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1 Zenas BioPharma Corporate Presentation May 2025 Enabling patients with autoimmune diseases to reimagine life
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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 anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include statements concerning Zenas’s plans, objectives, expectations and intentions; its future financial or business performance; the timing and results of ongoing and future clinical trials and potential regulatory approval and commercialization; its ability to identify strategic partners for its pipeline programs; the potential commercial opportunities for its product cand idates; the potential competition for its product candidates; the potential commercial attributes for its product candidates; the Company’s cash estimate at March 31, 2025 and cash guidance. The forward-looking statements in this presentation speak only as of the date of this presentation and are subject to a number of known and unkno wn risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losse s for the foreseeable future; and the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy an d expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any sig nificant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology comp anies, many of which already have approved therapies in the Company’s current indications; the Company’s ability to realize the benefits of the Company’s current or fut ure collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, and the risk that any such approval may be for a more narrow indication than the Company seeks; and other risks and uncertain ties described in the section “Risk Factors” in the Company’s Quarterly Report for the three months ended March 31, 2025, and subsequent reports filed with the SEC. The forward -looking statements in this presentation are inherently uncertain and are not guarantees of future events. Because forward -looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, you should not unduly rely on these forward-looking statements. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. MARKET AND INDUSTRY DATA: Unless otherwise indicated, market and industry data contained in this presentation, including potential commercial opportuni ties, is based on the Company’s management’s estimates and research, as well as industry and general publications and research and studies conducte d by third parties. Although the Company believes that the information from these third-party publications, research and studies included in this presentation is reliable, the Co mpany has not independently verified the accuracy or completeness of this information. Management’s estimates are derived from publicly available information, their knowledge of the Company’s industry and their assumptions based on such information and knowledge, which the Company believes to be reasonable. This data involves a number of assumptions and l imitations and the industry in which the Company operates is subject to a high degree of uncertainty and risk due to a variety of factors. TRADEMARKS: This presentation may include references to the Company’s trademarks and trademarks belonging to other entities. The Zenas Bi oPharma word mark, logo mark, and the “lightning bolt” design are trademarks of Zenas BioPharma, Inc. or its affiliated companies. Solely for convenience, some of the trademarks and trade names referred to in this presentation, including logos, artwork and other visual displays, may be listed without the ® or symbols, but such references are not intended to indicate in any way that Zenas will not assert, to the fullest extent under applicable law, Zenas’s rights or the rights of the applicable licensor to these trademar ks and trade names.
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3 Potentially highly differentiated I&I franchise molecule Obexelimab is the first bifunctional B cell targeting (CD19 x FcγRIIb) antibody in a Phase 3 trial (IgG4-Related Disease), and randomized Phase 2 trials (RMS and SLE), which represent a potential multi-billion-dollar commercial opportunity1 Well-funded into Q4:26 through meaningful Phase 3 and Phase 2 readouts Q1 2025 cash of approximately $314M2 Zenas: Creating a global, immunology-based development and commercial biotechnology company Enabling patients with autoimmune diseases to reimagine life 1Company estimate based on disease prevalence and pricing of advanced therapies within indication 2Q4:26 cash guidance is based on Company’s expectation Global capabilities and experienced Team Established global development and regulatory capabilities led by a team with a history of successful product approvals and commercial launches
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4 B cell targeting is clinically and commercially validated for multiple autoimmune diseases Normal Immune Response: • B cells provide protective immunity against infectious agents through: • Antibody and cytokine production • Activation of T cells through antigen presentation and co-stimulation • B cells evolve into plasma blasts and plasma cells, which produce large volumes of antibodies Autoimmune Disease: • B cells recognize self-antigens as foreign • Autoreactive B cells produce antibodies against healthy tissue resulting in inflammation, cell destruction, and tissue damage which can manifest as severe symptoms and lead to organ failure • Inflammation and cell destruction are further exacerbated by B cell-mediated T cell activation • Approved B cell therapies targeting CD20 or CD19 depend upon ADCC/CDC to kill/deplete B cells, which may be less efficient in tissue; dosing may not be optimal, and with the potential for an unfavorable safety profile ADCC/CDC= antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity
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5 Obexelimab’s B cell inhibition has the potential to achieve optimum disease control for autoimmune diseases Obexelimab Maintain effective disease control through potent inhibition of broad B cell lineage in tissue Once-weekly, self-administered, subcutaneous injection Potentially favorable safety profile related to infections and response to vaccination
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6 Obexelimab’s differentiated profile positions it well to potentially impact a variety of I&I diseases Consideration obexelimab CD19/20 Depletors (e.g. Rituxan, Uplizna) T Cell Engagers/Bispecifics Cell Therapy (CAR-T) Mechanism of action (inhibition vs. depletion) ✓ Potent B cell inhibition, including in tissue B cell depletion in blood, less in tissue Expected to have more effective B cell depletion than CD19/20 depletors Profound B cell depletion in tissue Durability of response ✓ Sustained B cell inhibition intended to maintain disease remission via weekly dosing Complete remission rates decrease as B cells reconstitute toward end of dosing intervals Expected to be equivalent or better durability than CD 19/20 depletors Profound B cell depletion expected to have durable response Safety and Tolerability ✓ Potential for lower infection rates & ability to vaccinate B cell depletion can lead to higher rates of infection/inability to vaccinate In addition to infection risk & inability to vaccinate, potential for CRS/ICANS Expected to have increased toxicity risks Dosing/Administration ✓ Convenient weekly at-home administration/much lower patient burden IV administration requires pre-treatment at an infusion center/increased infusion reaction risk SC administration unlikely and monitored administration likely Complex manufacturing and administration limited to specific CAR-T centers Market Access/reimbursement ✓ Part D drug means potential lower out of pocket costs for patients Part B drugs may result in significantly higher out of pocket costs for patients Part B drugs may result in significantly higher out of pocket costs for patients Significant cost, logistical and access challenges Obexelimab’s unique profile as a potent B cell inhibitor may position it as a potential front-line therapy ahead of B cell depletors Obexelimab is an investigational drug. No head-to-head comparative studies were conducted CRS=cytokine release syndrome, ICANS= immune effector cell-associated neurotoxicity syndrome
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7 Obexelimab: A potentially differentiated B cell targeted therapy 1Chu et al. Molecular Immunology 2008 & Zenas data on file 2Szili et al. mAbs 2014 3Chu et al. Journal of Translational Autoimmunity 2021 4Chu et al. Arthritis & Rheumatology 2014 Source: Zenas BioPharma • FcγRIIb mimics natural antigen-antibody complex for potent inhibition of B cells • Obexelimab binding affinity for human FcγRIIb increased approximately 230-fold relative to human native IgG1 due to Fc engineering2 • Engineered to avoid ADCC / CDC-mediated depletion; non- reliance upon the presence of immune effector cells • Impacts antibody production, proliferation, cytokine secretion, and antigen presentation to T cells • Continuous exposure results in inhibitory activity within tissue Obexelimab co-engagement of CD19 and FcγRIIb results in an inhibitory effect, rather than direct depletion1,2,3,4
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8 Targeting CD19 and FcγRIIb provides broad coverage of B cell lineage1 • CD19 and FcγRIIb broadly expressed across B cell lineage, including pro-B cells, pre-B cells, B cells, plasmablasts and select plasma cells1 Bone marrow Periphery & tissue Pro-B cell Pre-B cell Immature B cell Mature B cell Memory B cell Plasmablast Plasma cell Bone marrow FcƴRIIb (obexelimab) CD19 (obexelimab) CD20 BAFF BCMA 1Abeles et al. Annual Review of Immunology 2024; Verbeek et al. Front. Immunol 2019
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9 B cell responses are naturally downregulated by immune complexes through FcƴRIIb binding B cell responses orchestrate humoral immunity Immune complex binding to FcƴRIIb naturally downregulates B cell responses Source: Zenas BioPharma Obexelimab or
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10 Rapid and broad inhibition of B cell response after obexelimab administration in clinical trials Source: 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 treatment with obexelimab Ex Vivo Stimulated CD86 Expression Source: Wang, X. American College of Rheumatology 2022 poster presentation Rapid inhibition following a single obexelimab dose Potent inhibition across multiple B cell subtypes 0 1 0 1 -50 -25 0 25 50 75 100 % Inhibition Stimulated CD86 Expression ObexelimabPlacebo Day following a single 5 mg/kg dose in HVs Naive B cells Switched Memory B cells Unswitched Memory B cells Fold change in pBTK 0 2 4 6 Pre Post P=0.003 0 2 4 6 Pre Post P=0.005 0 2 4 6 8 Pre Post P=0.049
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11 Obexelimab inhibits B cell cytokine production, and B cell activation in tissue without depletion Non-depletion of tissue B cells by obexelimab surrogate Inhibition of tissue B cell activation by obexelimab surrogate Mice were treated with XENP8206 (obexelimab surrogate mAb) for 7 days after which blood LN and spleen B cells evaluated by flow cytometry; B cells were harvested from mice treated with XENP8206 and stimulated with IgM. B cell activation was evaluated using calcium mobilization assays (average of 5 experiments shown); Adapted from Chu et al. Journal of Translational Autoimmunity 2021. Modified from Szili et al. (2014) mAbs 6 (4): 991–99 BCR = B cell receptor; aBCR = anti-BCR stimulation; CpG = unmethylated cytosine-guanine; IL = interleukin; stim = stimulation; TNF = tumor necrosis factor; Obexelimab reduction of cytokine production from human B cells TNF-α IL-6 Pg/ml Untreated Obexelimab 0 1000 2000 p < 0.05 0 50 100 150 200 250 300 350 p < 0.05 0K 40K 80K 120K 160K 200K Intracellular calcium release (Fluo4 MFI) Lymph node Spleen p < 0.005 p < 0.05 0 5 10 15 20 Number of B Cells (x102 blood, 105 LN, 106 spleen) Lymph node Spleen n.s. Blood n.s. = B cells from control treated mice = B cells from obexelimab surrogate treated mice = Control treated mice = Obexelimab surrogate treated mice n.s. = not significant
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12 Obexelimab reduces antigen uptake by human B cells + CTRL = positive control (cytochalasian D); Obx = obexelimab; Unt = untreated Source: Zenas and Kerfoot Lab collaboration, unpublished Follicular B cells Marginal Zone B cells B1 B cells 0.0 0.2 0.4 0.6% B cells with internalized beads Unt Obx +CTRL 0.0 0.5 1.0 1.5 2.0 2.5% B cells with internalized beads Unt Obx +CTRL 0 5 10 15 20 25 30 % B cells with internalized beads Unt Obx +CTRL * * * ns * ns
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13 Obexelimab demonstrated clinical activity in multiple, completed clinical trials SAD = Single Ascending Dose, HV = Healthy Volunteers, PK = Pharmacokinetics, MAD = Multiple Ascending Dose 1Wang, X. American College of Rheumatology 2022 poster presentation 2Wang, X. American College of Rheumatology 2023 poster presentation 3Jaraczewska-Baumann et al EULAR 2015 poster presentation (obexelimab efficacy at all dose levels) 4Perugino, C. et al. Nature Reviews Rheumatology. 16, 702–714 (2020) 5Merrill, J. et al. Arthritis and Rheumatology. Vol. 75, 2185-2194 (2023) 6Wang, X. Japan College of Rheumatology 2023 oral presentation Trial Stage Description Outcome Phase 11 SAD HV, safety and PK • Demonstrated proof-of-mechanism Phase 1b/2a2 MAD Rheumatoid Arthritis (RA) • Proof-of-mechanism and clinical activity established • Day 85 (all dose levels): ACR20: 78%, ACR50: 33%, ACR70: 14%3 Phase 24 Pilot Study IgG4-Related Disease • Clinical activity established; rapid disease response (mean of 21 days), and sustained response achieved in 93% of patients Phase 25 Randomized Controlled Systemic Lupus Erythematosus (SLE) • Clinical activity established • Primary endpoint effect size of 17% for ITT population; 35% effect size for population with optimal exposure level (Ctrough) • Biomarkers potentially predictive of obexelimab response identified Phase 16 Bioequivalence HV, Subcutaneous (SC) versus Intravenous (IV) dosing • Established subcutaneous formulation with improved tolerability, and potential for optimized drug exposure (Ctrough)
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14 Optimized dose selected as higher PK (Ctrough) correlated with greater clinical activity in Phase 2 SLE Study 4th Quartile 3rd Quartile 2nd Quartile 1st Quartile Placebo Portion of patients without loss of improvement (flare) by Ctrough quartile Source: Wang, X. Japan College of Rheumatology 2023 oral presentation Clinical activity Obexelimab 250 mg SC QW dose expected to maximize the potential for clinical activity by 1) providing higher Ctrough and 2) maintaining a comparable AUC from an efficacious dose of 5 mg/kg IV Q2W Obexelimab concentration (µg/mL) 1st 2nd 3rd 4th Mean 1.2 2.3 3.8 6.0 Min 0.18 1.8 2.8 5.1 Max 1.8 2.8 4.7 8.0
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15 Obexelimab dose: 250 mg SC weekly selected for all clinical trials 1From PK simulation at the steady-state Source: Zenas BioPharma Starting point: Maximum PD in Phase1 HV SAD and Phase 2 IgG4-RD with 5 mg/kg IV Q2W 5 mg/kg IV Q2W 125 mg SC QW 250 mg SC QW 250 mg SC Q2W 375 mg SC Q2W Mean Cmax (µg/mL) 105 13.6 24.8 14.7 22.2 Mean Ctrough (µg/mL) ~3.0 8.8 17.1 4.0 6.6 Mean AUC µg/mL*h) (normalized to a same 14-day dose interval) 8,000 3,600 7,375 3,095 4,720 • Compared with 5 mg/kg IV Q2W, 250 mg SC QW can provide: • Optimal PK (higher Ctrough) and comparable AUC to maintain target engagement to potentially enhance clinical activity • ~4x lower Cmax to improve safety and tolerability
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16 • Scientific merit examples: Role of B cells in disease pathogenesis, prior preclinical or clinical data supporting activity of B cell therapies • Regulatory merit examples: Ease/clarity of regulatory path, validated endpoints, trial size and duration etc. • Commercial merit examples: Level of unmet need, epidemiology, competition, pricing etc. Development strategy: fast-to-market orphan indication followed by expansion into additional autoimmune diseases >40 indications initially considered for development Assessed based on scientific, regulatory, and commercial merit 6 indications selected for detailed evaluation; first 3 prioritized for clinical development; Multiple indications ongoing assessment IgG4-RD RMS SLE Others ongoing Obexelimab indication strategy encapsulated a “total business view” including scientific, clinical/regulatory and commercial assessments
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17 Obexelimab’s differentiated profile potentially positions it to be a market-leading therapy for multiple I&I diseases Indication Immunoglobulin G4 Related Disease (IgG4-RD) Multiple Sclerosis (RMS, PPMS) Systemic Lupus Erythematosus (SLE) Market Size ~20,000-40,000 patients (US) ~20,000-40,000 patients (EU) ~650,000 patients (US) ~670,000 patients (EU) ~150,000 patients (US) ~170,000 patients (EU) Commercial Insights Diagnosed patient population expected to increase with introduction of first approved therapies, validating targeting B cells via CD19 as a highly effective treatment mAbs targeting B cells are well validated and represent the leading therapeutic category (>$9 billion). Self administered SC dosing and non- depleting mechanism highly desired Tremendous need for new therapeutics that provide greater efficacy than currently approved agents in a >$8 billion market Obexelimab is well-positioned as a potential first-in-class B cell inhibitor across I&I indications Obexelimab Opportunity Currently 10,000+ patients could benefit from continuous therapy in the US alone, representing a ~$3 Billion US market Obexelimab has the potential to provide a front-line, convenient alternative to intermittently-dosed B cell “depletors” Existing obexelimab clinical data indicate the potential for the current dosing regimen to provide differentiated clinical benefit in SLE Obexelimab represents a potential multi-billion dollar franchise molecule across I&I indications
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18 Obexelimab: Multiple upcoming Phase 2 and Phase 3 data readouts 1Zenas acquired exclusive worldwide rights to obexelimab from Xencor, Inc. 2Bristol Myers Squibb & Co. holds exclusive development and commercialization rights in JPN, SK, TWN, HK, SGP, AUS 3Randomized versus placebo Program Indication Trial/Status Next Milestone Obexelimab1 CD19 x FcƴRIIb Bifunctional mAb IgG4-RD (Immunoglobulin G4-Related Disease) Phase 3 INDIGO trial enrolled2,3 Phase 3 topline results Expected around year end 2025 RMS (Relapsing Multiple Sclerosis) Phase 2 MoonStone trial enrolling3 Primary endpoint (12- week) data Expected early Q4 2025 SLE (Systemic Lupus Erythematosus) Phase 2 SunStone trial enrolling3 Primary endpoint (24- week) data Expected mid-2026
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19 Obexelimab: IgG4-RD
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20 Disease Overview: • Presents with single or multi-organ involvement • As disease progresses patients experience new or worsening symptoms (e.g., flare) • Early inflammatory disease state moves to a fibrotic stage, which can lead to major irreversible tissue damage and organ failure Pathophysiology: • Expansion of CD19+ and IgG4+ B cells and plasmablasts with tissue infiltration • These cells produce IgG4 and inflammatory cytokines, and activate T cells through antigen presentation exacerbating inflammation & fibrosis Patient Population: • We estimate the prevalence of IgG4-RD patients in the U.S. is approximately 20,000 to 40,000, and approximately 20,000 to 40,000 collectively in the UK, Germany, France, Italy, and Spain alone2 Frequent Occasional Infrequent KIDNEY FOCAL MASSES BILE DUCT STRICTURES LUNG MASSES AND NODULES, BRONCHIAL WALL THICKENING THYROID GLAND ENLARGEMENT LACRIMAL ENLARGEMENT PACHYMENINGES DIFFUSE THICKENING ORBITAL MASSES, EXTRA- OCULAR MUSCLE MYOSITIS MAJOR SALIVARY GLAND ENLARGEMENT PANCREAS ENLARGEMENT, DIABETES, EXOCRINE INSUFFICIENCY SOFT TISSUE MASS ENCASING THE ANTEROLATERAL AORTA AORTA WALL THICKENING 1Perugino, C. et al. Nature Reviews Rheumatology. 16, 702–714 (2020); Zhang, W & Stone, J. Lancet Rheumatology. 1(1), E55-E65 (2019); Mattoo et al J Allergy Clin Immunol. 2014; UpToDate 2Wallace et al 2023 and Zenas BioPharma research IgG4-RD: A debilitating chronic fibro-inflammatory disease affecting multiple organ systems1
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21 Glucocorticoids (GCs, e.g., prednisone) for 2–4 weeks followed by taper Current treatments are suboptimal due to relapse and long-term toxicities Obexelimab Opportunity Use of GCs and rituximab off-label are suboptimal due to: • High relapse rate for first line therapy; 40–50% will fail to completely remit or relapse within a year1-6 • 30–40% experience relapse following rituximab7,8 • Rituximab and GC toxicities including infection, and metabolic/endocrine complications1-3 • Reimbursement hurdles; no randomized controlled studies conducted with rituximab9 First-line agent for remission induction Treatment of flares 1Khosroshahi A, et al. Arthritis Rheumatol. 2015;67(7):1688-1699. 2Chen Y et al. Chin Med J (Engl). 2022;135(4):381-392. 3Masaki Y et al. J Clin Exp Hematop. 2014;54(2):95-101. 4Perugino CA et al. Nat Rev Rheumatol. 2020 Dec;16(12):702-714. 5Yunyun F et al. Sci Rep. 2017;7(1):6195. 6Yunyun F et al. Rheumatology (Oxford). 2019;58(1):52-60. 7Wallace et al. Rheumatology. 2016. 8 Ebbo et al. PLOS ONE 2017. 9Orozco-Galvez, et al. Autoimmun Rev. 2023:22(3):103273 and Zenas market research. 10Conventional drugs include cyclophosphamide, mycophenolate mofetil, azathioprine, mercaptopurine, methotrexate Patients with asymptomatic and symptomatic disease require treatment to reduce flares and prevent irreversible organ damage and complications Additional cycles of GCs ± steroid-sparing agents including conventional drugs and rituximab10
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22 Patients with IgG4-RD will likely experience continued flares despite first-line treatment 1Perugino, C. et al. Nature Reviews Rheumatology. 16, 702–714 (2020) 2As measured by secondary endpoints in ongoing Phase 3 INDIGO trial Repeated disease flares can damage new or existing disease sites1 Subclinical inflammatory processes left untreated can lead to fibrosis and irreversible organ damage1 Obexelimab once-weekly, self-administered, subcutaneous injection could potentially address the underlying disease burden2 = Flare Underlying disease burden Disease course over time ACR/EULAR threshold of 20 points for classification of IgG4-RD
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23 • Induction and Maintenance • 100% of patients who completed trial met primary endpoint2 • No flares or steroid use after Day 57 • 93% with ongoing response at end of trial • 80% with prior rituximab achieved complete remission • Well tolerated; most frequent AEs were IV infusion-related gastrointestinal events; three SAEs were not considered to be related to obexelimab Obexelimab: Phase 2 IgG4-RD results demonstrated rapid, robust, and sustained reduction in IgG4-RD disease activity1 Rapid and sustained IgG4-RD RI response 0 5 10 15 20 25 30 1 15 29 57 85 113 141 169 197 Completed Early termination obexelimab 5mg/kg IV Q2W x 12 doses (N=15) IgG4-RD RI Day 1Perugino et al. Lancet Rheumatology 2023. Open-label, single-arm Phase 2 PoC trial in 15 obexelimab-treated patients with moderate to severe disease as induction and maintenance, one or more organ systems involved and an IgG4-RD Responder Index (RI) of ≥ 3 2Primary endpoint: proportion of patients on Day 169 with a decrease in IgG4-RD RI > 2 points
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24 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 Note: No comparative head -to-head trials were conducted GC=glucocorticoid; RI=responder index Obexelimab (5mg/kg q14d x 12) Rituximab (1000 mg q15d x 2) Design Phase 2 single-arm, open label (n=15) Phase 2 single-arm, open label (n=30) Baseline characteristics RI score (12.0) Number of organs involved (4.0) RI score (11.0) Number of organs involved (3.5) Primary endpoint: decline of IgG4-RD RI > 2 points, no flares before month six, no GCs between two to six months 12/15 (80%) 23/30 (77%) GC use through 6 months (after tapering) 0 3/30 (10%) Sustained disease response 13/14 (93%) responders had ongoing response at month 6 22/30 (73%): Improvement of IgG4-RD RI > 2 points for 6 months Mean time to disease response (days) 21 43 Relapse within 6 months 1/15 (6.7%) 3/30 (10%)
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25 1Stone, DH et al. Inebilizumab for Treatment of IgG4-Related Disease. NEJM, November, 2024. MoA = mechanism of action; RoA = route of administration; RCP = Randomized controlled period INDIGO and MITIGATE trial designs substantially similar INDIGO (obexelimab) MITIGATE1 (Uplizna®) MoA B cell inhibitor B cell depletor RoA and frequency, dose 250 mg SC weekly PFS / auto-injector 300 mg IV on Day 1& Day 15→ Q6M Number of countries 20 22 Number of sites ~100 80 Trial design RCP 52 weeks; plus OLE RCP 52 weeks; plus OLE Number of patients ~190 135 Primary endpoint Time to first flare (Adjudicated/Investigator) Time to first flare (Adjudicated/Investigator) Results Expected around year-end 2025 87% reduction in IgG4-RD flare risk at 52-weeks compared to placebo (HR = 0.13, p < 0.001) 90% flare free at week 52, yet only 57% in flare-free, treatment-free complete remission at week 52 (p<0.001)
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26 INDIGO Trial Summary: • Design: Randomized, double-blind, placebo controlled • Treatment: weekly obexelimab 250 mg subcutaneous or placebo control; GC taper to 0 mg by week 8 • Primary endpoint: Time to disease flare through week 52 • Secondary endpoints include: 52-week flare rate, Achievement of complete remission, Use and quantity of rescue medication, Change in GC-associated toxicity as measured by the Glucocorticoid Toxicity Index (GTI) Phase 3 INDIGO IgG4-RD trial enrollment complete Trial of over 190 patients, the largest ever conducted, with topline results expected around year-end 2025 SCREENING • 20-60 mg GC Tx for flare • 20mg GC at trial entry Placebo Q1W for 52 weeks (n=~100) Open label extension 1:1 Obexelimab Q1W for 52 weeks (n=~100) GC taper to 0mg by week 8 GC taper to 0mg by week 8 1Stone, et al. Inebilizumab for Treatment of IgG4-Related Disease. NEJM. Nov 2024. GC = glucocorticoid 60% PBO rate for MITIGATE a derisking event for INDIGO assumptions1
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27 Patient preference for more convenient dosing and less out of pocket expense Patient preference for SC versus IV therapies in Autoimmune diseases1 2025 updates cap out-of-pocket expenses to Medicare Part D drugs Allen et al 2010 Borruel et al 2015 Dashiell-Aje et al Falanga et al 2019 Fernandes et al 2015 (SC user) Grisanti et al 2019 Kariburyo et al 2017 Perez et al 2017 Scarpato et al 2010 Van Deen et al 2020 100% 50% 0% 50% 100% Favors IV Favors SC 1Overton, et al. Patient Preference and Adherence 2021:15 811–834 2Assuming 3 vials for first-year of Uplizna dosing at WAC per 10ml/100mg, 1 vial = $137,095.29 (as of 1/6/25) • Provisions from the Inflation Reduction Act (IRA) of 2022 that take effect in 2025 cap an individual’s out-of-pocket expense for drugs covered under Medicare Part D at $2,000 per calendar year • Out-of-pocket expenses for intravenously administered drugs such as Uplizna and as covered under Medicare Part B potentially meaningfully higher than for Part D2
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28 Obexelimab potential differentiation in the evolving IgG4-RD treatment landscape Obexelimab potential attributes support its differentiation in the IgG4-RD treatment landscape • Potential to achieve higher complete remission rates • Possibility for fewer rates of severe/opportunistic infections and ability to vaccinate/treat serious infections • Anticipate no premedication required/no risk of infusion-related reactions • Patient preference for at home, subcutaneous injection • Possibility for lower out-of-pocket expense (Medicare Part D vs. B)
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29 Obexelimab represents a compelling $1billion+ commercial revenue opportunity in the U.S. alone Estimated U.S. prevalence: 30-40K Current U.S. diagnosed prevalence:~20K Treated with frontline Tx (steroids and non-steroidal immunosuppressants): ~20K Stable remission: ~8K-10K Chronic disease ~10K-12K ✓ Diagnosed prevalence for IgG4-RD expected to increase with introduction of first approved therapies ✓ Attractive orphan pricing creates a market opportunity of ~$3 billion in the U.S. alone ✓ Similar prevalence and potential for orphan pricing in Europe creates a similar multi-billion market opportunity in addition to the U.S. ✓ Zenas team has extensive track record successfully building commercial organizations and launching drugs in the U.S. and Europe Currently diagnosed patients eligible for maintenance therapies = $3 billion U.S. market opportunity at orphan pricing
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30 Obexelimab: Multiple Sclerosis
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31 Multiple Sclerosis: A debilitating chronic neuroinflammatory disease characterized by flares and disability progression Disease Overview: • Characterized by demyelinating lesions of the CNS. Symptoms include sensory and visual disturbances, coordination impairment and spasticity, fatigue, pain, weakness, and cognitive deficits • Three major forms: relapsing MS (RMS), secondary progressive (SPMS), and primary progressive (PPMS). RMS is characterized by episodes of neurological dysfunction (relapses) followed by complete or incomplete recovery ➢ Disability progression can occur independently of relapse activity; referred to as “smoldering” disease and can be measured clinically (PIRA) Pathophysiology: • B cells, including plasmablasts and plasma cells, represent the predominant cell type in meningeal inflammation Patient Population • ~650K diagnosed prevalent patients in the U.S. and ~670K diagnosed prevalent patients in major EU countries PIRA = Progression Independent of Relapse Activity T cells B cells Activated microglia Activated AstrocytesPlasmablasts Proinflammatory cytokine release Plasma cells Demyelination Axonal / neuronal loss Activation causes inflammation cascade, creates chronic inflammation
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32 B cell targeted treatments dominate RMS commercial landscape 1Source: 2024 Roche, Novartis, and TG Therapeutics company reports and SEC filings Note: All other therapies include Mavenclad, Tecfidera, Vumerity, Zeposia, Gilenya, Aubagio, Ponvory $- $2,000 $4,000 $6,000 $8,000 $10,000 $12,000 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 Ocrevus Kesimpta Briumvi Tysabri All other $-000s CD20 depleting B cell therapies Ocrevus® (ocrelizumab), Kesimpta® (ofatumumab), and Briumvi® (ublituximab) dominate RMS 50–60% current market share >$9Billion1 combined annual revenue
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33 Obexelimab’s attributes for potential success in RMS 1Chen, et al. J Immunol, 15 February 2016;196(4): 1541-1549 PIRA = progression Independent of Relapse Activity • Obexelimab’s co-engagement of CD19 and FcƴRIIb generates broader B cell lineage targeting than CD20 depleting mAbs Ocrevus® (ocrelizumab) and Kesimpta® (ofatumumab), which dominate the RMS market • Plasmablasts and plasma cells (not targeted by CD20-directed therapies) are implicated in MS pathogenesis1 • Co-engagement of CD19 and FcƴRIIb targets plasmablasts and subset of plasma cells, and has the potential to directly target innate cells • Obexelimab weekly subcutaneous dosing could avoid “wearing-off” symptoms associated with anti-CD20 dosed on a semi-annual basis and improve impact on “smoldering” disease (i.e., PIRA) • Potential for lower long-term side effects and ability to vaccinate patients • Superior activity of obexelimab in a preclinical MS model vs. depletion comparator Obexelimab potential attributes support its differentiation in the MS treatment landscape
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34 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 50 Vehicle Obexelimab Surrogate mAb p< 0.0001 Percent B cells of total lymphocytes at day - 5) EAE = Experimental Autoimmune Encephalomyelitis huFcγRIIb transgenic mice (human FcγRIIb knock-in). Obexelimab and anti-CD20 mAb dosed 10 mg/kg intraperitoneally 2x per week beginning day -7 continuing through day 24. Whole blood Immunophenotyping performed at day -5 by flow cytometry to measure percent B cells. Disease induction: Human MOG protein in Complete Freund’s Adjuvant administered on day 0 followed by pertussis toxin at days 0 and 3. Daily clinical scores measured from day 2 through day 27; mice sacrificed at clinical score of 4 Anti-CD20 mAb Anti-CD20 mAb EAE: a gold-standard nonclinical model for assessing autoimmune-mediated CNS disease
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35 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=62) *EDSS 5.5 = disability severe enough to preclude full daily activities. Able to walk without aid or rest for 100m Placebo Q1W (n=31) Obexelimab Q1W Week 12 Primary endpoint: Number of new T1Gd-enhancing lesions Week 24 Additional endpoints: including disease progression endpoints Week 12 Week 24 MoonStone Trial Summary: • Design: Double-blind, randomized, placebo controlled with placebo crossover at week 12 • Treatment: obexelimab 250mg SC weekly vs. placebo control (first 12 weeks) • Primary endpoint: Number of new T1 Gd-enhancing lesions at week 12 • Secondary endpoints: Utilizing standardized assessments, imaging and biomarkers to evaluate impact on disease progression/silent progression • 90% power to detect 90% reduction in T1-Gd lesions vs. placebo at week 12
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36 Obexelimab: Systemic Lupus Erythematosus
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37 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. Comorbidities, such as infections, malignancies, hypertension, lipid disorders and diabetes increase risk of patient disability and death Pathophysiology: • B cell dysfunction resulting in abnormal regulation of immune responses and the production of autoantibodies toward cellular and nuclear components results in tissue inflammation and multi-organ damage Therapeutic Opportunity • GC and immunosuppressants are the mainstay of treatment, only two moderately effective therapies are approved for moderate-to-severe disease 1 • Long-term GC use and irreversible organ damage has been reported to be a predictor of morbidity and mortality in SLE 2 Patient Population • ~150K patients in the U.S. and ~170K patients in major EU countries Alopecia Malar rash Glomerulonephritis Arthritis Pulmonary interstitial lung disease and fibrosis Congestive heart failure Anemia, leukopenia, thrombocytopenia 1BENLYSTA® and SAPHNELO® 2Pawlak-Buś, K. Current treatment of systemic lupus erythematosus: a clinician's perspective. Rheumatology Int. 2023
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38 Potential for improved clinical activity with an optimized obexelimab dosing regimen 17% 35% 52% 0% 10% 20% 30% 40% 50% 60% Intention-to-treat population1 Optimized exposure population2 Biomarker positive population3 Patients at W32 without loss of improvement (∆" vs. PBO") Source: Merrill et al. Arthritis Rheumatol. 2023 1Defined as all randomized patients receiving at least one dose of study medication 2Ctrough Quartiles 3 & 4 in efficacy evaluable analysis 3Biomarker positive defined as patients in predefined lupus phenotypic gene expression clusters 3 & 6 (~38% of evaluated population) Higher clinical activity observed with obexelimab in a Phase 2 trial with optimized exposure, and in biomarker positive population Screening Placebo IV Q2W for 32 weeks (n=52)1:1 Obexelimab 5mg/kg IV Q2W for 32 weeks (n=52) • Current approved therapies demonstrate modest effect sizes of 12–17% over placebo on SRI-4/BICLA assessments
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39 Primary Endpoint: Reduction of SLE disease activity at week 24 by BILAG-Based Composite Lupus Assessment (BICLA) Phase 2 SunStone SLE trial1 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-up1:1 Obexelimab Q1W for 24 weeks (n=95)GC taper to ≤5 mg by week 12 GC taper to ≤5 mg by week 12 1Double-blind, randomized, placebo-controlled • SC dosing to improve PK (steady state Ctrough above Phase 2 top (4th) quartile for all patients) • Powered on appropriate placebo response and effect size assumptions • Strict adjudication for eligibility and assessment (moderate/severe patients only); strict corticosteroid tapering rules to reduce placebo responses Incorporates learnings from previous Phase 2 trial to increase POS
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40 Strategic collaboration with Bristol Myers Squibb Exemplifies ability to transact on high-quality partnerships to maximize obexelimab’s commercial potential x • BMS has rights to develop and commercialize obexelimab in Japan, South Korea, Taiwan, Singapore, Hong Kong and Australia • $50M up front • $20M equity investment (Series C) • Development milestones in the tens of millions (covers obligations to Xencor plus a margin for Zenas) • Royalties cover obligations to Xencor plus a low single digit percentage margin for Zenas • Standard commercial/net sales milestones cover obligations to Xencor plus a margin for Zenas • BMS is funding a portion of the costs of the INDIGO Phase 3 trial in IgG4-RD in proportion to patients enrolled in their territory up to a cap and will do the same for any other registrational trial that it elects to participate in their territories
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41 Accomplished Executive Team Extensive experience developing and commercializing biopharmaceuticals Haley Laken, Ph.D. CSO Lonnie Moulder CEO & Chairman Joe Farmer President & COO Jennifer Fox CFO & CBO COLLECTIVELY, ZENAS MANAGEMENT HAS: • 70+ IND filings • 30+ BLA/NDA filings • 30+ Commercial product launches • Deep experience across numerous biotech and pharmaceutical companies Caroline Chevalier CHRO Orlando Oliveira CCO Jeff Held CLO Lisa von Moltke, M.D. Head of R&D & CMO
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42 Obexelimab, an I&I franchise molecule Obexelimab is a potentially differentiated B cell therapeutic in development for IgG4-RD, RMS and SLE, each representing a potential multi-billion-dollar commercial opportunity1 Multiple upcoming Phase 2 and Phase 3 data updates expected Obexelimab Phase 3 pivotal trial results expected for INDIGO (IgG4-RD) around year-end 2025, Phase 2 results for MoonStone (RMS) early Q4 2025 and Sunstone (SLE) mid-2026 Deeply experienced team Record of strong operational results: multiple clinical, regulatory and commercial successes Well-funded through results of ongoing obexelimab clinical trials Q1 2025 cash of approximately $314M; capitalized for clinical data readouts into Q4:262 Zenas: Creating a global, immunology-based development and commercial biotechnology company Enabling patients with autoimmune diseases to reimagine life 1Company estimate based on disease prevalence and pricing of advanced therapies within indication 2Q4:26 cash guidance is based on Company’s expectation