IR Conference Call on EYLEA (aflibercept) Injection in Diabetic Macular Edema. September 28, 2013

Transcription

1 IR Conference Call on EYLEA (aflibercept) Injection in Diabetic Macular Edema September 28, 2013

2 Safe Harbor Statement This presentation includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron, and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned, including without limitation EYLEA (aflibercept) Injection; unforeseen safety issues resulting from the administration of products and product candidates in patients; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's latestage product candidates and new indications for marketed products, such as the application of EYLEA (aflibercept) Injection in the treatment of Diabetic Macular Edema; ongoing regulatory obligations and oversight and determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainty of market acceptance of Regeneron's products and product candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be cancelled or terminated without any further product success; and risks associated with third party intellectual property and pending or future litigation relating thereto. A more complete description of these and. other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2012 and Form 10-Q for the quarter ended June 30, The reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

3 Intravitreal Aflibercept Injection for Diabetic Macular Edema Primary Results David M. Brown, M.D. Houston Methodist Hospital Houston, TX For the -DME/-DME Study Investigators

4 Diabetes: An Epidemic Ø 25.8 million people in the United States (~8.3% of the population) Ø After 15 years of diabetes, prevalence is approximately Ø 20% in patients with Type 1 diabetes. Ø 14% to 25% in patients with Type 2 diabetes Ø Leading cause of blindness in workingage Americans Accessed Sept 2013 Data from the 2011 National Diabetes Fact Sheet (released Jan. 26, 2011) Klein R, Klein B, Moss S, Davis M, DeMets D. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, IV: diabetic macular edema. Ophthalmology 1984;91:

5 TEXAS: Diabetes Statistics Over 2 million Texans affected.

6 Early Treatment Diabetic Retinopathy Study Vision Gain Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. - Arch Ophthalmol - 01-DEC-1985; 103(12):

7 ETDRS: Vision Loss Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. - Arch Ophthalmol - 01-DEC-1985; 103(12):

8 RIDE and RISE: Ranibizumab for Diabetic Macular Edema

9 Intravitreal Aflibercept Injection Fusion protein of key domains from human VEGF receptors 1 and 2 with human IgGFc Pre-clinical studies showed that aflibercept Traps multiple VEGF-A isoforms and placental growth factor (PlGF) Binds to VEGF-A and PlGF with higher affinity than native receptors Binds VEGF between its arms without risk of complex formation Purified and formulated preparation of aflibercept specifically for intravitreal injection Iso-osmotic solution compatible with intraocular environment Purified form to reduce unnecessary ingredients in the eye

10 Intravitreal Aflibercept Injection for Diabetic Macular Edema Primary Results

11 Study Sites Japan Europe Austria, Czech Republic, Denmark, France, Germany, Hungary, Italy, Poland, Spain USA 73 Centers 404 Patients Australia 54 Centers 461 Patients

12 Study Design Randomized, multicenter, double-masked trials in patients with clinically significant DME with central involvement and ETDRS BCVA 20/40 to 20/320 N=406 () N=466 () Patients randomized 1:1:1 IVT Aflibercept 2 mg q4 wks IVT Aflibercept 2 mg q8 wks* Laser Photocoagulation Primary endpoint: Mean change in BCVA Primary Endpoint: Week 52 Key Secondary endpoint: Change in DRSS *After 5 initial monthly doses Continued treatment through Year 3

13 Treatment Schedule IAI 2q4 Week IAI 2q8 Laser Laser (no more often than every 12 weeks) Sham laser (if re-treatment criteria met) Laser (as needed based on pre-specified criteria) Primary Endpoint IAI 2mg Year 2 Year 3 Sham injection IAI 2 mg (as needed based on pre-specified criteria) or sham Starting at Week 24 : Additional (rescue) treatment available to all patients Patients with BCVA below BSL and loss from previous best BCVA score of 15 letters at 1 visit or 10 letters on 2 consecutive visits

14 Key Eligibility Criteria Inclusion Criteria: Adults 18 years with Type 1 or 2 diabetes with DME involving central subfield ETDRS BCVA 20/40 to 20/320 Exclusion Criteria: No previous treatment for DME in last 3 months Active PDR IOP 25 mm Hg No previous vitreoretinal surgery Uncontrolled diabetes or blood pressure History of CVA or MI within 6 months

15 Patient Disposition Laser IAI 2q4 IAI 2q8 ALL IAI Randomized, n Received Study Medication, n Completed Week 52, n (%) 115 (85.2%) 125 (91.9%) 120 (88.9%) 360 (88.7%) Randomized, n Received Study Medication, n Completed Week 52, n (%) 145 (92.9%) 146 (93.6%) 144 (93.5%) 435 (93.3%)

16 Baseline Demographics Laser IAI 2q4 IAI 2q8 Laser IAI 2q4 IAI 2q8 N Age, years (SD) 63.9 (8.6) 62.6 (8.6) 64.2 (7.8) 61.7 (8.7) 62.0 (11.2) 63.1 (9.4) Gender (Women), n (%) 54 (40.9%) 53 (39.0%) 47 (34.8%) 69 (44.8%) 67 (43.5%) 73 (48.3%) Race, n (%) White 106 (80.3%) 109 (80.1%) 106 (78.5%) 131 (85.1%) 128 (83.1%) 125 (82.8%) Black 1 (0.8%) 0 1 (0.7%) 16 (10.4%) 16 (10.4%) 19 (12.6%) Asian 25 (18.9%) 27 (19.9%) 27 (20.0%) 3 (1.9%) 5 (3.2%) 2 (1.3%) Other HbA1c, mean % (SD) 7.7 (1.26) 7.8 (1.46) 7.7 (1.43) 7.6 (1.68) 7.9 (1.65) 7.9 (1.56) Proportion w/ >8%, n (%) 42 (31.8%) 55 (40.4%) 44 (32.6%) 45 (29.2%) 57 (37.0%) 57 (37.7%) Duration of Diabetes, years (SD) Full analysis set 14.5 (9.8) 14.3 (9.2) 14.1 (8.9) 17.2 (9.55) 16.5 (9.94) 17.6 (11.46)

17 Baseline Disease Characteristics Laser IAI 2q4 IAI 2q8 Laser IAI 2q4 IAI 2q8 N BCVA, ETDRS Letter score (SD) 60.8 (10.6) 60.8 (10.7) 58.8 (11.2) 59.7 (10.9) 58.9 (10.8) 59.4 (10.9) CRT, µm (SD) 540 (152) 502 (144) 518 (147) 483 (153) 485 (157) 479 (154) Prior Anti-VEGF Treatment, n (%) 11 (8.3%) 7 (5.1%) 14 (10.4%) 63 (40.9%) 66 (42.9%) 68 (45.0%) BCVA: Best-Corrected Visual Acuity CRT: Central Retinal Thickness (Central Subfield) Full analysis set

18 Baseline Disease Characteristics N DRSS, n (%) (27.3%) 31 (22.8%) 28 (20.7%) 60 (39.0%) 49 (31.8%) 52 (34.4%) (18.2%) 18 (13.2%) 27 (20.0%) 26 (16.9%) 26 (16.9%) 32 (21.2%) (26.5%) 44 (32.4%) 42 (31.1%) 42 (27.3%) 52 (33.8%) 40 (26.5%) Cannot grade 33 (25.0%) 39 (28.7%) 34 (25.2%) 4 (2.6%) 2 (1.3%) 3 (2.0%) 40 Laser IAI 2q4 IAI 2q8 Laser IAI 2q4 IAI 2q8 40 Proportion of Patients Level About 74% of patients in, and 98% of patients in could be graded DRSS: Diabetic Retinopathy Severity Score; Full analysis set Level

19 Exposure and Rescue Treatment

20 Treatment Experience Mean # of Active Injections* Mean # of Active Injections* Number of Treatments Mean # of Active Lasers* Mean # of Active Lasers* 2.7 Laser 2q4 2q8 0 SAF: Laser: n=133; 2q4: n=136; 2q8: n=135; SAF: Laser: n=154; 2q4: n=155; 2q8: n=152 *Not considering Rescue Treatment; 13 Injections possible; Minimum # of lasers = 1, maximum = 4/5

21 Additional (Rescue) Treatment Experience SAF Laser: n=133; 2q4: n=136; 2q8: n=135 SAF Laser: n=154; 2q4: n=155; 2q8: n=151 *Patients in IAI arms received laser and patients in the laser arm received IAI if Rescue Treatment Criteria were met. Proportion of Patients Receiving Rescue Treatment Proportion of Patients 100% 80% 60% 40% 20% 0% 24.1% 31.2% 4.4% 8.1% 2.6% 0.7% Laser 2q4 2q8

22 Fellow Eye Treatment Proportion of Patients Receiving anti-vegf Treatment Proportion of Patients 100% 80% 60% 40% 20% 24.1% 26.5% 25.2% 59.1% 59.1% 70.9% Laser 2q4 2q8 0% Laser: n=132; 2q4: n=136; 2q8: n=135 SAF Laser: n=154; 2q4: n=154; 2q8: n=151

23 Efficacy

24 Mean Change in Best-Corrected Visual Acuity ETDRS letters 14 Laser 2q4 2q Laser Laser Week ETDRS; Compared to baseline; FAS; LOCF Laser: n=154; 2q4: n=154; 2q8: n=151 - Laser: n=132; 2q4: n=136; 2q8; n=135

25 Mean Change in Best-Corrected Visual Acuity ETDRS letters Week ETDRS; Compared to baseline; FAS; LOCF Laser: n=154; 2q4: n=154; 2q8: n=151 - Laser: n=132; 2q4: n=136; 2q8; n=135 *P < vs. laser *P < vs. laser Laser 2q4 2q q q4 1.2 Laser q q Laser

26 Proportion of Patients Gaining 10 Letters 100% Proportion of Patients 80% 60% 40% 20% 25.8% 54.4%* 53.3%* 19.5% 64.9%* 58.3%* Laser 2q4 2q8 0% FAS- Laser: n=132; 2q4: n=136; 2q8: n=135 FAS- Laser: n=154; 2q4: n=154; 2q8: n=151 Compared to baseline; LOCF *P < vs. laser *P < vs. laser

27 Proportion of Patients Gaining 15 Letters 100% Proportion of Patients 80% 60% 40% 20% 32.4%* 41.6%* 33.3%* 31.1%* 9.1% 7.8% Laser 2q4 2q8 0% FAS- Laser: n=132; 2q4: n=136; 2q8: n=135 FAS- Laser: n=154; 2q4: n=154; 2q8: n=151 Compared to baseline; LOCF *P < vs. laser *P < vs. laser

28 Proportion of Patients Losing 15 Letters 50% Proportion of Patients 40% 30% 20% 10% 0% 10.6% 9.1% 0.7% 0.0% 0.6% 0.7% Laser 2q4 2q8 FAS- Laser: n=132; 2q4: n=136; 2q8: n=135 FAS- Laser: n=154; 2q4: n=154; 2q8: n=151 Compared to baseline; LOCF

29 0 Mean Change in Central Retinal Thickness Week Laser 2q4 2q *P < vs. laser Laser µm q q Laser q q8 - Laser: n=132; 2q4: n=136; 2q8: n=135 Laser: n=154; 2q4: n=154; 2q8: n=151 Central Sub-field; Compared to baseline; FAS; LOCF; SD-OCT *P < vs. laser

30 DRSS: Diabetic Retinopathy Severity Score Compared to baseline; LOCF Proportion of Patients with 2 Step Improvement in DRSS 100% Proportion of Patients 80% 60% 40% 20% 7.5% 33.3% 33.8% 27.7% 29.1% 14.3% Laser 2q4 2q8 0% n=80 n=81 n=83 P < q4 vs. laser P = q8 vs. laser n=154 n=151 n=154 P < q4 vs. laser P = q8 vs. laser

31 Safety

32 Safety Overview Laser IAI 2q4 IAI 2q8 ALL IAI Laser IAI 2q4 IAI 2q8 ALL IAI N Ocular AEs (study eye), n (%) Systemic AEs, n (%) Ocular SAEs (study eye), n (%) Systemic SAEs, n (%) 82 (61.7%) 76 (55.9%) 80 (59.3%) 156 (57.6%) 103 (66.9%) 96 (61.9%) 87 (57.2%) 183 (59.6%) 81 (60.9%) 92 (67.6%) 98 (72.6%) 190 (70.1%) 132 (85.7%) 125 (80.6%) 119 (78.3%) 244 (79.5%) 6 (4.5%) 2 (1.5%) 3 (2.2%) 5 (1.8%) 6 (3.9%) 3 (1.9%) 2 (1.3%) 5 (1.6%) 18 (13.5%) 19 (14.0%) 25 (18.5%) 44 (16.2%) 47 (30.5%) 48 (31.0%) 39 (25.7%) 87 (28.3%) (S)AE = (Serious) Adverse Event Safety analyses set

33 Intraocular Inflammation Study Eye Laser IAI 2q4 IAI 2q8 Laser IAI 2q4 IAI 2q8 Number of Injections Number of events, n (%) 1 (0.4%)* 4 (0.2%) 5 (0.4%) 1 (0.2%)* 4 (0.2%) 1 (0.1%) Endophthalmitis, n (%) *Patient did not receive an IVT injections in study eye Safety analyses set

34 APTC Events* N Any APTC event, n (%) 2 (1.5%) 2 (1.5%) 4 (3.0%) 6 (2.2%) Non-fatal MI 1 (0.8%) 1 (0.7%) 0 1 (0.4%) Non-fatal stroke 0 1 (0.7%) 2 (1.5%) 3 (1.1%) Vascular deaths 1 (0.8%) 0 2 (1.5%) 2 (0.7%) Laser IAI 2q4 IAI 2q8 ALL IAI N Any APTC event, n (%) 6 (3.9%) 7 (4.5%) 6 (3.9%) 13 (4.2%) Non-fatal MI 4 (2.6%) 3 (1.9%) 3 (2.0%) 6 (2.0%) Non-fatal stroke 2 (1.3%) 2 (1.3%) 3 (2.0%) 5 (1.6%) Vascular deaths 1 (0.6%) 2 (1.3%) 0 2 (0.7%) *As adjudicated by a masked committee; Only treatment emergent events included; APTC=Anti-platelet thromboembolic Collaboration Safety analyses set

35 Deaths Through Week 52 N Death, n (%) 1 (0.8%) 0 4 (3.0%)* 4 (1.5%) Acute MI 1 (0.8%) Cardiac failure (0.7%) 1 (0.4%) Hypertensive heart disease (0.7%) 1 (0.4%) Lung neoplasm (0.7%) 1 (0.4%) B-cell lymphoma (0.7%) 1 (0.4%) Laser N Death, n (%) 1 (0.6%) 2 (1.3%) 0 2 (0.7%) Death 0 1 (0.6%) 0 1 (0.3%) Myocardial infarction 0 1 (0.6%) 0 1 (0.3%) Sudden cardiac death 1 (0.6%) *Note: One additional death (MI) occurred in the 2q8 group in in year 2 (406 and 77 days after the first and last active injections, respectively), but due to data conventions it was included in the Year 1 clinical database Safety analyses set IAI 2q4 IAI 2q8 ALL IAI

36 Deaths Through Week 52 Kaplan Meier Plot of Time to Death Note: One additional death (MI) occurred in the 2q8 group in -DME in year 2 (406 and 77 days after the first and last active injections, respectively), but due to data conventions it was included in the Year 1 clinical database. Safety analyses set

37 Conclusions ETDRS letters q q q q Laser Laser Superiority of IAI over laser treatment seen through Week 52 On average, IAI 2q8 group performed similarly to the IAI 2q4 group No systemic safety signal in both IAI treatment groups evident through Week 52

38 Q&A 38