Viridian Therapeutics, Inc. · NASDAQ:VRDN
Viridian Therapeutics — ARVO 2023
15 slides from Viridian Therapeutics's conference presentation, April 2023
Slide 1: Phase 1/2 Trial of VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor, in TED
Phase 1/2 Trial of VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor, in Patients with Thyroid Eye Disease (TED) Roger Turbin*, Raymond S. Douglas, Shoaib Ugradar, Kimberly Cockerham, Jade Schiffman, Navdeep Nijhawan, Denis O’Shaughnessy, Rochelle Summerfelt, Angela She, Barrett Katz *Rutgers N
Slide 2: TED: Inflammation, Tissue Expansion, and Remodeling in the Orbit
TED: Inflammation, Tissue Expansion, and Remodeling in the Orbit • TED results in inflammation and tissue expansion in the fixed bony orbit. • These changes result in short-term and long-term consequences including proptosis and dysmotility. • Insulin-like growth factor-1 receptor (IGF- 1R) antagoni
Slide 3: VRDN-001 Proof-of-Concept Randomized, Double-Masked Trial Tested 3 Different Doses
VRDN-001 Proof-of-Concept Randomized, Double-Masked Trial Tested 3 Different Doses in Patients with Active TED Placebo (n=6*) VRDN-001 3 mg/kg Patients with active TED: (n=9) • Clinical activity score (CAS) of ≥4 • Onset of signs/symptoms within prior 12 months VRDN-001 10 mg/kg (n=6) VRDN-001 20 mg
Slide 4: Baseline Patient Characteristics
Baseline Patient Characteristics VRDN-001 VRDN-001 VRDN-001 VRDN-001 (3, 10, and 20 mg/kg) 3 mg/kg 10 mg/kg 20 mg/kg Placebo n 21 9 6 6 5 Proptosis, mean (SEM) 23.7 (0.7) 23.1 (1.2) 24.8 (1.2) 23.6 (1.3) 22.8 (2) CAS, mean (SEM) 5.4 (0.2) 5.4 (0.4) 5.2 (0.3) 5.5 (0.4) 5.0 (0.5) Diplopia, n (%) 13 (6
Slide 5: VRDN-001 Efficacy Measures at 6 Weeks
VRDN-001 Efficacy Measures at 6 Weeks Signs Symptoms Improvement in Improvement in clinical activity score proptosis (CAS) and diplopia score Overall response: Proptosis: Proptosis: CAS: CAS: Diplopia: Signs + symptoms Responder rate Mean change by Score of 0 or 1 Mean change Complete (% with ≥2-mm
Slide 6: Independent Teprotumumab Phase 3 Study Results at 6 Weeks
Independent Teprotumumab Phase 3 Study Results at 6 Weeks* Signs Symptoms Improvement in Improvement in clinical activity score proptosis (CAS) and diplopia score Overall response: Proptosis: Proptosis: CAS: CAS: Diplopia: Signs + symptoms Responder rate Mean change by Score of 0 or 1 Mean change Co
Slide 7: Exophthalmometry and MRI Together Provide Robust Assessment of Proptosis
Exophthalmometry and MRI Together Provide Robust Assessment of Proptosis Hertel Exophthalmometer Magnetic Resonance Imaging • Most commonly used and FDA- • More precise required for clinical studies • 3D reconstruction algorithm used • Successfully used as primary • Read by 2 independent masked endp
Slide 8: VRDN-001 Proptosis Improvement by Exophthalmometer and MRI
VRDN-001 Proptosis Improvement by Exophthalmometer and MRI Proptosis change by MRI per patient Mean proptosis change (preliminary results from baseline to Week 6) (by MRI, preliminary topline data) 2 1 Change from baseline proptosis (mm) Change from baseline proptosis (mm) * Placebo 0 * 0 n=5 * +0.0
Slide 9: Improvement in Signs and Symptoms as Measured by CAS
Improvement in Signs and Symptoms as Measured by CAS Mean change in CAS CAS of 0 or 1 at Week 6 Reduction in CAS (from baseline to Week 6) (from baseline to Week 6) 3 mg/kg: 67% 0 10 mg/kg: 83% VRDN-001 Placebo 20 mg/kg: 33% Change from baseline score -1 Placebo ≥5 43% 9/21 n=5 62% Responders -2 -1.
Slide 10: 54% of VRDN-001 Patients Had Complete Diplopia Resolution at Week 6
54% of VRDN-001 Patients Had Complete Diplopia Resolution at Week 6 Complete diplopia resolution at Week 6 Diplopia resolution rate 3 mg/kg: 20% 10 mg/kg: 75% defined as % of patients with 20 mg/kg: 75% 54% diplopia at baseline whose diplopia completely resolved S 0% VRDN-001 Placebo n=13 n=3 For pa
Slide 11: Durability of Response at 12 Weeks for VRDN-001 10 mg/kg Cohort
Durability of Response at 12 Weeks for VRDN-001 10 mg/kg Cohort • 80% (4/5) of VRDN-001 responders showed durability of effects at 12 weeks. • Both “overall responders” and “proptosis responders” showed such durability. • Mean proptosis reduction remained consistent (2.2 mm). • Preliminary topline M
Slide 12: Safety Profile
Safety Profile VRDN-001 VRDN-001 VRDN-001 3 mg/kg 10 mg/kg 20 mg/kg Placebo Adverse Reactions (n=9), n (n=6), n (n=6), n (n=6), n Muscle spasms 2 2 2** - Nausea 2 - - - - - - 1 No serious Alopecia adverse events Diarrhea 1 2** 1* - (SAEs), no infusion Fatigue - 1 - 3 reactions, and no Hyperglycemia
Slide 13: Pre/Post Treatment MRI Scans in VRDN-001 Responder
Representative Preliminary Observations: Pre/Post Treatment MRI Scans in VRDN-001 Responder Baseline (Week 0) After 2 VRDN-001 infusions (Week 6) Coronal sections of orbital scans from one patient pre/post treatment. Blue arrows highlight reduction in size of the inferior rectus muscle.
Slide 14: Patient Case Report After 2 Infusions of VRDN-001
Patient Case Report After 2 Infusions of VRDN-001 Baseline patient characteristics Following VRDN-001 treatment, at Week 6 • Proptosis: 29 mm • Change in proptosis by Hertel: -5 mm • CAS: 7 • Change in proptosis by MRI: -5.2 mm • Change in CAS: -6 points Photo taken by patient 2 days before first Ph
Slide 15: Conclusions
Conclusions • Based on the preliminary results of this phase 2 proof-of-concept study of 3 different doses, VRDN-001 shows promise for the treatment of TED. • The efficacy and safety of VRDN-001 for the treatment of TED will be further assessed in the ongoing THRIVE phase 3 clinical trial (NCT051766