Slides
Page 1
Topline Results of the KHK4951 Phase 2 study in nAMD patients September 9th, 2026 Chief Medical Officer (CMO) Yoshifumi Torii Kyowa Kirin Co., Ltd. NCT06116890
Page 2
2© Kyowa Kirin Co., Ltd. This document contains forward-looking statements regarding the outlook, targets, plans, and other future-related matters of the Company (including its consolidated subsidiaries in Japan and overseas). These statements are based on our reasonable judgments using current information and forecasts but involve uncertainties that could cause actual results to differ materially. These uncertainties include, but are not limited to, risks inherent in the domestic and international pharmaceutical industry, intellectual property rights, side effects, legal regulations, product defects, fluctuations in raw material/fuel prices, market prices, and exchange/financial markets. This document is for investor information purposes only and contains information on pharmaceuticals (including products under development), but it is not intended for promotional advertising or medical advice.
Page 3
© Kyowa Kirin Co., Ltd.3 Vision 2030 Provide pharmaceuticals for unmet medical needs We are focused on developing medicines for diseases where there is a clear patient need for new options. We make full use of multiple therapeutic modalities, including biotechnology such as antibody technology, and beyond, building on our Kyowa Kirin established strengths. Retain the trust of society We pursue world-class product quality and operational excellence to grow our business in ways which build long-term trust with our stakeholders Kyowa Kirin will realize the successful creation and delivery of life-changing value* that ultimately makes people smile, as a Japan-based Global Specialty Pharmaceutical company built on the diverse team of experts with shared passion for innovation. Address patient-centric healthcare needs By applying scientific insights and cutting-edge technologies cultivated through our pharmaceutical business, we aim to create new value that focuses on the needs of people living with diseases. We will continue to meet society’s medical needs through patient-centered innovation. * Make patients smile through dramatic improvements in quality of life by identifying the unmet medical needs of people battling with medical conditions and by creating and supplying new drugs or services that help them overcome those challenges. 3
Page 4
4© Kyowa Kirin Co., Ltd. KHK4951 Assets in focus disease areas Patients 2670k Global nAMD Existing Market Size2 1Trillion Yen~ In development for neovascular Age-related Macular Degeneration (nAMD) and Diabetic Macular Edema (DME) Pursuing the potential to deliver the first anti-VEGF eye drop treatment for diseases where intravitreal injection is the SOC1 DME Patients 2220k Existing Market Size2 500B~1Tyen Lancet 2012; 379: 1728–38 Nano-crystallized tivozanib Efficient posterior eye delivery Strategic Partnering Assets Global KHK4951 Disease areas Ophthalmology Modalities Small Molecule (Eye drop) Commercialization Exploring Strategic Partner Market Potential Market Potential 1 Standard of Care, 2 Market size is our own independent estimate based on the total of all products for the disease under development. Creating Innovative Life-changing value
Page 5
© Kyowa Kirin Co., Ltd.5 KHK4951 Phase 2 Summary of Test Results Achieved the company's pre-defined product profile targets Results suggest the potential of an eye drop-centered maintenance treatment strategy 1. IVT = Intravitreal; 2. Best-Corrected Visual Acuity; 3. Central Subfield Thickness Primary Evaluation Items The “statistical difference among dose groups in the proportion of patients with a reduction of 15 or more BCVA2 between 8 and 52 weeks" was not observed Safety and Tolerability No new safety signals were observed in this study Effectiveness In all treatment groups, including the low-dose group, 65-69% of subjects maintained their vision within 15 letters decrease in BCVA without any rescue IVT1 injection at Week 52 Secondary Evaluation Items In all groups, BCVA and CST3 remained stable throughout the treatment period.
Page 6
© Kyowa Kirin Co., Ltd.6 Clinical Needs for Eye Drop Maintenance Therapy in nAMD 01 Diseases requiring ongoing treatment nAMD requires ongoing intravitreal injection therapy with anti-VEGF agents and follow-up to maintain long- term vision 02 Burden of current treatment Treatment with intravitreal injections places a significant burden on patients and healthcare professionals, including repeated injections, regular visits to specialized medical institutions, patient mobility, and support The vision the KHK4951 aims for Developing maintenance treatment centered on eye drops after induction with intravitreal injections (maintaining visual acuity, reducing IVT injection count, and providing rescue treatment only when necessary)
Page 7
© Kyowa Kirin Co., Ltd.7 The Concept of KHK4951 as Eye Drop Maintenance Therapy Current Maintenance Therapy by Intravitreal Injection Maintenance Therapy Models Examined in KHK4951 • Focusing on extending the interval between intravitreal injections • Repeated procedures at specialized centers are necessary • The burden of injections and hospital visits continues • Maintenance therapy mainly involves daily eye drops • Daily self-management and professional rescue treatment as needed • Potential to reduce the number of injections and the burden of visiting clinics
Page 8
8© Kyowa Kirin Co., Ltd. KHK4951 0.5 w/v%、QD KHK4951 2 w/v%、QD2 KHK4951 2 w/v%、BID1 Screening Treatment (52W) IVT KHK4951 Design of Phase 2 Trials Overview Research Objectives ⚫ Evaluating the efficacy and safety of KHK4951 at different doses ⚫ Determining the optimal KHK4951 dose for the Phase 3 study Primary Evaluation Items ⚫ Evaluation of superiority of KHK4951 high dose to low dose: Statistically significant difference in the proportion of patients who lost 15 or more BCVA letters between W8 and W52 Eligible Patients ⚫ Treatment-naïve patients ⚫ Patients previously treated with anti-VEGF agents Sample size ⚫ 132 patients receiving KHK4951 treatment (no placebo arm) Three groups were set up according to the dosage 1. Twice daily; 2. Once-daily administration D-30 D1 W52 Follow-up after treatment (4W) W56W8 Screening EoT/ET EoS 1 2 3 1. Twice daily; 2. Once-daily administration; EoT/ET = End of Treatment/Early Termination; EoS = End of Study
Page 9
© Kyowa Kirin Co., Ltd.9 Approximately 65–69% of cases in all treatment groups maintained their vision within 15 letters decrease in BCVA without any rescue IVT injection ■15 or more letters decrease in BCVA: 31.1% (2.0% BID), 34.9% (2.0% QD), 31.8% (0.5% QD) ■No significant differences were observed among dose groups, and the primary endpoint was not met KHK4951 0.5 w/v% QD (N = 44) KHK4951 2.0 w/v% QD (N = 43) KHK4951 2.0 w/v% BID (N = 45) Participants Meeting Criteria 14 15 14 Proportion with Exact 95% CI (%) 31.82 (18.610, 47.578) 34.88 (21.008, 50.927) 31.11 (18.166, 46.649) Difference (%) vs. 0.5 w/v% QD (Reference Dose) — 3.07 -0.71 Adjusted Difference (%) (Stratified Newcombe 95% CI) — 2.35 (-17.040, 21.558) -0.43 (-19.213, 18.360) p-value — NA 0.965
Page 10
© Kyowa Kirin Co., Ltd.10 Mean change in BCVA during the KHK4951 dosing period In all groups, the mean BCVA remained stable from the KHK4951 administration. No clear differences were observed in the mean BCVA change among dose groups.
Page 11
© Kyowa Kirin Co., Ltd.11 Mean change in CST during the KHK4951 dosing period In all groups, the mean CST remained stable from the KHK4951 administration. Meanwhile, no clear differences were observed in the mean CST change among dose groups. ILM: Internal Limiting Membrane RPE: Retinal pigment epithelium
Page 12
© Kyowa Kirin Co., Ltd.12 Safety and Tolerability No new safety signals were observed in this study Parameter Main findings Ocular site A small number of dry eyes and punctate keratitis were mainly observed in the 2.0% BID cohort Systemic No significant new safety signals observed during KHK4951 treatment (e.g., increase in blood pressure) Study completion About 70% completed the study. The main reasons for study discontinuation were the need for alternative treatments or progression of nAMD (about 15%)
Page 13
© Kyowa Kirin Co., Ltd.13 Clinical Perspectives on Eye-Drop Maintenance Therapy — KOL Comments KOLs Feedbacks Dr. Pieramici ⚫ Although the absence of a true control group is the study’s primary limitation, making it difficult to attribute the observed outcomes directly to the drug, Dr. Pieramici noted that approximately 70% of patients maintained vision (lost less than 3 lines vision or needed rescue) after induction therapy, which may be better than expected from observation alone. Dr. Iida ⚫ Dr. Iida agreed Kyowa Kirin’s interpretation that this result shows therapeutic effect of KHK4951. ⚫ Based on Ph2 result, Ph3 plan should be carefully considered. At this time, non-inferiority study to aflibercept 2 mg with appropriate rescue criteria is reasonable for Ph3 study. Dr. Murata ⚫ It is exceeded our expectations that 70% of participants maintained their vision through Week 52 without any intravitreal anti-VEGF injections. This suggests that KHK4951 showed a therapeutic effect. ⚫ Even if there is a dose-dependent increase in the frequency of adverse events, these are manageable and acceptable compared to the invasiveness of intravitreal anti-VEGF injections.
Page 14
© Kyowa Kirin Co., Ltd.14 Summary and Conclusion Achieved the company's pre-defined product profile targets Results suggest the potential of an eye drop-centered maintenance treatment strategy Efficacy Evaluation Approximately 65–69% of subjects maintained their vision within 15 letters decrease in BCVA without any rescue IVT injection at Week 52 No difference was observed among dose groups; the primary endpoint was not met Secondary Endpoints In all groups, BCVA and CST remained stable throughout the treatment period. Potential for New Treatment Strategies Presenting the potential of a maintenance therapy strategy centered on eye drops that could help reduce the burden on patients and healthcare professionals. Based on the insights gained from this exam, our company will explore various options to maximize the value of this program
Page 15
© Kyowa Kirin Co., Ltd.15 Kyowa Kirin continuously creates Life-changing value by leveraging disease science and drug discovery technology From Story for Vision 2030 Disease Science Deeply Exploring Unmet Medical Needs (UMN) of Diseases, Their Causes, and Mechanisms ・Exploring treatment possibilities starting from unmet patient needs KHK4951: Focusing on UMN in patients with maintenance therapy that does not rely on frequent intravitreal injections Drug Discovery Technology Application of the optimal modality for achieving treatment ・Combining research and formulation technology expertise to verify treatment concepts in clinical practice KHK4951: Pursuing efficient posterior-segment delivery using nanocrystallized tivozanib KHK4951: Strategic Partnering Assets Assets beyond our focus areas – Maximizing value through collaboration with partners Creating Life-changing value
Page 16
～Contact for Inquiries Regarding This Material～ Kyowa Kirin Co., Ltd. Finance Dep., IR Group +81-3-5205-7206 / ir@kyowakirin.com