EX-99.2
VRDN-001 Phase 1/2 results in patients
with chronic TED July 2023 Exhibit 99.2
Cautionary note regarding
forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as, but not limited to,
"anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" or other similar terms or expressions that concern the Company’s
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No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to: the
potential efficacy and safety of VRDN-001, VRDN-002 and VRDN-003 for the treatment of thyroid eye disease (TED); the relationship between the results from the positive data from the Phase 1/2 clinical trial of VRDN-001 in patients with chronic TED
and the results of ongoing or future clinical trials; the timing, progress and plans for the Company’s ongoing and future research and clinical development programs; trial protocols for ongoing or future clinical trials, including the clinical
trials for VRDN-001, VRDN-002 and VRDN-003; expectations regarding the timing for data; uncertainty and potential delays related to clinical drug development; the duration and impact of regulatory delays in the Company’s clinical programs;
manufacturing risks; the Company’s ability to develop an SC formulation; the Company’s plans regarding a lead SC program candidate competition from other therapies or products; other matters that could affect the sufficiency of existing
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Opening Remarks Scott Myers, MBA,
President and Chief Executive Officer
Positive VRDN-001 preliminary data
establish proof-of-concept in chronic TED Key highlights VRDN-001 is an investigational therapy that is not approved for any use in any country. VRDN-001 data demonstrated clinically meaningful and rapid improvement in signs and symptoms of chronic
TED at week 6 after two infusions THRIVE-2 Phase 3 trial in patients with chronic TED planned to start in 3Q:2023 with topline results expected by YE:2024 Low dose data continue to support low-volume dosing profile for our subcutaneous candidates in
TED 1 3 4 Ongoing THRIVE Phase 3 trial to be amended to 5-dose VRDN-001 arm and placebo arm only to reflect our confidence and evolution of treatment landscape supported by our interactions with stakeholders 2 Important progress across subcutaneous
programs for lead program selection expected by YE:2023 5
Viridian is focused on key factors to
build a successful blockbuster product franchise in TED Best-in-class IV product Active + Chronic TED Expand prescriber base US + ex-US market access and sales First / best-in-class SC product Establish new treatment paradigms in TED Building a
blockbuster TED franchise
Building the Viridian team for
execution and growth Pre-commercial Product Development Medical Affairs Clinical Development Corporate Affairs
Today’s Presenters Kimberly
Cockerham, MD, FACS Barrett Katz, MD, MBA CHIEF MEDICAL OFFICER Thomas Ciulla, MD, MBA CHIEF DEVELOPMENT OFFICER
TED Overview and Unmet Medical Need
Kimberly Cockerham, MD, FACS
My background George Washington
Medical School: awarded a health professional scholarship from the US ARMY Fellowship-trained: Cosmetic, laser and reconstructive surgery of the face, eyelids, and eye muscles. Neuro-ophthalmology and orbital disease Former: Chief of Oculoplastics
and Orbital Disease at Walter Reed Army Medical Center; Director of Oculoplastics and Orbital Disease at UCSF Honors: two UCSF Star Awards for Excellence, American Academy of Ophthalmology Achievement Award, Senior Achievement Award, Distinguished
Service Award and a Special Recognition Award Founder of the Let’s Face It Together Foundation Principal investigator for over two dozen studies. Currently recruiting patients with thyroid eye disease for Phase 1-4 clinical trials. Adjunct
Clinical Associate Professor, Byers Eye Institute at Stanford University for 15 years Treat ~300 TED patients annually at the SENTA Clinic in San Diego, California
TED overview Autoantibodies trigger
IGF-1R/TSHR pathway1 Progressive disease consisting of an initial active phase, followed by a transition to a secondary chronic phase2 Main signs include proptosis (eye bulging), redness, swelling, diplopia (double vision), and lid retraction3
Severe cases can cause sight-threatening optic nerve compression4 Impacts more women than men, ~5 : 1 ratio5 Debilitating auto-immune disease 1. George A et al. Front. Endocrinol. 11:629925 (2021); R. S. Bahn. The New England Journal of Medicine
2010 Vol. 362 Issue 8 Pages 726-738 2. Bothun et al. Clinical Ophthalmology 2009:3 543–551. 3 Bartley GB et al. Am J Ophthalmol 1996;121:284-90. 4. Smith TJ et al. N Engl J Med. 2016;375(16):1552–1565. 5. Kendler DL, Lippa J, Rootman J.
The initial clinical characteristics of Graves' orbitopathy vary with age and sex. Arch Ophthalmol. 1993;111(2):197-201. © 2023 Viridian Therapeutics, Inc.
Dry Eye Disease Diplopia (double
vision) Photophobia (light sensitivity) Decreased Visual Acuity Visual Field Defects Reduced Color Vision Optic Neuropathy TED is associated with significant vision-threatening impairments 1. Bartley GB. Trans Am Ophthalmol Soc (1994)
92:477–588. 2. Chin et al. Clinical Endocrinology. 2020;93:363–374. 3. Dolman PJ. Ophthalmic Plast Reconstr Surg. 2018;34(4S suppl 1):S34-S40. 4. C. Terwee, F. Dekker and P. Bossuyt. J Clin Epidemiol 2002 Vol. 55 Issue 11 Pages 1156 . 5.
Patel VK et al. Endocr Pract. 2022 Feb;28(2):159-164. doi: 10.1016/j.eprac.2021.11.080.. 6. Smith TJ et al. N Engl J Med. 2016;375(16):1552–1565. 7. Smith TJ et al. N Engl J Med. 2016;375(16):1552–1565. Vision impairment in patients with
TED
Historically described as a
biphasic disease course from active to chronic TED Modified from Wang Y, Patel A, Douglas RS. Thyroid Eye Disease: How A Novel Therapy May Change The Treatment Paradigm. Ther Clin Risk Manag. 2019;15:1305-1318 Active Phase ~18 to 24 months Chronic
Phase ~5 to 7+ years Inflammatory signs and symptoms, such as pain, redness, swelling, proptosis, diplopia, and eyelid retraction are at peak levels Inflammatory signs such as redness and swelling are reduced but the pain, proptosis, diplopia, and
eyelid retraction are persistent throughout life Signs and Symptoms Severity Time
Current treatment options for
patients with TED 1. Stan MN, et al. . Randomized controlled trial of rituximab in patients with Graves’ orbitopathy. J Clin Endocrinol Metab. 2015;100(2):432–441. doi: 10.1210/jc.2014-2572 2. Perez-Moreiras JV, et al. Efficacy of
tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy: a randomized clinical trial. Am J Ophthalmol. 2018;195:181–190. Intravenous steroids Low benefit-risk for patients Risks include potential liver
failure, weight gain, diabetes, hypertension, osteoporosis, and/or infections 40% to 50% chance of relapse Orbital radiation 60% effective when right patient is selected Many patients are not eligible Off-label immunosuppressive agents rituximab1
associated with AEs and has shown no benefits over placebo tocilizumab2 has not achieved clinically meaningful reductions in proptosis Intravenous IGF-1R inhibitor teprotumumab (Tepezza®) is the only approved agent for TED in the US Surgical
management Orbital decompression, extraocular muscle surgery, eyelid repositioning, and cosmetic soft tissue redraping Limited to chronic TED
Unmet medical needs More convenient
IV treatment options Availability of subcutaneous treatment option New treatment regimens to drive longer-term benefit and value for patients Achieving a similar benefit as IV with a convenient home- based subcutaneous treatment Chronic maintenance
and/or retreatment-based regimens Lower treatment burden for patients with fewer infusions Shorter infusion times
VRDN-001 Background and POC trials
in TED Barrett Katz, MD, MBA, Chief Medical Officer
VRDN-001 IV is a differentiated
full antagonist anti-IGF-1R humanized antibody in TED *Zhao Y, et al. VRDN-001, a Full Antagonist Antibody to the Insulin-Like Growth Factor Receptor-1 (IGF-1R) in Development for Thyroid Eye Disease (TED), Binds to a Distinct Epitope from
Teprotumumab, 91st ATA, October 2022 In preclinical studies*, VRDN-001: Binds to distinct epitope of IGF-1R compared to teprotumumab Binds to epitope longer compared to teprotumumab More completely inhibits IGF-1 ligand binding to IGF-1R More
completely inhibits IGF-1R proximal and distal signaling Potential areas of commercial differentiation 12-week / 5 infusion course of therapy Lower dose Infusion time of 30 minutes VRDN-001 is an investigational therapy not approved for use in any
country.
Proptosis of ≥3 mm Clinical
activity score (CAS) of ≥4 Onset of symptoms within past 12 mo. Active TED Establish proof-of-concept in active and chronic TED 1st Proptosis of ≥3 mm Any CAS (0-7) Onset of symptoms >12 months prior Chronic TED 2nd
Presentations of VRDN-001 POC data
in active TED at medical congresses in 1H:23 Presidential Poster Competition Winner
VRDN-001 Phase 1/2 trial design in
patients with chronic TED Randomized, double-blind trial vs placebo Chronic TED Proptosis of ≥3 mm CAS 0-7 Onset of TED symptoms >12 months prior VRDN-001 10 mg/kg Q3W x 2 (n=6) Placebo (n = 2) VRDN-001 3 mg/kg Q3W x 2 (n=6*) Placebo (n=3)
*In the 3 mg/kg dose cohort, seven patients were randomized to receive VRDN-001 and three patients were randomized to receive placebo. One patient randomized to receive VRDN-001 3mg/kg discontinued the trial due to leaving the country for a family
emergency prior to receiving the second dose of VRDN-001, making six patients treated with VRDN-001 3 mg/kg evaluable for the week 6 clinical endpoint analyses. Cohort 1 Cohort 2
VRDN-001 POC data in Chronic TED
Kimberly Cockerham, MD, FACS
Exophthalmometry and MRI together
provide robust assessment of proptosis Hertel Exophthalmometer Most commonly used modality for measurement of proptosis Successfully used as primary endpoint in prior clinical trials in TED Magnetic Resonance Imaging (MRI) More precise measurement
Centrally read by 2 masked reviewers Exploratory measure to potentially differentiate overall data findings Representative illustration of proptosis measurement by MRI
Evaluating symptoms of TED using
clinical activity scoring scales Clinical Activity Score (0 to 7 points) Source: Bartalena L, et al. Eur Thyroid J 2016;5:926. GO: Graves’ Orbitopathy, also known as thyroid eye disease, or TED.; Chemosis: Swelling of conjunctiva, which is the
mucous membrane that covers the front of the eye and lines the inside of the eyelids; Caruncle: Small, pink, globular nodule at the inner corner (the medial canthus) of the eye; Plica: A small fold of bulbar conjunctiva on the medial canthus of the
eye. 0 1 2 3 4 5 6 7 severity +1 point for each sign/symptom Spontaneous orbital pain Gaze evoked orbital pain Eyelid swelling due to active GO Eyelid erythema Conjunctival redness due to active GO Chemosis Inflammation of caruncle or plica No pain,
redness, or swelling
Baseline patient characteristics in
chronic TED SEM = Standard error of the mean VRDN-001 (10 and 3 mg/kg) VRDN-001 10 mg/kg VRDN-001 3 mg/kg Placebo n 12 6 6 5 Proptosis, mean (SEM) 22.2 (1.2) 21.1 (2.2) 23.4 (1.1) 25.0 (1.6) CAS, mean (SEM) 3.3 (0.8) 2.5 (1.1) 4.0 (1.0) 2.8 (0.8)
Diplopia, n (%) 5 (41.7%) 3 (50.0%) 2 (33.3%) 2 (40%) Gorman Score, mean (SEM) 0.9 (0.4) 0.8 (0.4) 1.0 (0.6) 0.6 (0.4) Months since onset of TED signs/symptoms, mean (SEM) 94.0 (33.7) 96.0 (48.2) 92.0 (51.7) 194.4 (81.2) Age in years, mean (SEM)
50.7 (3.3) 48.3 (5.6) 53.0 (3.7) 49.4 (4.4) Female, n (%) 10 (83.3%) 4 (66.7%) 6 (100.0%) 5 (100.0%)
VRDN-001 clinical activity observed
in patients with chronic TED Preliminary data - *MRI available for 4 of 6 VRDN-001 10 mg/kg treated patients, 4 of 6 VRDN-001 3 mg/kg treated patients **2 patients with CAS of 0 at baseline excluded from calculation ***Includes only participants who
had diplopia present at baseline. Diplopia was present at baseline in 5 of 12 VRDN-001 treated patients; 2 in 3 mg/kg cohort, and 3 in 10 mg/kg cohort Proptosis: Responder rate (% with ≥2 mm reduction baseline to week 6) Proptosis: Mean change
by exophthalmometry (baseline to week 6) Proptosis: Mean change by MRI* (baseline to week 6) CAS: Score of 0 or 1** (% achieving CAS of 0 or 1 at week 6) Excludes Patients CAS=0 at baseline CAS: Mean change** (baseline to week 6) Patients CAS>0
at baseline Diplopia: Complete resolution*** (% improved to a score of 0 at week 6) VRDN-001 (10 and 3 mg/kg; week 6) n=12 42% -1.6 mm -2.0 mm 40% -2.3 0% 10 mg/kg / 3 mg/kg n=6 n=6 50% 33% -1.8 mm -1.5 mm -1.5 mm -2.6 mm 50% 33% -2.8 -2.0 0% 0%
Signs Improvement in proptosis Symptoms Improvement in Clinical Activity Score (CAS) and diplopia score
Reported change in proptosis from
baseline to week 6 MRI data is preliminary. **Blinded, centrally-reviewed MRI data were available for 4 of 6 VRDN-001 10 mg/kg treated patients, 4 of 6 VRDN-001 3 mg/kg treated patients, and 5 of 5 placebo-treated patients. All MRI images were
reviewed centrally by two independent, masked readers. Individual proptosis change (by exophthalmometer) Change from baseline proptosis (mm) Individual proptosis change (by MRI**) *2 placebo and 1 VRDN-001 treated participants were responders by
exophthalmometer, but were not confirmed by MRI Placebo VRDN-001 Change from baseline proptosis (mm) Mean proptosis change (by MRI**) Time (weeks) Placebo n=5 -0.2 mm VRDN-001 n=8 -2.0 mm Change from baseline proptosis (mm) 10 mg/kg 3 mg/kg * * * 0
0
Signs and symptoms as measured by
CAS at week 6 *Includes patients with CAS > 0 at baseline only; 2 patients with CAS of 0 at baseline excluded from calculation, Baseline mean CAS for patients > 0: Placebo = 2.8 and VRDN-001 treated patients = 4.0 Mean change in CAS* (Patients
CAS > 0 at baseline) Change from baseline score Time (weeks) VRDN-001 n=10 -2.3 Placebo n=5 -1.2 Individual patient CAS change (All Patients) Change from baseline score 10 mg/kg 3 mg/kg CAS at baseline 0 0 1 1 2 5 5 6 6 6 1 6 0 0 0
VRDN-001 10 & 3 mg/kg (n=13*),
n Placebo (n=5), n Back pain 2 (15%) 0 (0%) Muscle spasms 2 (15%) 0 (0%) Headache 1 (8%) 2 (40%) Ear discomfort 0 (0%) 1 (20%) Fatigue 0 (0%) 1 (20%) Flatulence 0 (0%) 1 (20%) Pruritus 0 (0%) 1 (20%) Safety profile across all chronic TED cohorts No
serious adverse events (SAEs); no hearing impairment or hyperglycemia events Preliminary data are as of data cut-off of May 30, 2023. *Though not evaluable at week 6 for clinical activity, the 7th patient randomized in the 3 mg/kg cohort who
discontinued the trial prior to week 6 due to leaving the country for a family emergency was followed for safety until their discontinuation. Reported adverse events occurring in ≥ 10% of patients
Summary of VRDN-001 Phase 1/2 data
in patients with chronic TED With one approved medicine in TED, clinicians and patients are in need of new differentiated treatment options VRDN-001 showed improved clinical activity after 2 doses at week 6 VRDN-001 was generally well tolerated in
TED patients with substantial chronicity Clinically meaningful improvement can be achieved with fewer than 8-infusions Data and updated Phase 3 trial design are expected to be received positively by TED treater and patient communities
THRIVE Phase 3 program and SC
progress Thomas Ciulla, MD, MBA, Chief Development Officer
THRIVE Phase 3 trial design in
patients with active TED Topline results expected in the middle of 2024 *Q3W = once every three-week dosing Screening (up to 4 weeks) Double-Blind Treatment Period (15 weeks) Placebo (n=30) Active TED CAS ≥3 Proptosis of ≥3 mm Onset of
active TED symptoms within prior 15 months Randomization 2:1 N=90 VRDN-001 10 mg/kg Q3W* (n=60) Week 15 Primary Endpoint Analysis Proptosis Responder Rate
THRIVE Phase 3 amendment reflects
our confidence in 5-dose regimen and key stakeholder feedback VRDN-001 IV Q3W x 5 (12 weeks) potentially improves benefit-risk for patients VRDN-001 data demonstrated clinically meaningful and rapid improvement in signs and symptoms of TED at week 6
after 2 infusions Physician feedback suggests preference in a shortened IV dosing regimen compared to Q3W x 8 (21 weeks) dosing regimen Q3W x 5 increases IV dosing convenience for patients by eliminating 3 trips to the infusion center
THRIVE-2 Phase 3 trial design in
patients with chronic TED Trial initiation planned for 3Q 2023 with topline expected by YE:2024 *Q3W = once every three-week dosing Screening (up to 4 weeks) Double-Blind Treatment Period (15 weeks) Placebo Chronic TED Any CAS (0-7) Proptosis of
≥3 mm Onset of TED symptoms ≥15 months VRDN-001 10 mg/kg Q3W* Week 15 Primary Endpoint Analysis
Viridian is developing multiple
potential best-in-class subcutaneous (SC) programs in TED VRDN-001, -002, and -003 are investigational therapies that are not approved for any use in any country. Mechanism Full antagonist Full antagonist Partial antagonist Half-life ~10 to 11 days
Expected to match or exceed VRDN-002 up to 43 days Administration Q1W or Q2W SC Q2W or Q4W SC Q2W or Q4W SC Same extended half-life mutations Same binding domain VRDN-001 SC VRDN-003 VRDN-002
VRDN-001, VRDN-002, & VRDN-003
SC program progress and priorities SC formulation work completed for all three SC programs at 150 mg/mL concentration allowing for administration of 300 mg / 2 mL VRDN-001 SC IND amendment submitted to FDA VRDN-003 IND filing submitted to FDA
VRDN-002 Phase 1 trial with single IV and single SC dose cohorts enrolled Pen device supply partnership expected in 2H23 VRDN-001 SC Phase 1 trial initiation expected in 3Q23, with data expected in 4Q23 VRDN-003 Phase 1 trial initiation expected in
3Q23, with data expected in 4Q23 Lead SC program selection on track for year-end 2023 Lead SC program pivotal Phase 2/3 trial planned for the middle of 2024
Closing Remarks Scott Myers, MBA,
President and Chief Executive Officer
VRDN SC Potential
first/best-in-class self-administered SC pen Plan to launch with a potentially best-in-class IV followed by a self-administered SC pen in TED * Pictures used for illustrative purposes only VRDN-001 IV Potential best-in-class Q3W IV treatment for TED
2 1
Viridian is focused on key factors
to build a successful blockbuster product franchise in TED Best-in-class IV product Active + Chronic TED Expand prescriber base US + ex-US market access and sales First / best-in-class SC product Establish new treatment paradigms in TED Building a
blockbuster TED franchise
Launch potential best-in-class IV
TED therapy in US and ex-US Follow with potential best-in-class SC TED therapy Replicate drug development and launch excellence in additional autoimmune and rare diseases Our long-term vision: building a fully-integrated biopharmaceutical company
Growth Potential
Q&A Session
Q&A Session Participants Scott
Myers, MBA PRESIDENT AND CEO Thomas Ciulla, MD, MBA CHIEF DEVELOPMENT OFFICER Todd James SVP, CORPORATE AFFAIRS & IR Kimberly Cockerham, MD, FACS Barrett Katz, MD, MBA CHIEF MEDICAL OFFICER Kristian Humer CHIEF FINANCIAL & BUSINESS
OFFICER
Thank you!
