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KPI - 012 for Rare Ocular Surface Disease: Key Opinion Leader Insights into PCED July 16, 2025
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Disclaimers and Notices 2 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. Any statements in this presentation about KALA’s future expectations, plans and prospects, including but not limited to KALA’s expectations with respect to potential advantages of KPI-012 and its MSC-S platform; anticipated timelines to report topline data for the CHASE Phase 2b clinical trial of KPI-012; the design of the CHASE Phase 2b clinical trial; KALA’s belief that the CHASE Phase 2b trial could serve as the first of two pivotal trials required to support the submission of a BLA to the FDA; the clinical utility of KPI-012 for PCED; KALA’s plans to pursue research and development of KPI-012 and its MSC-S platform for other indications; KALA’s ability to realize potential milestones payments under the transaction with Alcon and the risk that KALA may notrealize the expected benefits of the transaction; the sufficiency of KALA’s existing cash resources for the period anticipated and other statements containing the words“anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,”“will,” “would,” and similar expressions constitute forward-looking statements. Actual results may differ materially from those indicatedby such forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation and conduct of preclinical studies and clinical trials; uncertainties regarding availability and timing of data from clinical trials; whether results of early clinical trials or trials in different disease indications will be indicative of the results of ongoing or future trials; whether results of the Phase 1b clinical trial of KPI-012 will be indicative of results for any future clinical trials and studies of KPI-012, including the CHASE Phase 2b clinical trial; whether interim data from a clinical trial will be predictive of the results of the trial; uncertainties associated with regulatory review of clinical trials and applications for marketing approvals; KALA’s ability to retain and hire key personnel; the sufficiency of cash resources and need for additional financing and other important factors, any of which could cause KALA’s actual results to differ from those contained in the forward-looking statements, discussed in the “Risk Factors” section of KALA’sAnnual Report on Form 10-K, most recently filed Quarterly Report on Form 10-Q and other filings KALA makes with the Securities and ExchangeCommission. All information in this presentation is as of July 16, 2025 and should not be considered current after such date. KALA does not assume any obligation to update any forward-looking statements, whetheras a result of new information, future events or otherwise, except as required by law. KOL Day | July 2025
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Topic Speaker KALA BIO Overview and Commercial Opportunity Todd Bazemore PCED Overview and Unmet Need Francis Mah, MD PCED Patient Journey Anthony Aldave, MD MSC-S and KPI -012 Overview Stephen Pflugfelder, MD KPI-012 Clinical Trial Experience and CHASE Study Overview Melissa Toyos, MD KPI-012 Product Candidate Profile, Upcoming Milestones & Closing Remarks Todd Bazemore PCED, persistent corneal epithelial defect; CHASE, Corneal Healing After SEcretome Therapy; MSC-S, mesenchymal stem cell secretome.3 KOL Insights into PCED: Agenda KOL Day | July 2025
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Todd Bazem ore Interim Chief Executive Officer and President, KALA BIO Francis Mah, MD 1,3 Director of Cornea and External Disease & Co-Director, Refractive Surgery, Scripps Clinic Medical Group Anthony Aldave, MD 2,3 Professor of Ophthalmology, Co-Chief of the Cornea and Uveitis Division, Jules Stein Eye Institute Stephen Pflugfelder, MD 2 Professor and James and Margaret Elkins Chair in Ophthalmology, Baylor College of Medicine Melissa Toyos, MD 2,3 Partner, Research Director, Comprehensive Ophthalmology Toyos Clinic 4 Meet Today’s Speakers K e y O p i n i o n L e a d e r s K A L A B I O M a n a g e m e n t Te a m KOL Day | July 20251. Chief Medical Consultant, KALA BIO. 2. Consultant, KALA BIO. 3. CHASE Trial Investigator
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KALA BIO Overview and Commercial Opportunity Todd Bazemore Interim Chief Executive Officer and President, KALA BIO KOL Day | July 2025
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KALA BIO Overview CHASE, Corneal Healing After SEcretome therapy; CIRM, California Institute for Regenerative Medicine; FDA, Food and Drug Administration; IND, investigational new drug; LSCD, limbal stem cell deficiency; PCED, persistent corneal epithelial defect. 6 • Mesenchymal Stem Cell Secretome (MSC-S) Platform enables product candidates for multiple potential rare diseases • KPI-012: Enrolled patients in CHASE Phase 2b for PCED, and evaluating for LSCD & other rare corneal diseases • KPI-014: Preclinical program for rare inherited retinal diseases Late-Stage Lead Program with “Pipeline-in-a-Product” Potential Strong Corporate Position KPI-012 Milestones Strong Corporate Position • Q4 2022: KPI-012 PCED IND filed and accepted • Q2 2023: CHASE Phase 2b trial in PCED cohort 2 initiated • Q2 2023: KPI-012 granted Fast Track designation for PCED by FDA • Q2 2025: CHASE Phase 2b enrollment completed • Q3 2025: CHASE Phase 2b topline data in PCED expected • Experienced team • April 2023: Announced award of $15M by CIRM to support ongoing KPI-012 program for the treatment of PCED • Cash, cash equivalents, and investments of $42.2M as of 3/31/25 • Projected cash runway into Q1 2026 KOL Day | July 2025
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Persistent Corneal Epithelial Defect (PCED) is a Potential $3B+ Orphan Market Opportunity 1 • Estimated PCED incidence of 100,000 patients in the U.S. and 238,000 in the U.S., EU, and Japan combined • Currently, there are no FDA-approved prescription therapies with a broad PCED indication • Oxervate®, limited to NK only (~1/3 of PCED patients), reported US 2024 annual sales exceeding $1.1B2 • Oxervate® 2023-2024 annual US sales growth: ~35% NK-related PCED (1/3 of patients) All other PCED Etiologies (~2/3 of patients) KPI-012 could be the first approved therapy with a broad PCED indication and differentiated product profile • Potential for rapid and sustained healing, improved tolerability, more convenient administration, and a broad MOA to address all etiologies Specialized call point: ECP target list of ~1,800 cornea specialists allows for a capital efficient rare disease commercial model Overvate® is a registered trademark of Dompé farmaceutici S.p.A. ECP, eye care provider; FDA, Food and Drug Administration; MOA, mechanism of action; NK, neurotrophic keratitis; PCED, persistent corneal epithelial defect. 1. KALA BIO data on file. Calculation includes PCED incidence, pharmacotherapy pricing and ophthalmologist treatment and prescription pattern assumptions. 2. Italian Chambers of Commerce, Dompe Farmaceutici S.P.A 2025 filing. Available at: https://italianbusinessregister.it/en/7 KPI-012 is designed to address the full PCED market KOL Day | July 2025 0 250 500 750 1,000 1,250 2021 2022 2023 2024 $460M $610M $828M Reported US Oxervate® Sales ($M)2 $1,127M
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PCED Overview and Unmet Need Francis Mah, MD Scripps Clinic La Jolla, CA KOL Day | July 2025
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In a healthy eye, the cornea continuously renews to function as a barrier Corneal epithelial homeostasis involves a complex and choreographed process of proliferation, migration, adhesion differentiation, and stratification1,2 1. Dutta T, et al. Pathogens. 2023;12:261. 2. Liu C, et al. Prog Mol Biol Transl Sci. 2015;134:61-71. 9 KOL Day | July 2025
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Upon injury or insult, a healthy cornea re-epithelizes within 7-10 days Corneal wound healing is a highly structured process that involves a complex interplay of various cellular signals and growth factors1,2 Re-epithelized layer 1. Ghafar N, et al. Asian Biomed (Res Rev News). 2021;15:199-212. 2. Krolo I, et al. Surv Ophthalmol. 2024;69:805-817. Epithelial Defect Healing in a Normal Cornea Growth factors and inflammatory mediators are released 10 KOL Day | July 2025
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Any impairment in the normal healing process can result in a PCED A PCED is a defect that fails to re-epithelialize within 14 days, with or without standard supportive treatment1 11 • Stromal scarring • Corneal melting • Corneal perforation PCED, persistent corneal epithelial defect. Image credit for corneal ulcer: Ioannidis AS, et al. J Med Case Rep. 2011;5:539. Image credit for corneal perforation: Peng R, et al. BMC Ophthalmol. 2024. 1. Vaidyanathan U, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. C o r n e a l u l c e r Representative patient C o r n e a l p e r fo r a t io n Representative patient Patients with an Untreated PCED May Experience Significant Complications 1 • Significant vision loss • Risk of infection • Corneal ulceration KOL Day | July 2025
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PCED is Clinically Burdensome with High Unmet Needs 1. Single therapy that addresses multiple etiologies ▪ PCED patients often have multiple underlying etiologies that all need to be addressed for effective wound healing ▪ Oxervate is limited to the treatment of neurotrophic keratitis or NK (one etiology; ~1/3 of PCED patients)1 ▪ Across two pivotal studies supporting FDA approval for the treatment of NK, Oxervate demonstrated a mean healing rate improvement of 41.8% over placebo2 ▪ Non-NK PCED patients were not included in the Oxervate pivotal studies and lack a benchmark for a clinically meaningful pharmacotherapy treatment 2. Rapid and sustained healing of corneal defects ▪ Patients are at risk of developing permanent vision loss if defects are not healed quickly enough 3. Well-tolerated and easily administered treatment ▪ Oxervate requires 6 times a day dosing and a 19-step preparation process1 ▪ 16% of patients treated with Oxervate report eye pain as an AE; Other post-marketing AEs include eye irritation, blepharitis, and corneal neovascularization1 Current prescription therapy only addresses a subset of PCED patients, causes ocular pain in a significant number of patients, and is complex and burdensome for patients to administer AE, adverse event; FDA, Food and Drug Administration; PCED, persistent corneal epithelial defect. 1. OXERVATE® (cenegermin-bkbj) ophthalmic solution 0.002% (20 mcg/mL). US Package Insert. Dompé U.S. Inc.; Boston, MA: Oct 2019. 2. Oxervate Clinical Review(s), available at accessdata.fda.gov12 KOL Day | July 2025
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PCED Patient Journey Anthony Aldave, MD Jules Stein Eye Institute Los Angeles, CA Investigator in CHASE Phase 2b Clinical Trial KOL Day | July 2025CHASE, Corneal Healing After SEcretome Therapy; PCED, persistent corneal epithelial defect.
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Defective Epithelial Adhesion Limbal Stem Cell Deficiency Inflammation • Recurrent corneal erosions • Toxic keratopathy • Band keratopathy • Scarring and trauma • Limbal stem cell deficiency • Alkali-induced chemical injury • Trauma • Infectious keratitis • Sjögren’s syndrome • Stevens-Johnson syndrome • Graft vs host disease Neurotrophic Mechanical Idiopathic & Hereditary Disorders • Diabetes mellitus • Current or past herpetic keratitis • Traumatic or postoperative nerve damage • Lagophthalmos • Severe DED (mucin deficiency) • Corneal burns from chemical or thermal injuries • Exposure keratopathy • Aniridia • Corneal, stromal, and epithelial basement membrane dystrophies 14 DED, dry eye disease; PCED, persistent corneal epithelial defect. Vaidyanathan U, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. Numerous Etiologies are Associated with PCED KOL Day | July 2025 Not an exhaustive list of all causative diseases.
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PCED D iagnosis is Primarily Clinical, Relying on a Combination of Patient History and Exam1,2 PCED, persistent corneal epithelial defect. Image credit: Kowk A. Review of Optometry. 2018. 1. Golhait P, Peseyie R. StatPearls Publishing, Treasure Island (FL); 2021. 2. Vaidyanathan U, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. • Patient history can reveal duration of epithelial defect, mechanism of trauma, prior surgeries, associated ocular & systemic comorbidities, family history, immune status, and prior treatment • Symptoms may include pain, tearing, foreign body sensation, blurring of vision, redness, and photophobia • Fluorescein staining determines size and location of an epithelial defect Representative patient with PCED 15 KOL Day | July 2025
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Representative patient with PCED 16 PCED Etiology Stevens-Johnson syndrome and severe dry eye disease Treatments Bandage contact lenses, topical cyclosporine 0.05%, and artificial tears BCVA, best-correct visual acuity; PCED, persistent corneal epithelial defect. Lim P, Ridges R, Jacobs DS, et al. Am J Ophthalmol. 2013 ;156:1095-1101. PCED Patient Case: 32-Year-Old Female KOL Day | July 2025
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Representative patient with PCED 17 PCED Etiology Diabetic keratopathy Treatments Bandage soft contact lens (changed lens QID), ofloxacin QID PCED Patient Case: 67 -Year-Old KOL Day | July 2025 PCED, persistent corneal epithelial defect; QID, four times daily. Data on file.
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Stepwise Approach to PCED Management 1,2 1. Treat underlying and iatrogenic causes 2. Aggressive lubrication (preservative free artificial tears and ointments) 3. Punctal plugs 4. Bandage or scleral contact lens 5. Amniotic membrane (self -retaining) 6. Debridement, tarsorrhaphy, botulinum toxin A 7. T etracyclines, prophylactic antibiotics and steroids 8. Other biologics: Oxervate (topical rhNGF indicated for neurotrophic keratitis, one cause of PCED) • PCED management is complex and may involve several treatments • Patients require extensive follow-up, often multiple times a week or even daily PCED, persistent corneal epithelial defect; PROSE, Prosthetic Replacement of the Ocular Surface Ecosystem; rhNGF, recombinant human nerve growth factor. 1. VaidyanathanU, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. 2. Golhait P, et al. StatPearls Publishing. Jan 2024. Current Standard Management • Medical: ˗ Autologous serum drops ˗ Whole blood derived products ˗ Scleral lenses/PROSE • Surgical: ˗ Amniotic membrane transplantation (sutured) ˗ Corneal epithelial stem cell transplantation ˗ Boston keratoprosthesis Treatment of Refractory Cases 18 KOL Day | July 2025
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• Goal of PCED treatment is to provide protection and favorable conditions for epithelial cells to migrate, proliferate, adhere to basement membrane, and regenerate • Defects treated earlier will heal more rapidly and completely • PCEDs should be treated early to minimize serious complications FDA, Food and Drug Administration; PCED, persistent corneal epithelial defect. VaidyanathanU, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. Image credit: Sepulveda-Beltran PA, et al. Int Ophthalmol Clin. 2022 ;62:65-77. Representative patient with PCED Currently, there is no FDA-approved treatment with a broad PCED indication covering all etiologies 19 KOL Day | July 2025
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MSC-S and KPI-012 Overview Stephen Pflugfelder, MD Baylor College of Medicine Houston, TX MSC-S, mesenchymal stem cell secretome. KOL Day | July 2025
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Pathological Changes in Wound Healing of a Diseased Cornea 21 ECM, extracellular matrix; HGF, hepatocyte growth factor; PCED, persistent corneal epithelial defect PEDF, pigment epithelium derived factor; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2. 1. Krolo I, et al. Surv Ophthalmol. 2024;69:805-817. 2. Vaidyanathan U, et al. Med Hypothesis Discov Innov Ophthalmol. 2019;8:163-176. Image adapted from Krolo I, et al. Surv Ophthalmol. 2024;69:805-817. Penetration of Bowman’s layer may result in stromal fibrosis and visual impairment1 1 2 3 4 56 Changes include1: 1. Increased keratocyte apoptosis 2. Activation of quiescent keratocytes 3. Keratocyte-to-myofibroblast transformation 4. Fibrosis & deposition of extracellular matrix 5. Delayed epithelial healing 6. Chemokine release resulting in continuous polymorphonuclear infiltration Additionally, loss of basement membrane integrity occurs during this process Epithelial cells are unable to migrate centrally, resulting in epithelial cell growth on the edges of the PCED1 Any impairment in the normal healing process can result in a PCED2 • A PCED is a persistent non -healing corneal defect that is refractory to conventional treatments KOL Day | July 2025
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Mesenchymal Stem Cells or MSCs • MSCs are more than differentiation • MSCs can ‘influence’ other cells and tissues: ▪ Immunomodulation (typically suppression) ▪ Promotion of cell survival ▪ Modulation of new blood vessel formation ▪ Reduction or prevention of scarring ▪ Healing and repair of wounds MSC, mesenchymal stem cell. Ibraheim H, et al. Expert Rev Gastroenterol Hepatol. 2018;12:141-153. Image source: Ibraheim H, et al. Expert Rev Gastroenterol Hepatol. 2018;12:141-153. MSCs are found in multiple tissues… …And can differentiate into various cell types 22 KOL Day | July 2025
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Proprietary Mesenchymal Stem Cell Secretome (MSC -S) Platform • Healing and regenerative capacity of MSCs is attributed to the multifactorial biological factors secreted or ‘secretome’ • Secretomes are produced by collecting biomolecules secreted by cells into the extracellular space to support their health and viability ▪ KPI-012 is manufactured from a master proprietary cell bank of human bone-marrow derived MSCs • Secreted factors can include: Cytokines/growth factors, neurotrophic factors, protease inhibitors, and matrix proteins • Benefits demonstrated by third parties in corneal injury1-5, retinal degeneration6-10, glaucoma11-14, and dry eye disease15- 17 Mesenchymal Stem Cell Secretome MSC, mesenchymal stem cell. 1. Samaeekia R, et al. Invest Ophthalmol Vis Sci. 2018;59:5194 -5200. 2. Fernandes -Cunha GM, et al. Stem Cells Transl Med. 2019;8:478 -489. 3. Jabbehdari S, et al. Curr Eye Res. 2020;45:1490 -1496. 4. An S, et al. Int J Mol Sci. 2022;23:11510. 5. Huerta VS, et al. Curr Ther Res Clin Exp. 2025;103:100799. 6. Limoli PG, et al. Antioxidants (Basel). 2020;9:983. 7. Adak S, et al. Stem Cell Rev Rep. 2021;17:1154 -1173. 8. Reboussin É, et al. J Neuroinflammation. 2022;19:63. 9. Brown C, et al. Stem Cell Res Ther. 2022;13:148. 10. Usategui -Martín R, et al. Invest Ophthalmol Vis Sci. 2022;63:27. 11. Johnson TV, et al. Invest Ophthalmol Vis Sci. 2010;51:2051 -2059. 12. Mead B, et al. Invest Ophthalmol Vis Sci. 2018;59(2):702 -714. 13. Seong HR, et al. Int J Mol Sci. 2023;24:8073. 14. Yu F, et al. Neural Regen Res. 2023;18:2301 -2306. 15. Møller-Hansen M. Acta Ophthalmol. 2023;101 Suppl 277:3 -27. 16. Randall Harrell C, et al. J Ophthalmol. 2025;2025:5552374. 17. Habibi A, et al. BMC Ophthalmol. 2025;25:299. 23 MSC-S platform is a cell-free, regenerative approach to disease management KOL Day | July 2025
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Protease Inhibitors TIMP-1 TIMP-2 Serpin E1 Matrix Proteins Fibronectin Collagen Growth Factors HGF Neurotrophic Factors PEDF KPI-012: Lead MSC -S Candidate in Development for PCED • Contains key secretome biofactors associated with corneal wound healing • Provides a multifactorial approach to addressing impaired corneal healing • Formulated as a topical, non-preserved, single unit dose formulation • Potential to treat multiple rare cornealdiseases KPI-012 is currently being investigated in a pivotal Phase 2b clinical study in PCED, with top-line data expected in late Q3 2025 KPI-012 Secretome Biofactors 24 HGF, hepatocyte growth factor; PCED, persistent corneal epithelial defect PEDF, pigment epithelium derived factor; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2. KOL Day | July 2025
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KPI-012 MOA KPI-012 Addresses Multiple Biologic Pathways Associated with Impaired Corneal Healing in PCED Protease inhibitors (e.g., TIMP-1, TIMP-2, Serpin E1) inhibit proteases that degrade ECM components in the wound bed and promote uncontrolled inflammatory response Matrix proteins (e.g., fibronectin, collagen) facilitate ECM remodeling and assembly in wound bed, supporting cell adhesion, migration, and maturation Growth factors (e.g., HGF) suppress inflammation and promote epithelial proliferation, migration, adhesion, and wound re-epithelization Neurotrophic factors (e.g., PEDF) promote maintenance and regrowth of neurons to support corneal health and epithelial function and survival 25 ECM, extracellular matrix; HGF, hepatocyte growth factor; PCED, persistent corneal epithelial defect PEDF, pigment epithelium derived factor; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2. Image adapted from Krolo I, et al. Surv Ophthalmol. 2024;69:805-817. KOL Day | July 2025
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KPI-012 Clinical Trial Experience Melissa Toyos, MD Toyos Clinic Nashville, TN Investigator in CHASE Phase 2b Clinical Trial CHASE, Corneal Healing After SEcretome Therapy. KOL Day | July 2025
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Successful Phase 1b Trial of KPI-012 in PCED Supports Progression to Phase 2 Study Phase 1b Study Design • Key inclusion: Participants with a PCED (of any etiology) for at least 10 days without improvement with one or more conventional, non-surgical treatments • Lead-in safety cohort: 3 participants dosed BID for one week demonstrated no safety or tolerability issues • Efficacy cohort: 8 participants dosed BID for 1 to 8 weeks and followed for up to 19 weeks • Key efficacy endpoint: Healing of the PCED based on corneal fluorescein staining 27 BID, twice daily; PCED, persistent corneal epithelial defect. Huerta VS, et al. Curr Ther Res Clin Exp. 2025;103:100799. KOL Day | July 2025
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Phase 1b Data Validate KPI -012 Potential in PCED Mean Median PCED Size at Baseline (mm x mm) 5.1 x 3.5 5.6 x 2.9 PCED Duration at Baseline (Days) 58 32 PCED Healing Time with KPI-012 (Days) 12 7 Day 1 Day 7 • 6 of 8 participants had complete healing of PCED with KPI-012 BID ▪ 4 of 6 completely healed after 1 week ▪ 1 of 6 completely healed after 2 weeks ▪ 1 of 6 completely healed after 4 weeks • Improvement in lesion size was observed in the 2 participants who did not heal completely • All healed participants remained healed through end of follow-up • KPI-012 was well-tolerated with no treatment-related serious AEs Representative Images of One Participant with Complete Healing at Day 7: 28 AE, adverse event; BID, twice daily; ECM, extracellular matrix; PCED, persistent corneal epithelial defect. Huerta VS, et al. Curr Ther Res Clin Exp. 2025;103:100799. KOL Day | July 2025
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Twice-Daily KPI -012 Resulted in Complete Healing of PCEDs in 6 of 8 Participants Within 4 Weeks in Phase 1b Clinical Trial Patient ID PCED Etiology Baseline Defect Duration (Size, mm)* Week 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 1-05 Neurotrophic (Diabetic) 17 days (6.5x5.5) 1-06 Neurotrophic (Diabetic) 28 days (6x5.9) 1-07 Neurotrophic (Diabetic) 15 days (5.2x2.5) 1-08 Neurotrophic (Diabetic) 41 days (6.2x3.3) 2-01 Stevens-Johnson/ Dry Eye 213 days (4.7x2) 2-03 Post-Infectious Keratitis 37 days (2.2x1.5) 2-04 Neurotrophic (Diabetic) 35 days (5.7x2.4) 2-05 Neurotrophic/ Dry Eye 871 days (3x2) KPI-012 BID Follow-up Defect Completely Healed Follow-up Assessment Defect size at last dose=1.7x1.5 mm Defect size at last dose=3.7x0.5 mm *Mean PCED size at baseline=5.1x3.5 mm; Mean PCED duration at baseline=58 days; Mean PCED healing time with KPI-012 BID=12 days. BID, twice-daily; PCED, persistent corneal epithelial defect. Huerta VS, et al. Curr Ther Res Clin Exp. 2025;103:100799. 6 of 8 participants with complete healing remained healed through end of follow-up; Improvement in PCED lesion size was observed in participants who did not heal completely Rapid and Sustained Healing in Patients with Varying Etiologies and Duration of Disease SuggestsPotential for Broad Efficacy in PCED 29 KOL Day | July 2025
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0 1 2 3 4 100% 67% 100% 0 2 4 6 8 10VAS Pain Score* Treatment Week 1- 05 1- 06 1- 07 1- 08 2- 01 Study Subject reported pain reduction by Week 1 reported 0 pain score by Week 1 reported 0 pain score by Week 3 Participants Experienced Significant Pain Relief Within 1 Week of Twice-Daily KPI -012 in Phase 1b Clinical Trial Rapid Reduction in Pain in PCED Participants Treated with KPI-012 *VAS Score: Pain level due to defect on scale of 0-10 where 0=no pain at all and 10=worst possible pain. VAS, Visual Analogue Scale; PCED, persistent corneal epithelial defect. Huerta VS, et al. Curr Ther Res Clin Exp. 2025;103:100799. Pain Decreased in All 6 Participants Who Reported Pain at Baseline 30 KOL Day | July 2025
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CHASE Phase 2b Clinical Trial Study Design Corneal Healing After SEcretome Therapy KOL Day | July 2025
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KPI-012-C-001: CHASE Phase 2b Clinical Trial • Multi-cohort study to evaluate safety and efficacy of 2 doses of KPI-012 ophthalmic solution compared with vehicle • Dosed QID for 56 days in the study eye of participants with PCED at least 14 days duration at the Day 1 visit Cohort 1: Complete • Design: Multi-center, open-label safety evaluation • Objective: Evaluate safety of high-dose 3 U/mL KPI-012 QID based on presence or absence of dose -limiting toxicities • Results: No safety findings (n=2) Cohort 2: Enrollment Complete • Design: Multi-center, randomized, controlled, double -masked study • Objective: Evaluate safety and efficacy of 2 concentrations of KPI -012 (1 U/mL and 3 U/mL) QID compared with vehicle dosed for 8 weeks CHASE, Corneal Healing After SEcretome Therapy; PCED, persistent corneal epithelial defect; QID, four times daily.32 KOL Day | July 2025
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CHASE Phase 2b Study Overview • Clinical sites: ~56 (mix of academic and private) in US, Argentina, Brazil, Colombia and Peru • Target enrollment: Enrollment completed in Q2 2025 with a total of 79 evaluable patients randomized • Primary endpoint: Proportion of participants completely staining free at Week 8, with no staining at the site of the original lesion at Week 10 and no persistent staining elsewhere in the cornea at Week 10 * *based on central-reader assessment of corneal fluorescein staining photos CHASE, Corneal Healing After SEcretome Therapy; PCED, persistent corneal epithelial defect; QID, four times daily. 1. OXERVATE® (cenegermin-bkbj) ophthalmic solution 0.002% (20 mcg/mL). US Package Insert. Dompé U.S. Inc.; Boston, MA: Oct 2019. 33 KOL Day | July 2025 Randomized 1:1:1 Low Dose KPI-012 QID High Dose KPI-012 QID Vehicle QID Clinical diagnosis of PCED of ≥7 days at Screening Follow-up: 2 weeks and 6 months Treatment period: 8 weeks 7-day run-in with only non- preserved artificial tears and antibiotic Randomization if lesion size not decreased by >10%
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Phase 2b Key Inclusion Criteria Key Inclusion Criteria 1. 18 years of age or older 2. Written informed consent and HIPAA authorization prior to any study- related procedures 3. Medically documented PCED at least 7 days duration prior to Screening that is refractory to one or more non-surgical treatments (e.g., preservative free artificial tears, therapeutic contact lenses) ▪ NOTE: Primary cause of PCED must be documented on the participant’s record, and may include, but is not limited to: AT, artificial tears; HIPAA, Health Insurance Portability and Accountability Act; PCED, persistent corneal epithelial defect; LSCD, limbal stem cell deficiency; GvHD, graft-versus-host disease. 34 • Neurotrophic keratopathy • Diabetic keratopathy or post diabetic vitrectomy • Post corneal transplant • LCSD (mild to moderate) • Infectious keratitis (mild to moderate) • Severe dry eye disease (including Sjögrens) • Stevens-Johnson syndrome • Ocular GvHD • Ocular cicatricial pemphigoid • Chemical (particularly alkali) burns of the cornea • T oxic keratopathy (eg, topical anesthetic abuse) • Exposure keratopathy • Mechanical trauma • Thermal burns • Surgical epithelial debridement KOL Day | July 2025
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KPI-012 Product Candidate Profile Todd Bazemore Interim Chief Executive Officer and President, KALA BIO KOL Day | July 2025
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KPI-012 Has the Potential to Treat Broad PCED With a Differentiated Product Profile 1. Multi-factorial mechanism of action targeting all PCED etiologies ▪ Protease inhibitors (TIMP-1, TIMP-2, Serpin E1) inhibit proteases that degrade wound bed extracellular matrix (ECM) components ▪ Matrix proteins (collagen) facilitate ECM remodeling and assembly in wound bed ▪ Growth factors (HGF) suppress inflammation and promote wound re-epithelization ▪ Neurotrophic factors (PEDF) promote maintenance and regrowth of neurons to support corneal health 2. Rapid and sustained healing of corneal defects ▪ Ph 1b Clinical Study results: 6 of 8 participants had complete healing of PCED with KPI-012 BID • 4 of 6 completely healed after 1 week • 1 of 6 completely healed after 2 weeks • 1 of 6 completely healed after 4 weeks 3. Well-tolerated and easily administered ▪ 4 times a day dosing using convenient single-use unit dose vial that requires no preparation by the patient ▪ Ph 1b Clinical Study key secondary outcomes: Of patients reporting pain at baseline (6 of 8), 100% reported pain reduction at Week 1 and 100% reported complete resolution of pain by Week 3 36 BID, twice dailly; HGF, hepatocyte growth factor; PCED, persistent corneal epithelial defect PEDF, pigment epithelium derived factor; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2. KOL Day | July 2025
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37 Thaw and Seed Working Cell Bank Vial Bioreactor Production Harvest Secretome Processing Drug Substance Final Drug Product • Formulation/Fill • Blow-fill-seal unit dose KPI-012 manufacturing process is robust and scalable • Currently manufactured at scale to support pivotal clinical studies and early commercialization, if approved • Final Drug Product currently manufactured using industry-standard unit dose blow -fill-seal formulation and filling process • US-based manufacturing process; tariff impact, if any, not expected to be significant Final Drug Product released based on product potency, consistency and stability methods consistent with FDA Pre-IND and Type C meeting feedback, including protein Critical Quality Attributes (CQAs), and a cell-based potency assay • Validated assays developed for protein CQAs • Multiple engineering batches assaying CQAs and additional KPI-012 constituents support robust and consistent manufacturing process Process Control Analytics KPI-012 is Currently Manufactured at Commercial Scale KOL Day | July 2025FDA, Food and Drug Administration; IND, Investigational New Drug.
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Upcoming Milestones and Closing Remarks Todd Bazemore Interim Chief Executive Officer and President, KALA BIO KOL Day | July 2025
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KPI-012 Clinical Development Updates Progressing Toward Top-line Phase 2b data in late Q3 2025 • Orphan Drug and Fast Track designations granted by FDA for PCED • CHASE Phase 2b clinical trial Cohort 2 initiated in Q2 2023 and enrollment completed in Q2 2025, with top- line data expected in late Q3 2025 ▪ If results are positive, it could serve as a pivotal trial to support BLA submission • Based on FDA Type C meeting in April 2024, CMC and potency assay program is aligned with FDA expectations for Phase 3 and BLA submission • Expect to leverage KPI-012 PCED CMC program and other IND-enabling activities to support follow-on rare corneal diseases for KPI-012 • Potential U.S. regulatory exclusivity and IP protection beyond 2040 39 BLA, Biologics License Application; CHASE, Corneal Healing After SEcretome Therapy; CMC, Chemistry, Manufacturing, and Controls; Food and Drug Administration; IND, Investigational New Drug; PCED, persistent corneal epithelial defect. IP, intellectual property KOL Day | July 2025
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An Innovative Pipeline Based on our Proprietary MSC -S Platform Product Candidate* Indication Route of Administration Pre-Clinical Phase 1 Phase 2 Phase 3 KPI-012 Rare Ocular Surface Diseases Persistent Corneal Epithelial Defect (PCED) T opical Limbal Stem Cell Deficiency (LSCD) T opical Other rare corneal diseases T opical KPI-014 Rare Inherited Retinal Diseases Intravitreal Injection Targeting the Treatment of Rare Front and Back of the Eye Diseases *Product candidates are investigational and have not been approved by any regulatory authority. MSC-S, mesenchymal stem cell secretome.40 KOL Day | July 2025
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41 Approximate U.S. Prevalence Anterior Segment Persistent Corneal Epithelial Defect (PCED) 100,000 Limbal Stem Cell Deficiency 100,000 Sjögren’s (Moderate-to-Severe) 95,000 Corneal Ulcers 50,000 Corneal Burns (Chemical Injury) 36,000 Ocular Chronic Graft v Host Disease 3,000 Stevens-Johnson Syndrome 1,000 Posterior Segment Retinitis Pigmentosa 95,000 Stargardt Disease 37,000 Non-arteric Anterior Ischemic Optic Neuropathy 28,000 Leber’s Hereditary Optic Neuropathy 9,000 0 20,000 40,000 60,000 80,000 100,000 MSC-S Has Potential Applications in Multiple Rare Ocular Disease Segments Sources: ClearView Analysis; PEDMarketInsights, Epidemiology, and Market Forecast—2030 Delveinsight, 2020; Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498999/.Accessed4Feb2021. KPI-012 Ph 2b Program KPI-012 Clinical Development Under Evaluation KOL Day | July 2025
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Q&A KOL Day | July 2025
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KOL Day | July 2025 Thank You