EX-99.1 2 tm2322241d1_ex99-1.htm EXHIBIT 99.1

Exhibit 99.1

Building the Next Immunology Leader Corporate Presentation – July 2023

 

 

©2023 Zura Bio Ltd. This communication includes “ forward - looking statements ” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995 . Words such as “ expect ,” “ estimate ,” “ project ,” “ budget ,” “forecast,” “ anticipate,” “ intend,” “ plan,” “ may,” “ will,” “could,” “should,” “believe ,” “ predict ,” “potential,” “ continue ,” “ strategy ,” “ future ,” “ opportunity ,” “would,” “seem,” “seek,” “outlook” and similar expressions are intended to identify such forward - looking statements . Forward - looking statements are predictions , projections and other statements about future events that are based on current expectations and assumptions and, as a result , are subject to risks and uncertainties that could cause the actual results to differ materially from the expected results . These statements are based on various assumptions , whether or not identified in this communication . These forward - looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability . Actual events and circumstances are difficult or impossible to predict and will differ from assumptions . You should carefully consider the risks and uncertainties described in the “Risk Factors” sections of Zura Bio’s recent filings with the SEC . These filings would identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward - looking statements . Many of these factors are outside Zura Bio’s control and are difficult to predict . Many factors could cause actual future events to differ from the forward - looking statements in this communication , including but not limited to : ( 1 ) the outcome of any legal proceedings that may be instituted against Zura Bio ; ( 2 ) volatility in the price of Zura Bio’s securities ; ( 3 ) the ability of Zura Bio to successfully conduct research and development activities , grow and manage growth profitably , maintain relationships with customers and suppliers , and retain key employees ; ( 4 ) costs related to financing transactions and the ongoing costs relating to operating as a public company ; ( 5 ) changes in the applicable laws or regulations ; ( 6 ) the possibility that Zura Bio may be adversely affected by other economic , business , and / or competitive factors ; ( 7 ) the risk of downturns and a changing regulatory landscape in the highly competitive industry in which Zura Bio operates ; ( 8 ) the impact of the global COVID - 19 pandemic ; ( 9 ) the potential inability of Zura Bio to raise additional capital needed to pursue its business objectives or to achieve efficiencies regarding other costs ; ( 10 ) the enforceability of Zura Bio’s intellectual property, including its patents, and the potential infringement on the intellectual property rights of others , cyber security risks or potential breaches of data security ; and ( 11 ) other risks and uncertainties described in the Registration Statement and such other documents filed by Zura Bio from time to time with the SEC . These risks and uncertainties may be amplified by the COVID - 19 pandemic or other unanticipated global disruption events , which may continue to cause economic uncertainty . Zura Bio cautions that the foregoing list of factors is not exclusive or exhaustive and not to place undue reliance upon any forward - looking statements, including projections, which speak only as of the date made . Zura Bio gives no assurance that it will achieve its expectations . Zura Bio does not undertake or accept any obligation to publicly provide revisions or updates to any forward - looking statements, whether as a result of new information, future developments or otherwise, or should circumstances change, except as otherwise required by securities and other applicable laws . Forward - Looking Statements Disclaimer 2

 

 

©2023 Zura Bio Ltd. 3 ▪ Experienced management team with proven ability to successfully execute and build a leading market position ▪ Multiple Phase 2 ready assets in important, underserved indications including SSc, HS and Asthma ▪ Public on Nasdaq in March 2023 ▪ Well capitalized with > $100M cash,* including $80M PIPE in June ( Deep Track Capital, Great Point Partners, Suvretta Capital, others ) to support development and operations through 2026, including key data readouts © 2023 Zura Bio Ltd. (*) As of July 2023 ABBREVIATIONS: HS, Hidradenitis suppurativa; SSc, Systemic sclerosis

 

 

©2023 Zura Bio Ltd. Experienced management team with proven ability to successfully execute and build a leading market position Verender Badial Chief Financial Officer Someit Sidhu M.D. Chief Executive Officer and Director Chris Cabell M.D. Chief Medical Officer and Head of Research and Development Gary Whale Ph.D. Chief Technology Officer Mike Howell Ph.D. Chief Scientific Officer and Head of Translational Science Kim Davis Chief Legal Officer 4 Amit Munshi Chairman Jennifer Jarrett Director Steve Schoch Director Garry Neil, M.D. Director Parvinder Thiara Director Sandeep Kulkarni, M.D. Director Neil Graham, M.D. Director BOARD OF DIRECTORS

 

 

©2023 Zura Bio Ltd. Sizeable Total Addressable Market Exists Across Number of Validated Mechanisms 5 Sources: Evaluate Pharma. FactSet. Data as of 07/21/23. (1) Assets included in projected TAM: Cosentyx, Taltz, Bimzelx and Siliq (IL - 17), Tezspire (TSLP), Benlysta (BAFF) and itepekimab and tzorakimab (IL - 33). $0 $5B $10B $15B $20B 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 IL - 17 TSLP BAFF IL - 33 Projected TAMs (revenue forecasts for commercial products) (1) Large TAM present a ~$20B opportunity Mechanisms validated across an array of indications

 

 

©2023 Zura Bio Ltd. Clinical stage pipeline targeting key immunology pathways Zura Bio Program Indication Next Clinical Phase Expected Key Milestone Preclinical Phase 1 Phase 2 Phase 3 ZB - 106 tibulizumab Anti - BAFFxIL - 17 Systemic sclerosis Hidradenitis suppurative Initiation of asset transfer Open IND Rheumatology Division Phase 2 initiation ZB - 880 torudokimab Anti - IL - 33 Asthma Transition Asset from Lily Gain FDA feedback on Ph 2/3 design Ph2 initiation* ZB - 168 Anti - IL - 7R Alopecia areata Transition Asset from Pfizer CMC Tech Transfer Ph2 initiation** (*) pending expected phase 2 and 3 external catalysts in Asthma and Chronic obstructive pulmonary disease (COPD) (**) pending expected phase 2 external catalysts in Atopic dermatitis (AD), Ulcerative colitis (UC) and Sjögrens syndrome ( SjS ) Note: Zura Bio development plan(s) subject to review 6

 

 

©2023 Zura Bio Ltd. ZB - 106 is a Potential First - in - Class, Dual Antagonist Combining tabalumab and ixekizumab (TALTZ®) 7 ZURA’S LEAD ASSET Source: 1. Liu et al. 2016. J Inflam Research ; 2. Manetta et al. 2014. J Inflam Research ; 3. Benschop et al. 2019. MAbs IgG - scFv engineered by the fusion of ixekizumab (TALTZ®) and tabalumab 1,2,3 ▪ Neutralizes IL - 17A or BAFF regardless of other binding sites occupancy ▪ Binds to IL - 17 and BAFF similarly to Taltz and tabalumab, respectively ▪ Activity is mediated through direct target engagement and not ADCC ▪ Terminal half - life > 26 days Robust existing clinical and non - clinical data package ▪ Two Phase 1b studies completed by Eli Lilly (RA and Sjögren’s Syndrome) ▪ 78 participants dosed to date Safety profile is consistent with ixekizumab (TALTZ ® ) and IL - 17A class ▪ Chronic toxicity studies completed with no adverse findings Durable and deep IL - 17 and BAFF signaling blockade observed with subcutaneous dosing every 4 weeks ▪ At target Q4W doses BAFF and IL - 17 achieve maximum receptor occupancy Low rate of immunogenicity ▪ Only 1 participant in the MAD study positive for Anti - drug Antibodies (ADAs)

 

 

©2023 Zura Bio Ltd. ZB - 106 Disrupts IL - 17 and/or BAFF - Mediated Inflammation 8 ZB - 106 has the potential to treat diseases driven by B - cell and T - cell signaling POTENTIAL T - CELL AND B - CELL SYNERGY ▪ Multiple T - cell driven diseases remain sub - optimally treated despite the growth in “p ure play” anti - IL - 17 drugs ▪ B - cell driven diseases often have a T - c ell driven autoimmune component contributing to the pathology ▪ Combined approach to address T - cell and B - cell drivers of autoimmunity has the potential to increase clinical benefit Source: 1. Liu et al. 2016. J Inflam Research; 2. Smulski and Eibel . 2018. FrontImmunol BAFF Binds to BAFF trimer and BAFF 60 - mer preventing binding to BAFF - R, TACI, and BCMA 2 IL - 17 Binds to IL - 17A preventing IL - 17A/A and IL - 17A/F heterodimerization 1 Figure Generated with BioRender

 

 

ZB - 106 tibulizumab | Anti BAFFxIL - 17 | Systemic sclerosis (SSc) Potential First - in - Class, Dual Antagonist Combining tabalumab and TALTZ®

 

 

©2023 Zura Bio Ltd. Systemic sclerosis is a rare & life - threatening disease with insufficient therapy available Rare and life - threatening autoimmune disease characterized by tissue inflammation and fibrosis ▪ One of the deadliest of the rheumatic diseases ▪ Associated with severe disability, fibrosis - related organ failure, and premature death - Up to 50% of patients develop interstitial lung disease (ILD), the most common cause of mortality in these patients - Severe impact on patients’ lives with a variable constellation of symptoms, including Raynaud’s phenomenon, arthritis, painfu l u lcers on fingers and toes, thickening and scarring of the skin, shortness of breath, hypertension, and severe fatigue High unmet medical need with insufficient therapy currently available ▪ Standard of care relies on immunosuppression therapy and rather toxic biologic agents ▪ Symptom management with pain relief through nonsteroidal, anti - inflammatory medications or corticosteroids ▪ Two disease - modifying drugs are approved for severe lung complications of the disease (SSc - ILD), but no effective treatment exis ts that combats the disease across organ systems ~200,000 people with SSc in US, EU and Japan 1 40 - 60% mortality in 10 years 2 Zero SSc - specific drugs approved $2B+ annual potential market opportunity 10 Source: Medscape, BMJ best practice 1. Health Advanced, LLC; Lenabasum Commercial Market Assessment 2. Tyndall et al, 2010 3. Bergamasco, A. et al., Clin Epidemiol . 2019 Apr 18;11:257 - 273 4. Zura Bio internal analysis and benchmarking, 5. Internal assumption based on demand research and rare disease analogues

 

 

©2023 Zura Bio Ltd. ZB - 106 is Clinically De - Risked Through P1b 11 78 Participants Dosed Across Three P1/1b studies 57 participants with single dose; 21 participants with multiple dose up to 12 weeks ▪ SAD Studies: No deaths or SAEs ▪ MAD study: No deaths, single related SAE of neutropenia with resolution ▪ Most frequent TEAE: Headache, transient neutropenia, nausea, diarrhea ▪ No TEAE of infection at target doses ▪ In the MAD study, one participant had TE - ADAs detected at a low titer SAFETY and ADA ▪ t 1/2 is 26.9 days ▪ Bioavailability after SC doses was 62.9% ▪ At doses tested there is evidence of maximum target engagement with clinical safety supporting 6 - fold “window” between max target engagement and max human dose tested PHARMACOKINETICS Established dosing regimen ▪ In Ph1b healthy volunteer study in RA participants there was multiple impacts on PD markers: - Decrease in CD20+ B - cells with higher doses generally associated with larger changes from baseline - Decrease in hs - CRP AUC was associated with higher ZB - 106 AUCs PHARMACODYNAMICS Demonstrated PD in participants in ph1b Safety / ADA profile in line with TALTZ® ZB - 106 is a highly validated molecule that enables the opportunity to deliver on the promise of both IL - 17 and BAFF inhibition i n autoimmune disease ABBREVIATIONS: MAD, multiple ascending dose; SAD, single ascending dose

 

 

©2023 Zura Bio Ltd. IL - 17 and BAFF Inhibition Pathways Have Shown Efficacy in Placebo Controlled Trials in Systemic sclerosis (SSc) 12 ZB - 106 has the potential to treat the TH17 and BAFF components of SSc IL - 17 efficacy in SSc ▪ Brodalumab treatment in SSc leads to improved clinical outcomes 1 ▪ IL - 17 known to play key role in the fibrotic process of various organs like lung, kidney, heart and skin ▪ Th17 cell – derived IL - 17 was significantly higher in the skin and serum of SSc patients 2 Role of BAFF in SSc ▪ Belimumab therapy shows efficacy in open label studies and one single center PBO study 3 ▪ Phase 2/3 initiated in SSc - ILD by GSK ▪ SSc patients have B cell abnormalities characterized by chronic hyper - reactivity of memory B cells 4 ▪ BAFF and auto - antibodies are key biomarkers in SSc 5,6 Stromal cells T1 - IFN BAFF Plasma cell CXCR5 + T fh cell TLS GC B cell CXCL13 Source: 1. Fukasawa et al. 2022. AnnalsRheumDisease; 2. Yang et al. Arthritis Research & Therapy 2014 3. Ebata et al. 2021. Lancet Rh eum atol 4.Sato et al. 2004. MolImmunol.; 5. Senecal et al 2020. JSclerodermaRelatDisord; 6. Sato et al. 2000. JImmunol.

 

 

©2023 Zura Bio Ltd. Treatments in SSc have Demonstrated Improved Clinical Outcomes 13 Source: Ebata et al. 2021. Lancet Rheumatol , Gordon et al..2018. ArthRheumatol , Fukasawa et al. 2022. AnnalsRheumDisease ; Gordon et al..2018. ArthRheumatol . CD20+ B cells in HS Lesions Brodalumab IL - 17 receptor antagonist ▪ Achieved primary endpoint of treatment difference of least square mean: −21.2 [95% CI - 23.9, 18.5]; P<0.0001), and demonstrated a rapid, sustained reduction in mRSS over 52 weeks 1 ▪ Demonstrated therapeutic effects on lung/respiratory functions, digital ulcers, the symptoms of gastroesophageal reflux disease, and QOL without noteworthy safety concerns Belimumab BAFF antagonist ▪ 52 - week, investigator initiated, single center, double blind, placebo - controlled pilot study in 20 participants with dcSSC on MMF ▪ No significant difference of AEs in active and placebo arms ▪ Both treatment groups experienced improvements in mRSS favoring belimumab (p=NS) ▪ All secondary endpoints favored belimumab with statistical significance in 2 endpoints: SHAQ DI and VAS Raynaud’s phenomenon ▪ Orphan Drug Designation granted ▪ P 2/3 RCT has been initiated for SSc - ILD Rituximab CD20 B - cell depleter ▪ Multiple Studies demonstrated effectiveness of Rituximab in SSc (mainly open label and observational) ▪ The most compelling data comes from the DESIRES double blind – placebo - controlled trial in 56 pts with SSc1 ▪ Primary endpoint: mRSS change after 24 weeks of treatment ▪ Rituximab - 6.30 points vs. PBO +2.14 points (p < 0.0001) ▪ 48 / 56 participants had SSc - ILD 2.96% FVC improvement at 24 weeks vs. PBO (p=0.04)

 

 

©2023 Zura Bio Ltd. Proposed Phase 2 SSc Trial Design* 14 ▪ mRSS 10 - 29 ▪ Participant presented the first symptoms of sclerosis other than Raynaud's phenomenon within 60 months before enrollment KEY INCLUSION CRITERIA: DOUBLE BLIND, PLACEBO - CONTROLLED TRIAL ~40 participants per arm ZB - 106 DOSE LEVEL 1 ZB - 106 DOSE LEVEL 2 PRIMARY EFFICACY PERIOD (24 WEEKS) PLACEBO R ▪ ACR - CRISS ▪ Change in mRSS ▪ SHAQ DI ▪ VAS (RP, Pain, Ulcers, Breathing) ▪ FVC, DLCO ▪ PK / PD assessments KEY EFFICACY ENDPOINTS: ▪ General Safety and Tolerability ▪ Severe infection ▪ Neutropenia ▪ ADA / nAb KEY SAFETY ENDPOINTS: (*) Trial design is preliminary and subject to change

 

 

ZB - 106 tibulizumab | Anti BAFFxIL - 17 | Hidradenitis suppurativa (HS) Potential First - in - Class, Dual Antagonist Combining tabalumab and TALTZ®

 

 

©2023 Zura Bio Ltd. Overview of Hidradenitis suppurativa (HS) 16 ▪ Hidradenitis Suppurativa is an inflammatory follicular skin disease ▪ Skin lesions develop in axillae, in the groin, and under the breasts, are formed as a result of inflammation & infection of sweat glands and are characterized by: - Recurrent boil - like nodules and abscesses that culminate in pus - like discharge - Difficult - to - heal open wounds (sinuses) and scarring - Increased Th1/Th17 and B cell mediated inflammation 1 - 3 - Disproportionately affects women between adolescent age to 55 years of age 4,5 Estimated ~300K people living with Hidradenitis Suppurativa in the U.S. (1 - 2% global prevalence) Average of 7 years to diagnose globally High unmet need only 1 approved drug Only Humira is FDA - approved in HS CURRENT TREATMENTS ONLY AIM TO MANAGE SYMPTOMS AND INCLUDE PALLI ATIVE CARE SUCH AS OTC EYEDROPS, TOPICAL CYCLOSPORINE AND OFF - LABEL STEROIDS OR IMMUNOSUPPRESSANT S TO MANAGE SYSTEMIC SYMPTOMS DISEASE OVERVIEW CLINICAL OPPORTUNITY Source: 1. Moran et al. JID 2017; 2. Banerjee et al. 2017. Immunol. Invest. ; 3. Sabat et al. JACI 2022; 4. Garg et al. 2017 JAMA Dermat ol; 5. Ingram. 2020. BrJDermatol

 

 

©2023 Zura Bio Ltd. 17 Multiple P3 Studies Shows IL - 17 is Clinically Validated Pathway to Treat HS Phase 2 data show efficacy ceiling may have been reached Fostamatinib data provide evidence of B - Cell importance Sources: Company Presentations, Publications and Research. 1. Represents data from psoriasis trial. 2. Represents safety data from psoriatic arthritis trial. RECENT HS DATA Company (Asset) Humira Cosentyx Bimzelx Bimzelx Sonelokimab Izokibep Fostamatinib Mechanism TNF - α IL - 17 A IL - 17 A/F IL - 17 A/F IL - 17 A/F IL - 17 A/A SYK inhibitor Administration SC SC/IV SC SC SC SC PO Phase PIONEER I & II Phase 3 SUNSHINE & SUNRISE Phase 3 BE HEARD I & II Phase 3 Phase 2 Phase 2 Pase 2b Part A Open - Label Phase 2 Dosing 40mg QW for 12W 30mg Q2W for 16W 320mg Q2W for 16W 320mg Q2W for 12W 120mg Q2W for 12W 160mg QW for 12W 150 mg BID for 12W Total Patients n = 633 n = 360 Est. n = 579 n=88 n=234 n=30 n=20 Efficacy (HISCR50) Non - Placebo Adjusted 42% - 59% 42% - 45% 48% - 52% 63% 66% 71% 85% Placebo Adjusted 16% - 31% 11%+ 19% - 20% 35% 38% N/A N/A Efficacy (HISCR75) Non - Placebo Adjusted N/A N/A 33 - 36% 50% 43% 57% 70% Placebo Adjusted N/A N/A 15% - 20% 29% 29% N/A N/A Safety / Tolerability Most Common AEs Headache 9% - 13% Headache 9% - 12% Hidradenitis 7% - 9% Infections 44% Nasopharyngitis 15% Injection site reactions Nausea 30% Candidiasis 0% 1 0% - 3% 1 4% - 7% 9% 10.5% 0% 2 0%

 

 

©2023 Zura Bio Ltd. Addition of BAFF has Potential to Provide Superior Efficacy to IL - 17 Alone 18 Clinical data in HS ▪ B cell depletion with rituximab provided therapeutic benefit 5 ▪ 4/5 cases report complete remission of HS lesions 5 ▪ Modulating B cell function using fostamatinib (SYK inhibition) provided therapeutic benefit in HS 6 B cell disruption is efficacious in HS BAFF in HS ▪ Increased BAFF expression in HS lesions and tunnels 2 - 4 ▪ Lesional upregulation of BAFF and BAFF receptors is attributed to B cells and plasma cells 2,4 ▪ Neutralization of BAFF with a soluble variant of BAFF - R in HS lesional explants reduced the expression of key genes associated with B and plasma cell function 2 BAFF gene expression in HS B - cells in HS lesions ▪ HS lesions have increased numbers of CD20+ B and CD138+ Plasma Cells 1 ▪ B - cell activating factor (BAFF) is produced by B cells, macrophages, dendritic cells, and neutrophils ▪ BAFF regulates B - cell survival, maturation and differentiation CD20+ B cells in HS Lesions Source: Van der Zee et al. 2012. Br J Derm ; 2 Rumberger et al. 2020. J Inflam Research; 3.Sabat et al 2022. JACI; 4. Gudjonsson et al. 2020. JCI Insight.; 5. Seigel et al 2023. JCutanMedicSurgery ; 6. Jepsen et al. 2023. JAAD Week 12 % Achieving HiSCR50 % Achieving HiSCR75 Fostamatinib (SYK inhibition) 6 85% 70% Izokibep (IL - 17) 3 71% 57%

 

 

©2023 Zura Bio Ltd. Dermal Tunnels: Role in HS Pathogenesis ▪ Recent literature highlights the role of dermal tunnels in the pathogenesis of HS 1,2 ▪ The presence of dermal tunnels increased the amount of time needed to achieve HiSCR50 with adalimumab 3 ▪ One significant drawback of the HiSCR is the lack of a dynamic measurement of draining tunnel; therefore, not fully capturing the anti - inflammatory properties of a therapeutic ▪ Dermal tunnels in HS are characterized by increased numbers of neutrophils and B cells; and Sabat et al. demonstrated increased BAFF production by neutrophils 2,4 ▪ The International Hidradenitis Suppurativa Severity Score System (IHS4) was developed to assess inflammatory nodules (1 point), abscesses (2 points) and draining tunnels (4 points) 19 Treatment with fostamatinib (SYK Inhibitor) significantly reduced IHS4 scores and draining tunnel counts 5 Source: Frew et al. 2021 Clin Exper Derm; 2. Sabat et al JACI 2023; 3. Moran et al. JID 2017; 4. Gudjonsson et al. 2020; 5. Jepsen et a l. 2023. JAAD

 

 

©2023 Zura Bio Ltd. Proposed Phase 2 HS Trial Design* 20 ▪ Moderate to Severe HS ▪ Hurley Stage II/III ▪ Total abscess and inflammatory count (AN) ≥ 3 KEY INCLUSION CRITERIA: DOUBLE BLIND, PLACEBO - CONTROLLED TRIAL ~40 participants per arm ZB - 106 DOSE LEVEL 1 ZB - 106 DOSE LEVEL 2 PRIMARY EFFICACY PERIOD (16 WEEKS) PLACEBO R ▪ HiSCR (50, 75, 100) ▪ Improvement in baseline AN counts ▪ IHS4 ▪ PGA ▪ DLQI ▪ PK / PD assessments KEY EFFICACY ENDPOINTS: ▪ General Safety and Tolerability ▪ Severe infection ▪ Neutropenia KEY SAFETY ENDPOINTS: (*) Trial design is preliminary and subject to change

 

 

ZB - 168 Anti - IL - 7R | Alopecia areata (AA) A Potential Best - in - Class Anti - IL - 7R Inhibiting Both IL - 7 and TSLP Pathways

 

 

©2023 Zura Bio Ltd. 22 ZB - 168 – Asset Overview Source: 1. doi : 10.1038/s41467 - 018 - 06804 - y, 2. 10.1172/jci.insight.126054, 3. Clinical study report, 4. doi:10.3389/fimmu.2020.01557, 5. https ://www.frontiersin.org/articles/10.3389/fimmu.2020.01557/full, 6. Herold, K. C. et a. JCI Insight. 2019; 4(23):e126054. 7. doi : 10.1056/NEJMoa2034975 ABOUT ZB - 168 ▪ IL - 7Rα implicated in two key immune pathways 1 : IL - 7 and TSLP ▪ Only anti - IL - 7R program to date with human clinical data showing impact on key T - cell sub - populations 2 ▪ Well tolerated in >90 participants and patients dosed in Phase 1 studies conducted by Pfizer 2, 3 ▪ Utility in multiple T - cell driven diseases 4 ▪ 91 subjects dosed to date MECHANISM OF ACTION ▪ Inhibition of IL - 7Rα blocks both IL - 7 and TSLP signaling 5 ▪ Blocking IL - 7Rα selectively inhibits survival/activity of effector memory and central memory CD4 and CD8 T cells while preserving the T regs compartment 1, 5 ▪ T cell transcriptomics show downregulation of genes associated with activation, differentiation and trafficking of Th1, Th2 and Th17 6 ▪ Blocking TSLP reduces Asthma exacerbations in both Th2 high and low populations 7 INDICATION AREAS OF POTENTIAL INTEREST ▪ Respiratory ▪ Dermatologic ▪ Gastrointestinal MARKET OPPORTUNITY ▪ Advances in the field further validate IL - 7 and TSLP in multiple type Th1 & Th2 immune disorders with significant global opportunities ▪ Potential 1st - in - class opportunities within several indications

 

 

©2023 Zura Bio Ltd. 23 TSLP and IL - 7 have a Broad Impact on Epithelial - Driven Inflammation TSLP AND IL - 7 PATHWAYS • Thymic stromal lymphopoietin (TSLP) is an epithelial - derived cytokine primarily expressed in the lungs, skin and gastrointestinal tract 1 • TSLP is released from the epithelium by disease exacerbating environmental factors and is an important amplifier of Th2 immune response, including the production of IL - 4, - 5, - 9 and - 13. 1 • TSLP inhibition is clinically validated in severe asthma and has shown positive therapeutic benefit in additional Th2 driven diseases 2,3 • IL - 7 is a growth factor that binds to the heterodimeric receptor of IL - 7R:gC and is critical for the survival, development and homeostasis of central and effector memory T cells 4 • Due to the high expression of IL - 7R on T eff compared to T reg , inhibition results in a 20 - fold greater activity in reducing T eff , leading to an increase in Treg:Teff ratio 5, 6 • Dual inhibition of TSLP and IL - 7 has potential to modulate Th1, Th2, and Th17 - driven inflammation in a targeted manner across a broad number of allergic and autoimmune diseases 7 Source: 1. Ebina - Shibuy , 2022. Nat Rev Immunol, 2. Marone , 2019. Expert Opin Investig Drugs, 3. Menzies - Gow , 2020. Respir Res, 4. Chen, 2021. Frontiers Immunol, 5. Herold, 2019 JCI Insight, Graphic created in BioRender ; 5. doi.org/10.3389/fimmu.2018.02692, 6. doi.org/10.1016/j.isci.2020.101421, 7. https://www.frontiersin.org/articles/10.3389/fimm u.2 020.01557/full

 

 

©2023 Zura Bio Ltd. ZB - 168 is Potentially Best - in - Class Asset at TSLP Inhibition 24 ZB - 168 (IL - 7R α ) UPB - 101 ( α - TSLPR) Tezepelumab (TSLP) ADX - 914 (IL - 7R α ) IL - 7R α mAb α - TSLPR mAb TSLP mAb IL - 7R α mAb TSLP - Induced Signals ▪ 7.5 ng/ml / 0.05nM (CCL17) (1) ▪ 11 ng/ml / 0.07nM (CCL22) (1) ▪ 0.08 nM (CCL2) (4) 16.1 ng/ml / 0.1nM (CCL17) (3) 67 ng/ml / 0.44nM (CCL17) (3) 24 nM ( CCL2 ) (4) IL - 7 - Induced Signals 0.46nM (pSTAT5) (2) Neg Neg ▪ 0.6 nM (IL - 7 at 0.25ng/ml) (4) ▪ 2.1nM (IL - 7 at 2.5ng/ml) (4) ▪ ZB - 168 is nearly 10 - fold more potent than AZ/AMG’s tezepelumab , and tezepelumab does not inhibit IL - 7 signaling ▪ ZB - 168 is > 300 - fold more potent than Q32Bio / Horizon’s ADX - 914 in TSLP - induced markers, but similar in IL - 7 - induced pSTA5 4 Source: 1. Zura Internal Data, 2. doi : 10.1172/jci.insight.126054, 3. doi : https://doi.org/10.1124/jpet.121.000686, 4. BMS patent https://patents.google.com/patent/WO2020154293A1/en % inhibition of TSLP stimulated CCL17 secretion from human monocytes ZB - 168 Anti - TSLPR IgG Tezepelumab % inhibition log (nM)

 

 

©2023 Zura Bio Ltd. ZB - 168 is Impactful on T effector Memory Cells 25 Source: 1. doi : 10.1172/jci.insight.126054, 2. doi:10.1208/s12248 - 019 - 0401 - 3 CLINICAL DATA IN PARTICIPANTS DEMONSTRATES IMPACT ON KEY T - CELL SUBPOPULATIONS CD8+ T effector cells 1 Dose 1 Dose 2 Dose 3 Dose 4 ▪ Dose dependent response in impact on T - cells ▪ Up to 70% reduction in CD8+ T effector memory cells ▪ Similar reductions seen for naïve and central memory T - cells Ratio of T reg to T effector cells 2 Dose 1 Dose 2 Dose 3 ▪ Increases in ratios observed for all doses tested ▪ ZB - 168 shows 20x greater potency for T effector memory vs T reg cells ▪ Observed increase in the Treg:TEM ratio may shift the balance from autoimmunity towards immune tolerance

 

 

ZB - 880 torudokimab | Anti - IL - 33 | Asthma A Potential Best - in - Class Anti - IL - 7R Inhibiting Both IL - 7 and TSLP Pathways

 

 

©2023 Zura Bio Ltd. 27 ZB - 880 Asset Overview About ZB - 880 (torudokimab) ▪ IL - 33 implicated in driving Th2 biology through ST2 and Th1/Th17 through alternative signaling 1 ▪ Well tolerated in Ph1 and Ph2 trials conducted by Eli Lilly 2 - 141 healthy volunteers in Ph1 study - 103 participants with moderate to severe atopic dermatitis in Ph2 - A nalyses confirmed key biomarker reductions (IL13, periostin and CCL17/TARC) and no ADA impact 3 - Potential utility in diseases driven by epithelial inflammation 1 ▪ The target engagement evaluation suggested binding to IL - 33 and treatment emergent ADA had no apparent impact on PK or target engagement Mechanism of Action ▪ Inhibition of IL - 33 blocks both ST2 and RAGE signaling 4 Initial Focus on Respiratory, Dermatologic, Gastrointestinal and Orphan Autoimmune Indications ▪ Potential for 1st - in - class opportunities ▪ Validated pathways in COPD4 and asthma 5 Source: 1. Cohen et al. 2015 Nature, 2. https://clinicaltrials.gov/ct2/show/NCT03913260; https://clinicaltrials.gov/ct2/show/NCT03343 587 ; https://clinicaltrials.gov/ct2/show/NCT03831191, Section 6.1, DSUR for period 23 - Sep - 2019 to 22 - Sep - 2020, 3. doi.org/10.1111/bjd.21631 4. Okragly et al Journal of Inflammation Research 2021:14 3823 – 3835, 5.. doi:10.1056/NEJMoa2024257

 

 

©2023 Zura Bio Ltd. 28 ZB - 880 IL - 33 Pathway IL - 33 PATHWAY ▪ IL - 33 is a member of the IL1 cytokine family that is constitutively expressed in structural and lining cells including fibroblasts, endothelial, and epithelial cells of skin, gastrointestinal tract, and lungs 1 ▪ IL - 33 is released from the epithelium by disease exacerbating environmental factors and is an important amplifier of innate inflammation during exacerbations 2 ▪ Polymorphisms in IL - 33 and ST2 are associated with increased eosinophil production as well as respiratory diseases such as COPD and severe asthma. ▪ IL - 33 inhibition clinically validated in severe asthma, COPD 3 , and subsets of other epithelial disorders 4 ▪ Pre - clinical data demonstrates superior activity of torudokimab compared with etokimab suggesting the potential for best - in - class activity 5 ▪ Emerging biology suggests expanding opportunity for IL - 33 in fibrotic and autoimmune conditions 6 Source: 1. Chan, 2019. Frontiers Immunol, 2. doi.org/10.1016/j.cyto.2022.155891, 3. https://doi.org/10.1038/ng.323 and doi:10.1016/j. jac i.2020.04.051 , 4. .:https://doi.org/10.1016/S2213 - 2600(22)00005 - 4; doi:10.1056/NEJMoa2024257 and doi : 10.1126/scitranslmed.aax2945 , 5. Sci Trans Med., Zura Bio Internal data, 6. doi : 10.1111/imm.12174; https://doi.org/10.3389/fphys.2021.781012 and https://doi.org/10.3389/fmed.2021.739489

 

 

©2023 Zura Bio Ltd. ZB - 880 Has Potential for “Best - in - Class” Activity 29 Antibody k on (M - 1 s - 1 ) k off (s - 1 ) k d ( pM ) Torudokimab Potency torudokimab (LY3375880) 1.7 x 10 6 6.7 x 10 - 5 39 etokimab ( AnaptysBio ) 9.4 x 10 5 1.2 x 10 - 4 112 2.9x itepekimab (Regeneron) 7.6 x 10 5 1.6 x 10 - 4 215 5.5x Torudokimab was 2.9 and 5.5 - fold more potent than etokimab and itepekimab , respectively, inhibiting IL - 33 - induced GM - CSF production by human mast cells Source: Zura Bio Internal data

 

 

©2023 Zura Bio Ltd. 30 Financial Summary and Milestones CASH, CASH EQUIVALENTS & INVESTMENTS $118.2 million 1 MARKET CAP $398 million 2 TOTAL SHARES OUTSTANDING Fully Diluted, incl warrants, options 1 66,765,163 1 COVERING ANALYSTS Yatin Suneja , Guggenheim Securities Steven Seedhouse, PhD , Raymond James Matthew Barcus , PhD , Chardan (1) Pro - forma adjusted for $80m private placement. Source: S - 1 filling 21st July 2023: https://www.sec.gov/Archives/edgar/data/1 855644/000110465923083115/tm235378 - 3_s1a.htm (2) Closing price $6.62/ share (as of 26 - Jul - 2023) , fully diluted share outstanding incl. warrants Zura Bio Program Indication Expected Key Milestone ZB - 106 tibulizumab Anti - BAFFxIL - 17 Systemic sclerosis Hidradenitis suppurative Initiation of asset transfer Open IND Rheumatology Division Phase 2 initiation ZB - 880 torudokimab Anti - IL - 33 Asthma Transition Asset from Lily Gain FDA feedback on Ph 2/3 design Ph2 initiation* ZB - 168 Anti - IL - 7R Alopecia areata Transition Asset from Pfizer CMC Tech Transfer Ph2 initiation** (*) pending expected phase 2 and 3 external catalysts in Asthma and Chronic obstructive pulmonary disease (COPD) (**) pending expected phase 2 external catalysts in Atopic dermatitis (AD), Ulcerative colitis (UC) and Sjögrens syndrome ( SjS ) Note: Zura Bio development plan(s) subject to review

 

 

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