Zenas Biopharma, Inc. · NASDAQ:ZBIO
Zenas Biopharma — Investor Presentation (December 2024)
36 slides from Zenas Biopharma's investor presentation, Dec 2, 2024
Slide 1: Zenas BioPharma Corporate Presentation December 2024
1 Zenas BioPharma Corporate Presentation December 2024 Enabling patients with autoimmune diseases to reimagine life
Slide 2: Disclaimer
2 Disclaimer FORWARD - LOOKING STATEMENTS This presentation contains “forward - looking statements” which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from antici
Slide 3: Disclaimer continued
3 Disclaimer continued MARKET AND INDUSTRY DATA Unless otherwise indicated, market and industry data contained in this presentation, including potential commercial opportunities, is based on the Company’s management’s estimates and research, as well as industry and general publications and research
Slide 4: Zenas: Creating a global, immunology-based development and commercial company
4 Immunology Focus Pipeline ad dressing significant unmet needs for patients with autoimmune disease, the 2 nd largest pharmaceutical category Franchise Molecule Obexelimab is a potentially differentiated B cell therapeutic in development for IgG4 - RD, RMS, SLE, which combined represents a potentia
Slide 5: Accomplished Executive Team
5 Accomplished Executive Team Extensive experience developing and commercializing biopharmaceuticals Allen Poma, MD SVP, Clinical Development Gan Wei SVP, Global Technical Operations Lonnie Moulder CEO & Chairman Joe Farmer President & COO Jennifer Fox CBO & CFO COLLECTIVELY, ZENAS MANAGEMENT HAS: •
Slide 6: Zenas 2024 achievements towards creating a leading global I&I company
6 Zenas 2024 achievements towards creating a leading global, I&I development and commercial company » Completed upsized $200M Series C and $259M IPO, financing Zenas through value - driving Phase 2 and Phase 3 data readouts » Completed targeted enrollment in obexelimab Phase 3 INDIGO trial for IgG4
Slide 7: Obexelimab: Rapidly building a global franchise
7 NEXT MILESTONE TRIAL/STATUS INDICATION PROGRAM Phase 3 topline results end of 2025 Phase 3 INDIGO trial enrolled 2,3 IgG4 - RD (Immunoglobulin G4 - Related Disease) Obexelimab 1 CD19xFc ƴ RIIb Bifunctional mAb Primary endpoint (12 - week) data Q3:25 Phase 2 MoonStone trial enrolling 3 RMS (Relapsi
Slide 8: Obexelimab clinical development outcomes
8 Outcome Description • Demonstrated proof - of - mechanism SAD HV, safety and PK Phase 1 1 • Proof - of - mechanism and clinical activity established • Day 85 (all dose levels): ACR20: 78%, ACR50: 33%, ACR70: 14% 3 MAD Rheumatoid Arthritis (RA) Phase 1b/2a 2 • Clinical activity established; rapid d
Slide 9: Targeting CD19 offers broad coverage of B cell lineage
9 Targeting CD19 offers broad coverage of B cell lineage 1 1 Adapted from I. Abeles, B Cell - Directed Therapy in Autoimmunity, Annual Review of Immunology 2024 Bone marrow Periphery & tissue Pro - B cell Pre - B cell Immature B cell Mature B cell Memory B cell Plasmablast Plasma cell Bone marrow CD
Slide 10: B cell responses are naturally downregulated through FcγRIIb binding
10 B cell responses are naturally downregulated by immune complexes through Fc ƴ RIIb binding B cell responses orchestrate humoral immunity Immune complex binding to Fc ƴ RIIb naturally downregulates B cell responses Source: Zenas BioPharma
Slide 11: Obexelimab: a differentiated B cell targeted agent
11 Obexelimab: a differentiated B cell targeted agent Broader B cell inhibition, tissue penetrance, and non - depleting MoA provide clear differentiation » Fc γ RIIb broadly expressed across B cell lineage , including pro - B cells, pre - B cells, B cells, plasmablasts and select plasma cells 1 • Ob
Slide 12: Rapid and broad inhibition of B cell response after obexelimab administration
12 Rapid and broad inhibition of B cell response after obexelimab administration in clinical trials S ource: Perugino et al. (2023) Lancet Rheumatol 5: e442 Supplement pBTK = phosphorylated Burton’s tyrosine kinase Fold - change in the induction of pBTK with anti - IgG/IgM treatment before and after
Slide 13: Obexelimab inhibits B cell cytokine production without depletion
13 Obexelimab inhibits B cell cytokine production, and B cell activation in tissue without depletion Non - depletion of tissue B cells by obexelimab Inhibition of tissue B cell activation by obexelimab Mice were treated with XENP8206 (obexelimab surrogate mAb) for 7 days after which blood LN and spl
Slide 14: Obexelimab reduces antigen uptake by human B cells
14 Obexelimab reduces antigen uptake by human B cells Unt Obx +CTRL Unt Obx Unt Obx + CTRL = positive control (cytochalasian D); Obx = obexelimab; Unt = untreated Follicular B cells Marginal Zone B cells B1 B cells +CTRL +CTRL Source: Zenas and Kerfoot Lab collaboration, unpublished
Slide 15: Dose selection: Higher PK correlates with greater clinical activity
15 Dose selection: Higher PK ( C trough ) correlates with greater clinical activity as observed in Phase 2 SLE Study 4 th Quartile 3 rd Quartile 2 nd Quartile 1 st Quartile Placebo Portion of patients without loss of improvement (flare) by C trough quartile C trough Quartile (5 mg/kg IV) 4 th 3 rd 2
Slide 16: Obexelimab dose selection for IgG4-RD Phase 3 INDIGO Trial
16 Obexelimab dose selection: 250 mg SC QW selected for IgG4 - RD Phase 3 INDIGO Trial 375 mg SC Q2W 250 mg SC Q2W 250 mg SC QW 1 125 mg SC QW 5 mg/kg IV Q2W 22.2 14.7 24.8 13.6 105 Mean C max (µg/mL) 6.6 4.0 17.1 8.8 ~3.0 Mean C trough (µg/mL) 4,720 3,095 7,375 3,600 8,000 Mean AUC µg/mL*h) ( norma
Slide 17: Obexelimab: IgG4-RD
17 Obexelimab: IgG4 - RD
Slide 18: IgG4-RD disease overview
18 Disease Overview: • IgG4 - RD may present with single or multi - organ involvement, and as disease progresses patients experience new or worsening symptoms ( e.g., flare). E arly inflammatory disease state moves to a fibrotic stage, which can lead to major irreversible tissue damage and organ fai
Slide 19: Phase 2 IgG4-RD trial: rapid remission and durable responses
19 Phase 2 IgG4 - RD trial: Obexelimab induced rapid remission of active flares and maintained durable responses Source: Perugino CA et al. Lancet Rheumatol. 2023; Carruthers MN et al. Ann Rheum Dis. 2015 RI=responder index Note: No comparative head - to - head trials were conducted GC=glucocorticoi
Slide 20: Phase 2 IgG4-RD results: rapid, robust, sustained reduction in disease activity
20 Obexelimab: Phase 2 IgG4 - RD results demonstrated rapid, robust, and sustained reduction in IgG4 - RD disease activity • Primary Endpoint: Proportion of patients on Day 169 with a decrease in IgG4 - RD RI ≥2 points » 100% of patients who completed trial met primary endpoint ▪ No flares or steroi
Slide 21: Strong rationale for obexelimab in IgG4-RD
21 Strong rationale for obexelimab in IgG4 - RD 1 Company estimate based on disease prevalence and those patients estimated to require maintenance treatment and potential pric ing of advanced therapies De - risking of Phase 3 trial design based upon the results of the Phase 3 MITIGATE trial with Upl
Slide 22: Phase 3 INDIGO IgG4-RD trial enrollment complete
22 Phase 3 INDIGO IgG4 - RD trial enrollment complete INDIGO Trial Summary: • Design: Randomized, double - blind, placebo controlled • Treatment: weekly obexelimab 250mg subcutaneous or placebo control; GC taper to 0 mg by week 8 • Primary endpoint: Time to disease flare through week 52 • Secondary
Slide 23: Obexelimab: Multiple Sclerosis
23 Obexelimab: Multiple Sclerosis
Slide 24: Multiple Sclerosis: a debilitating chronic neuroinflammatory disease
24 Multiple Sclerosis: a debilitating chronic neuroinflammatory disease characterized by flares and disability progression Disease Overview: • C haracterized by demyelinating lesions of the CNS. Symptoms include sensory and visual disturbances, coordination impairment and spasticity, fatigue, pain,
Slide 25: Strong rationale for obexelimab in MS
25 Potential for i mproved impact on “smoldering” disease (i.e., PIRA 2 ) through broader B cell coverage with CD19 and continuous drug exposure via SC self administration Continuous inhibition of B cell s, including in tissue Potential for l ess risk of opportunistic infection and ability to vaccin
Slide 26: Obexelimab surrogate suppressed disease activity in EAE model without B cell depletion
26 Obexelimab surrogate mAb suppressed disease activity in EAE model without B cell depletion vs. an anti - CD20 depleting mAb 0 1 2 3 4 5 0 5 10 15 20 25 30 Vehicle (n=3) Obexelimab surrogate (n=6) Rituximab surrogate (n=7) Days post MOG Injection p<0.05 Clinical Score (Mean+/ - SD) 0 10 20 30 40 5
Slide 27: Phase 2 MoonStone RMS trial enrolling
27 Phase 2 MoonStone RMS trial enrolling Gold - standard design with MRI measurements; highly predictive of successful outcome in large randomized trials SCREENING Active RMS ( relapsing remitting MS or relapsing secondary progressive MS) : • EDSS <5.5 * Open label extension 2:1 Obexelimab Q1W (n=58
Slide 28: Obexelimab: Systemic Lupus Erythematosus
28 Obexelimab: Systemic Lupus Erythematosus
Slide 29: Systemic Lupus Erythematosus: a debilitating chronic autoimmune disease
29 System Lupus Erythematous (SLE): a debilitating chronic autoimmune disease that attacks healthy tissue Disease Overview: • SLE is a complex, chronic autoimmune disease characterized by unpredictable flares in joints, skin, kidneys and other vital organs that cause progressive organ damage. Comorb
Slide 30: Strong rationale for obexelimab in SLE
30 Strong rationale for obexelimab in SLE Currently approved therapies (Benlysta ® (belimumab) and Saphnelo ® (anifrolumab) are considered to have modest efficacy (effect sizes of 12 - 17% over placebo on SRI - 4/BICLA assessments) SLE is estimated to be a ~$9 billion 1 commercial opportunity in the
Slide 31: Potential for improved clinical activity with optimized dosing regimen
31 Potential for improved clinical activity with an optimized obexelimab dosing regimen Higher clinical activity observed with optimized exposure, and in biomarker positive population 17% 35% 52% 0% 10% 20% 30% 40% 50% 60% Intention - to - treat population 3 Optimized exposure population 4 Biomarker
Slide 32: Phase 2 SunStone SLE trial enrolling
32 Phase 2 SunStone SLE trial 1 enrolling Designed to confirm obexelimab activity in all - comer and biomarker populations SCREENING Active SLE: • BILAG ≥1A or ≥2B • SLEDAI ≥6 • PI confirmation Stable steroids Placebo Q1W for 24 weeks (n= 95 ) Follow - up 1:1 Obexelimab Q1W for 24 weeks (n= 95 ) GC
Slide 33: Obexelimab: warm Autoimmune Hemolytic Anemia (wAIHA)
33 Obexelimab: warm Autoimmune Hemolytic Anemia (wAIHA)
Slide 34: Preliminary results from Phase 2 SApHiAre trial (wAIHA)
34 Preliminary results from Phase 2 open label SApHiAre trial (wAIHA) Open Label Safety and Dose Confirmation Run - In Period (SRP) SCREENING • Primary or secondary wAIHA • Failed 1 prior therapy • Hgb ≥7 to <10 g/dL Obexelimab 250 mg weekly SC administration for 24 weeks » Nine patients (8 patients
Slide 35: Obexelimab demonstrated improvement in anemia in patients with wAIHA
35 Obexelimab demonstrated improvement in anemia and corresponding markers in patients with wAIHA • 5 of 8 patients achieved Hgb increase ≥ 1 g/dL over baseline during Week 8 - 24, without influence of concomitant medication • A Hgb increase of ≥ 2 g/dL measured from Hgb nadir to peak observed in 5
Slide 36: Obexelimab, an I&I franchise molecule
36 Obexelimab, an I&I franchise molecule Deeply experienced team Well - funded through results of ongoing obexelimab clinical trials Zenas: Creating a global, immunology - based development and commercial company * Company estimate based on disease prevalence and pricing of advanced therapies within
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