Slide 1: Long-Term Efficacy and Safety of Oral, Once-Daily Paltusotine Treatment in Acromegaly
Long-Term Efficacy and Safety of Oral, Once-Daily Paltusotine Treatment in Acromegaly: Two-Year Interim Results From the ACROBAT Advance Study Harpal Randeva, MBChB, FRCP, FAcad TM, PhD1; Monica R. Gadelha, MD, PhD2; Murray B. Gordon, MD3; Mirjana Doknic, MD, PhD4; Emese Mezősi, MD, PhD, DSci5; Mikl
Slide 2: SfE BES 2022 - Conflict of Interest
SfE BES 2022 - Conflict of Interest Name: Harpal Randeva √ I have the following potential conflicts of interest to report: √ Research Contracts Presenter: Peter Trainer, VP Clinical Endocrinology, Crinetics Pharmaceuticals Employee and stockholder CRINETICS PHARMACEUTICALS | 2
Slide 3: Paltusotine an oral, small non-peptide somatostatin agonist, highly selective to SST2
Paltusotine an oral, small non-peptide somatostatin agonist, highly selective to SST2 Octreotide Paltusotine MW=456 Common Ligand Receptor Binding Recognition Pocket Region MW=1019 Extracellular Cell sst2 sst2 Paltusotine (CRN00808) Membrane High Oral Bioavailability 70% Long Observed Half Life 42-5
Slide 4: ACROBAT Edge & Evolve: Phase 2 studies in acromegaly
ACROBAT Edge & Evolve: Phase 2 studies in acromegaly Exploratory population (groups 2-5; n=22): uncontrolled subjects on SRL + CAB or ≤ IGF-1 1x with intensive therapy CRINETICS PHARMACEUTICALS | 4
Slide 5: ACROBAT Edge: Paltusotine maintained IGF-1 and GH levels for 13 weeks
ACROBAT Edge: Paltusotine maintained IGF-1 and GH levels for 13 weeks after switching from injected SRL peptide depots Results from the Primary Population (Group 1) of the Edge study median (Interquartile Range [IQR]: 25th, 75th percentiles) 3.0 3.0 p<0.0001 * IGF-1 p<0.0001 * GH 2.5 2.5 p>0.6285 p=
Slide 6: ACROBAT Advance: Open label extension study design
ACROBAT Advance: Open label extension study design To evaluate long-term safety and efficacy of paltusotine in the treatment of patients with Acromegaly Interim results; for up to 2 years Screening Expected titration Long-Term Period period Dosing Period -4 up 65 to WEEK 1 4 8 12 16 24 32 40 48 52 t
Slide 7: IGF-1 Maintained at Baseline Levels After Switching to Paltusotine From Injected SRLs
IGF-1 Maintained at Baseline Levels After Switching to Paltusotine From Injected SRLs (All Patients) Evolve/ ACROBAT Advance Edge ALL PATIENTS 3.0 LA- Wash Median IGF-1 ± IQR SRL -out 2.5 IGF-1 (× ULN) 2.0 1.5 1.0 ULN 0.5 0.0 Week 3 15 31 39 47 51 64 77 90 103 N 43 43 43 42 39 37 38 37 31 27 21 10 C
Slide 8: IGF-1 Maintained at Baseline Levels in Patients Who Previously Participated in ACROBAT Evolve
IGF-1 Maintained at Baseline Levels in Patients Who Previously Participated in ACROBAT Evolve ACROBAT Advance Evolve Evolve subset LA- Wash Median IGF-1 ± IQR 3.0 SRL -out 2.5 IGF-1 (x ULN) 2.0 1.5 1.0 ULN 0.5 0.0 Week 3 15 31 39 47 51 64 77 90 103 N 11 11 11 11 11 11 11 11 8 7 4 1 Cumulative discon
Slide 9: Safety Summary
Safety Summary • 6 serious AEs in 5 patients: gallstone pancreatitis, worsening of Adverse events, n (%) m Any dose (N=43) coronary artery disease followed by sinus arrest, renal mass, Any AE 36 (83.7) 249 deep vein thrombosis, and arthralgia (elective hip AEs Occurring in ≥3 patients replacement) H
Slide 10: HbA1c Remained Stable Throughout Paltusotine Treatment Period
HbA1c Remained Stable Throughout Paltusotine Treatment Period ACROBAT Advance ALL PATIENTS LA- Median change from baseline in HbA1c ± IQR 0.50 SRL Baseline in HbA1c (%) Change From 0.25 0.00 -0.25 -0.50 Week 11 23 39 51 77 103 N 43 38 38 36 26 10 CRINETICS PHARMACEUTICALS | 10
Slide 11: Conclusions
Conclusions • Once daily, oral paltusotine lowered and maintained IGF-1 at levels comparable to prior injected SRL therapy for up to 103 weeks ‒ This was observed in all subsets of patients representing a wide range of baseline disease control • Paltusotine was well tolerated in this phase 2 study w
Slide 12: Acknowledgements
Acknowledgements The authors acknowledge the patients, nurses, and investigators who made this study possible. Funding for this study is provided by Crinetics Pharmaceuticals, Inc. CRINETICS PHARMACEUTICALS | 12