Crinetics Pharmaceuticals, Inc. · NASDAQ:CRNX
Crinetics Pharmaceuticals — 35th Brazilian Congress of Endocrinology and Metabolism (CBEM) 2022
16 slides from Crinetics Pharmaceuticals's conference presentation, Sep 3, 2022
Slide 1: Paltusotine Shows Long-term Safety and IGF-1 Maintenance in the ACROBAT Advance Study
Paltusotine Shows Long-term Safety and IGF-1 Maintenance in the ACROBAT Advance Study Mônica R. Gadelha for the ACROBAT Study Group Presented at the 35th Brazilian Congress of Endocrinology and Metabolism (CBEM); 03-07, September 2022; Sao Paulo, Brazil.
Slide 2: ACROBAT Study Author Group
ACROBAT Study Author Group Monica R. Gadelha, MD, PhD1; Murray B. Gordon, MD2; Mirjana Doknic, MD, PhD3; Emese Mezősi, MD, PhD, DSci4; Miklós Tóth, MD, PhD, DSci5; Cesar Boguszewski6 ;Harpal Randeva, MBChB, FRCP, FAcadTM, PhD7; Marcello D. Bronstein, MD, PhD8; Christine Ferrara-Cook, MD, PhD9; Aless
Slide 3: Disclosures
Disclosures Principal investigator - clinical trials: Crinetics, Novartis and Recordati Rare Diseases Speaker fee: Crinetics, Novo Nordisk, Ipsen, Recordati Rare Diseases, Novartis Advisory board member: Recordati Rare Diseases, Crinetics, Ipsen, Novo Nordisk Funding for this study is provid
Slide 4: Paltusotine: an oral, small non-peptide somatostatin agonist, highly selective to SST2
Paltusotine: an oral, small non-peptide somatostatin agonist, highly selective to SST2 Peptide: Octreotide Nonpeptide: paltusotine Survive proteolysis Diffuse through lipid bilayer Aided by gut permeabilizing Transcellular Paltusotine agents absorption (CRN00808) High Oral Bioavailability 70% Long O
Slide 5: ACROBAT Edge & Evolve: Phase 2 studies in acromegaly
ACROBAT Edge & Evolve: Phase 2 studies in acromegaly Evolve—Median Dose 20 mg/day Randomized Primary Screening Paltusotine Treatment Withdrawal Washout if IGF ≤ 1.0 Population WEEK -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Subjects treated with octreotide or lanreotide 10 20 30 mg
Slide 6: ACROBAT Edge: Paltusotine maintained IGF-1 and GH levels for 13 weeks after switching
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 3.0 IGF-1 p<0.0001 GH 2.5 p>0.6 2.0 IGF-1 ( ULN) p>0.6 p=0.6285 1.5 1.0 0.5 0.0 Baseline Paltusotine 4 Wks (Before Sw
Slide 7: ACROBAT Advance: Open label extension study design
ACROBAT Advance: Open label extension study design Screening Expected titration Long-Term Period period Dosing Period -4 up 65 to WEEK 1 4 8 12 16 24 32 40 48 52 to W1 208 Paltusotine ACROBAT Evolve and Paltusotine dose maintenance. Cabergoline add-on re-initiated and Edge completers enter to 40 mg
Slide 8: Baseline Characteristics ACROBAT Advance
Baseline Characteristics ACROBAT Advance All Subjects N=43 Age, Mean (SD) 53.0 (11.61) Sex, Female, n (%) 24 (55.8) Months since diagnosis, Mean (SD) 129.4 (78.42) Prior pituitary surgery, n (%) 37 (86.0) Pre-trial medical treatment1 Lanreotide, n - 60/90/120 mg/month 1/2/14 Octreotide, n - 20/30/40
Slide 9: Subjects from Parent Trials Enrolled into ACROBAT Advance
Subjects from Parent Trials Enrolled into ACROBAT Advance Primary Population Subjects treated with octreotide or lanreotide Evolve Baseline IGF-1 ≤1x ULN 9 Weeks 4 Weeks 4 Weeks Paltusotine Treatment Rand. Withdraw Washout ACROBAT Advance Open Label Extension Study Paltusotine Treatment Edge Subject
Slide 10: IGF-1 Maintained at Injected LA-SRL Baseline Levels After Switching to Paltusotine
IGF-1 Levels IGF-1 Maintained at Injected LA-SRL Baseline Levels After Switching to Paltusotine from Injected SRLs (all subjects) Evolve/ ACROBAT Advance Edge ALL SUBJECTS 3.0 LA- UT2 Median IGF-1 ± IQR SRL1 2.5 2.0 IGF-1 1.5 (x ULN) 1.0 ULN 0.5 0.0 Week 3 15 31 39 47 51 64 77 90 103 N 43 43 43 42 3
Slide 11: IGF-1 Maintained in Subjects Who Previously Participated in ACROBAT Evolve
IGF-1 Maintained at Injected LA-SRL Baseline Levels in Subjects Who Previously Participated in ACROBAT Evolve (Controlled with LA-SRL Monotherapy at Baseline) ACROBAT Advance Evolve EVOLVE SUBSET 3.0 LA- UT2 Median IGF-1 ± IQR SRL1 2.5 2.0 IGF-1 1.5 (x ULN) 1.0 ULN 0.5 0.0 Week 3 15 31 39 47 51 64 7
Slide 12: Subjects' Treatment Preference
Subjects' Treatment Preference • At 52 weeks in the study (or at the last visit for those who discontinued the study), participants were asked to choose their preferred treatment option. • Thirty-two (89%) of respondents preferred once daily paltusotine, two (5.5%) had no preference, and two (5.5%)
Slide 13: Safety Summary
Safety Summary TEAEs Occurring in ≥3 subjects Any Dose • During the study, there were 6 nontreatment-related TESAEs in 5 N=43 subjects: gallstone pancreatitis, worsening of coronary artery TEAEs n (%) m disease followed by sinus arrest post coronary artery bypass Headache 13 (30.2) 20 surgery, renal
Slide 14: HbA1c Remained Stable Throughout the Treatment Period
HbA1c Remained Stable Throughout the Treatment Period ACROBAT Advance ALL SUBJECTS 0.50 LA- Median Change from Baseline in HbA1c ± IQR SRL1 0.25 HbA1c 0.00 -0.25 -0.50 Week 11 23 39 51 77 103 N 43 38 38 36 26 10 1. Baseline (screening) from Evolve/Edge studies while on injected SRL therapy. CRINETIC
Slide 15: Conclusions
Conclusions • Once daily, oral paltusotine lowered and maintains IGF-1 at levels comparable to prior injected SRL therapy for up to 103 weeks. This was seen in all subsets of subjects representing a wide range of baseline disease control. • Paltusotine was well tolerated in this phase 2 study with a
Slide 16: Acknowledgements
Acknowledgements Thank you to the patients, nurses and investigators who made this study possible!