Disclosures

1. A single-arm, multicentre, open-label, phase III clinical trial to evaluate the safety and tolerability of prophylactic emicizumab▼ in persons with haemophilia A (PwHA) with FVIII inhibitors (STASEY): interim analysis results Victor Jiménez-Yuste,1 Robert Klamroth,2 Giancarlo Castaman,3 Margareth Ozelo,4 Susan F. Robson,5 Oliver Meier,5 and Elena Santagostino6 1Hospital Universitario La Paz, Autonoma University, Madrid, Spain; 2Comprehensive Care Haemophilia Treatment Centre, VivantesKlinikum, Berlin, Germany; 3Careggi University Hospital, Florence, Italy4University of Campinas (UNICAMP), Campinas, SP, Brazil; 5F. Hoffmann-La Roche Ltd, Basel, Switzerland 6IRCCS Fondazione Ca’Granda, Ospedale Maggiore Policlinico, Milan, Italy ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. These should be reported to the Regulatory authorities in your country according to your national requirements.

2. Disclosures • Disclosures for Victor Jiménez-Yuste

3. Background • Emicizumab is a bispecific, humanised monoclonal antibody that restores the function of missing activated FVIII in PwHA1–3 • Evidence from four phase 3 studies, HAVEN 1–4,4–7 has supported the approval of emicizumab prophylaxis to treat PwHA with or without FVIII inhibitors across all age groups • The STASEY study was designed to evaluate the safety and tolerability of emicizumab in PwHA with FVIII inhibitors over a 2-year treatment period8 Aim • To provide safety and efficacy results from an interim analysis of theSTASEY study F, factor; PwHA, persons with haemophilia A 1. Kitazawa T, et al. ThrombHaemost 2017;117:1348–57; 2. Kitazawa T, et al. Nat Med 2012;18:1570–4; 3. Sampei Z, et al. PLoS One 2013;8:e57479 4. Oldenburg J, et al. N Engl J Med 2017;377:809–18; 5. Young G, et al. ASH 2018; oral presentation #623; 6. Mahlangu J, et al. N Engl J Med 2018;379:811–22 7. Pipe SW, et al. Lancet Haematol 2019;DOI:10.1016/S2352-3026(19)30054-7; 8. https://clinicaltrials.gov/ct2/show/NCT03191799

4. STASEY study design Persons aged≥12 years with congenital haemophilia A of any severity who have inhibitors against FVIII (N=198) Loading dose: Emicizumab SC 3 mg/kg/week Maintenance does: Emicizumab SC 1.5 mg/kg/week 4 weeks 2 years A pre-planned interim analysis was performed with a data cut-off of 15 October 2018 and included patients from 17 participating countries* who had received treatment with emicizumab for ≥24 weeks *Australia, Belgium, Brazil, Canada, Switzerland, Germany, Spain, Finland, UK, Hungary, Italy, Mexico, Panama, Poland, Portugal, Russian Federation, and SwedenAE, adverse event; HRQoL, health-related quality of life; PK, pharmacokinetic; SC, subcutaneously (administered); TE, thromboembolic events; TMA, thrombotic microangiopathy

5. Patient disposition (interim analysis) • The first patient is expected to complete study treatment in September 2019 Started maintenance emicizumab(1.5 mg/kg/week) N=88 Treatment ongoing N=85 Prematurely discontinued study N=3 Reasons for discontinuation Death 1 Physician decision 1 Withdrawal by participant 1

6. Baseline demographics *Two patients had FVIII inhibitor titre <2 BU; 14 patients had unknown titreBU, Bethesda units; ITI, immune tolerance induction

7. Median duration of exposure: 39.2 weeks (range, 4.4–57.1 weeks) Emicizumab was well tolerated, with no reportedTEs Coded using MedDRA version 21.1; *Polytrauma with fatal head injury, unrelated to emicizumabMultiple occurrences of the same AE in one individual are counted only once except for "Total number of AEs" row, in which multiple occurrences of the same AE are counted separatelyISR, injection-site reaction; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event

8. SAEs were infrequent and the most common treatment-related AEs were ISRs • The most common (≥10% of patients)AEs (non-serious) were ISRs (14.8%), arthralgia (13.6%), headache (11.4%), and nasopharyngitis (11.4%) • The most common emicizumab-related AEs were ISRs (n=12; 13.6%) • All ISRs were mild (n=12; 13.6%) or moderate (n=1; 1.1%) in severity *SAE rate per 100 patient-years (95% CI):19.68 (10.48, 33.66); †These 3 SAEs occurred in a single patient; ‡These 2 SAEs occurred in a single patient§The only SAE deemed treatment-related by the investigator was one case of catheter-site abscessCI, confidence interval

9. Effective bleed control was achieved with once-weekly emicizumab across all bleed-related endpoints Model-based ABR* (ITT population) Proportion of patients with zero bleeds 94.3 (n=83) 92.0 (n=81) 89.8 (n=79) 80.7 (n=71) 1.4 (0.91–2.24) 63.6 (n=56) 0.5 (0.29–1.00) 0.3 (0.10–0.84) 0.2 (0.08–0.34) 0.1 (0.03–0.18) † ‡ † ‡ • The median ABR for treated bleeds was 0.0 (IQR, 0.0–0.0) • Of 17 patients who received treatment for a bleed, 16 received rFVIIa, and one received standard FVIII • No TE or TMA events occurred with concomitant treatment for breakthrough bleeds *Model-based ABR, calculated using the negative binomial regression methodABR, annualised bleeding rate; IQR, interquartile range; ITT, intention to treat; rFVIIa, recombinant factor VIIa

10. Clinically meaningful improvements in HRQoL domains were reported by adults and adolescents over time Physical Health and Total Scores over time Work & School* / Sport & School† Scores over time Adults (≥18y) Adolescents (≥12–<18y) Haem-A-QoL, n 55 48 45 3 Haemo-QoL-SF, n 15 14 16 5 Mean score change from baseline to month 6 Haem-A-QoL, n 69 64 61 3 Haemo-QoL-SF, n 15 14 16 5 *Haem-A-QoL Domain, completed by participants ≥18 years; †Haemo-QoL SF Domain, completed by participants ≥12 and <18 years; ‡Threshold for clinically meaningful change was exceededLower scores indicate less impairment and larger increases from baseline indicate greater improvementHaem-A-QoL, Haemophilia-specific Quality of Life questionnaire for adults; Haemo-QoL-SF, Haemophilia-specific Quality of Life Index Short Form for children/adolescents; SD, standard deviation

11. The majority of patients preferred emicizumab to their prior therapy • Of the 80 patients who completed the EmiPref survey, 76 (95.0%) preferred emicizumab to their prior therapy EmiPref survey results Prefer the new study drug treatment (SC) n=76, 95.0% [95% CI 87.69–98.62] N=80 respondents Have no preference n=4, 5.0% [95% CI 1.38–12.31] • No patients preferred their prior haemophilia treatment to emicizumab prophylaxis [95% CI 0.00–4.51] EmiPref, Emicizumab Preference survey; SC, subcutaneous

12. Download this presentation: http://bit.ly/2IRQ49u Summary • The interim results from the STASEY study confirmed the safety and tolerability of emicizumab previously reported1–4 in 88 patients with a median 39.2 weeksof exposure • No new safety signals were identified • The most common treatment-related AEs were mild/moderate ISRs (13.6%) • No events of thromboembolism or TMAs were reported • Bleeding rates in PwHA with FVIII inhibitors receiving emicizumab in the STASEY study were in line with previously reported observations in patients with inhibitors1,2 • Clinically meaningful improvements from baseline in HRQoL were observed for Physical Health and Total Score domains • Most participants (95.0%) preferred emicizumab to their prior therapy 1. Oldenburg J, et al. N Engl J Med 2017;377:809–18; 2. Young G, et al. ASH 2018; oral presentation #623 3. Mahlangu J, et al. N Engl J Med 2018;379:811–22; 4. Pipe SW, et al. Lancet Haematol 2019; DOI:10.1016/S2352-3026(19)30054-7

13. Download this presentation: http://bit.ly/2IRQ49u Acknowledgements • The patients and their families • The study investigators, and their co-ordinators and nurses • The sponsor, F. Hoffmann-La Roche Ltd • Writing assistance was provided Maria Alfaradhi, PhD, of Gardiner-Caldwell Communications, and funded by F. Hoffmann-La Roche Ltd