Kalaris Therapeutics, Inc. · NASDAQ:KLRS
Kalaris Therapeutics — Allovir — Merger or Acquisition (December 2024)
39 slides from Kalaris Therapeutics's merger presentation, Dec 9, 2024
Slide 1: Company Overview December 2024
Company Overview December 2024
Slide 2: Disclaimer
Disclaimer This communication has been prepared solely for the purpose of considering a proposed merger involving AlloVir, Inc. (“AlloVir”) and Kalaris Therapeutics, Inc. (“Kalaris”). This communication does not propose to contain all information that may be required to evaluate a proposed merger. T
Slide 3: Our Vision, Our Mission
Your Vision Our Misson We are a clinical stage biopharmaceutical company dedicated to the development and commercialization of treatments for prevalent retinal diseases with major unmet medical needs, such as neovascular Age-related Macular Degeneration (nAMD), Diabetic Macular Edema (DME), Diabetic
Slide 4: Investment highlights: TH103 Phase 1 trial enrolling
Phase 1 clinical trial of TH103 for the treatment of nAMD is currently enrolling, with initial data expected Q3 2025 $14 Billion1 and growing retinal neovascular / exudative disease branded market, with significant remaining unmet need Invented by VEGF pioneer and scientific co-founder Dr. Napoleone
Slide 5: VEGF has been the primary target for retinal diseases for ~20 years
VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years TH103 Kalaris is focused on driving the next wave of innovation for retinal neovascular / exudative disease Dawn of anti-VEGF era à Expansion of anti-VEGF therapeutics market Next-gen anti-VEGF 2004 2006
Slide 6: Proposed Merger of Kalaris Therapeutics and AlloVir
Proposed Merger of Kalaris Therapeutics and AlloVir Transaction Summary & Structure Post-Closing Capitalization Merger with Kalaris, a clinical-stage company focused on retinal diseases Implied ownership split post-combination per the following: Kalaris: 74.95% / AlloVir: 25.05% (without giving effe
Slide 7: Anticipated Milestones
Anticipated Milestones Phase 1 clinical trial initial data readout (Q3 2025) Phase 2 clinical trial initiation (1H 2026) Additional follow-up data from Phase 1 (2026) Cash post-transaction expected to fund the combined company into Q4 2026 *Assumes $95 million AlloVir net cash at closing Following t
Slide 8: Anti-VEGF Therapeutics Background
Anti-VEGF Therapeutics Background
Slide 9: VEGF-A is the primary mediator and key target in retinal disease
VEGF-A is the primary mediator and the key target for pathologic angiogenesis and exudation (permeability) in retinal disease1 Anti-VEGF therapy has revolutionized treatment for major retinal diseases2 VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years $
Slide 10: Growth and leakage from abnormal vessels leads to visual impairment
Growth and leakage from abnormal vessels leads to visual impairment in diseases such as nAMD and DME. VEGF-A is a primary mediator of this pathology. Normal Vision Macular Degeneration (representative) Normal Retina Macular Degeneration Pathologic exudation and angiogenesis Normal Retina Macular Deg
Slide 11: Anti-VEGF therapy has revolutionized treatment for major retinal diseases
Anti-VEGF therapy has revolutionized treatment for major retinal diseases Anti-VEGFs have a potent anti-permeability effect, causing reduction or resolution of pathological fluid, often leading to visual acuity improvements Retinal neovascular diseases treated with anti-VEGF as standard of care incl
Slide 12: VEGF has been the primary target for over ~20 years
VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years *Vabysmo product label1: “The contribution of Ang-2 inhibition to the treatment effect and clinical response for nAMD, DME, and RVO has yet to be established”. (Off-label use) VEGF VEGF VEGF VEGF VEGF 20
Slide 13: $14B global branded anti-VEGF market
~$9.7B at peak (2022)2 $14B global branded anti-VEGF market, projected to grow to approximately $18B by 20291 Sources: 1) 2024 Retinal Pharmaceuticals Market Report, Market Scope September 2024; 2) Company annual and quarterly reports Global Anti-VEGF Units in Retinal Disease (2023)1 Compounded beva
Slide 14: Onerous visit frequency and suboptimal outcomes
Best outcomes may require clinic visits as frequently as every 1-2 months for monitoring and injections. Onerous visit frequency Physicians attempt to extend the time between patient visits, reducing injection frequency. Current Solution Reduced injection frequency can lead to undertreatment and red
Slide 15: Suboptimal real-world outcomes compared to clinical trial results
Suboptimal Real-World outcomes as compared to clinical trial results1,2,3,4,5 Sources: 1) Prenner, J.L. ∙ Halperin, L.S. ∙ Rycroft, C., Am J Ophthalmol. 2015; 160:725-731.e1; 2) Varano, M. ∙ Eter, N. ∙ Winyard, S., Clin Ophthalmol. 2015; 9:2243-2250; 3) Monés, J. ∙ Singh, R.P. ∙ Bandello, F.,
Slide 16: Lead asset invented by Napoleone Ferrara, MD
Co-discoverer of VEGF and VEGF isoforms while at Genentech Inventor of Anti-VEGF Agents, Avastin, Lucentis and TH103 Winner of Major Awards including Lasker Award, Champalimaud Vision Award and Breakthrough Prize in Life Sciences Napoleone Ferrara Kalaris Co-Founder Genentech Fellow | Professor, UC
Slide 17: Our Solution: TH103
( Our Solution: TH103
Slide 18: TH103 potential best-in-class anti-VEGF agent
TH103 is a fully humanized, recombinant fusion protein designed for intravitreal delivery, with potential to be a best-in-class anti-VEGF agent. TH103 acts against VEGF as a soluble decoy receptor and has been engineered for longer-acting and increased anti-VEGF activity. TH103
Slide 19: TH103 leverages key domains from VEGF receptors
TH103 leverages 2 key domains from VEGF Receptor 1 (VEGFR1) Domain 2 is from VEGFR1, and domain 3 is from VEGFR2, fused to IgG Fc. Both domain sequences are from VEGFR1, fused to IgG Fc. EXTRACELLULAR DOMAINS 1 2 3 4 5 6 7 1 2 3 4 5 6 7 VEGFR1 VEGFR2 EXTRACELLULAR DOMAINS VEGFR1 1 2 3 4 5 6 7 2 3 af
Slide 20: TH103's VEGFR1 domain may confer sustained retinal retention
TH103's domain 3 from VEGFR1 has the potential to confer sustained retinal retention, possibly leading to longer treatment effect Source: 1) Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc N
Slide 21: Pre-Clinical Development
( Pre-Clinical Development
Slide 22: TH103 achieved 100% inhibition of endothelial cell proliferation vs 80% aflibercept
aflibercept: 80% inhibition aflibercept TH103: 100% inhibition TH103 Source: Xin, H., Biswas, N., Li, P., Zhong, C., Chan, T. C., Nudleman, E., & Ferrara, N. (2021). Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders. Proceedings of the
Slide 23: Mouse laser CNV model experiment design
Source: Adapted from Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc Natl Acad Sci U S A, 118. Experiment Design Mouse laser choroidal neovascularization (CNV) model to evaluate anti-VEGF ac
Slide 24: TH103 reduced mean CNV area at Day -1 dosing
Source: Adapted from Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc Natl Acad Sci U S A, 118. TH103 demonstrated increased reduction in mean CNV area after administration at Day -1 at equim
Slide 25: Greater affinity for heparan sulfate proteoglycan may prolong retention
TH103’s greater affinity for heparan sulfate proteoglycan has the potential to prolong its ocular retention Sources: 1) Clark SJ, Keenan TD, Fielder HL, et al. 2011. 'Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid, and sclera', Invest Ophthalmol Vis Sc
Slide 26: Increased retention in retina vs aflibercept at two weeks
TH103 demonstrated increased retention in the retina as compared to aflibercept at two weeks Source: Ferrara Lab, University of California San Diego Note: Darker immunohistochemistry staining indicates higher drug levels present Rabbit Retina Cross-Sections at Day 14 aflibercept TH103 In a rabbit mo
Slide 27: Durability experiment design with earlier administration
Source: Adapted from Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc Natl Acad Sci U S A, 118. Mouse laser CNV model with earlier drug administration to evaluate durability of anti-VEGF acti
Slide 28: Increased duration of action at Day -14 administration
Source: Adapted from Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc Natl Acad Sci U S A, 118. TH103 demonstrated increased duration of action in reducing mean CNV area after administration
Slide 29: TH103 remained more active in reducing CNV growth after 21 days
Source: Adapted from Xin H, Biswas N, Li P, et al. 2021. 'Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders', Proc Natl Acad Sci U S A, 118. TH103 demonstrated increased duration of action in reducing mean CNV area after administration
Slide 30: Preclinical results summary
Preclinical Results: Increased inhibition of VEGF-induced endothelial cell proliferation (in vitro) Increased reduction in mean CNV area after administration at Day -1 (in vivo) Increased retention in the retina at two weeks post-injection (in vivo) Increased duration of action in reducing mean CNV
Slide 31: Clinical Development Program
Clinical Development Program
Slide 32: Clinical Development Program Summary
Received IND clearance from the FDA in June 2024 for a Phase 1 clinical trial of TH103 for nAMD Currently enrolling treatment-naïve, nAMD subjects in Phase 1 clinical trial Initial clinical trial data are anticipated Q3 2025, with additional Phase 1 data expected in 2026 Initiation of a Phase 2 clin
Slide 33: Phase 1 trial design
Part 2 Open label study of TH103 pharmacodynamics Part 1 Open label, single ascending dose study for safety and pharmacokinetics Population Age 50+, diagnosed nAMD, treatment naïve, > 325 microns CST Up to 5 dose cohorts, 3 subjects per cohort* *Option to expand cohorts up to 6 subjects Study Object
Slide 34: Development pipeline
Product Candidate Indication Discovery IND Enabling Phase 1 Phase 2 Phase 3 TH103 nAMD TH103 DME / DR* TH103 RVO & other Retinal Diseases* *Subject to IND submission and clearance Development pipeline aiming to address unmet need in a range of retinal diseases
Slide 35: Corporate
Corporate
Slide 36: Intellectual Property
TH103 Compositions of Matter Issued/allowed in United States, Japan, China, Australia, Colombia, and Eurasia Pending in Europe, Korea, India, Brazil, Mexico, Singapore, New Zealand, Hong Kong, and Israel Intellectual Property 1 TH103 Methods of Use Issued/allowed in United States, Europe, Japan, Chi
Slide 37: Management and Board
Management and Board with experience developing and commercializing retina therapeutics and successfully building biopharma companies Current Management Team Current Board of Directors* Jeffrey Nau, PhD COO, Kalaris Genentech; Ophthotech (Iveric); Oyster Point Napoleone Ferrara, MD Director & Co-Fou
Slide 38: Summary: TH103 Phase 1 trial and market opportunity
Phase 1 clinical trial of TH103 for the treatment of nAMD is currently enrolling, with initial data expected Q3 2025 $14 Billion1 and growing retinal neovascular / exudative disease branded market, with significant remaining unmet need Invented by VEGF pioneer and scientific co-founder Dr. Napoleone
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