Kalaris Therapeutics, Inc. · NASDAQ:KLRS
Kalaris Therapeutics — Technical Presentation (December 2025)
41 slides from Kalaris Therapeutics's technical presentation, December 2025
Slide 1: TH103 Phase 1a Initial Data Release
TH103 Phase 1a Initial Data Release December 2025
Slide 2: Forward-Looking Statements & Disclaimer
Forward-Looking Statements & Disclaimer This presentation contains “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and Section 21E of the Securities Exchange Act of 1934, as amended, that involve substantial risk and uncertainties. All sta
Slide 3: Kalaris Therapeutics
S Kalaris Therapeutics
Slide 4: Agenda
Agenda 1 Kalaris Overview & KOL Introductions Andrew Oxtoby, CEO Kalaris Therapeutics nAMD Overview & Unmet Needs 2 Donald J. D’Amico, MD, Professor and Chairman, Weill Cornell Medical College Ophthalmologist-in-Chief, New York-Presbyterian Hospital TH103 Preclinical Review & Phase 1a Initial Data S
Slide 5: Your Vision Our Mission
Your Vision Our Mission Kalaris is a clinical stage biopharmaceutical company dedicated to the development and commercialization of treatments for prevalent retinal diseases Our lead asset, TH103, was invented by Dr. Napoleone Ferrara, whose pioneering research established the anti-VEGF class of the
Slide 6: Neovascular Age Related Macular Degeneration (nAMD)
Neovascular Age Related Macular Degeneration (nAMD) A Closer Look at Lesion Biology and Heterogeneity, Visual Prognosis, New Monitoring Techniques, Current Treatment Strategies, and Unmet Medical Need Donald J. D’Amico, MD • John Milton McLean Professor and Chairman • Weill Cornell Medical College •
Slide 7: nAMD affects the visually critical central retina, called the macula
nAMD affects the visually critical central retina, called the macula OCT imaging is a non-invasive technique that provides high resolution cross- sectional images of nAMD pathology 7
Slide 8: In nAMD, abnormal MNV lesions erupt, leak and bleed, leading to acute central vision loss
In nAMD, abnormal macular neovascular (MNV) lesions erupt, leak and bleed, leading to acute central vision loss Color Leakage Blood Blood MNV Fluid Early FA Late FA OCT https://www.aao.org/education/preferred-practice-pattern/age-related-macular-degeneration-ppp, accessed on 08NOV2025 Sadda SR, Guym
Slide 9: Heterogeneity in nAMD: lesion components, effect on visual acuity, and prognosis
Heterogeneity in nAMD: different lesion components, effect on visual acuity, and prognosis Same diagnosis, very different biology and prognosis. 9
Slide 10: Heterogeneity in nAMD: lesion components, effect on visual acuity, and prognosis
Heterogeneity in nAMD: different lesion components, effect on visual acuity, and prognosis Same diagnosis, very different biology and prognosis. 20/100 20/40 20/60 20/80 Intraretinal Fluid (IRF) Subretinal Fluid (SRF) Sub-RPE Fluid (PED) SHRM 10
Slide 11: The Three nAMD Lesion Subtypes of Macular Neovascularization
The Three nAMD Lesion Subtypes of Macular Neovascularization Type 1 Type 2 Type 3 MNV MNV MNV Prevalence: ~50-60% Prevalence: ~20-30% Prevalence: ~10-15% Prognosis: Most favorable Prognosis: Variable Prognosis: Most aggressive = retinal pigment epithelium (RPE) CATT Research Group. Martin DF, Maguir
Slide 12: Stage 3 is the most severe form of Type 3 (RAP) lesion
Stage 3 is the most severe form of Type 3 (RAP) lesion Intraretinal neovascularization IRF Outer retinal disruption Retinal-choroidal anastomosis Type 3 (Stage 3) lesions produce the highest VEGF levels, responding to anti- Type 3, Stage 3 VEGF treatment but prone to recurrence. Kim JH, Chang YS, Ki
Slide 13: Baseline IRF correlates with 4-6 fewer letters gained at one year
Intraretinal Fluid (IRF) is associated with poorer outcomes compared with subretinal or sub-RPE fluid Subretinal Fluid Intraretinal Fluid Mean difference between eyes with and without IRF at 12M (letters) Baseline IRF correlates Trial with 4-6 fewer letters HARBOR VIEW1/2 gained at one year ARIES CA
Slide 14: Novel artificial intelligence quantification of abnormal fluid accumulation
Novel artificial intelligence quantification of abnormal fluid accumulation Image courtesy of RetinSight® Image courtesy of RetinAI Discovery® 14
Slide 15: Current anti-VEGF agents require 3-4 initial monthly loading doses
With current anti-VEGF agents, 3-4 initial monthly loading doses are required to achieve optimal outcomes Aflibercept 8mg Phase 3 Faricimab Phase 3 Aflibercept 2q8 Aflibercept 8q12 Aflibercept 8q16 Aflibercept 2mg Q8W Faricimab up to every 16 weeks 7.6 6.7 5.8 6.2 5.1 -126 µm -129 µm -142 µm -137 µm
Slide 16: Current anti-VEGF agents leave many patients with incomplete responses and frequent injections
Treatment with current anti-VEGF agents leaves many patients with incomplete responses and frequent injections Aflibercept Phase 3 Faricimab Phase 3 Persistent retinal fluid in 37-48% of nAMD patients More than half (55%) of nAMD patients needed treatment even after completing 3 monthly loading dose
Slide 17: Take Home Messages
1 nAMD is biologically heterogeneous – lesion type and location of retinal fluid matter. 2 Type 3 (RAP) and any nAMD eye with IRF at baseline have more aggressive disease and worse prognosis. Take Home Messages Loading doses are biologically rational and supported 3 by multiple randomized trials, bu
Slide 18: TH103 Preclinical Review & Phase 1a Initial Data Summary
TH103 Preclinical Review & Phase 1a Initial Data Summary 18
Slide 19: TH103: Dual-targeting, next generation drug engineered by Dr. Napoleone Ferrara
TH103: Dual-targeting, next generation drug engineered by anti-VEGF pioneer Dr. Napoleone Ferrara to address major unmet needs in retina disease Optimized VEGF Binding: Leverages higher-affinity VEGFR11, potentially leading to enhanced VEGF inhibition Extended Ocular Retention: Leverages high-affini
Slide 20: TH103: Increased VEGF-inhibitory activity vs. aflibercept in preclinical studies
TH103: Increased VEGF-inhibitory activity vs. aflibercept in preclinical studies TH103 achieved 100% inhibition vs. aflibercept 80% inhibition of TH103 increased reduction in mean choroidal neovascularization VEGF-induced endothelial cell proliferation (CNV) area after administration at Day -12 (in
Slide 21: TH103: Demonstrated prolonged retinal retention vs. aflibercept in preclinical studies
TH103: Demonstrated prolonged retinal retention vs. aflibercept in preclinical studies TH103 demonstrated increased retention in the retina as compared to TH103 demonstrated reduced systemic exposure after aflibercept at two weeks post-injection intravitreal administration1 (in vivo, rabbit model) (
Slide 22: TH103: Demonstrated prolonged bioactivity vs. aflibercept in an animal model
TH103: Demonstrated prolonged bioactivity vs. aflibercept in an animal model Mean CNV Area In a second murine experiment, rather Standard error = than at Day -1, TH103 and aflibercept (ratio to IgG control) were administered at Day -14 prior to Mean CNV Area laser injury to assess durability of trea
Slide 23: Phase 1a initial data summary
Phase 1a initial data summary ✓ Safety: TH103 generally well tolerated, supporting exploration of further dose-escalation ✓ Efficacy: rapid, robust response on BCVA and OCT parameters observed across dose levels at one month ✓ Durability: - PK analysis consistent with greater TH103 intraocular reten
Slide 24: Phase 1a Single Ascending Dose TH103 Study in Treatment-Naive nAMD
Phase 1a Single Ascending Dose TH103 5.0 mg x 1 (SAD) Study in TH103 Treatment-Naïve TH103 2.5 mg x 1 nAMD TH103 1.5 mg x 1 Multi-center U.S. study to 0.5 mg x 1 evaluate safety, tolerability, pharmacokinetics, and anti- Study Details VEGF activity following a single ● Primary timepoint for analysis
Slide 25: Key baseline characteristics of patients in Phase 1a trial of TH103
Key baseline characteristics of patients in Phase 1a trial of TH103 who have reached study completion Study Cohort 0.5 mg 1.5 mg 2.5 mg All Patients (n=13) 1 (n=3) (n=7) (n=3) Age (mean) 78 77 82 79 Sex (female / male) 3/0 5/2 1/2 9/4 BCVA (ETDRS letters, 58 (44-71) 59 (35-73) 49 (36-63) 57 (35-73)
Slide 26: Phase 1a initial data summary
Phase 1a initial data summary ✓ Safety: TH103 generally well tolerated, supporting exploration of further dose-escalation 26
Slide 27: Safety Summary from Phase 1a Trial
Safety Summary from Phase 1a Trial1 w/ Additional Original Manufacturing Process ● No dose limiting toxicity (DLT) or serious adverse events Processing Steps (SAEs) observed 0.5mg 1.5mg 2.5mg 2.5mg (n=3) (n=7) (n=3) (n=6)* ● Transient, mild-moderate intraocular inflammation (IOI) presented at Day 4
Slide 28: Phase 1a initial data summary
Phase 1a initial data summary ✓ Safety: TH103 generally well tolerated, supporting exploration of further dose-escalation ✓ Efficacy: rapid, robust response on BCVA and OCT parameters observed across dose levels at one month 28
Slide 29: Mean letter gain in BCVA after a single TH103 injection at Month 1
Mean 10 letter gain in BCVA letter score after a single TH103 injection at Month 1 Mean BCVA Change Over Time 12 +10 letters 54% 10 (7/13 patients) Gained ≥ 10 letters at Month 1 ETDRS Letters 8 6 4 23% 2 (3/13 patients) Gained ≥ 20 letters at Month 1 0 D1D2 D4 W1 W2 M1 Time ETDRS = Early Treatment
Slide 30: Rapid, robust improvement in CST and total retinal fluid volume
Rapid, robust improvement in CST and total retinal fluid (TRF) volume at Week 1 and Month 1 Mean CST Change Over Time1 Case Example (1.5 mg) 0 -20 -40 Mean ~87% resolution CST Change (𝛍𝛍m) -60 of TRF by Week 12 Mean ~90% resolution Single Dose TH103 -80 of TRF at Month 12 -100 -120 -140 -129𝛍𝛍m…
Slide 31: Rapid and consistent resolution of intraretinal fluid volume across doses
Rapid and consistent resolution of intraretinal fluid (IRF) volume observed across doses Case Example (2.5 mg) IRF Volume Over Time (nL) 160 by Subject Central Subfield IRF Volume (nL) 140 120 Single Dose TH103 100 80 60 Mean ~95% IRF Mean ~99% IRF resolution at Week 1 40 resolution by Month 1 Week
Slide 32: Phase 1a initial data summary
Phase 1a initial data summary ✓ Safety: TH103 generally well tolerated, supporting exploration of further dose-escalation ✓ Efficacy: rapid, robust response on BCVA and OCT parameters observed across dose levels at one month ✓ Durability: - PK analysis consistent with greater TH103 intraocular reten
Slide 33: Initial SAD plasma PK data is consistent with greater TH103 intraocular retention
Initial SAD plasma PK data is consistent with greater TH103 intraocular retention Plasma Drug Levels Treatment Cmax* Cmax/Dose* TH103 2.5 mg (ng/mL) (nM/mmol) Plasma Levels (Cmax/Dose): Eylea 2 mg1 40.5 20.6 Eylea HD 8 mg2 247 31.2 27x lower than Eylea 2mg Vabysmo 6 mg3 234 39.0 41x lower than Eylea
Slide 34: Single-dose durability signal suggests potential for stronger durability outcomes
Single-dose durability signal suggests potential for stronger durability outcomes Phase 1a Single-Dose Time to Retreatment (n = 13) after standard four- dose loading regimen Time to first retreatment 38% ≥ 4M Without any retreatment 31% ≥ 6M M1 M2 M3 M4 M5 M6 Single TH103 Ongoing Phase 1b/2 study de
Slide 35: Case Example: TH103 single-injection durable response past Month 6
Case Example: TH103 single-injection durable response past Month 6 CST Change Over Time 550 Single Dose TH103 (0.5mg) 500 CST Change (𝛍𝛍m) 450 Week 1 400 234 𝛍𝛍m improvement at Month 6 Month 1 350 300 Month 6 250 W1 W2 M1 M2 M3 M4 M5 M6 Time Source: As measured by independent reading center 35
Slide 36: First-in-Human data support TH103's potential to be best-in-class
First-in-Human data support TH103’s potential to be best-in-class, first-line treatment for prevalent retinal diseases ✓ Safety: TH103 generally well tolerated, supporting exploration of further dose-escalation - No dose-limiting toxicities or TH103-related SAEs observed - 2 cases of mild/moderate I
Slide 37: Phase 1b/2 & Next Steps
>) Kalaris Phase 1b/2 & Next Steps
Slide 38: Actively Enrolling Phase 1b/2 Trial in nAMD; interim data 2H 2026
Actively Enrolling Phase 1b/2 Trial in nAMD; interim data 2H 2026 Open label, multiple ascending dose design followed by randomized, masked, multi-dose cohort-expansion phase Dose Levels (n~80) Study Phase Extension Phase 5.0mg 2.5mg • Monthly disease activity assessment 1.5mg • Patients exit study
Slide 39: Kalaris is accelerating TH103 development into later stage studies
Kalaris is accelerating First-in-Human data support TH103's potentially clinically TH103 1 meaningful differentiation and advancement into multi-dose development clinical trials into later stage studies with preliminary readout expected in 2H 2026 Actively enrolling a Phase 1b/2 multiple ascending d
Slide 40: erapeutics
erapeutics
Slide 41: Kalaris Therapeutics
S Kalaris Therapeutics
Kalaris Therapeutics — Technical Presentation (December 2025) on 6ix