Microperimetry in BlebThis presentation contains forward-looking statements that reflect AGTC's plans, estimates, assumptions and beliefs. Forward-looking statements include statements regarding the company’s (i) clinical and pre-clinical programs, including the proposed Phase 2/3 (Vista) trial design for XLRP, the anticipated timeline for initiating and reporting data in the Vista trial and the Phase 1/2 expansion (Skyline) trial for XLRP, (ii) ability to enroll patients (ii) regulatory progress with FDA, (iii) potential growth and market opportunities, and (iv) ability to be competitive. Forward-looking statements include all statements that are not historical facts and can be identified by terms such as "anticipates," "believes," "could," "seeks," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," "would" or similar expressions and the negatives of those terms. Actual results could differ materially from those discussed in the forward- looking statements, due to a number of important factors. Risks and uncertainties that may cause actual results to differ materially include, among others: AGTC cannot predict when or if it will obtain regulatory approval to continue to progress its clinical trials, commercialize a product candidate or receive reasonable reimbursement; uncertainty inherent in clinical trials and the regulatory review process; risks and uncertainties associated with drug development and commercialization; risks related to the COVID-19 outbreak that may delay clinical trial enrollment; gene therapy is still novel with only a few approved treatments so far; factors that could cause actual results to differ materially from those described in the forward- looking statements are set forth under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent periodic reports filed with the SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements, which speak only as of the date of this presentation. Except as required by law, AGTC assumes no obligation to update or revise these forward-looking statements, whether as a result of new information, new events or otherwise.
• Attendees – Sue Washer CEO
– Q&A
– Closing Remarks
• Activity retained on microperimetry measure through Month 12 – Centrally Treated Patients
• Responders identified in Groups 5 & 6 at Month 6
• Statistically significant difference between treated & untreated decibel response distributions
– Peripherally Treated Patients • Longer term analysis required
• Safety retained through Month 12
• BCVA remains supportive trend through Month 12 and at Higher Doses
• Additional feedback from FDA – No further comments or requests regarding pre-clinical or CMC sections
– Received clarification of clinically meaningful improvement on microperimetry
• Completion of on-going Phase 1/2 dose escalation – Long term follow-up
• Initiation of Skyline Trial—extension of Phase 1/2
• Initiation of Vista Trial—Phase 2/3
IND ENABLING PHASE 1/2 PHASE 2/3 NEXT MILESTONE* KEY CAPABILITY
OCULAR
XLRP High dose data 4Q 2020
Expand ongoing Phase 1/2 trial 4Q 2020 Initiate Phase 2/3 trial 1Q 2021
ACHM Interim data new adult groups 4Q 2020
Interim data new adult groups 4Q 2020
Retinitis Pigmentosa Partnership with Bionic Sight; complete dosing
Dry AMD IND filing, 2H 2022
Stargardts IND filing, 1H 2023
NEURODEGENERATIVE
ALS Development candidate
Non-Syndromic Hearing Loss Partnership with Otonomy; IND filing, 1H 2022
*Anticipated milestones based on calendar year, not AGTC’s fiscal year
CNGB3 (ORPHAN DRUG)
RPGR (ORPHAN DRUG)
CNGA3 (ORPHAN DRUG)
ABCA4
PROGRANULIN
C9ORF72
GJB2
AGTC-501
Dose Group C36 Change >7dB @ >5 Loci At Month 6 Number of Responders
2# Yes 1/1
4
No
2/7
Yes
No
No
Yes
No
No
5
Yes*
4/7
Yes
Yes
No
No
No
Yes
• These data presented the analysis using the >7dB @ >5 Loci definition within Central 36
• It also included new information on the Group 5 dose
# There is an additional Group 2 patient with no microperimetry data available * Month 3 data
Central 36 Perimetry Grid
* Month 3 data
**Three patients do not meet new inclusion criteria; so responders are 5/8 or 62%
Additional patient does not meet strict criteria but treated eye is statistically better than untreated eye
**One patient does not meet new inclusion criteria; so responders are 2/7 or 28%
Additional two patients do not meet strict criteria but treated eye is statistically better than untreated eye
# There is an additional Group 2 patient with no microperimetry data available
Dose Group
Number of Responders
Number of Responders
4
No
2/7
No
2/7
G A
36 perimetry grid
Dose Group
*** P < 0.01 * P < 0.05
Key
KS Test
Patient responder based on 5 loci achieving 7 dB improvement in treated eye
Patient responder based on different sensitivity profile in treated eye relative to untreated eye
Patient does not meet responder criteria by individual loci or distribution profile
These patients represent responders by two different assessments
These patients would not be enrolled in Skyline and Vista Trials
These patients are considered non-responders
Group 2 & Group 4 – Month 12 data; Group 5 & Group 6 – Month 6 data
-15
-10
-5
0
5
10
15
20
• Supportive evidence of improved visual acuity across all centrally-dosed groups
TREATED EYE
• Supportive evidence of improved visual acuity maintained one year following treatment
* Includes Group 2 patient that does not have microperimetry data
• Based on new FDA Letter we are incorporating an analysis of pre- specified loci, as the primary endpoint, in addition to other microperimetry assessments
• Safety/efficacy range fully explored and current data release supports low & high dose selection
• Study will include untreated control arm as comparator
• BCVA to continue as supportive secondary endpoint
• Ora-VNC™ mobility maze as additional supportive endpoint*
• Use of updated and validated PRO survey
*Ora Visual Navigation Challenge (Ora-VNC™)
BCVA (ETDRS Letters) MAIA CFB Sensitivity (dB)
Patient numbering based on chronology of dosing
Retinal Sensitivity Change (dB)Visual Acuity Change (ETDRS Letters) C36 Retinal Sensitivity Change (dB)
Age Study Eye Baseline VA Baseline Sensitivity
15 OS OD: 66 OS: 62
Treated: 5.8 dB Untreated: 7.3 dB
HISTOGRAM M12
U N
T R
E A
T E
D T
R E
A T
E D
Improvements in the intensity and area of sensitivity for the treated eye (top row) versus untreated eye (bottom row); sensitivity values are from within bleb
BASELINE MONTH 1 MONTH 6
5.84 dB 6.08 dB 8.06 dB
7.28 dB 5.78 dB
MAIA Color Scale (dB)
30 OD OD: 64 OS: 70
Treated: 1.9 dB Untreated: 1.1 dB
Visual Acuity Change (ETDRS Letters) Retinal Sensitivity Change (dB)C36 Retinal Sensitivity Change (dB)
-5
0
5
1.14 dB 0.80 dB 0.92 dB 0.86 dB
BASELINE MONTH 1 MONTH 3 MONTH 6
MAIA Color Scale (dB)
U N
T R
E A
T E
D T
R E
A T
E D
Improvements in the intensity and area of sensitivity for the treated eye (top row) versus untreated eye (bottom row); sensitivity values are from within bleb
BCVA (ETDRS Letters) MAIA CFB Sensitivity (dB)
Patient numbering based on chronology of dosing
Retinal Sensitivity Change (dB)Visual Acuity Change (ETDRS Letters) C36 Retinal Sensitivity Change (dB)
Age Study Eye Baseline VA Baseline Sensitivity
18 OS OD: 67 OS: 49
Treated: 7.6 dB Untreated: 9.9 dB
-5
0
5
BASELINE MONTH 1 MONTH 6
Improvements in the intensity for the treated eye (top row) versus decay in the untreated eye (bottom row); sensitivity values are from within bleb
7.60 dB 12.33 dB 9.80 dB
9.93 dB 8.47 dB 5.80 dB
MAIA Color Scale (dB)
Visual Acuity Change (ETDRS Letters) Retinal Sensitivity Change (dB)C36 Retinal Sensitivity Change (dB)
-5
0
5
15 OS OD: 82 OS: 80
Treated: 8.3 dB Untreated: 9.4 dB
U N
T R
E A
T E
D T
R E
A T
E D
MAIA Color Scale (dB)
8.34 dB 8.61 dB 6.90 dB
8.15 dB
MONTH 12
6.44 dB
No improvements in the intensity or area of sensitivity for the treated eye (top row) versus untreated eye (bottom row); sensitivity values are from within bleb
• Activity retained on microperimetry measure through Month 12 – Centrally Treated Patients
• Responders identified in Groups 5 & 6 at Month 6
• Statistically significant difference between treated & untreated decibel response distributions
– Peripherally Treated Patients • Longer term analysis required
• Safety retained through Month 12
• BCVA remains supportive trend through Month 12 and at Higher Doses
• Additional feedback from FDA – No further comments or requests regarding pre-clinical or CMC sections
– Received clarification of clinically meaningful improvement on microperimetry
• Six dose groups over a 100-fold range in concentration
• Improvements in visual function sustained over time
• Favorable safety profile
– No secondary inflammation
– Earlier groups now 12-24 months past enrollment date with continued safety
• Well-designed vector construct
AGTC BIIB MGTX
BCVA + - unknown
secondary inflammation
Construct (expression) ++ - -
Construct (stability) + + -
Competitive Comparison*
*Based on reported data on specific population of patients; BIIB and MGTX have dosed additional patients
• Extensive pre-clinical NHP studies – Contribution of vector & manufacturing components
– Impact of neutralizing antibodies
– Feasibility of multiple blebs
– Re-administration to the same eye & contralateral eye
• Selecting optimal dose range – Efficacy & GLP toxicology studies in the same animal model
• Clinical experience in Phase 1/2 dose escalation – Steroid regimen developed in 5 clinical studies
(IVT, SR) dosing ~130 patients
Secondary inflammation requiring steroid re-administration1,2
AGTC 0/28 (0%)
BIIB 7/18 (39%)
MGTX 2/10 (20%)
CAPSID PROMOTER TRANSGENE
GRK1-GFP IRBP-GFP
Our manufacturing was developed with flexibility & scalability in mind – Same cell line used for any/all programs – Dozens of stable HSV constructs are available – Planning today reduces our future costs and execution risks
Exceptional productivity – at commercial scale for ophthalmology – Planning for manufacturing facility build-out
COMPARED TO TRANSFECTION
60x
50x
40x
30x
20x
10x
Vials > 2,000 > 230 58
Process Improvement ComparisonAAV Volumetric Productivity
Integrated manufacturing & analytics platform – Over 20 assays qualified/validated to late Phase requirements – No changes to final characterization plan for XLRP recommended in FDA letter
Unparalleled quality and safety – Dramatic reduction in process residuals to below detection level in many cases
Sedimentation Coefficient & Peak Area
COMMERCIAL VS EARLY PHASE
• Expertise led to clinical success to date
– Optimized product design, breadth of preclinical data supported • Safety profile supports higher dosing
• Sustained and robust improvements in visual function
– Patient focus generated creative clinical solutions, including continued data collection during pandemic
• Improved manufacturing process – No further process development or scale-up required to support commercial launch
– Superior quality supports clinical safety profile
• Intermediate analysis points create opportunities for future acceleration – Phase 1/2 Expansion, Skyline, expected timeline
• 3Q 2021: 3-month data for masked dose expansion of groups 2 and 5
– Phase 2/3, Vista, expected timeline
• 3Q 2022: 6-month data