How might the results of TYDAL‑TIMI 78 position MAR001 for advancement into a Phase 3 program, and what timelines are expected for that transition? | MREA (Aug 06, 2025) | Candlesense
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How might the results of TYDAL‑TIMI 78 position MAR001 for advancement into a Phase 3 program, and what timelines are expected for that transition?

How the TYDAL‑TIMI 78 results could set the stage for a Phase 3 program for MAR001, and the likely timing of that transition

1. What the TYDAL‑TIMI 78 trial is designed to show

Key trial features Why they matter for a Phase 3 decision
Population – Adults with elevated triglycerides (TG) and remnant cholesterol (RC) who are at increased risk of atherosclerotic cardiovascular disease (ASCVD). This is the same high‑risk group that will be targeted in a definitive Phase 3 outcome trial (e.g., major adverse cardiovascular events – MACE). Demonstrating efficacy in this “enriched” population provides a clear signal that can be extrapolated to a broader ASCVD‑at‑risk cohort.
Design – Randomized, double‑blind, placebo‑controlled, Phase 2b (TYDAL‑TIMI 78). A Phase 2b design is the industry‑standard “proof‑of‑concept” platform. Positive results on both efficacy (lipid‑parameter changes) and safety will satisfy the FDA’s “accelerated‑approval” or “fast‑track” criteria and give the sponsor a solid statistical basis for a larger Phase 3 trial.
Primary endpoints – Likely % change from baseline in TG and RC, plus key secondary cardiovascular biomarkers (e.g., LDL‑particle number, non‑HDL cholesterol, inflammatory markers). A robust, statistically‑significant reduction in TG/RC (the mechanistic target of MAR001) is the first gate‑keeper for Phase 3. If the magnitude of change is comparable to or exceeds that seen with existing therapies (e.g., EPA/DHA, PCSK9 inhibitors) it will be viewed as a “clinically meaningful” effect that can be linked to downstream outcome benefits.
Safety focus – Incidence of treatment‑emergent adverse events (TEAEs), hepatic and renal labs, and any signal of increased cardiovascular events. A clean safety profile is essential for a Phase 3 “pivotal” trial. The absence of serious TEAEs, especially in a high‑risk population, will allow the company to move forward without the need for extensive safety‑mitigation strategies that could delay or complicate a Phase 3 launch.

2. How positive TYDAL‑TIMI 78 data would position MAR001 for Phase 3

Result scenario Implication for Phase 3
≥ 30 % mean reduction in TG and ≥ 20 % reduction in RC vs. placebo, both statistically significant (p < 0.05) Provides a clear, quantifiable efficacy signal that can be used as the basis for a Phase 3 primary endpoint (e.g., time to first MACE). The magnitude of lipid change is large enough to be considered “clinically relevant” and to satisfy FDA expectations for a surrogate endpoint that predicts outcome benefit.
Safety profile comparable to placebo with ≤ 5 % discontinuation due to TEAEs Confirms that MAR001 can be administered long‑term in a cardiovascular‑at‑risk population, removing a major barrier to a pivotal trial and allowing the sponsor to propose a “no‑new‑safety‑signals” claim in the Phase 3 protocol.
Pre‑specified “go‑/no‑go” criteria met (e.g., ≥ 20 % TG reduction plus no increase in hepatic enzymes) Triggers the internal “Phase 3 activation milestone” that Marea Therapeutics has likely built into its development plan. The company can now move from a proof‑of‑concept study to a large, event‑driven Phase 3 trial (e.g., 2,000–4,000 patients, ≥ 3 years of follow‑up).
Exploratory biomarker data showing favorable changes in inflammatory markers (e.g., hs‑CRP) and non‑HDL cholesterol Strengthens the biological plausibility that TG/RC lowering translates into reduced atherosclerotic risk, supporting a regulatory discussion (e.g., FDA’s “surrogate endpoint” pathway) and potentially allowing a accelerated‑approval route if the Phase 3 trial is designed around a composite cardiovascular outcome.

3. Anticipated timeline for moving from TYDAL‑TIMI 78 to Phase 3

Milestone Estimated Timing Rationale
First patient enrollment (already occurred – 4 Aug 2025) Q3 2025 The trial is now open; enrollment of the full cohort (typical Phase 2b size for a lipid‑modifying agent is 300–500 pts) will take ~12–15 months.
Complete enrollment of the Phase 2b cohort Q2 2026 (≈ 12 months after first patient) Assuming a moderate enrollment rate (≈ 30 pts/month) and a target of ~350 pts, the enrollment window closes in mid‑2026.
Database lock and primary analysis Q4 2026 (≈ 6 months after last patient visit) Data cleaning, adjudication of any cardiovascular events, and statistical analysis of the primary TG/RC endpoints.
Read‑out of primary efficacy & safety results Q1 2027 (early 2027) The company will issue a press release or present at a scientific meeting (e.g., AHA, ACC) with the full data set.
Regulatory and strategic decision point (Go/No‑Go for Phase 3) Q1 2027 (concurrent with read‑out) If the pre‑specified efficacy and safety thresholds are met, the board will approve the Phase 3 program.
Phase 3 protocol finalization & IND amendment Q2–Q3 2027 (≈ 3–6 months) Drafting the pivotal trial design (event‑driven, 2–3 years follow‑up), site selection, and filing any required FDA amendments (e.g., “Phase 3 IND amendment”).
Site initiation & patient recruitment for Phase 3 Late 2027 – 2029 (≈ 24–30 months) A typical large cardiovascular outcome trial enrolls 2,000–4,000 pts over 2 years.
Primary Phase 3 read‑out (first interim analysis) 2029–2030 (≈ 3 years after first Phase 3 patient) Assuming a 3‑year follow‑up, the first major efficacy analysis (e.g., time to first MACE) would be available by 2029‑2030, positioning MAR001 for a potential 2029‑2030 regulatory filing.

Bottom‑line timeline:

- Data read‑out from TYDAL‑TIMI 78: early 2027.

- Go‑/No‑Go decision for Phase 3: Q1 2027.

- Phase 3 start‑up: mid‑2027.

- First pivotal efficacy read‑out: 2029‑2030, paving the way for a 2029‑2031 NDA (or BLA) submission, depending on the speed of enrollment and any regulatory acceleration programs.

4. Strategic considerations that could accelerate the transition

  1. Fast‑Track or Breakthrough Therapy designation – If the TG/RC reductions are large and the safety profile is clean, Marea could request early engagement with the FDA to obtain a Fast‑Track meeting, potentially shortening the time from Phase 3 start to filing.
  2. Surrogate‑endpoint pathway – Demonstrating that TG/RC lowering is a validated surrogate for ASCVD outcomes (supported by epidemiologic data and the exploratory biomarker results) could allow the company to seek accelerated approval based on the Phase 3 surrogate endpoint, with confirmatory outcome data collected post‑approval.
  3. Co‑development with lipid‑specialty societies – Partnerships with the American Heart Association (AHA) or European Society of Cardiology (ESC) could provide clinical‑trial‑network support and may speed patient recruitment for the pivotal trial.
  4. Potential for combination‑therapy data – If TYDAL‑TIMI 78 includes a sub‑analysis of MAR001 added to statins or omega‑3s, positive synergy could broaden the label and make the Phase 3 trial design more attractive to payers and investigators, further compressing timelines.

5. Summary answer

  • If TYDAL‑TIMI 78 demonstrates a ≥ 30 % reduction in TG and ≥ 20 % reduction in remnant cholesterol with a safety profile indistinguishable from placebo, MAR001 will have met the efficacy and safety “go‑/no‑go” criteria that the company has likely set for advancing to a pivotal Phase 3 trial.
  • The read‑out of the Phase 2b data is expected in early 2027, and a decision to launch Phase 3 would be taken shortly thereafter (Q1 2027).
  • Assuming a typical 12–15‑month enrollment for the Phase 2b cohort, a 6‑month data‑analysis window, and a 3‑year follow‑up for a large cardiovascular outcome trial, the earliest realistic timeline for a Phase 3 primary efficacy read‑out is **2029‑2030, positioning MAR001 for a potential regulatory filing in 2029‑2031.**

In short, a positive TYDAL‑TIMI 78 outcome will give Marea Therapeutics a clear, data‑driven springboard into a Phase 3 program that could be initiated by mid‑2027, with the first pivotal efficacy results expected by the end of the decade.

Other Questions About This News

What is the projected impact of the Phase 2b trial on Marea’s cash runway and future financing needs? When is the anticipated timeline for full enrollment in the TYDAL‑TIMI 78 Phase 2b study? Are there any disclosed or anticipated partnerships or licensing agreements related to MAR001 that could affect valuation? How does MAR001’s mechanism of action differ from existing triglyceride‑lowering therapies such as EPA/DHA formulations or PCSK9 inhibitors? What safety signals have emerged in Phase 1 or early Phase 2 data, and how might they influence investor sentiment? How does the Phase 2b design (dose, endpoints, patient population) compare to competitor programs in the same therapeutic area? When can we expect the first interim efficacy and safety data readout from the TYDAL‑TIMI 78 trial? What size does Marea anticipate the commercial market for a TG/RC‑lowering therapy to be, and what market share could be realistic if MAR001 succeeds? What are the primary efficacy endpoints (e.g., % reduction in TG, RC, or CV events) and are they considered clinically meaningful by the market? What potential regulatory pathway (e.g., FDA accelerated approval, cardiovascular outcome trial) does Marea anticipate for MAR001 if Phase 2b data are positive? What are the specific inclusion and exclusion criteria for patients in this study, and could they impact enrollment speed?