Slide 1: Hemodynamic effects of TX45, a long-acting Fc-relaxin fusion, in Group 2 PH patients
Hemodynamic effects of TX45, a long-acting Fc-relaxin fusion, in Group 2 pulmonary hypertension (PH) patients Anthony J. Muslin, Robert Rogers, Alisa Lacey, Vasile Corcea, Marcella Ruddy 17 May 2025
Slide 2: Relaxin is a peptide hormone that activates the G protein coupled receptor RXFP1
Relaxin is a peptide hormone that activates the G protein coupled receptor RXFP1 • TX45 is a long-acting Fc domain of IgG1-relaxin fusion protein Pharmacology AGONIST Natural ligand of RXFP1 receptor No RXFP1 internalization from relaxin agonism no desensitization with chronic therapy Relaxin upregu
Slide 3: Relaxin is a pulmonary and systemic vasodilator with lusitropic, anti-fibrotic and anti-inflammatory activity
Relaxin is a pulmonary and systemic vasodilator with lusitropic, anti-fibrotic and anti-inflammatory activity * * * * Acute onset of effect
Slide 4: Phase 1b single ascending dose, open-label acute hemodynamic trial in PH-HF
Phase 1b single ascending dose, open-label acute hemodynamic trial in PH-HF (LVEF>40%, NYHA II/III) • Pure intention to treat (ITT) analysis performed: all data points included in the analysis. • Hemodynamic data prespecified to be pooled across all doses. After IV administration, all doses resulted
Slide 5: Phase 1b demographics and medical history were consistent with PH-HFpEF/PH-HFmrEF
Phase 1b demographics and medical history were consistent with PH-HFpEF/PH-HFmrEF All Subjects Key Concomitant All Subjects N = 19 Medications N = 19 Age (mean, SD) 65.1 (8.7) ACEi/ARB [n (%)] 10 (52.6 %) Females [n (%)] 7 (36.8%) MRA [n (%)] 16 (84.2 %) BMI (mean, SD) 28.9 (3.6) SGLT2i [n (%)] 8 (4
Slide 6: Phase 1b - Summary of baseline hemodynamics were consistent with PH-HFpEF/PH-HFmrEF
Phase 1b - Summary of baseline hemodynamics were consistent with PH-HFpEF/PH-HFmrEF Baseline Value Parameter PVR < 2WU 2 WU ≤ PVR < 3WU PVR ≥3 WU mean (SD) Heart Rate (bpm) 68.9 (11.4) 10 4 5 Systolic Blood Pressure (mm Hg) 127.8 (11.5) Diastolic Blood Pressure (mm Hg) 79.0 (6.1) Right Atrial Pressu
Slide 7: Phase 1b - TX45 was well-tolerated
Phase 1b - TX45 was well-tolerated • There were 10 treatment-emergent Treatment-emergent adverse events (# of subjects) adverse events (TEAEs) in 8 patients – Cohort A Cohort B Cohort C Total Preferred Term all mild/moderate and self-limited 0.3 mg/kg 1 mg/kg 3 mg/kg N=19 (n=3) (n=7) (n=9) • There w
Slide 8: TX45 improved hemodynamics in PH-HF patients
Phase 1b results TX45 improved hemodynamics in PH-HF patients CFB^ Average % CFB^ Secondary Endpoints mean [95% CI] mean [95% CI, P-value^] Hemodynamics (Key 2o ) (N = 19) Mean PCWP in all participants - 3.2 [-4.3 to -2.1,***]mm Hg -19.0% [-26.1 to -11.9%,***] Mean PVR in CpcPH (PVR ≥ 2 WU) (n=
Slide 9: TX45 reduced PCWP in both IpcPH and CpcPH patients; TX45 improved PVR in CpcPH patients
Phase 1b results TX45 reduced PCWP in both IpcPh and CpcPH patients; TX45 improved PVR in CpcPH patients Change in PCWP All Subjects* Change in PVR by baseline PVR* ^The only patient with increased PCWP post treatment had a PCWP greater than dPAP PVR≥2 (CpcPH): All subjects had decreased suggesting
Slide 10: TX45 increased cardiac output; enhanced in patients with higher baseline PVR
Phase 1b results TX45 increased cardiac output; enhanced in patients with higher baseline PVR Cardiac Output Baseline Treatment Period Absolute CFB Average % CFB (L/min) (L/min) (L/min) mean [95% CI] mean (SD) mean (SD) mean [95% CI] All subjects 4.48 (1.06) 5.21(1.04) +0.73 [0.39 to 0.72] +18.5% [1
Slide 11: TX45 hemodynamic effects were similar in subjects with HFmrEF and HFpEF
Phase 1b results TX45 hemodynamic effects were similar in subjects with HFmrEF and HFpEF CFB* Average % CFB* mean [95% CI] mean [95% CI] PCWP (N = 19) Mean PCWP in all participants - 3.2 [-4.3 to -2.1] mm Hg -19.0% [-26.1 to -11.9%] Mean PCWP in HFpEF (LVEF ≥ 50%) (N = 9) - 3.6 [-4.3 to -3.0] mm
Slide 12: PVR/SVR ratio: TX45 preferentially dilates pulmonary vessels in CpcPH
Phase 1b results PVR/SVR ratio: TX45 preferentially dilates pulmonary vessels in CpcPH, is a balanced vasodilator in IpcPH PVR/SVR Ratio in Subjects with PVR/SVR Ratio in Subjects with Baseline* PVR ≥ 2 WU (n= 9) Baseline* PVR < 2 WU (n= 10) PVR/SVR=0.15 PVR/SVR=0.12 PVR/SVR=0.08 PVR/SVR=0.09 *Mean
Slide 13: Echo results suggest sustained improvement in hemodynamics with TX45
Phase 1b results Echo results suggest sustained improvement in hemodynamics with TX45 • TX45 administration increased tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) and RV fractional area of change (RVFAC) *Nominal P<0.05, **Nominal P<0.01 for treated (Day
Slide 14: Conclusions
Conclusions • In this open-label single ascending dose study, TX45 was well-tolerated in Group 2 PH patients with HF (LVEF>40%) • TX45 administration resulted in acute hemodynamic improvement, including decreased PCWP, mPAP, and TPR, and increased CO and SV in entire cohort • TX45 decreased PVR in C