Slide 1: Differential Anatomic Response to Aflibercept 8 mg Versus 2 mg in DME Patients Who Met Shortening Criteria
Differential Anatomic Response to Aflibercept 8 mg Versus 2 mg in DME Patients Who Met Shortening Criteria in the Phase 2/3 PHOTON Trial Diana Do,’ on behalf of the PHOTON study investigators ‘Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA
Slide 2: Key Takeaways
Key Takeaways The PHOTON trial showed that: * ~90% of patients treated with aflibercept 8 mg did not meet shortening criteria and maintained their randomized dosing intervals through week 48 * In this subgroup of patients, aflibercept 8 mg achieved similar visual and anatomic outcomes compared to af
Slide 3: PHOTON Study Design
PHOTON Study Design Multi-center, randomized, double-masked study in patients with DME? Randomized 1 (2q8) : 2 (8q12) : 1 (8q16) Note: 2 mg arm received 5 initial monthly injections versus 8 mg arms, which received only 3 initial monthly injections 2q8 Aflibercept 2 mg every 8 weeks after 5 initial
Slide 4: PHOTON: Dosing Schedule and Dose Regimen Modifications in Year 1
PHOTON: Dosing Schedule and photon Dose Regimen Modifications in Year 1 4 Note: 2 mg arm received 5 initial monthly injections versus 8 mg arms, which received only 3 initial monthly injections DRM Criteria for Shortening Dosing Interval* DRM in Year 1 . . Intervals can only be p + >40-letter loss i
Slide 5: Objective
Objective DME * This post hoc analysis aimed to characterize visual and anatomic outcomes of patients with DME over the matched dosing phase through Week 12 among patients who did or did not meet the dosing interval shortening criteria any time from Week 16 through Week 48 Matched monthly Extended d
Slide 6: Methods
Methods Patients in the 8q12 and 8q16 groups who met the shortening criteria in any DRM evaluation visit from pb wEe Week 16 through Week 48 had their dosing intervals shortened — Patients in the 2q8 group who hypothetically met shortening criteria from Week 16 to Week 48 continued with every 8-week
Slide 7: Proportion of Patients Who Did Versus Did Not Meet Shortening Criteria
Proportion of Patients Who Did Versus Did Not Meet Shortening Criteria e s vn 2 c 8 =] 3 Q - i} Ss & = f-} 2 ° 2 o Met shortening criteria FAS, patients who completed Week 48 visit FAS, full analysis set aHypathetically shortened. 91.0% 39.1% Did not meet shortening criteria = 2q8 (n=157) = 8q12 (n=
Slide 8: Demographics
Demographics Met shortening criteria Did not meet shortening criterigOME Age, years, mean (SD) Female, n (%) Hispanic or Latino, n (%) Race, n (%) White Asian Black or African American FAS, patients who completed Week 48 visit. SD, standard deviation.
Slide 9: Baseline Characteristics
Baseline Characteristics DME Met shortening criteria Did not meet shortening criteria 31.1 29.3 BMI, kg/m2, mean (SD) (4.2) (66) 29.8 (6.7) Duration of diabetes, years, 19.9 11.1 mean (SD) (11.8) (9.7) 15.6 (10.0) 8.4 7.8 HbAtc, %, mean (SD) (1.1) (1.4) 8.1 (1.5) 5 15 Prior DME treatment, n (%) (71.
Slide 10: Treatment Exposure Through Week 48
Mean number of injections 10 . Treatment Exposure Through Week 48 protaD Met shortening criteria Did not meet shortening criteria DME 8.0 7.9 6.4 55 5.9 5.0 Through Week 48, aflibercept 8 mg patients who met shortening criteria on average received more injections versus those who did not Aflibercept
Slide 11: Mean Change in BCVA and CRT Through Week 12 in Patients Who Met Shortening Criteria
Mean Change in BCVA and CRT Through Week 12 in Patients Who Met Shortening Criteria BCVA CRT Mean change in BCVA, ETDRS letters #298 (n=7) + 8q12 (n=27) k-8q16 (n=17) —@2q8 (n=7) -lK8q12 (n=27) #8 q16 (n=17) Week a S a FAS, patients who completed Week 48 visit, observed cases (data post-ICE were exc
Slide 12: Mean Change in BCVA and CRT Through Week 12 in Patients Who Did Not Meet Shortening Criteria
Mean Change in BCVA and CRT Through Week 12 in Patients who Did Not Meet Shortening Criteria BCVA CRT —@2q8 (n=150) —-H8q12 (n=273) —=%-8q16 (n=139) —@2q8 (n=150) -f-8q12 (n=273) —*%-8q16 (n=139) Week 4 8 ND 3 a Mean change in BCVA, ETDRS letters 3 Mean change in CRT, pm In patients who did not meet
Slide 13: Proportion of Patients With no IRF and SRF in the Center Subfield
Proportion of Patients With no IRF and SRF in the Center Subfield at Baseline and Week 12 DME Met shortening criteria Did not meet shortening criteria #298 (n=7) + 8q12 (n=27) -&k-8q16 (n=17) #298 (n=150) l-8q12 (n=273) —k-8q16 (n=139) ° f=) fo) f=) for) f=) for) fo) fo) o fon) o os o S o nN i=) Pro
Slide 14: Proportion of Patients With no IRF in the Center Subfield
Proportion of Patients With no IRF in the Center Subfield at Baseline and Week 12 DME Met shortening criteria Did not meet shortening criteria #298 (n=7) + 8q12 (n=27) -&k-8q16 (n=17) #298 (n=150) l-8q12 (n=273) —k-8q16 (n=139) ° f=) fo) f=) for) f=) for) fo) fo) o fon) o os o S o nN i=) Proportion
Slide 15: Proportion of Patients With no SRF in the Center Subfield
Proportion of Patients With ° f=) 5 a f=) L Proportion of patients, % nN PS Oo f=) o . . : 7 in the Center Subfield at Baseline and Week 12 DME Met shortening criteria Did not meet shortening criteria 248 (n=7) ‘8q12 (n=27) 8q16 (n=17) —@2q8 (n=150) ‘8q12 (n=273) 8q16 (n=139) 100.9 100.0 98.0 974 97
Slide 16: Time to CRT <300 um Through Week 48
Time to CRT <300 ym Through Week 482 Met shortening criteria 3@ 100 298 (n=7) EK 8q12 (n=27) —k-8q16 (n=17) > 80 —— 85.3% £ & 74.1% = 60 ¢ + + + + © 57.1% 3s 40 4 Median time, 5 7 weeks a Q a Oo 0 r r ; ; ; 1 - 0 4 8 12 16 20 24 28 32 36 40 44 48 Hazard ratio . 171 1.86 (95% Cl) (0.56, 5.18)} (0.58,
Slide 17: Univariate Analysis of Baseline Factors Associated With Time to CRT <300 um
Univariate Analysis of Baseline Factors Associated With Time to CRT <300 um Met shortening criteria Did not meet shortening criteria HR (95% Cl) HR (95% Cl) Age (per 10-year increase) 0.914 (0.68, 1.21) 0.97 (0.87, 1.08) Sex (male vs female) 0.82 (0.39, 1.71) 1.08 (0.85, 1.37) Race (white vs non-Whi
Slide 18: Multivariate Analysis of Baseline Factors Associated With Time to CRT <300 um
Multivariate Analysis of Baseline Factors Associated With Time to CRT <300 pm Did not meet shortening criteria HR? (95% Cl) CRT (Per 50-um increase) 0.86 (0.81, 0.91) <0.0001 0.0 0.5 1.0 1.5 Longer time to Faster time to CRT <300 pm HR (95% Cl) CRT <300 pm — —— os Higher baseline CRT was associated
Slide 19: Limitations
Limitations « This was a post hoc analysis with no adjustment for multiplicity, and findings should be considered hypothesis-forming only * The number of patients who met shortening criteria was low, limiting the interpretation of the results
Slide 20: Conclusions
Conclusions In patients who met shortening criteria: Mean Change in CRT and Proportion of Patients With no IRF and SRF in the Center Subfield at Week 12 CRT No IRF and SRE In patients who did not meet shortening criteria: Mean Change in CRT and Proportion of Patients With no IRF and SRF in the Cente