7% versus 3.5%, P=0.043) and VLDL-C (15.0% versus 10.9%, P=0.033).

I don't really understand the division of study populations into "pharmacodynamic vs. per protocol" but it seems perhaps a way to cherry pick data to achieve a desired outcome, shifting TC reduction from NS to just barely "statistically" significant.

(2) From Table 5:

EPA, µg/mL Baseline* End of treatment† % ?†
EPA+DPA-FFA 14.4 (13.1–15.8) 138 (124–153) 848 (754–952)
EPA-EE 14.8 (13.5–16.2) 115 (104–128) 692 (614–778)

So they do show higher end of treatment EPA levels of 138 µg/mL with MAT9001 vs 115 µg/mL with Vascepa... not sure how significant this is (848% vs 692% change from baseline are both huge).

I do recall seeing earlier claims of advantages of MAT9001 over Vascepa, and just noticed these again yesterday in the MTNB annual report:

LYPDISO
The Company continues to evaluate potential options for its legacy asset, LYPDISO. LYPDISO is a prescription-only omega-3 fatty acid-based composition, comprised primarily of EPA and DPA, intended for the treatment of cardiovascular and metabolic conditions. This next-generation omega-3 therapy has been shown in two head-to-head studies to provide effective triglyceride-lowering and significantly higher EPA blood levels than Vascepa ®. A global process to identity and potentially secure a partner to continue development of LYPDISO remains ongoing.

(3) It seems to me the undesirable side effects of MAT9001 are significant relative to Vascepa, and deemphasized in the paper:

In general, both treatments were well tolerated in this study. All adverse events were mild or moderate in nature, there were no serious adverse events, and there were no laboratory results of clinical concern. However, as in the previous 2-week examination of EPA+DPA-FFA,9 in this 4-week trial, more subjects reported adverse events when taking EPA+DPA-FFA (44.3%) than when taking EPA-EE (28.0%). More subjects reported nausea and diarrhea when taking EPA+DPA-FFA (11.3% and 10.3%, respectively, compared with 0.0% and 4.0% with EPA-EE). These events did not lead to subject discontinuation but could impact the clinical acceptability of EPA+DPA-FFA for some patients, which might affect adherence. A longer study is needed to better assess the long-term tolerability of EPA+DPA-FFA.

Maybe nausea and diarrhea are both included in this category, but Table 6 showing adverse events reports for Gastrointestinal disorders 25% (25.8) for MAT9001 vs. 11% (11.0) for Vascepa, which makes Vascepa the clear winner!

If it weren't for the adverse effects, I have thought perhaps Amarin would be interested in acquiring MAT9001 asset (which Matinas is clearly looking to do something with), as it could with greater bioavailability help make the once a day and/or combo EPA-Statin pill viable. Considering that MTNB's entire market cap is currently $127M and they're shifting their interest (per https://www.matinasbiopharma.com) to other LNC products (MAT2203, a broad-spectrum antifungal drug for immunocompromised patients; and MAT2501 - an orally-administered LNC formulation of the gram-negative antibiotic agent – amikacin), MAT9001 could be affordable as an acquisition to Amarin, though I don't think they do or should want it. It is interesting that both companies are in Bedminster NJ.

I initially thought Lypdiso was EPA+DHA like Strength and many other failed omega-3 combo formulations, and wondered if there might be a way to do an LNC EPA-only formulation with the Matinas technology... with the theory is that the lipid nanocrystal encapsulation increases bioavailability. But then today I realized Lypdiso is "a highly bioavailable free fatty acid formulation of EPA+DPA (docosapentaenoic acid). The paper describes it as "a long-chain omega-3 FFA concentrate in a 1-g capsule that contains a proprietary and patented mixture of predominantly EPA, with meaningful amounts of DPA, with trace levels of docosahexaenoic acid (DHA) and other omega-3 fatty acids." Perhaps the DPA is an essential part of the lipid nanocrystal technology that can't be eliminated? No idea.

Apparently DPA is much less studied than DHA, and I learned a bit more about DPA from this link: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/docosapentaenoic-acid

Finally, I saw in the MTNB earnings call transcript 2 instances where Matinas said they are moving away from Lypdiso:

10:19 As we transitioned away from LYPDISO in early 2021, we focused on execution of the EnACT trial, which we believed would yield critical clinical data validating our LNC platform technology, highlighting the impressive efficacy and safety of an oral amphotericin formulation, while at the same time serving as a very important demonstration of how our LNC technology was able to carry drug across the blood-brain barrier and target tissues that have been very challenging to reach with oral therapies.

39:29 Yeah. I mean, obviously, we're continuing to invest in the platform, but we're doing so in a disciplined way, adding head count has increased sort of the R&D spend modestly over the period. We don't expect huge increases and any increases or any additional investment we're also we believe is going to have the opportunity to offset those with some non-dilutive capital. So we're not evaluating any sort of capital raise at the moment, we're generally comfortable with our cash position taking into account some of the catalysts and milestones we have ahead. But for 2022 it's going to look consistent with what we've spent, I would say, over the last 6 months internally here as we've shifted away for from LYPDISO and that would continue sort of on a straight line through 2023 as well.

So it seems LYPDISO is being put to rest, no longer competition of concern for Vascepa, although still intriguing for it's ability to achieve higher EPA plasma levels.