Kalaris Therapeutics, Inc. · NASDAQ:KLRS
Kalaris Therapeutics — Merger or Acquisition (November 2024)
39 slides from Kalaris Therapeutics's merger presentation, Nov 25, 2024
Slide 1: Company Overview November 2024
Company Overview November 2024 1
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 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: Potential best in class anti-VEGF therapeutic for common retinal neovascular / exudative diseases
Potential best in class anti-VEGF therapeutic for common retinal neovascular / exudative diseases $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 Ferrara, lead asse
Slide 5: VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years
VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years 2004 2006 2019 2023 TH103 Dawn of anti-VEGF era Expansion of anti-VEGF therapeutics market NEXT-GEN ANTI-VEGF 2005 (off-label use) 2011 2022 Kalaris is focused on driving the next wave of innovation fo
Slide 6: Proposed Merger of Kalaris Therapeutics and AlloVir
Proposed Merger of Kalaris Therapeutics and AlloVir • Merger with Kalaris, a clinical-stage company focused on retinal diseases • Implied ownership split post-combination per the following: o Kalaris: 74.95% / AlloVir: 25.05% (without giving effect to any bridge financing) • Kalaris / AlloVir busine
Slide 7: Cash post-transaction expected to fund the combined company into Q4 2026
Cash post-transaction expected to fund the combined company into Q4 2026 Following the merger closing, the combined company is expected to have pro forma cash of ~$100 million*, which is projected to fund the combined company into Q4 2026, including Phase 1 data generation and readiness for Phase 2
Slide 8: Anti-VEGF Therapeutics Background
Anti-VEGF Therapeutics Background
Slide 9: Lessons from over two decades of using Anti-VEGF to treat retinal disease
Lessons from over two decades of using Anti-VEGF to treat 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
Slide 10: VEGF-A is the primary mediator and key target for pathologic angiogenesis and exudation
VEGF-A is the primary mediator and the key target for pathologic angiogenesis and exudation (permeability) in retinal disease 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 Retina Normal Ret
Slide 11: Anti-VEGF therapy has revolutionized treatment for major retinal diseases
Anti-VEGF therapy has revolutionized treatment for major retinal diseases Pre-Anti-VEGF Treatment • 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-
Slide 12: VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years
VEGF has been the primary target for neovascular / exudative retinal diseases for over ~20 years AGENT TARGET YEAR INTRODUCED VEGF 2004 (Off-label use) VEGF 2005 VEGF 2006 VEGF 2011, 2023 VEGF 2019 VEGF, Ang-2* 2022 *Vabysmo product label1: “The contribution of Ang-2 inhibition to the treatment effe
Slide 13: $14B global branded anti-VEGF market, projected to grow to approximately $18B by 2029
$14B global branded anti-VEGF market, projected to grow to approximately $18B by 20291 Global Anti-VEGF Units in Branded Anti-VEGF Therapies 2023 Global Net Sales2 Retinal Disease (2023)1 ~$2.7B in first full calendar year $14B (2023); ~$3.5B 2024 YTD through Q32 faricimab $12B aflibercept HD $10B C
Slide 14: Unmet need remains high, with suboptimal real-world outcomes
Unmet need remains high, with suboptimal real-world outcomes Best outcomes may require clinic Onerous visit “Although multiple anti-VEGF therapies visits as frequently as every 1-2 exist, unmet need remains high owing to frequency months for monitoring and injections. treatment underutilization…”1 P
Slide 15: Suboptimal real-world outcomes as compared to clinical trial results
Suboptimal Real-World outcomes as compared to clinical trial results1,2,3,4,5 Registrational Clinical Trial6 Real World Study7 0.5 mg of ranibizumab Ranibizumab 8 0.3 mg of ranibizumab 6 Mean Visual Activity Difference from Baseline (LOCF) (letters) Mean Change in Visual Acuity 4 (no. of letters) 2
Slide 16: TH103 invented by VEGF pioneer and Lasker Award winner Napoleone Ferrara, MD
Our lead asset, TH103, was invented by VEGF pioneering scientist and Lasker Award winner 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
Slide 17: Our Solution: TH103
Our Solution: TH103
Slide 18: TH103
TH103 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. 18
Slide 19: TH103 leverages key domains from VEGF Receptor 1 (VEGFR1)
TH103 leverages 2 key domains from VEGF Receptor 1 (VEGFR1) TH103 aflibercept EXTRACELLULAR DOMAINS EXTRACELLULAR DOMAINS 1 2 3 4 5 6 7 1 2 3 4 5 6 7 VEGFR1 VEGFR1 1 2 3 4 5 6 7 VEGFR2 2 3 Fc Fc 2 3 Fc Both domain sequences are from VEGFR1, fused to IgG Fc. Domain 2 is from VEGFR1, and domain 3 is f
Slide 20: TH103's domain 3 from VEGFR1 has the potential to confer sustained retinal retention
TH103's domain 3 from VEGFR1 has the potential to confer sustained retinal retention, possibly leading to longer treatment effect 2 3 2 3 TH103 Fc Fc aflibercept Fc Domain 3 from VEGFR1: In contrast, domain 3 from VEGFR2: Binds strongly to heparan sulfate Binds less strongly to HSPG, leading to prot
Slide 21: Pre-Clinical Development
Pre-Clinical Development
Slide 22: TH103 achieved 100% inhibition of VEGF-induced endothelial cell proliferation vs. 80% by aflibercept
TH103 achieved 100% inhibition of VEGF-induced endothelial cell proliferation vs. 80% by aflibercept TH103 aflibercept aflibercept: TH103: 80% 100% inhibition inhibition Note: Bovine choroidal endothelial cell proliferation assay; human choroidal endothelial cells proliferate in nAMD pathologic angi
Slide 23: Mouse laser choroidal neovascularization (CNV) model to evaluate anti-VEGF activity
Mouse laser choroidal neovascularization (CNV) model to evaluate anti-VEGF activity The rodent laser-induced CNV Experiment Design model is the most widely used animal model to study the effects Laser of anti-VEGFs in inhibiting CNV • While not a direct model of AMD, this model assesses anti- neovas
Slide 24: TH103 demonstrated increased reduction in mean CNV area at Day -1
TH103 demonstrated increased reduction in mean CNV area after administration at Day -1 at equimolar dosing 1.5 Mean CNV Area (ratio to IgG control) 1.0 Mean CNV Area In a murine model, TH103 showed smaller 0.5 mean CNV area compared to equimolar aflibercept 0.0 Control aflibercept aflibercept TH103
Slide 25: TH103's greater affinity for heparan sulfate proteoglycan may prolong ocular retention
TH103’s greater affinity for heparan sulfate proteoglycan has the potential to prolong its ocular retention HSPG is ubiquitous in the human retina & vitreous1; published third-party preclinical animal model data showed HSPG to be upregulated near growing CNVs2 Adult Human Retina Cross-section1 Domai
Slide 26: TH103 demonstrated increased retention in the retina as compared to aflibercept at two weeks
TH103 demonstrated increased retention in the retina as compared to aflibercept at two weeks Rabbit Retina Cross-Sections at Day 14 TH103 aflibercept Note: Darker immunohistochemistry staining indicates higher drug levels present In a rabbit model, more TH103 remained in the retina 14 days following
Slide 27: Mouse laser CNV model with earlier drug administration to evaluate durability
Mouse laser CNV model with earlier drug administration to evaluate durability of anti-VEGF activity Experiment Design Laser Rather than at Day -1, in this experiment TH103 and aflibercept were administered 14 days prior to laser injury to Day -14 Day 0 Day 7 assess durability of treatment effect TH1
Slide 28: TH103 demonstrated increased duration of action in reducing mean CNV area at Day -14
TH103 demonstrated increased duration of action in reducing mean CNV area after administration at Day -14 1.5 Mean CNV Area (ratio to IgG control) Mean CNV Area 1 In the second murine experiment, T H103 showed smaller mean CNV area 0.5 compared to equimolar aflibercept ^^^ 21 days after injection.
Slide 29: TH103 demonstrated increased duration of action in reducing mean CNV area at Day -14
TH103 demonstrated increased duration of action in reducing mean CNV area after administration at Day -14 Limited Effect on Significant Reduction No Effect on CNV Size CNV Size in CNV Size 29 Control aflibercept (4.8µg) TH103 (4.8µg) Note: TH103 and aflibercept administered 14 days prior to laser in
Slide 30: TH103: potential best-in-class treatment for retinal neovascular / exudative diseases
TH103: potential best-in-class treatment for retinal neovascular / exudative diseases 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 ret
Slide 31: Clinical Development Program
Clinical Development Program
Slide 32: Clinical Development Program Summary
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 ex
Slide 33: Development pipeline aiming to address unmet need in a range of retinal diseases
Development pipeline aiming to address unmet need in a range of retinal diseases Product Indication Discovery IND Enabling Phase 1 Phase 2 Phase 3 Candidate TH103 nAMD TH103 DME / DR* RVO & other TH103 Retinal Diseases* *Subject to IND submission and clearance 33
Slide 34: Corporate
Corporate
Slide 35: Intellectual Property
TH103 Compositions of Matter 1 • 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 2 TH103 Methods of Use Property • Issued/allowed in United States, Europe, Ja
Slide 36: Management and Board with experience developing and commercializing retina therapeutics
Management and Board with experience developing and commercializing retina therapeutics and successfully building biopharma companies Current Current Select Key Accomplishments Board of Directors* Management Team Samir Patel, MD Andrew Oxtoby • Discoverer of VEGF, VEGF receptors, VEGF Exec. Chair an
Slide 37: Potential best in class anti-VEGF therapeutic for common retinal neovascular / exudative diseases
Potential best in class anti-VEGF therapeutic for common retinal neovascular / exudative diseases $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 Ferrara, lead asse
Slide 38: Proposed Merger of Kalaris Therapeutics and AlloVir
Proposed Merger of Kalaris Therapeutics and AlloVir • Merger with Kalaris, a clinical-stage company focused on retinal diseases • Implied ownership split post-combination per the following: o Kalaris: 74.95% / AlloVir: 25.05% (without giving effect to any bridge financing) • Kalaris / AlloVir busine
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