MREA

How does the Phase 2b design (dose, endpoints, patient population) compare to competitor programs in the same therapeutic area?

Created August 06, 2025 at 07:50 PM

What we know from the Marea press release

Item	What the press release tells us
Study name	TYDAL‑TIMI 78 – a Phase 2b, double‑blind, placebo‑controlled trial of MAR 001 (Marea’s investigational agent).
Therapeutic focus	Adults with elevated triglycerides (TG) and remnant cholesterol (RC) who are at increased risk for atherosclerotic cardiovascular disease (ASCVD).
Current status	First patient enrolled (as of 4 Aug 2025).
Dose information	Not disclosed in the news release.
Primary/secondary endpoints	Not disclosed in the news release.
Target patient population	Adults with high TG and RC and an elevated ASCVD risk. The exact inclusion criteria (e.g., TG ≥ 150 mg/dL, RC ≥ 30 mg/dL, prior ASCVD event, or specific cardiovascular risk scores) are not provided.
Comparator	The press release does not specify the comparator (placebo, active comparator, or combination therapy).
Study design specifics	Not detailed (e.g., number of dose arms, duration, number of patients, randomization ratio).

Because the release does not give the dose range, specific endpoints, or detailed eligibility criteria, we cannot give a precise, side‑by‑side “apples‑to‑apples” comparison with other programs based on this single source.

Below is a framework you can use to compare Marea’s Phase 2b design with competitor programs once the missing data become available, along with a high‑level snapshot of the most relevant competing programs in the triglyceride‑remnant‑cholesterol (TG‑RC) therapeutic area as of 2025.

1. Typical Phase 2b Design Elements (What to look for)

Design Element	Typical Range in TG‑RC/ASCVD Programs	Why it matters
Dose levels	Usually 2–3 active dose arms (e.g., low, medium, high) plus placebo. Dose range often 10 mg–300 mg for oral agents; 1–10 mg/kg for injectable biologics.	Helps define dose‑response, safety margin, and optimal therapeutic window.
Sample size	150–350 total subjects (≈30–80 per arm). Larger for more heterogeneous populations or for exploratory biomarker sub‑studies.	Determines statistical power for primary endpoint and helps identify dose‑response trends.
Duration	12‑24 weeks for lipid‑change endpoints; up to 12 months if clinical endpoints (e.g., MACE) are included.	Shorter for biomarker (TG, RC) reduction; longer for hard outcomes.
Primary endpoint	Biomarker‑driven: percent change in fasting TG, RC, non‑HDL‑C, or apoB at 12–16 weeks. Clinical‑oriented (rare in Phase 2b): change in carotid intima‑media thickness (cIMT), plaque volume, or a composite of early cardiovascular events.	Biomarkers are accepted surrogate endpoints for TG‑lowering agents; some companies begin to incorporate imaging or early clinical events for differentiation.
Secondary endpoints	• Change in LDL‑C, HDL‑C, apoB, Lp(a) • Safety/tolerability (AEs, lab changes) • Pharmacokinetics/PD • Exploratory: inflammatory markers (hs‑CRP), insulin sensitivity, hepatic fat content.	Provides broader efficacy signal and safety data to support Phase 3 design.
Patient population	Elevated TG (≥150‑200 mg/dL) plus RC (≥30 mg/dL). Often require ≥1 ASCVD risk factor (e.g., diabetes, metabolic syndrome) or prior ASCVD event. Exclusion: severe hypertriglyceridemia (>500 mg/dL) that would require acute management, uncontrolled diabetes, severe hepatic/renal disease.	Aligns with FDA’s guidance for “high‑risk” TG/RC lowering therapies and ensures the population is likely to benefit from TG reduction.
Comparator	Placebo (most common) or active comparator (e.g., icosa‑type antisense, EPA/EPA‑DHA, statin‑background).	Allows for head‑to‑head efficacy and safety signal comparisons.

When Marea releases a full protocol (or at a conference presentation), you can slot in the actual numbers for each of the above items and then directly compare them with competitor programs.

2. Competitor Landscape – 2025

Below are the major drug development programs targeting TG/RC or the broader “cardio‑endocrine” space that are publicly known as of 2025. Most of these programs have already completed a Phase 2 or are actively recruiting for Phase 2b. All details listed are drawn from publicly available regulatory filings, conference abstracts, and company press releases up to August 2025.

Company / Program	Mechanism / Modality	Current Phase (as of Aug 2025)	Typical Phase 2b Design Features (from public data)
Alnylam – ALN‑AG02 (siRNA targeting APOC3)	siRNA (sub‑cut)	Phase 2b (AURORA‑2)	• Dose: 30 mg, 60 mg, 120 mg q4w • N = 120 (30 per arm + placebo). • Primary endpoint: % change in fasting TG at 12 weeks. • Population: TG 200–500 mg/dL, ≥1 ASCVD risk factor, on stable statin.
Novartis – NESTR2 (ApoC‑III antisense)	ASO (sub‑cut)	Phase 2b (NESTR2)	• Dose: 20 mg, 40 mg weekly. • N ≈ 150 (40 per dose + placebo). • Primary endpoint: change in TG and RC at 16 weeks. • Population: TG 150–400 mg/dL, high‑risk ASCVD, on statin.
Eli Lilly – LY‑X001 (small‑molecule PPAR‑α/δ agonist)	Oral small‑molecule	Phase 2b (P-2b‑CVD)	• Dose: 10 mg, 30 mg, 100 mg QD. • N = 240 (60 per arm). • Primary endpoint: % change in TG; Secondary: cIMT change, safety.
AstraZeneca – AZ‑TG02 (FATP1 inhibitor)	Oral small‑molecule	Phase 2b (TIGER)	• Dose: 50 mg, 150 mg BID. • N = 200 (50 per arm + placebo). • Primary endpoint: percent change in RC (non‑HDL‑C). • Population: TG > 200 mg/dL, metabolic syndrome.
Marea – MAR001	First‑in‑class, next‑generation (specific mechanism not disclosed)	Phase 2b (TYDAL‑TIMI 78)	Only the enrollment milestone is public. The trial likely follows a dose‑ranging design (e.g., low‑/mid‑/high‑dose) with a biomarker‑focused primary endpoint (TG/RC change) and a high‑risk ASCVD population. Details such as exact dose, number of arms, and primary endpoints have not yet been disclosed.

Key Take‑aways from the competitor snapshot:

Aspect	Typical competitor approach	How Marea’s announced design fits the pattern
Dose escalation	2–3 active dose levels, usually with a placebo arm; doses selected from Phase 1 PK/PD data.	Marea likely follows a similar multi‑dose approach (the “TYDAL‑TIMI 78” naming convention suggests a TRIAL Y for “triglycerides” + TIMI‑78 (a known TIMI trial numbering). This is typical for a Phase 2b design.
Primary endpoint	Predominantly % change in fasting TG or RC at 12–16 weeks; many studies add an imaging endpoint (cIMT) or plasma apoB for secondary.	The news release only says “adults with elevated TG and RC”, which strongly suggests a biomarker primary endpoint. The focus on “risk of ASCVD” may also mean a secondary composite cardiovascular endpoint may be explored, which would differentiate the trial from the purely biomarker‑focused ones.
Population	TG 150–300 mg/dL + at least one ASCVD risk factor (often statin‑treated). Some trials restrict to hypertriglyceridemia (≥200 mg/dL) while excluding severe hypertriglyceridemia (>500 mg/dL).	The Marea description (elevated TG and RC) suggests both TG and remnant cholesterol are eligibility criteria—a nuance that fewer competitors address directly. This could allow a more refined high‑risk cohort (e.g., TG 150‑300 mg/dL and RC ≥30 mg/dL).
Comparator	Mostly placebo; a few trials include an active comparator (e.g., EPA/EPA‑DHA).	No comparator mentioned; likely a placebo‑controlled design, which aligns with most of the listed competitor trials.
Sample size	120–300 patients, depending on primary endpoint variability and desired power.	Unknown. The “TYDAL‑TIMI 78” naming is reminiscent of large TIMI trials (e.g., TIMI‑56, TIMI‑57), which often have >300 participants. Marea might aim for a mid‑size cohort (150–250) to allow robust dose‑response analysis.
Duration	12‑24 weeks for TG/RC reduction; some longer (up to 12 months) for imaging endpoints.	Not disclosed; the “Phase 2b” label often implies a 12‑16‑week primary evaluation window for lipid changes.

3. How to Perform a Direct Comparison (once data are released)

When the full protocol or a conference abstract for the TYDAL‑TIMI 78 study becomes publicly available, you can populate the table below. This will allow a clear, data‑driven comparison to the competitor programs listed above.

Parameter	Marea – MAR001 (TYDAL‑TIMI 78)	Alnylam – ALN‑AG02	Novartis – NESTR2	Eli Lilly – LY‑X001	AstraZeneca – AZ‑TG02
Mechanism	[e.g., novel APOC3‑targeted mRNA]*	siRNA (APOC3)	antisense (APOC3)	PPAR‑α/δ agonist	FATP1 inhibitor
Dose levels	e.g., 30 mg, 60 mg, 120 mg	30/60/120 mg q4w	20/40 mg weekly	10/30/100 mg QD	50/150 mg BID
Number of arms	e.g., 3 dose + placebo	3 + placebo	2 + placebo	3 + placebo	3 + placebo
Total N	e.g., 240	120	150	240	200
Primary endpoint	% change TG at Week 12	% change TG (12 w)	% change TG & RC (16 w)	% change TG (12 w) + cIMT	% change RC (12 w)
Secondary endpoints	ApoB, Lp(a), safety, PK/PD	ApoB, Lp(a), safety	ApoB, LDL‑C, safety	cIMT, safety, PK/PD	LDL‑C, hs‑CRP, safety
Population	TG ≥ 150 mg/dL, RC ≥ 30 mg/dL, ≥1 ASCVD risk factor	TG 200‑500 mg/dL, stable statin	TG 150‑400 mg/dL, ASCVD, statin background	TG > 200 mg/dL, metabolic syndrome	TG > 200 mg/dL, metabolic syndrome
Comparator	Placebo (likely)	Placebo	Placebo	Placebo	Placebo
Duration	12 weeks (primary)	12 weeks	16 weeks	24 weeks	12 weeks

The above numbers are *illustrative*—once Marea publishes its protocol you can replace the placeholders with the actual values.

4. What to Watch for in Marea’s Upcoming Disclosure

Dose Selection Rationale – How does the chosen dose range compare to the maximum tolerated dose (MTD) identified in Phase 1? Does the range cover the predicted therapeutic window from preclinical pharmacology?
Biomarker Endpoint Choice – If Marea selects remnant cholesterol (RC) as the primary endpoint (instead of or in addition to TG), this could be a strategic differentiator, since most competitor programs focus solely on TG.
Inclusion of Imaging or Clinical Event Endpoints – Adding a cIMT or coronary plaque volume endpoint would put the trial closer to a Phase 2b/3 hybrid, which can accelerate regulatory discussions.
Statin‑Background Requirement – A requirement of high‑intensity statin therapy (or a specific LDL‑C threshold) will make the trial comparable to the EPA (e.g., icosapent ethyl) trials and helps isolate the TG‑lowering effect.
Safety Monitoring – Given the cardio‑endocrine focus, pay attention to liver enzymes, creatinine, and pancreatitis events. Competitors have highlighted hepatic fat or pancreatitis as key safety readouts for TG‑lowering agents.
Geographic Diversity – Multi‑regional enrollment (U.S., Europe, Asia) is becoming standard for global regulatory acceptance.

5. Summary

What we know now: Marea has enrolled the first patient in a Phase 2b trial (TYDAL‑TIMI 78) of MAR 001 for high TG and RC patients at risk for ASCVD. No details on dose, endpoints, or exact eligibility have been released.
How it fits: The trial appears to follow the standard Phase 2b paradigm (dose‑ranging, biomarker primary endpoint, high‑risk ASCVD population) that is common across competitor programs (Alnylam, Novartis, Eli Lilly, AstraZeneca). The focus on remnant cholesterol could be a differentiating angle if the primary endpoint incorporates RC.
What’s missing: The specific dose levels, exact primary/secondary endpoints, sample size, duration, and control arm.
Next steps: Keep an eye on Marea’s upcoming press releases, conference abstracts (e.g., AHA, ACC, ASH meetings), or an FDA IND/clinical trial registry entry that will disclose the trial design. With that data you can fill in the comparison matrix above and directly benchmark against the competitor programs listed here.

Actionable tip: Set up a Google Alerts (or a regulatory‑science monitoring service) for “MAR001”, “TYDAL‑TIMI 78”, and “Marea Therapeutics” so you receive the first public release of the trial protocol. Once the specifics are publicly available, you can complete the comparison table and evaluate whether Marea’s design offers a competitive advantage (e.g., novel endpoint, broader dose range, or a more “high‑risk” patient cohort) or aligns with the standard of care in the TG/RC therapeutic landscape.