Tectonic Therapeutic (TECX) investor relations material

Clinical program updates

• Two clinical programs are ongoing: relaxin (phase II in Group 2 pulmonary hypertension with preserved ejection fraction heart failure, readout expected in the next few months) and TX2100 (APJ antagonist for hereditary hemorrhagic telangiectasia, phase I completed with strong safety profile).

• TX2100 will advance to phase I-B in severe patients by year-end and a phase II randomized study in early 2027.

• Biomarker analysis (TMDD) confirmed target engagement and informed dose selection for upcoming studies.

• Dose selection for TX2100 is supported by both biomarker and preclinical model data, increasing confidence in exposure targets.

Hereditary hemorrhagic telangiectasia (HHT) program insights

• Phase I data for TX2100 showed no hypertension or major safety issues, differentiating it from VEGF inhibitors.

• Clinically meaningful efficacy in HHT is defined as a 1-point drop in Epistaxis Severity Score or a 30% reduction from baseline, with daily diaries being validated for future endpoints.

• Efficacy of APJ antagonist was maintained over time in preclinical models, unlike VEGF inhibitors.

• APJ inhibition targets endothelial cells, potentially offering better safety and efficacy than AKT or VEGF inhibitors.

• Competing approaches in HHT target different pathways, but APJ antagonism is unique and may offer disease-modifying benefits.

Relaxin program and cardiometabolic insights

• Phase I-B data for relaxin in PH-HFpEF showed improvements in heart function and pulmonary hemodynamics, with evidence of efficacy and good tolerability.

• Previous failures in the relaxin class were attributed to wrong patient populations and dosing, leading to fluid retention and safety issues.

• Recent data from AstraZeneca and others have not shown similar safety concerns, and current studies are de-risked for these issues.

• No evidence of tachyphylaxis with relaxin; efficacy and target engagement sustained over six months in recent studies.

• Dose optimization is critical to balance efficacy and fluid retention, with current data supporting this approach.