TYDAL-TIMI 78 and CTX310

Two early-phase lipid trials from LBS.05 at AHA 2026 (Monday 9 November). TYDAL-TIMI 78 Part A, presented by Michelle O'Donoghue (TIMI Study Group) and published simultaneously in NEJM: 235 adults with elevated triglycerides and remnant cholesterol randomised to subcutaneous MAR001 (a monoclonal antibody against ANGPTL4) 300, 450 or 900 mg or placebo every four weeks for 24 weeks. Figures from the Marea Therapeutics release (the NEJM abstract is not yet readable to us): placebo-adjusted fasting triglyceride reduction at week 12 of 39.1, 40.9 and 45.5 percent (P less than 0.001 for all); 52.8, 53.7 and 57.2 percent in those with baseline triglycerides of 300 mg/dL or more; 31.0, 35.1 and 51.7 percent reached below 150 mg/dL versus 3.4 percent on placebo; remnant cholesterol minus 37.3 to minus 40.8 percent; treatment-emergent adverse events 69.5 versus 77.6 percent, serious adverse events 2.8 versus 6.9 percent, injection-site reactions 14.1 versus 19.0 percent, no pancreatitis, no deaths, no worsening of HbA1c. Part B (about 100 patients with triglycerides 450 to 2,000 mg/dL) has started; a half-life-extended successor MAR005 is the phase 3 candidate. CTX310, presented by Ashish Sarraju (Cleveland Clinic; figures from the Cleveland Clinic release, the CRISPR Therapeutics release being unreachable): phase 1b, ten adults with severe hypertriglyceridaemia, one intravenous infusion of an in vivo CRISPR-Cas9 editor that inactivates ANGPTL3 in the liver; at 30 days triglycerides fell by a mean 63 percent (up to 85 percent) and ANGPTL3 by more than 65 percent, with lower non-HDL cholesterol and apoB; no treatment-related serious adverse events. Both are hypothesis-generating: no outcomes, short follow-up, sponsor-reported figures.