Slides
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Kodiak Sciences
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These slides contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding: the progress and anticipated benefits of our ABCD platform; the prospects and anticipated milestones of the candidates in our pipeline, including tarcocimab, KSI-501, and KSI-101; the expected enhancements and benefits of a new formulation; our and Lonza’s (our manufacturing counterpart) ability to successfully execute on our manufacturing development plan; the timing and success of our planned Biologics License Application (“BLA”) package; the timing of anticipa ted topline data readouts; and the potential to provide continued revenue stream starting from 2027. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "could," "expect," "plan," "belie ve," "intend," "pursue," and other similar expressions among others. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. The risks and uncertainties include, but are not limited to: the risk that cessation or delay of any of the on-going clinical studies and our development of tarcocimab, KSI-501 or KSI-101 may occur; the risk that ongoing clinical trial results may not provide the evidence, insights, or benefits as anticipated; the risk that safety, efficacy, and durability data observed in our product candidates in current or prior studies may not continue or persist; the risk that the results of the tarcocimab Phase 3 studies may not be sufficient to support a single BLA submission for DR, RVO and wet AMD; the risk that a BLA may not be accepted by, or receive approval from, the FDA or foreign regulatory agencies when expected, or at all; future potential regulatory milestones of tarcocimab, KSI-501 or KSI-101, including those related to current and planned clinical studies, may be insufficient to support regulatory submissions or approval; the risk that a new formulation of tarcocimab, KSI-501 or other ABC Platform derived molecules may not provide the benefits expected; our research and development efforts and our ability to advance our product candidates into later stages of development may fail; the risk that KSI-501 may not inhibit VEGF and IL-6 or have an impact on the treatment of patients as expected; any one or more of our product candidates may not be successfully developed, approved or commercialized; our manufacturing facilities may not operate as expected; adverse conditions in the general domestic and glob al economic markets, which may significantly impact our business and operations, including our clinical trial sites, as well as the business or operations o f our manufacturers, contract research organizations or other third parties with whom we conduct business; as well as the other risks Identified in our filings with the Securities a nd Exchange Commission. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and Kodiak undertakes no obligation to update forward- looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. Kodiak®, Kodiak Sciences®, ABC , ABC Platform , and the Kodiak logo are registered trademarks or trademarks of Kodiak Sciences Inc. in various global jurisdictions FORWARD- LOOKING STATEMENTS 2
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THE KODIAK OPPORTUNITY 3 Victor Perlroth, MD
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Retinal vascular diseases remain a large and growing market driven by aging populations and increased prevalence of diabetes wet AMD RVO 1.5 – 2M ~8M 1.5 – 2M 1. Sales refer to branded intravitreal agents only. Company SEC filings and press releases. 2. Market Scope Retinal Market Report 2023. DR 0 5 10 15 20 $ Billions 2014 2017 2020 2023 2028 $14B $18B ~$14B1 in 2023 ~$18B2 Estimated in 2028 • U.S. remains the growth driver by geography • 10% (US) vs 5% (rest of world) CAGR in the past decade 60% 40% US AMD: age-related macular degeneration; DR: diabetic retinopathy; RVO: retinal vein occlusion 4 Global Net Sales of Branded Intravitreal Biologics for Retinal Vascular Diseases Rest of world Retinal Vascular Disease Prevalence 10 – 15M patients in the U.S.
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In wet AMD, established Gen 1.0 anti-VEGF agents achieve modest vision gains in the real world and require frequent injections to maintain vision wet AMD U.S. prevalence 1.5 – 2M Real world treatment pattern of wet AMD patients1 • Gen 1.0 anti-VEGF agents achieve only modest vision gains in Year 1 despite frequent injections (7 injections with a mean interval of 7 weeks in between) 1. Adapted from Wykoff et al. Ophthalmology Science 2024; 4: 100421 7 12 13 14 15 15 7 6 5 5 5 4 Year of follow-up 1 2 3 4 5 6 Mean no. of anti-VEGF injections per year Mean anti-VEGF injection interval (weeks) 3 1 0 -2 -3 -5 Year of follow-up 1 2 3 4 5 6 Change in visual acuity from baseline (ETDRS letters) Real world visual outcomes of wet AMD patients1 • Frequent injections are not sustained over the long term, which leads to vision loss over time 5
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“Gen 1.5” anti-VEGFs provide modest dosing interval extension in the real world 21% Q8W 33% Q16W 45% 1. Adapted from Roche 2024 ASRS IR event. Phase 3 TENAYA / LUCERNE Year 1 treatment interval (Pooled analysis) Independent UK real-world data 11% 14% 14% 22%20% ≤Q6W Q8W Q10W Q12WQ14W Q16W 18% 8% 17% 36%31% 8% ≤Q6W Q8W Q10W Q12W Q14W Year 1 Moorfields (n=172) Year 1 Liverpool (n=101) Q16W: 45% wet AMD U.S. prevalence 1.5 – 2M • Accumulating evidence suggests newer anti-VEGF agents such as faricimab only achieve modest dosing intervals extension in real-world data • Real-world durability of faricimab does not match that demonstrated in Phase 3 studies1 Q16W: 18% Q12W Q16W: 0% 6 Faricimab in wAMD Clinical Trials Faricimab in wAMD Real World
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• In clinical trials, fewer than half of faricimab patients achieved 4-month dosing in Year 1 • Real-world evidence shows that switching anti-VEGF experienced patients to faricimab achieves very modest extension in dosing intervals DME (n= 3,001) RVO (n= 535) “Is a more durable drug needed? It's definitely needed. Half of my clinic needs more treatment dosing than Q7W or Q6W with faricimab or with 8mg aflibercept.” – Dr. David Brown “I think that signature durability profile that we saw of tarcocimab, that has continued to resonate through the trials in direct head-to-head comparisons with aflibercept. I think that is being driven by the biopolymer conjugate and that's still quite meaningful to me. I see that durability as a huge value-add in the space.” – Dr. Charles Wykoff Retina specialists are still looking for more durable therapies 1. Yuan et al. Switching to Intravitreal Faricimab in Treatment-Experienced Patients in Routine Clinical Practice: Efficacy, Safety and Durability Outcomes. 2024 ARVO Poster Presentation. Number of eyes in study (n) Patients switching to faricimab achieve only a modest extension in dosing All Indications (n=13,021) Wet AMD (n= 9,288) Mean extension in dosing interval by faricimab (days) 7.6 8.4 4.8 0.8 Average dosing interval extension with faricimab across all indications +7.6 days¹ 7 Durability remains the leading unmet need even with faricimab and aflibercept HD
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“Gen 1.5” anti-VEGFs also do not provide additional vision benefits in the real world over Gen 1.0 agents 61.9 60.4 60.462.3 61.5 59.6 Number of faricimab injections 3 6 9 Before switch After switch 1. Adapted from Khanani presentation “The Real-World Efficacy and Safety of Faricimab in Neovascular Age- Related Macular Degeneration: The TRUCKEE Study – 2 years results” at Roche 2024 ASRS IR event Real world visual acuity (ETDRS letters ) of wet AMD patients that were switched to faricimab1 wet AMD U.S. prevalence 1.5 – 2M • Newer anti-VEGF agents such as faricimab does not provide additional vision benefits in real-world data compared to previously approved anti-VEGF agents 8
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In diabetic retinopathy, current “wait and watch” approach does not treat retinopathy or prevent progression to vision threatening complications 1. Maturi et al. JAMA. 2023;329(5):376–385. NPDR: non-proliferative diabetic retinopathy; PDR: proliferative diabetic retinopathy; CI-DME: center-involved diabetic macular edema Left untreated, 57% of patients with NPDR progressed to PDR or developed CI-DME over 4 years1 DR U.S. prevalence ~8M < 1% are currently treated due to treatment burden with existing anti- VEGF therapies • Currently, patients with diabetic retinopathy are generally not treated given high treatment burden associated with frequent injections of approved therapies • The “watch and wait” approach is known to result in progression of retinopathy and development of vision threatening complications 9
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Tarcocimab and KSI-501 are being developed as “mainstay” intravitreal biologic monotherapies that provide high efficacy and high durability and a flexible 1-month through 6-month label 10 HIGH LOW HIGH Gen 1.0 • Eylea • Lucentis Gen 1.5 • Eylea HD • Vabysmo Gene TherapiesTKIs Onerous monitoring and inflammation control. Long-term safety unknown Maintenance agents to be used in subset of patients after intravitreal biologic monotherapies have established disease control “Alternative” therapies for different subsets of patients after evaluating mainstay intravitreal biologics: “Mainstay” intravitreal biologic monotherapies for all patients: LOW EFFICACY DURABILITY Gen 2.0 – Kodiak Investigational Medicines KSI-501Tarcocimab Dual inhibition of IL-6 and VEGF with potential for additional efficacy beyond anti- VEGF monotherapies while maintaining signature durability of ABCD platform Strong immediacy and longest durability for all patients • OTX-TKI (Ocular Therapeutix) • EYP-1901 (EyePoint) • CLS-AX (Clearside Biomedical) • 4D-150 (4DMT) • RGX-314 (Regenexbio) • ADVM-022 (Adverum)
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Despite limited differentiation and label limitations, each incremental improvement has resulted in blockbuster commercial opportunities for the mainstay biologics $9.2B in 2023 $2.0B in 2023 Q4W Q8W Q12W Q16W Q20W Q24W TARCOCIMAB TARCOCIMAB TARCOCIMAB TARCOCIMAB *Dosing regimen per label for approved biologics and in ongoing or completed pivotal clinical studies for tarcocimab ^Indication not included in label for approved biologics and not expected to be in initial BLA for tarcocimab 11 tarcocimab tedromer Wet AMD DME DR RVO RVO DR^ RVO DR RVO^ DME^ Gen 1.0: Good efficacy Limited durability Gen 1.5: Incremental durability Dosing Regimen for Intravitreal Biologics* Gen 2.0: Strong efficacy Best durability Worldwide net sales $2.4B in 2023 Est. peak sales > $4B $570M in 1H24 Each 1% share gain is estimated to translate into $200 – 300M net sales Wet AMD DR Wet AMD DME DR Wet AMD DME Wet AMD DME RVO
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In addition, KSI-101 has the potential to be an important and differentiated medicine in retinal inflammatory conditions, a greenfield market segment 12 A relevant case study A Greenfield Market • Launched into a nonexistent market: high unmet need with no approved therapy • Sales approached blockbuster status in 1 st year of launch, substantially outperforming management expectation of “$30 – 40 million” 1 $820M $1,660M $1,970M $1,770M 2020 2021 2022 2023 TEPEZZA Net Sales2 TEPEZZA in thyroid eye disease • A similar greenfield market opportunity • Broad patient population • High unmet need with no approved intravitreal biologics • Gateway indication to a broad set of diseases; could include all retinal diseases with “macular edema” Market opportunity • Dual inhibition (anti-IL-6 and VEGF trap) with a synergistic effect on normalizing blood retinal barrier function vs. anti-IL-6 monotherapy • High strength formulation (100 mg/mL) and high potency provide the fire power needed to treat “angry” inflammation and macular edema • Exploring accelerated development options including pediatric population The KSI-101 Difference The KSI-101 Opportunity Launch in Feb 2020 Acquired by Amgen 1. Fierce Pharma, Jan 21, 2020. 2. Company SEC filings
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Kodiak’s clinical portfolio has the potential to provide continued revenue stream starting from 2027, with built-in life cycle management and risk diversification 13 Net sales (USD) 2024 2025 2026 2027 2028 2029 2030 2031 Tarcocimab KSI-501 KSI-101 Net sales Potential of Kodiak Clinical Portfolio (Illustrative) Tarcocimab launch in DR, wet AMD and RVO Potential launch of KSI-501 in wet AMD Potential launch of KSI-101 in MESI Kodiak owns full commercial rights to our portfolio, which allows us the flexibility in our commercialization decisions to support adoption of our products Potential for best efficacy AND durability “Next gen” product to fast follow tarcocimab Best durability and strong immediacy Incremental share translates into meaningful revenue Revenue potential diversified away from ABCD medicines
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Longstanding and significant investment in commercial manufacturing has positioned Kodiak well to launch multiple ABCD products into large and growing markets 14 Ursus, a premium commercial manufacturing facility • A commercial scale facility dedicated to the manufacture of Kodiak’s ABC medicines • Custom designed for large scale premium manufacturing of complex antibody conjugate biotherapies • Mechanical completion in 1H2022; commissioned as a cGMP facility in Jan 2023 • Successfully manufactured and released commercial scale cGMP of tarcocimab tedromer enhanced formulation in Nov 2023
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VETi + tarcocimab for home monitoring Ophthalmology Consumer Train Your Brain Visual Acuity Train Your Vision Biological Age Fluid Analysis DRSS Scoring Glaucoma Analysis Pupillometry Neuro/Cardio Metabolic Analysis Parkinson's Analysis Alzheimer's Analysis Blood Oxygen Retinal images and OCT by VETi VETi + AI + VETi as Part of Kodiak’s Commercial Franchise Government Population Health Many applications 15VETi: Visual Engagement Technology and Imager
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KODIAK TODAY Victor Perlroth, MD Chairman and CEO 16
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We believe Kodiak is primed for near-term and long-term success 17 Agile R&D Mindset We have made key course corrections and implemented them into late-stage studies Excellence in Execution Living by our “we care more” philosophy Diversified Late- Stage Pipeline • Late-stage pipeline activities showcase our design, manufacturing and drug development capabilities • Emerging ABCD Platform opens a new generation of targeted multifunctional “poly-API” molecules • Dual mechanism glaucoma and geographic atrophy pipeline programs maturing • 8 pivotal studies • 2,500+ patient years of clinical experience • >13,000 intravitreal injections in patients • 55,000+ clinical study visits • Technical leadership and ownership in-house across the board, enabling timely and cost-effective execution 3 shots on goal, each in a BLA-facing development plan, filing as early as 2026 Independence Flexibility to make each right choice for Kodiak stakeholders • Tarcocimab tedromer: 90% of clinical and CMC costs already incurred, enhanced formulation designed to deliver “the “pulse and the durability”, commercial market still poised • KSI-501: Potential for combination of greater efficacy and durability • KSI-101: Greenfield commercial market, uncorrelated to ABC platform, fast follow with dual MOA and high dose strength • We own global commercial rights to all our molecules • Built and completed an approved high volume commercial manufacturing facility for Kodiak ABC’s (URSUS) • Freedom and flexibility in how best to commercialize • Cash runway is expected to support operations into 2026
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2020-2021 RVO: retinal vein occlusion; DME: diabetic macular edema; AMD: age -related macular degeneration; DR: diabetic retinopathy; Kodiak strives to be a learning organization. Through our journey, we have gathered key insights and transformed learnings into actions 18 • Tarcocimab and ABC platform well tolerated • Differentiated 6-month durability is real • Ocular PK data support signature durability • The ABC is a true medicinal platform Feb. 2022 Aug. 2022 Nov. 2023 Aug. 2023 Oct. 2023 2020- 2021 Sept. 2024 Feb. 2024 Aug. 2024 Well tolerated and with a 6-month durability profilePHASE 1B DAZZLE (Phase 2b/3) BEACON (Phase 3) GLEAM & GLIMMER (Phase 3) GLOW1 (Phase 3) URSUS Pipeline Expansion GLOW2 DAYBREAK APEX Human Ocular PK Strong durability in wAMD. First sign of immediacy issue in wet AMD. Overly aggressive study design Durability reinforced in RVO Enhanced formulation manufactured and released, reflecting course correction Signature 6-month durability reinforced in DME. Strong immediacy. Increased cataract rate specific to DME noted Signature 6-month durability reinforced in DR. First line profile Human ocular PK data support signature durability profile KSI-501 with potential for greater efficacy and ABC Platform durability KSI-101 portfolio diversification in a greenfield market opportunity New high PTRS clinical studies enrolling POSITIVES • Immediacy deficit in wet AMD • Increased cataract rate specific to DME • Overly aggressive study designs ISSUES • Enhanced formulations to course correct issues identified in wAMD and DME • New study designs educated from prior studies anticipated to have high probability of success • Diversified portfolio to include KSI-101: superior product in a greenfield market opportunity against sham arm. ACTIONS
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Indication Clinical trial 2025 2026 2027 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q Tarcocimab Diabetic Retinopathy (DR) Phase 3 GLOW 2 Wet AMD Phase 3 DAYBREAK KSI-501 KSI-101 Macular Edema Secondary to Inflammation (MESI) Phase 1b APEX Phase 2b/3 PEAK Phase 2b/3 PINNACLE Summary of clinical programs and timeline of anticipated milestones TODAY Actively enrolling Open label data readouts Actively enrolling Topline data readout Target enrollment complete Topline data readout Target enrollment complete Primary endpoint: average of Week 40, 44 and 48 Primary endpoint: Week 48 Target enrollment start 19 Target enrollment complete Topline data readout Primary endpoint: Week 16 On track to complete enrollment for GLOW2 and DAYBREAK in 1H25 Emerging APEX data in 1Q and 2Q of 2025 Aiming to select two dose levels to progress into pivotal program in 2Q25
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Spotlight on KSI-101 20
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We have diversified our portfolio with a third clinical program: KSI-101, an ABC platform-independent, first-in-class bispecific protein in a greenfield market 21 • First-in-class dual inhibition: anti-IL-6 and VEGF Trap • Uncorrelated from the ABC Platform • 100 mg/mL formulation provides high-strength and potency • Greenfield market segment • Unmet need with no approved intravitreal biologic • Near-term readout of Phase 1b data • Direct to Phase 3 accelerated development plan • 16-week primary endpoint versus sham, aligned with the FDA Design Opportunity Development High-strength formulation can provide disease control 110,000 at risk patients in US Phase 1b underway to advance into dual pivotals As an unconjugated protein, KSI-101 is a traditional intravitreal biologic with a profile uncorrelated to the ABC Platform A potent, high-strength bispecific protein designed to address macular edema secondary to inflammation (“MESI”) for which no approved intravitreal biologic therapies exist today KSI-101
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Macular edema is the leading cause of vision loss in patients with intraocular inflammation • Up to 50% of patients experience reduced vision • 10-15% of patients become blind Intraocular inflammation is the 4th leading cause of vision loss in the developed world • Approximately 110,000 patients in the U.S. 1/3 of patients with intraocular inflammation develop macular edema Studies show that inflammation and vascular permeability have a synergistic effect on driving disease progression and vision loss due to macular edema -- but there are no approved therapies that target both drivers of disease 22
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• Off-label use • Used as steroid-sparing agents • Up to 50% of patients do not have macular edema resolved • ~35% of patients do not experience improvement in macular edema • Associated with elevated intraocular pressure/glaucoma that often require therapy and even surgery as well as cataract progression • 30–40% of patients do not respond Current treatment algorithm for macular edema secondary to inflammation: unmet need for safer therapies that target the underlying mechanisms of disease Sources: 1. Tomkins-Netzer O et al. Ophthalmology. 2015. 122:2351-2359. 2. Jaffe et al. N Engl J Med. 2016. 375:932-43. 3. Rosenbaum et al. Sem Arthrit. 2019. 49: 438-445. Local or systemic corticosteroids First line: Mainstay of treatment Immunomodulators Biologic Anti-VEGF agents Second line Second or third line Third or fourth line or adjunct • Adalimumab (anti-TNFα) is the only FDA-approved non-steroid therapy for NIU • ~55% of patients experienced treatment failure over 85 weeks • No significant impact on macular edema • Associated with serious side effects (e.g., infections, malignancies) NIU: non-infectious uveitis • Used for patients with persistent macular edema associated with inflammation that fail conventional therapies • However, underlying inflammatory component of the pathophysiological process is not addressed by inhibiting VEGF alone There is an unmet need for minimally invasive potent targeted therapies with a better safety profile 23
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Vamikibart (Roche, anti-IL-6) has shown that anti-IL-6 monotherapy can provide visual and anatomical improvement in patients with inflammatory macular edema 24 Change from Baseline in BCVA Change from Baseline in CST Sharma, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023 A clear dose response is seen with IL-6 monotherapy in patient with inflammatory macular edema
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25 While intravitreal IL-6 monotherapy is useful, ~50% of patients have persistent IRF, which is similar to the overall failure rate of systemic adalimumab1, leaving room for improvement 1. Jaffe et al. N Engl J Med. 2016. 375:932-43. 2. Figure from Sharma, et al. A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL Study. Presented at the American Society of Retina Specialists, Seattle, WA, July 28 – August 1, 2023; Persistent intraretinal fluid (IRF) is known to cause deleterious and permanent effects in visual function ~50% of patients have persistent IRF
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Phase 1b APEX study: multiple dose study of KSI-101 in patients with macular edema secondary to inflammation End of Study Subjects with macular edema secondary to inflammation (MESI) (n ~ 36) Weeks 0 4 8 12 16 20 24 2.5 mg 5 mg 10 mg 26 KSI-101 injection Actively recruiting • Emerging APEX data in MESI starting in 1Q of 2025 • Meaningful clinical response in both vision and retinal anatomy observed with all dose levels tested • Aiming to select two dose levels to progress into pivotal phase in MESI in 2Q25 New Phase 1b Data
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Baseline Week 1 Week 4 Week 8 Week 12 Phase 1b APEX MESI clinical cases: strong treatment response demonstrated at all KSI- 101 dose levels, driving program acceleration 27 KSI-101 2.5 mg KSI-101 5 mg KSI-101 10 mg BCVA 66 letters CST 760 microns BCVA +7 CST -353 BCVA +3 CST -456 BCVA +6 CST -525 BCVA +9 CST -541 BCVA 50 letters CST 778 microns BCVA +4 CST -476 BCVA +13 CST -495 BCVA 62 letters CST 517 microns BCVA +18 CST -222 BCVA +10 CST -520 Cases with the longest follow-up in each dose level in MESI cohort. Follow-up current to 13-Jan-2025 New Phase 1b Data
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Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 KSI-101 low dose (n ~ 75) KSI-101 high dose (n ~ 75) Sham (n ~ 75) Phase 2b/3 pivotal program based on regulatory input: primary endpoint at Week 16 and safety to Week 48 KSI-101 low dose injection KSI-101 high dose injection Individualized injection / sham Sham injection PRN: pro re nata (as needed); BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study; VTC: vision threatening complications Primary endpoint: Proportion of eyes improving ≥ 15 ETDRS letters at Week 16 Patients developing VTCs Last dosing visit Secondary endpoint 28 Schedule B Patients diagnosed with a vision threatening complication will be switched to Schedule B, by which they will receive 4 monthly injections of low dose KSI-101 followed by PRN dosing till study end Primary endpoint
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KSI-101 has the potential to become an important medicine in treating pediatric patients with intraocular inflammation and macular edema 29 • Up to 15% of patients referred to tertiary uveitis clinics are pediatric patients • Like adults, macular edema is a major vision-threatening complication in children with uveitis • We are exploring whether our second pivotal study could be run in the pediatric and/or adolescent setting Management of pediatric patients presents unique challenges today There is a significant unmet need for effective and safe therapies that target underlying disease mechanisms in this patient population • Diagnosis often delayed with complications such as macular edema already present • Inflammation more likely to be recurrent or chronic and can persist into adulthood • Risk of macular edema may increase over time with persistent disease in some patients • Systemic and local corticosteroids, immunosuppressants and biologics are often needed to treat macular edema—can take >2 years to resolve • Macular edema can be refractory to existing therapies • Systemic use of steroids or immunosuppressive agents have limited utility because they have adverse effects on growth, nutrition, infectious diseases and fertility 1. Nguyen AH, Mekonnen B, Kim E, Acharya NR. J Ophthalmic Inflamm Infect. 2021 Mar 15;11(1):8. 2. Eiger-Moscovich M, et al. Am J Ophthalmol 2019; 202: 72-78. 3. Smith JA, et al. Ophthalmology 2009; 116:1544-1551. 3. Smith JR. Pediatr Drugs 2002; 4 (3): 183-189 4. Holland GN and Stiehm ER. J Ophthalmol 2003;135:867–878
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With 3 clinical programs leveraging our 15 years of learning, Kodiak is at a decisive moment and represents an exciting investment opportunity • A Generation 2.0 intravitreal biologic for patients of all disease severity • Enhanced formulation delivers high immediacy and high durability • Tracking to a registration package in 2026 for DR, RVO and wet AMD • Being developed as a “mainstay” intravitreal biologic in a $14B+ market • Potential for combination of improved efficacy based on dual MOA and signature 6-month predominant durability based on the ABC platform TARCOCIMAB TEDROMER Enhanced anti-VEGF “ABC” KSI-501 Enhanced anti-IL-6 and VEGF trap bispecific “ABC” Topline Phase 3 data: 1H26 for GLOW2 and DAYBREAK Our Vision for 2026 KSI-101 Topline data readouts from two pivotal studies in MESI & BLA preparation Tarcocimab BLA filing in DR, RVO and wAMD supported by 5 successful studies KSI-501 1 study away from registration Antibody Biopolymer Conjugates (“ABC”s) for Retinal Vascular Diseases Phase 3 Phase 3 30 KSI-101 High-strength anti-IL-6 and VEGF trap bispecific protein • Greenfield commercial space (macular edema secondary to inflammation) with risks uncorrelated to Kodiak’s ABC investigational medicines • Phase 1b APEX MESI clinical cases: excellent treatment response demonstrated in all KSI-101 dose levels, driving program acceleration Phase 1b APEX study clinical data 1H25 Phase 3 initiation 1H25 UPCOMING MILESTONES Unconjugated protein for Inflammatory Retinal Diseases Phase 1b Cash Equivalents ~$200 million as of end of 3Q24 to support operations into 2026 New Phase 1b Data Topline Phase 3 data: 1H26 for DAYBREAK 30
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SCIENCE OF DURABILITY 31
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Tarcocimab and the ABCD platform are supported by our science of durability Tarcocimab's extended durability stems directly from its underlying science of durability CONJUGATE DESIGN The ABCD Platform leverages a proprietary, high molecular weight, phosphorylcholine-based biopolymer that enables an extended ocular residence time POTENCY Tarcocimab demonstrates strong potency in in vitro assays that is comparable to aflibercept ANIMAL OCULAR HALF-LIFE Tarcocimab and other ABCD molecules demonstrate 3x longer ocular half-life in rabbit models compared to aflibercept or faricimab HUMAN OCULAR HALF-LIFE Tarcocimab demonstrates 3x longer human ocular half-life compared to aflibercept or faricimab 4 key elements support the science of durability 32
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CONJUGATE DESIGN 33
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Principal of Design: Ocular half-life increases proportionally with molecular size Vitreous Half-Life (Days) Molecular Weight (kDa) 10 100 1000 100001 0.1 1 10 100 1. Adapted from Crowell SR, et al. Trans Vis Sci Tech. 2019;8(6):1. Rabbit Non-Human Primate Human Relationship between ocular half-life and molecular weight (MW, kDa)¹ 34 Strong positive correlation between the ocular half-life of an intravitreally injected protein therapeutic and its molecular size
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35 The Antibody Biopolymer Conjugate (“ABC”) Platform is the foundation of tarcocimab tedromer and KSI-501 Any biologic such as an antibody can be conjugated to the biopolymer via a stable, site-specific linkage Engineered to make medicines last longer and extend their therapeutic benefit. The biopolymer is optically clear and made of phosphorylcholine, the primary hydrophilic component of human cell membranes Antibody or Other Biologic High molecular weight Biopolymer Antibody Biopolymer Conjugate (“ABC”) Kodiak’s ABC platform leverages a proprietary, high molecular weight, phosphorylcholine-based biopolymer to enable an extended ocular residence time
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Brolucizumab (Beovu) Ranibizumab (Lucentis) Aflibercept (Eylea) Faricimab (Vabysmo) Tarcocimab : 950 kDa 26 kDa 48 kDa 115 kDa 149 kDa Antibody 150 kDa Biopolymer 800 kDa Kodiak’s ABC investigational medicines, tarcocimab and KSI-501, have a high molecular weight which increases their ocular half-life compared to today's anti-VEGFs 36 KSI-501 : 1000 kDa Antibody Trap Fusion Protein 200 kDa
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POTENCY 37
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Tarcocimab unconjugated protein and conjugated protein both demonstrate high binding affinity and potency in pre-clinical assays Both the tarcocimab conjugate and the anti-VEGF antibody demonstrate similarly high binding affinity for VEGF-A. High Potency in Inhibiting VEGF Binding to its Receptors High Potency in Inhibiting VEGF-mediated cell proliferation* High Binding Affinity for VEGF-A *Proliferation of Human Retinal MicroVascular Endothelial Cells. 1. Kodiak data on file. VEGF-A binding affinity determined from Kinetic Exclusion Assay 1. Tarcocimab unconjugated protein and conjugated protein have the same or similar binding affinity and potency as aflibercept. 2. The increased molecular size from conjugation to the biopolymer does not impact binding affinity or potency. OD 450 nm OD 450 nm Log [Antibody] pMLog [Antibody] pM Binding Affinity to VEGF-A1 Tarcocimab (conjugate) 6.75 pM Tarcocimab (mAb) 3.43 pM Inhibition of VEGF:VEGFR Binding IC50 (nM) Maximal Inhibition (%) Tarcocimab (conjugate) 3.72 94% Tarcocimab (mAb) 3.97 84% Aflibercept 4.50 75% Inhibition of HRMVEC Proliferation IC50 (nM) Maximal Inhibition (%) Tarcocimab (conjugate) 0.96 65% Tarcocimab (mAb) 0.85 59% Aflibercept 0.74 54% 0 1 2 3 4 5 6 0.0 0.2 0.4 0.6 0.8 1.0 Tarcocimab (mAb) Tarcocimab (conjugate) Aflibercept 1 2 3 4 5 6 0.5 1.0 1.5 2.0 Tarcocimab (mAb) Tarcocimab (conjugate) Aflibercept OD 450 nm OD 450 nm Log [Antibody] pM Log [Antibody] pM 38
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ANIMAL OCULAR HALF -LIFE 39
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Tarcocimab’s ocular half-life is significantly longer than approved intravitreal biologics in the rabbit model Ranibizumab² (48 kDa) 3 Days Half-life (Days) 2 4 6 8 10 12 14 16 Faricimab4 (149 kDa) 4 Days Aflibercept3 (115 kDa) 4 Days Tarcocimab¹ (950 kDa) 11 Days 1. Kodiak data on file. Ocular half life was determined from a single 50 µL intravitreal injection of 0.725 mg of tarcocimab (conjugate) in rabbits. 2. Gaudreault, et al. Retina 2007, 27: 1260-1266. 3. Park SJ, et al. IOVS 2016, 57: 2612-2617. 4. Pharmacology / Toxicology BLA Review and Evaluation40 3x – 4x longer half-life versus Lucentis, Eylea and Vabysmo
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HUMAN OCULAR HALF -LIFE 41
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1 10 100 1000 10000 100000 0 4 8 12 16 20 24 28 Tarcocimab’s ocular half-life in humans was calculated by measuring aqueous humor concentrations over time from patients in the Phase 1b Study • Aqueous humor samples were collected from 47 subjects in the tarcocimab Phase 1b study in patients with wet AMD, DME and RVO and were used to evaluate tarcocimab ocular half life in patients • Aqueous humor samples were collected at baseline and at Week 4, 12, 14, 16, 18, 20 and 24 and measured for tarcocimab concentrations • Samples collected between the last loading dose and the next re-dose were used to determine ocular half-life of tarcocimab 42 Data from one individual patient from the Phase 1b study of tarcocimab is used to illustrate the methodology here. Patients received as-needed redosing after week 8 and aqueous humor samples collected after a redose were excluded from the analysis Using Aqueous Humor Concentration of Tarcocimab to Determine Ocular t1/2 in human Weeks Tarcocimab aqueous humor concentration (ng/ml) AH samples from Week 12 – 24 were used to determine tarcocimab t1/2 3 loading doses of intravitreal injections of 5mg tarcocimab
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Tarcocimab achieved an extended ocular half-life of >20 days in 45% of sampled patients from the Phase 1b Study Each line represents one individual patient from the Phase 1b study of tarcocimab in patients with wet AMD, DME and RVO. N= 47 patients, all received an intravitreal injection of 5mg tarcocimab clinical formulation on day 1. *Mean and standard deviations are plotted, though SDs are not visible due to small magnitude43 All Patients (n=47) Weeks Tarcocimab aqueous humor concentration (ng/ml) t1/2 = 6.1 days t1/2 = 10.1 days t1/2 = 16.9 days t1/2 = 27.5 days Select Individual Patients* Weeks 12 16 20 24 1 10 100 1000 10000 100000 19% 36% 45% Patients Ocular t½ Distribution (N=47) >20 Days 11-20 Days ≤11 Days 12 16 20 24 1 10 100 1000 10000 100000 t1/2 = 39.8 days
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Tarcocimab has a mean ocular half-life in humans of 20 days, which is 3x longer than faricimab Human Ocular Half-Life (Days) 10-90th percentiles 8.3 (10th percentile) 31.8 (90th percentile) 19.8 days (Mean) 5.2 (10th percentile) 11.2 (90th percentile) 7.5 days (Mean) Tarcocimab Faricimab t½ <5 days t½ >11 days Faricimab Tarcocimab Percent of Patients Each dot represents an individual patient. VABYSMO (faricimab solution for injection) Prescribing Information. South SanFrancisco, USA: Genentech, Inc. PK and ER of Faricimab, Report # 1105763 0% 81% 10% 10% 0 20 40 60 80 100 44
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Tarcocimab demonstrated consistent ocular half-life across wet AMD, DME and RVO Patients 45 All Wet AMD DME RVO 0 10 20 30 40 50 Acqueous humor t1/2 (days) n=47 n=23 DME n=8 n=16 Height of the box represents the mean; error bars represent standard deviation. Tarcocimab Human Ocular Half-Life by Indication RVO n=16 wAMD n=23 All n=47
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From Principal of Design to Human Durability (“A Science of Durability”): Tarcocimab's Ocular Half-Life in Human is Much Longer Than Approved Intravitreal Biologics Tarcocimab⁶ 950 kDa T½: 20 Days (aqueous humor) Aflibercept3,4 115 kDa T½: 8.8 Days (aqueous humor) Ranibizumab² 48 kDa T½: 7.2 Days (aqueous humor) Faricimab⁵ 149 kDa T½: 7.5 Days (aqueous humor & serum) Brolucizumab*¹ 26 kDa T½: 5.1 Days (serum) Human Ocular Half-Life and Molecular Weight of Current Intravitreal Biologics1,2 Molecular Weight (kDa) Human t½ (Days) A linear relationship is observed between ocular t½ and molecular weight *Half-life for brolucizumab is systemic half-life determined from serum pharmacokinetics 1. Holz FG, et al. Ophthalmology 2016;123:1080–1089. 2. Krohne TU, et al. Am J Ophthalmol 2012;154:682–686.e2. 3. Do DV, et al. Retina 2020;40:643–647; 4. Caruso A, et al. Retina. 2020 Apr;40(4):e13. doi. 5. VABYSMO (faricimab solution for injection) Prescribing Information. South San Francisco, USA: Genentech, Inc. 6. Kodiak data on file. The design of tarcocimab translates in human into an extended ocular half- life of approximately 3x compared to marketed intravitreal biologics 46
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What is the evidence this longer ocular half-life in human translates into clinical durability? 47
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Durability Interval at Year 1 Q16W 8% Q12W 11% Q8W 28% 6-month durability 50% Q16W 10.3% Q16W 10.3% Q12W 30.3% Q20W 4% Q16W 8% DME GLEAM and GLIMMER Studies1 wAMD DAZZLE Study2 DR GLOW1 Study Number of doses in the second 6 months of Year 1 RVO BEACON Study 0-1 doses 75% 2 doses 18% 4-6 doses 2% 3 doses 5% 5-month durability 59.4% 6-month durability 100% 6-month durability 75% 3 DME: diabetic macular edema; DR: diabetic retinopathy; RVO: retinal vein occlusion; wAMD: wet age-related macular degeneration. 1. Pooled analyses. The studies did not meet the primary endpoint. 2. Treatment intervals were capped at 5 months (6-month dosing was not tested). The study did not meet the primary endpoint. 3. Estimated durability interval based on patients that received no injections (46%) or 1 injection (29%) over the second 6 months of Year 1. Consistent with its science of extended ocular half life, tarcocimab has shown a differentiated clinical durability profile in all retinal vascular diseases tested 48
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0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 250 300 350 400 450 500 GLEAM and GLIMMER Pooled Mean BCVA Over Time in Pseudophakic Patients Week ETDRS Lettersµm 1. Data points may not add up to 100% due to rounding. Observed values. BCVA: best-corrected visual acuity; ETDRS: early treatment diabetic retinopathy study. OCT: optical coherence tomography; CST: central subfield thickness 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 60 65 70 75 80 Aflibercept Q8W (n=112) Tarcocimab Q8W-Q24W (n=108) Durability intervals for pseudophakic patients at Year 1 in the GLEAM & GLIMMER Studies1 Q8W 23% Q12W 9% Q16W 5% Q20W 9% Q8W 23% Q20W 9% Q16W 5% Q12W 9% 6-month durability 55% Q24W 55% Wait a minute. The DME studies did not meet their primary endpoint. How do we know the durability is real? Pseudophakic patients treated with tarcocimab achieved comparable improvements vs aflibercept patients, with significantly fewer doses (5 tarcocimab vs 10 aflibercept) Mean OCT CST Over Time in Pseudophakic Patients 49
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0 4 8 12 16 20 24 28 32 36 40 44 48 52 200 300 400 Q12W: every 12 weeks; Q16W: every 16 weeks; Q20W: every 20 weeks. BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study. CST: central subfield thickness Q12W 30.3% Q16W 10.3% Durability intervals at Year 1 in the DAZZLE Study Mean BCVA Over Time in Tarcocimab Patients on 5-Month Dosing vs Aflibercept Patients 5-month durability 59.4% ETDRS Letters Mean OCT CST Over Time in Tarcocimab Patients on 5-Month Dosing vs Aflibercept Patients µm Week 0 4 8 12 16 20 24 28 32 36 40 44 48 52 55 60 65 70 75 Aflibercept Q8W Tarcocimab Q20W Wait a minute. The wAMD durability study did not meet its primary endpoint. What is the durability evidence here? In DAZZLE, ~2/3 of tarcocimab patients achieved 5-month durability with visual and anatomical improvements comparable to the overall aflibercept group 50
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1. All patients were randomized to receive either tarcocimab every six months after 3 initiating doses or to receive sham injections. 21.0% 2.3% 0% 5% 10% 15% 20% 25% 30% Sham Tarcocimab 89% risk reduction P<0.0001 Proportion of patients developing any sight-threatening complication from Baseline to Week 48 Any Sight-Threatening Complication 1.4% 41.1% 0% 10% 20% 30% 40% 50% Sham Tarcocimab Proportion of patients with ≥2-Step improvement in DRSS from Baseline to Week 48 29x increased response rate ratio P<0.0001 DME CST of ≥320 µm and a 5-letter decrease in BCVA from Day 1; or CST of ≥350 µm PDR NVD, NVE, or VH ASNV ASNV or NVG DRSS: diabetic retinopathy severity scale; DME; diabetic macular edema; PDR; proliferative diabetic retinopathy; ASNV: anterior segment neovascularization; CST; central subfield thickness; BCVA; best corrected visual acuity; NVD: neovascularization of the disc; NVE; neovascularization elsewhere; VH: vitreous hemorrhage; NVG; neovascular glaucoma. Weighted percentages are based on weighted average of observed estimates across strata using CMH weights. p-values are based on the difference in response rates How relevant is 6-month durability in Diabetic Retinopathy? With only 4 doses in the first year (a ‘gentle on-ramp’) and 100% of tarcocimab patients on 6-month dosing, the drug treats current retinopathy and prevents diabetic complications Treatment of Retinopathy Prevention of Complications Primary endpoint met 51
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RVO: retinal vein occlusion; BRVO: branched retinal vein occlusion; 1. Estimated durability interval based on patients that received no injections (46%) or 1 injection (29%) over the second 6 months of Year 1. 0% 10% 20% 30% 40% 50% 1 2 3 4 5 6 7 8 9 10 11 Tarcocimab BRVO Tarcocimab All RVO Aflibercept BRVO Aflibercept All RVO Number of injections through Year 1 Proportion of subjects Tarcocimab 78% received ≤ 5 doses Aflibercept 93% received ≥ 6 doses Tarcocimab Number of doses in the second 6 months of Year 1 0-1 doses 75% 2 doses 18% 4-6 doses 2% 3 doses 5% 6-month durability 75% 1 Is there any durability benefit in RVO? Even after receiving 2 fewer initiating doses (4 vs 6, respectively), tarcocimab treated patients at one year had a ~30% higher chance of not requiring any additional doses versus aflibercept Primary endpoint met 52
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Tarcocimab and the ABC platform are supported by our SCIENCE OF DURABILITY Designed-in Extended Tissue Residence Time A proprietary phosphorylcholine-based polymer is conjugated to an antibody to increase molecular size which extends ocular half-life High in-Vitro Potency Extended Ocular Half-Life in Animals Extended Ocular Half-Life in Humans Extended Clinical Durability Both unconjugated protein and conjugated protein demonstrate high VEGF-A binding affinity and anti- VEGF potency in vitro, comparable to aflibercept 3x the ocular t½ of approved intravitreal biologics when measured in rabbits following an intravitreal injection 3x the ocular t½ of faricimab when measured from aqueous humor in patients following an intravitreal injection 5 to 6-month predominant durability demonstrated in pivotal trials across all high-prevalence retinal vascular diseases 53
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Does this durability come at a cost? 54
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0 4 8 12 16 20 24 28 32 36 40 44 48 -250 -200 -150 -100 -50 0 Aflibercept Q8W (n=281) Tarcocimab Q4W (n=276) Observed values. OCT: optical coherence tomography; CST: central subfield thickness. -117 (114) -109 (121) Week 48 (SD) Mean Change in OCT CST Over Time In the wet AMD DAYLIGHT Study Week µm Comparable potencyImmediacy gap Immediacy seems to be the cost. A deficit is seen in the loading phase, in the “immediacy” of the effect. After the loading phase, the drying potential or “potency” is comparable to aflibercept 55
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We have applied course corrections to solve this challenge in immediacy 56
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ENHANCED FORMULATION 57
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5 mg Strength (Total Anti-VEGF mAb) 5 mg 5 mg Proportion of Conjugates 4 mg n/a Proportion of Free Protein 1 mg Tarcocimab Old Formulation Tarcocimab Enhanced Formulation Unconjugated protein at 20% • Improved manufacturability • Increased ease of dosing and safety • Maintenance of dose and potency • Maintenance of signature durability and • Improved immediacy Reduced conjugates from 100% to 80% The enhanced formulation was designed to confer several key benefits: Identical strength 58 How can the enhanced formulation solve the immediacy issue? By including free protein (unconjugated), the enhanced formulation is primed to solve the immediacy issue 100% Conjugates 80% Conjugated 20% Unconjugated
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Brolucizumab Ranibizumab Aflibercept Faricimab Tarcocimab Old Formulation Tarcocimab Enhanced Formulation Molecule Type Single-Chain Antibody Fragment Antibody Fragment Fusion Protein Antibody Antibody Biopolymer Conjugate (ABC) Unconjugated Antibody + ABC Molecular Structure Molecular Weight 26 kDa 48 kDa 115 kDa 149 kDa 950 kDa 150 kDa 950 kDa Clinical Dose 6 mg 0.3-0.5 mg 2 mg 6 mg 5 mg By weight of antibody 5 mg 1 mg 4 mg Equivalent Molar Dose 11 0.5 1.0 2 3.5 0.7 2.8 The unconjugated portion of the enhanced formulation of tarcocimab contains A high molar equivalent to approved intravitreal biologics Equivalent values are shown as fold changes relative to aflibercept. kDa = kilodalton Equivalent to 1.3 mg of aflibercept Equivalent to 2 mg of faricimabEquivalent to 0.7 mg of ranibizumab 59
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The 20% of free protein alone in the enhanced formulation is equivalent to 67% of the full clinical dose of aflibercept 1 mg free protein Aflibercept 2mg Equivalent to 1.3mg of aflibercept 1.3 mg 60 Adapted from Heier, et al. Ophthalmology 2012;119:2537–2548. 2q4: 2mg aflibercept dosed every 4 weeks; 0.5q4: 0.5mg aflibercept dosed every 4 weeks Tarcocimab: 5 mg 4 mg Conjugated protein 1 mg Free protein How much unconjugated protein is there? Is it enough? The unconjugated portion is equivalent to 1.3 mg of aflibercept, sufficient to provide a strong immediacy after dosing -200 -150 -100 -50 0 0 4 8 12 0.5 mg aflibercept achieved similar CST improvements as the full clinical dose of aflibercept (2 mg) in wAMD Time (Weeks) Mean CST change from baseline (µm) Aflibercept 2q4 Aflibercept 0.5q4
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Adapted from Sahni, et al. JAMA Ophthalmol. 2020;138(9):955-963. In the Phase 2 AVENUE Trial, similar BCVA and CST improvements were observed across all 3 arms at Week 16 after 4 monthly loading doses Similar efficacy benefits were observed among ranibizumab 0.5 mg, faricimab 1.5 mg and faricimab 6 mg Faricimab 1.5 mg Faricimab 6 mg Ranibizumab 0.5mg Adjusted mean BCVA change from baseline (ETDRS letters) BCVA Change from Baseline Adjusted mean CST change from baseline (µm) Time (Weeks) CST Change from Baseline 61 What is the objective of each component? The unconjugated protein delivers a strong “pulse” of VEGF inhibition, meanwhile the conjugate continues to deliver sustained durability Ranibizumab 0.5 mg Tarcocimab: 5mg 4 mg Conjugated protein Faricimab: 6mg 3 mg anti-Ang 2 Equivalent to 0.7mg of ranibizumab Equivalent to 2mg of faricimab (1mg of anti- VEGF) 1 mg Free protein • The high molar equivalent of the 1 mg free protein suggests it should meaningfully improve immediacy to that similar or slightly superior to 1.5 mg faricimab or 0.5 mg ranibizumab The 1 mg of free protein in the enhanced formulation is expected to meaningfully improve immediacy 0.2 mg Ranibizumab: 0.5mg 1 mg 2 mg anti-VEGF
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0 4 8 12 -150 -100 -50 0 Aflibercept 2mg and 8mg Tarcocimab (clinical formulation) The purpose of the 80% conjugated protein (4 mg) is to maintain the 6-month predominant durability as seen in tarcocimab pivotal studies to date *Approximate CST changes are plotted based on pivotal clinical studies of aflibercept and tarcocimab Closing the gap 62 CST Reduction Through Loading Dose Phase in Wet AMD* CST Change from Baseline (µm) Weeks Tarcocimab (old formulation) Aflibercept 2mg and 8mg The purpose of the 20% unconjugated protein (1 mg) is to improve the immediacy of the drying effect during the loading dose phase, “closing the gap" What is the objective? A key objective of the enhanced formulation was to close the immediacy gap, while improving manufacturability, dose administration and patient safety
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Bringing it all together: modeling the expected pharmacology of tarcocimab in patients 63
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Tarcocimab extends human ocular t1/2 by 3x vs faricimab; modeling suggests tarcocimab may meaningfully extend dosing intervals for patients while providing immediacy Human Ocular Half-Life (Days) 10-90th percentiles Tarcocimab Faricimab VABYSMO (faricimab solution for injection) Prescribing Information. South SanFrancisco, USA: Genentech, Inc. PK and ER of Faricimab, Report # 1105763 64 1 10 100 1000 10000 0 30 60 Ocular Drug Quantity Time (days) Illustrative Patient 1: Short Ocular T1/2 0 30 60 90 120 150 Time (days) Illustrative Patient 2: Average Ocular T1/2 0 30 60 90 120 150 180 210 240 Time (days) Illustrative Patient 3: Long Ocular T1/2 Faricimab Tarcocimab Conjugated ProteinTarcocimab Unconjugated Protein Tarcocimab extends t1/2 from 4 to 10 days Tarcocimab extends t1/2 from 7 to 18 days Tarcocimab extends t1/2 from 12 to 28 days Tarcocimab extends dosing from monthly to every 2 months Tarcocimab extends dosing from every 8 weeks to every 6 months Tarcocimab extends dosing from every 3 months to > every 6 months Faricimab and Tarcocimab free protein t1/2 = 7 days Tarcocimab conjugate t1/2 =18 days
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We have extended these formulation improvements into all our ABC medicines 65
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5.0 mg Strength (Total mAb) 5.0 mg 4.0 mg Proportion of Conjugates 3.5 mg 1.0 mg Proportion of Free Protein 1.5 mg We have incorporated the enhanced formulation into KSI-501 Enhanced Formulation Tarcocimab Enhanced Formulation KSI-501 Based on antibody mass (injection volume of 100 µL at 50 mg/mL) Proportion of conjugates further reduced to 3.5 mg due to larger protein size 1.5 mg of unconjugated free protein The enhanced formulation for KSI-501 also features an optimized combination of conjugated and unconjugated (free protein) forms 66
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CLINICAL PROGRAM OVERVIEW TARCOCIMAB TEDROMER KSI-501 KSI-101 67
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TARCOCIMAB TEDROMER Design Differentiation Development • 1 successful pivotal study away from BLA submission • BLA package in 3 indications • Anticipate high PTRS study outcomes • ~90% of all investment needed completed • Anti-VEGF antibody biopolymer conjugate (“ABC”) • Only intravitreal biologic supported by the science of durability • Enhanced formulation delivers “the pulse and the durability” ~90% of clinical & manufacturing activities already completed • High efficacy with high durability remains a key unmet need • 6-month durability profile across retinal vascular diseases • Developed for all retinal vascular disease patients • Flexible dosing, from monthly to 6-month dosing Uncompromising Immediacy with go to market formulation • Only intravitreal biologic that has demonstrated consistent 6-month predominant durability in high-prevalence retinal vascular diseases • Intended to be a mainstay biologic that can be used in all patients • Supported by a clinical science of immediacy and durability “Why wouldn’t I use it in all my patients after Avastin?” 68
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Tarcocimab: planned BLA package in 2026 for 3 disease indications supported by 5 pivotal studies in diabetic retinopathy, wet AMD & RVO based on FDA alignment AMD: age-related macular degeneration; RVO: retinal vein occlusion; DR: diabetic retinopathy; BEACON: NCT04592419; GLOW1: NCT05066230; DAYLIGHT: NCT04964089; GLOW2: NCT06270836; DAYBREAK: NCT06556368 DAYLIGHT Study BEACON Study GLOW1 Study GLOW2 Study DAYBREAK Study Two Phase 3 studies actively enrolling: using the enhanced formulation of tarcocimab Wet AMD Retinal vein occlusion Diabetic retinopathy Diabetic retinopathy Wet AMD Completed Phase 3 studies: Primary endpoint met and extended durability demonstrated using the old clinical formulation 69 FDA alignment on study design, population and primary endpoint (similar to GLOW1) • FDA alignment on study design, population and primary endpoint • FDA considered that the inclusion of both tarcocimab and KSI-501 is appropriate • FDA considered that the proposed combination of active and comparator arms is appropriate FDA considered this package of five Phase 3 studies – DAYLIGHT, BEACON, GLOW1 run with the old clinical formulation and GLOW2 and DAYBREAK run with the enhanced formulation, if successful – acceptable and sufficient to file a BLA for the 3 indications of DR, RVO and wet AMD
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• Proportion of eyes improving ≥2 steps on DRSS from baseline at Week 48 DRSS: diabetic retinopathy severity score; GLOW 1 study NCT05066230; GLOW2 study NCT06270836 New DR Phase 3 study: GLOW2 features a similar study design as the successful GLOW1 study, with the benefit of an additional 3rd monthly loading dose Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 Tarcocimab 5 mg Extended dosing n ~ 125 Sham n ~ 125 3 monthly loading doses 12-week interval 24-week interval Tarcocimab injection Non-treatment Visit Sham treatment Primary endpoint Additional loading dose at Week 4 Actively recruiting 70 1.4% 41.1% 0% 10% 20% 30% 40% 50% Sham Tarcocimab 29x increased response rate ratio The GLOW1 study met the primary endpoint with high statistical significance (p<0.0001)
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New wAMD Phase 3 study: DAYBREAK is designed as a registrational study for both tarcocimab tedromer and KSI-501 BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study; 71 Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 – 88 92 96 Tarcocimab Q4-24W (n~225) KSI-501 Q8W (n~225) Aflibercept Q8W (n~225) Primary endpoint Mean change in BCVA Tarcocimab injection Aflibercept injection KSI-501 injection Sham injection Individualized treatment/sham Tarcocimab objective Assess 6-month durability potential with individualized Q4W to Q24W dosing KSI-501 objective Explore the efficacy potential of bispecific IL-6 and VEGF inhibition in fixed Q8W dosing with additional individualized monthly dosing The study optimizes treatment for each individual patient using objective disease activity criteria that are relevant to how physicians practice in their clinics End of StudySame dose regimen in Year 2 Actively recruiting
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Tarcocimab already failed in a wAMD durability study. What has changed? The DAYBREAK Study is designed to address each of the flaws of the DAZZLE Study BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study; 72 DAZZLE Flaw DAYBREAK Solution Underdosing • Adding a 4th loading dose • Allowing shorter intervals, down to monthly dosing • Having flexible intervals Reactive dosing • A treat-to-dryness proactive dosing, enabled by using presence of fluid as a disease activity marker Loose retreatment criteria • Using presence of fluid as a disease activity marker, instead of a combination of CST and vision loss, and expanding the evaluable area 9-fold (from 1mm2 to 3mm2) Lack of immediacy • Using the enhanced formulation of tarcocimab Q12W Q16W Q20W Q4W Q8W Q12W Q16W Q20W Q24W DAZZLE Study Allowed Intervals DAYBREAK Study Allowed Intervals Shorter intervals prevent underdosing Enables 6-month durability evaluation
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354 microns of OCT CST ? Would you treat? What is so special about DAYBREAK’s disease activity criteria? Using fluid volumes instead of CST as a marker of disease activity resembles retina specialists’ practice, optimizes each patient’s treatment, and generates data on how the molecule will perform in the real world Loss of 5 letters ? From best prior BCVA ? 1 mm2 Maybe? 3 mm2 Definitely 73
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So patients will be treated more. That means less durability, right? Not necessarily. It means that patients will receive treatment only when indeed needed. This is intended to maximize both the chance of meeting non-inferiority and having a strong and real durability profile DAYBREAK disease activity criteria • Presence of intraretinal fluid (IRF) in central 3mm2 • Presence of subretinal fluid (SRF) in central 3mm2 • Presence of macular hemorrhage Using a fluid tool provides meaningful advantages by treating patients only when they truly need it • Optimizes treatment for each patient o High need patients: treats until dry, enables monthly dosing and detects disease reactivations earlier o Long durability patients: allows patients without active disease to safely go to 6-month dosing • Standardized, quantitative, objective evaluation: a precision medicine tool for each patient 74
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First-in-class bispecific ABC designed to address vascular permeability and retinal inflammation simultaneously with the potential for best efficacy and best durability in high prevalence retinal vascular diseases KSI-501 75 Design Differentiation Development • First-in-class dual inhibition: anti-IL-6 and VEGF Trap • Supported by our science of durability of the “ABC” platform • Enhanced ABC formulation • Designed to address two key unmet needs: better efficacy and greater durability • Bispecific mechanism demonstrates superior blood retinal barrier normalization vs monotherapies • Exploring potential for better efficacy with intensive dosing, which also optimizes for high PTRS Enhanced formulation delivers both immediacy and durability Potential for better efficacy and best durability After DAYBREAK, 1 study away from BLA submission KSI-501, our second ABC investigational medicine, now reflects the enhanced formulation with the potential for best efficacy and best durability
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New wAMD Phase 3 study: DAYBREAK is designed as a registrational study for both tarcocimab tedromer and KSI-501 BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study; 76 Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 – 88 92 96 Tarcocimab Q4-24W (n~225) KSI-501 Q8W (n~225) Aflibercept Q8W (n~225) Primary endpoint Mean change in BCVA Tarcocimab injection Aflibercept injection KSI-501 injection Sham injection Individualized treatment/sham Tarcocimab objective Assess 6-month durability potential with individualized Q4W to Q24W dosing KSI-501 objective Explore the efficacy potential of bispecific IL-6 and VEGF inhibition in fixed Q8W dosing with additional individualized monthly dosing The study optimizes treatment for each individual patient using objective disease activity criteria that are relevant to how physicians practice in their clinics End of StudySame dose regimen in Year 2 Actively recruiting
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Why allow monthly dosing? Meaningfully better visual outcomes have been observed with monthly dosing in patients with persistent fluid BCVA: best corrected visual acuity; ETDRS: early treatment diabetic retinopathy study; Adapted from Jaffe et al. Ophthalmology 2016;123:1856-1864 77 Allowing monthly dosing for KSI-501 enhances the possibility to observe better efficacy outcomes and assess the full potential of the bispecific IL-6 VEGF MoA BCVA in aflibercept’s registrational VIEW studies in wAMD Patients without persistent fluid (~80% of the population) No differences in BCVA gains between monthly and every-other-month dosing with aflibercept Patients with persistent fluid (~20% of the population) Significantly better BCVA gains are achieved with monthly dosing (~4.2 letters) 0 3 6 9 12 15 0 4 8 12 16 20 24 28 32 36 40 44 48 52 BCVA (EDTRS letter Score) Aflibercept monthly Aflibercept bimonthly 0 3 6 9 12 15 0 4 8 12 16 20 24 28 32 36 40 44 48 52 BCVA (EDTRS letter Score)
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78 TARCOCIMAB TEDROMER KSI-501 KSI-101 • Anti-VEGF “ABC” • Three Phase 3 studies complete • Consistent 6-month predominant durability • Two new Phase 3 studies actively enrolling • Enhanced formulation designed to deliver “the pulse and the durability” while improving dose preparation, dose administration and safety • A “mainstay” intravitreal biologic that delivers high efficacy and high durability for the $14B+ market of retinal vascular diseases • First-in-Class, bispecific anti-IL-6 , VEGF trap “ABC” • Designed to address vascular permeability and retinal inflammation simultaneously • Benefits from the science of immediacy of the enhanced formulation and extended durability of the ABC platform • Phase 3 DAYBREAK study actively enrolling, designed to explore the power of the dual MoA to deliver improved efficacy Target indications at launch: wet AMD, DR and RVO Indications of interest: wet AMD, DME, RVO and DR 3 clinical programs advancing in parallel, collectively addressing limitations of today’s therapies across a broad spectrum of retinal diseases Retinal Vascular Diseases • First-in-Class, bispecific anti-IL-6 , VEGF trap protein • Designed to address the underlying disease mechanisms of macular edema secondary to inflammation (“MESI”) for which no approved intravitreal biologic therapies exist today • Uncorrelated from the ABC Platform in a greenfield market • Can be a fast follower to Roche’s vamikibart (anti-IL-6), with differentiation of having dual inhibition mechanism and high strength 100 mg/mL formulation Inflammatory Retinal Diseases Target indication: macular edema secondary to inflammation Phase 3 Phase 3 Phase 1