Viridian Therapeutics, Inc. · NASDAQ:VRDN
Viridian Therapeutics — Technical Presentation (September 2023)
23 slides from Viridian Therapeutics's technical presentation, September 2023
Slide 1: VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor: In Vitro Pharmacology and Phase 1/2 Results in TED
VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor: In Vitro Pharmacology and Phase 1/2 Results in Patients With Thyroid Eye Disease (TED) Raymond S. Douglas1, Roger E. Turbin2, Kimberly Cockerham3, Navdeep Nijhawan4, Rosa Tang5, Michael T. Yen6, Chantal Boisvert7, David Kaufman8, Andrea Kossler
Slide 2: Disclosures
Disclosures • These studies were sponsored by Viridian Therapeutics, Inc. All data are proprietary. • VRDN-001 is an investigational therapy not approved in any country. All authors met the ICMJE authorship criteria and had full access to relevant data. • All data from the active TED phase 2 proof-o
Slide 3: Learning objectives
Learning objectives Better understand: – Thyroid eye disease (TED) pathophysiology – VRDN-001 preclinical data, VRDN-001 distinct binding and antagonist properties – VRDN-001 phase 2 proof-of-concept (POC) study results
Slide 4: Thyroid eye disease (TED) pathophysiology
Thyroid eye disease (TED) pathophysiology
Slide 5: TED: Stimulation of TSHR/IGF-1R signaling complex results in inflammation and tissue expansion
TED: Stimulation of TSHR/IGF-1R signaling complex results in inflammation and tissue expansion in the fixed bony orbit ©2023 Viridian Therapeutics, Inc. All rights reserved.
Slide 6: VRDN-001 preclinical data: distinct binding & antagonist properties
VRDN-001 preclinical data: distinct binding & antagonist properties
Slide 7: Inhibition of IGF-1 binding to IGF-1 receptor
Inhibition of IGF-1 binding to IGF-1 receptor 30 nM biotinylated IGF-1 binding to FreeStyle™ 293-F Cells 50000 VRDN-001 Mean fluorescence intensity Teprotumumab 40000 No Ab 30000 20000 • VRDN-001 gives near- 10000 complete inhibition at ≥50 nM 0 0.001 0.01 0.1 1 10 100 1000 • Teprotumumab gives part
Slide 8: VRDN-001 fully antagonizes markers of IGF-1 receptor signaling
VRDN-001 fully antagonizes markers of IGF-1 receptor signaling Proximal signaling Distal signaling (inhibition of IGF-1R phosphorylation) (inhibition of AKT phosphorylation) 120 140 VRDN-001 VRDN-001 teprotumumab 120 teprotumumab % Max signal (lowest dose) % Max signal (lowest dose) 100 100 80 80 60
Slide 9: VRDN-001 and teprotumumab have distinct IGF-1 receptor epitopes
VRDN-001 and teprotumumab have distinct IGF-1 receptor epitopes Teprotumumab 0.6 VRDN-001 0.6 WT (Binding strength) (Binding strength) 0.4 0.4 I285A Δλ (nm) Δλ (nm) L286A 0.2 0.2 0 0 0 100 200 300 400 500 600 0 100 200 300 400 Time (s) Time (s) In the presence of IGF-1R mutations (I285A and L286A):
Slide 10: VRDN-001 phase 2 proof-of-concept study results in active TED
VRDN-001 phase 2 proof-of- concept study results in active TED
Slide 11: Proof-of-concept randomized, double-masked trial tested 3 different doses in active TED
Proof-of-concept randomized, double-masked trial tested 3 different doses in active TED Placebo Patients received 2 infusions 3 weeks apart (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
Slide 12: Baseline patient characteristics
Baseline patient VRDN-001 (3, 10, and 20 mg/kg) Placebo characteristics n 21 5 Proptosis, mean (SEM) 23.7 (0.7) 22.8 (2) CAS, mean (SEM) 5.4 (0.2) 5.0 (0.5) Diplopia, n (%) 13 (62%) 3 (60%) Gorman diplopia score, 1.3 (0.3) 1.6 (0.7) mean (SEM) Months since onset of TED 7.4 (0.8) 7.0 (2.0) signs/symp
Slide 13: Summary of VRDN-001 outcome measures
Summary of VRDN-001 outcome measures Preliminary data after 2 infusions (6 weeks) Overall Proptosis Proptosis Diplopia responder responder mean change CAS score CAS mean complete Week 6 rate rate by Hertel of 0 or 1 change resolution* All VRDN-001, 67% 71% -2.3 mm 62% -4.1 54% n=21 3 mg/kg, n=9 56%
Slide 14: Proptosis reductions by exophthalmometer and MRI/CT
Proptosis reductions by exophthalmometer and MRI/CT Preliminary data after 2 infusions (6 weeks) Individual Hertel proptosis change Individual MRI/CT proptosis change Mean MRI/CT proptosis change (all VRDN-001 patients) (all patients with scans**) (all patients with scans**) 0 2 1 Placebo, n=5 Chang
Slide 15: Improvement in CAS
Improvement in CAS Preliminary data after 2 infusions (6 weeks) Mean change in CAS Reduction in CAS CAS of 0 or 1 at Week 6 (from baseline to Week 6) (from baseline to Week 6) 0 3 mg/kg: 67% Change from baseline score 10 mg/kg: 83% VRDN-001 Placebo -1 20 mg/kg: 33% Placebo 62% ≥5 43% -2 n=5 9/21 (13
Slide 16: Complete diplopia resolution by Gorman score
Complete diplopia resolution by Gorman score Preliminary data after 2 infusions (6 weeks) Complete Completediplopia diplopiaresolution resolutionrate at Week at Week 6 6 3 mg/kg: 20% 10 mg/kg: 75% 20 mg/kg: 75% Diplopia resolution rate defined as 54% % of patients with diplopia at (7/13) S baseline
Slide 17: Safety profile
Safety profile VRDN-001 3 mg/kg VRDN-001 10 mg/kg VRDN-001 20 mg/kg Placebo Preliminary data Adverse Reactions (n=9), n (n=6), n (n=6), n (n=6), n Muscle spasms 2 2 2** - Nausea 2 - - - No serious adverse Alopecia - - - 1 events (SAEs), infusion Diarrhea 1 2** 1* - reactions, or Fatigue - 1 - 3 disc
Slide 18: Patient #1
Patient #1 Baseline (Week 0) After 2 VRDN-001 infusions (Week 6) White arrows highlight reduction in size of the inferior rectus muscle.
Slide 19: Patient #2
Patient #2 Baseline at Week 0 Week 6 2 days before first infusion of VRDN-001 2 days following second infusion of VRDN-001 Patient photos taken by patient used with patient and investigator permission. Patient received 2 infusions in the study; in extended follow-up off treatment, TED symptoms have
Slide 20: VRDN-001 phase 2 POC study in chronic TED
Update: VRDN-001 phase 2 POC study in chronic TED Preliminary data • 12 patients with a mean duration of TED of 7.8 years were treated with 2 infusions of VRDN-001 • Outcome measures at 6 weeks demonstrated clinical activity of both 3 and 10 mg/kg doses Proptosis Proptosis mean Diplopia responder Pr
Slide 21: VRDN-001 phase 2 POC study in chronic TED: safety
Update: VRDN-001 phase 2 POC study in chronic TED Preliminary data • VRDN-001 was generally well tolerated with a similar safety profile to that observed in active TED • No serious adverse events (SAEs); no hearing impairment or hyperglycemia events Adverse events VRDN-001 occurring in ≥10% 3 & 10 m
Slide 22: Conclusions
Conclusions • VRDN-001 shows distinct binding and antagonist properties • Preliminary phase 2 POC results show 2 IV infusions of VRDN-001 were well tolerated and led to meaningful improvements in symptoms of both active and chronic TED • The safety and efficacy of VRDN-001 will be further assessed i
Slide 23: Thank you! Questions?
Thank you! Questions? VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor: In Vitro Pharmacology and Phase 1/2 Results in Patients With Thyroid Eye Disease (TED) Raymond S. Douglas Cedars-Sinai Medical Center, Los Angeles, CA #OP-09-01
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