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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

 

Form 8-K

 

 

 

Current Report

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

 

September 9, 2024

Date of Report (Date of earliest event reported)

 

 

 

Zura Bio Limited

(Exact name of registrant as specified in its charter)

 

Cayman Islands   001-40598   98-1725736
(State or other jurisdiction of
incorporation)
  (Commission
File Number)
  (I.R.S. Employer
Identification No.)

 

1489 W. Warm Springs Rd. #110

Henderson, NV 89014

(Address of principal executive offices,

including zip code)

 

(702) 825-9872

(Registrant’s telephone number, including area code)

 

(Former name or former address, if changed since last report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class   Trading Symbol(s)   Name of each exchange on which registered
Class A Ordinary Shares, par value $0.0001 per share   ZURA   The Nasdaq Stock Market
         
Warrants, each whole warrant exercisable for one Class A Ordinary Share at an exercise price of $11.50 per share   ZURAW   The Nasdaq Stock Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

 

 

 

Item 7.01 Regulation FD Disclosure.

 

On September 9, 2024, Zura Bio Limited (“ZURA”, the “Company”) provided an updated corporate presentation that may be used in connection with presentations at conferences and investor meetings. The full text of the Company’s corporate presentation is filed as Exhibit 99.1 hereto, and incorporated herein by reference, and may also be accessed through the “News & Events” section of the Company’s website at investors.zurabio.com.

 

The information furnished under this Item 7.01, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, or subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, or the Securities Act. The information in this Item 7.01, including Exhibit 99.1, shall not be deemed incorporated by reference into any other filing with the SEC, made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

 

Item 9.01. Financial Statements and Exhibits

 

(d) Exhibits.

 

Exhibit No. Description
99.1 Corporate presentation, dated September 9, 2024
104 Cover Page Interactive Data File (embedded within the Inline XBRL document)

 

 

 

 

 SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

  ZURA BIO LIMITED
   
Date: September 9, 2024 By: /s/ Kim Davis
    Kim Davis
    Chief Legal Officer

 

 

 

 

Exhibit 99.1

 
 

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©2024 Zura Bio Ltd. Nasdaq Ticker: ZURA Three Unique Dual-Pathway Biologics, Clinically Validated for Therapeutic Areas with Unmet Needs September 2024

 

 

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©2024 Zura Bio Ltd. 2 Forward Looking Statements Disclaimer 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 the negatives of such terms 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 forward-looking statements may include, but are not limited to: expectations with respect to development and regulatory plans, trial designs, and the costs, timing and results thereof; expectations with respect to milestones and key events, including the timing of study initiation and completion; expectations with respect to Zura Bio’s development program, including clinical trials and the timing thereof, and expectations with respect to development programs, data readouts and product candidates of other parties; Zura Bio's cash resources and projected cash runway; the potential to raise additional capital to support the company's operations; the potential of pipeline assets to offer broader and improved clinical responses; expectations with respect to addressable markets, projected CAGRs and patient populations; and expectations with respect to the use of proceeds from any financing transactions. 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 are difficult or impossible to predict and could differ materially from those expressed or implied in such forward-looking statements, as a result of these risks and uncertainties, which include, but are not limited to: the potential of Zura Bio's product candidates and their related benefits, competing product candidates and products both in development and approved; Zura Bio's vision and strategy; the timing of key events and initiation of Zura Bio's studies and release of clinical data may take longer than anticipated or may not be achieved at all; the potential general acceptability and maintenance of Zura Bio's product candidates by regulatory authorities, payors, physicians, and patients may not be achieved; Zura Bio's ability to attract and retain key personnel; Zura Bio's future operating expenses, capital requirements and needs for additional financing may not be achieved; Zura Bio has not completed any clinical trials, and has no products approved for commercial sale; Zura Bio has incurred significant losses since inception, and expects to incur significant losses for the foreseeable future and may not be able to achieve or sustain profitability in the future; Zura Bio requires substantial additional capital to finance its operations, and if it is unable to raise such capital when needed or on acceptable terms, Zura Bio may be forced to delay, reduce, and/or eliminate one or more of its development programs or future commercialization efforts; Zura Bio may be unable to renew existing contracts or enter into new contracts; Zura Bio relies on third-party contract development manufacturing organizations for the manufacture of clinical materials; Zura Bio relies on contract research organizations, clinical trial sites, and other third parties to conduct of its preclinical studies and clinical trials; Zura Bio may be unable to obtain regulatory approval for its product candidates, and there may be related restrictions or limitations of any approved products; Zura Bio may be unable to successfully respond to general economic and geopolitical conditions; Zura Bio may be unable to effectively manage growth; Zura Bio faces competitive pressures from other companies worldwide; Zura Bio may be unable to adequately protect its intellectual property rights; and other factors set forth in documents filed, or to be filed by Zura Bio, with the SEC, including the risks and uncertainties described in the “Risk Factors” section of Zura Bio's Annual Report on Form 10-K for the year ended December 31, 2023 and other filings with the SEC. These risks and uncertainties may be amplified by health epidemics 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 we will achieve our 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. This presentation discusses product candidates that are under clinical study, and which have not yet been approved for marketing by the US Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. Caution should be exercised when comparing data across trials of different products and product candidates. Differences existing between trial designs and patient populations and characteristics. The results across such trials may not have interpretative value on Zura Bio’s existing or future results. Statements included herein concerning clinical trials for the product candidates have not been reviewed or endorsed by Eli Lilly ("Lilly") or Pfizer. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

 

 

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zurabio.com Company Summary 2022 2023 2024 Nasdaq: ZURA Zura founded as a limited company incorporated under the laws of England and Wales crebankitug in-licensed from Pfizer torudokimab in-licensed from Eli Lilly and Co. Began trading on Nasdaq under “ZURA” ticker tibulizumab in-licensed from Eli Lilly and Co. $80M private placement closed Rob Lisicki and Dr. Kiran Nistala join Zura Bio Executive Leadership Formed SAB Inclusion into the Russell 2000® and 3000® Indexes Arnout Ploos van Amstel joined Board Entered into sponsored research agreement with Benaroya Research Institute $112.5M private placement closed Completed IPO warrants exchange, simplifying share capital structure (*) Studies conducted by Pfizer and Eli Lilly & Co. Sources: Zura Bio Press Releases and Filings Acronyms: HS, hidradenitis suppurativa; Q, quarter; SAB, scientific advisory board; SSc, systemic sclerosis ©2024 Zura Bio Ltd. High-Potential Biologics: Three novel, clinically validated* dual-pathway biologics, each targeting multi-billion-dollar markets, advancing towards Phase 2 trials Lead Asset Development: Tibulizumab Phase 2 study for SSc expected to commence in 4Q 2024, with a subsequent trial for HS anticipated in 2Q 2025 Strategic Milestones: Anticipating 2 key internal catalysts and up to 11 external readouts over the next 36 months, with potential to significantly drive value creation Proven Leadership: An experienced team with a demonstrated history of driving over $8 billion in mergers and acquisitions within the last three years, showcasing their ability to execute strategic growth and value creation Financial Strength: Cash runway to support operations as currently planned through 2027 3

 

 

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©2024 Zura Bio Ltd. Torudokimab has been studied in three Phase 1/2 clinical studies to date *** 244 participants dosed - n= 81 single dose - n=163 multiple doses up to 52 weeks Actively assessing the competitive landscape and evaluating potential therapeutic indications to guide our future development efforts. Pipeline of Novel Dual-Pathway Biology Designed to Meaningfully Advance Outcomes in I&I Diseases 4 (*) Phase 1/1b studies conducted by Eli Lilly & Co. (Phase 1 SAD in participants with rheumatoid arthritis, Phase 1b MAD in participants with Sjogren’s syndrome, Phase 1 SAD in healthy Japanese and Caucasian participants) (**) Phase 1/1b studies conducted by Pfizer. (Phase 1a SAD in healthy adult volunteers, Phase 1b MAD in participants with type-1 diabetes, Phase 1b MAD in participants with multiple sclerosis) (***) Phase 1/2 studies conducted by Eli Lilly & Co. (Phase 1 SAD, MAD and Safety / PK in in healthy participants, Phase 2 in participants with atopic dermatitis) Sources: Clinical Study Reports Acronyms: BAFF, B cell-activating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HS, hidradenitis suppurativa; I&I, inflammation and immunology; IL, interleukin; Q, quarter; SSc, systemic sclerosis; TSLP, thymic stromal lymphopoietin Tibulizumab has been studied in three Phase 1/1b clinical studies to date * 78 participants dosed across 3 studies - n=57 single dose - n=21 multiple doses up to 12 weeks Planning to initiate Phase 2 studies of tibulizumab for SSc in 4Q 2024 and for HS in 2Q 2025. tibulizumab Pipeline-in a-product Only bispecific antibody targeting IL-17A and BAFF Phase 1 Phase 2 Crebankitug has been studied in three Phase 1/1b clinical studies to date ** 93 participants dosed - n=60 single dose - n=33 multiple doses up to 12 weeks Actively assessing the competitive landscape and evaluating potential therapeutic indications to guide our crebankitug future development efforts. Potential best-in-class IL-7R and TSLP Inhibition with potential best in class TSLP inhibition torudokimab Potential best-in-class Best in class in inhibiting GM-CSF production by human mast cells Nasdaq: ZURA ixekizumab Anti-IL-17 scFv tabalumab Anti-Baff Ab

 

 

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©2024 Zura Bio Ltd. Dual-Biology Pathways Present Opportunities for High-Impact Therapeutic Targets with Attractive Market Potential 5 (*) Germany, France, Italy, Spain, and United Kingdom Sources: 1 Clarivate/DRG. Accessed 19 August 2024. Projected Prevalence and TAM 2032; “Alopecia Areata - National Alopecia Areata Foundation.” NAAF, www.naaf.org/alopecia-areata; Internal Analysis; Evaluate Pharma Acronyms: k, kilo-thousand; M, million; TAM, total addressable market Prevalence1 U.S., EU5* and Japan Potential Therapeutic Area TAM ($USD) U.S., EU5* and Japan 270 k SSc systemic sclerosis $2,500 M 700 k HS hidradenitis suppurativa $3,200 M 7 M AA alopecia areata $5,200 M 32 M COPD chronic obstructive pulmonary disease $23,692 M 25 M AD atopic dermatitis $31,000 M 47 M Asthma $25,247 M ~112 M $90,839 M Nasdaq: ZURA

 

 

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©2024 Zura Bio Ltd. 6 Zura is Led by a Strong Leadership Team with a Proven Track Record in Drug and Business Development ROBERT LISICKI Chief Executive Officer and Director GARY WHALE PhD Chief Technology Officer VERENDER BADIAL Chief Financial Officer KIM DAVIS JD Chief Legal Officer and Corporate Secretary KIRAN NISTALA MBBS, PhD Chief Medical Officer and Head of Development MICHAEL HOWELL PhD Chief Scientific Officer and Head of Translational Medicine Nasdaq: ZURA

 

 

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©2024 Zura Bio Ltd. Key Anticipated Events Through 2026 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 2024 2025 2026 Tibulizumab SSc study 1 (4Q-2024) Phase 2 study Initiation (4Q-2026) Phase 2 study completion (2Q-2025) Phase 2 study Initiation (3Q-2026) Phase 2 study completion Tibulizumab HS study 1 Anticipated External Events 2 (3Q-2024) Ph3 in Asthma (reducing corticosteroid) AstraZeneca / Amgen tezepelumab TSLP (*) Other IL-7Rα clinical data sources that may be available include a Phase 2 trial of lusvertikimab in ulcerative colitis. Sources: 1 Zura Planning Assumptions; 2 clinicaltrials.gov; Company Presentations Acronyms: AA, alopecia areata; AD, atopic dermatitis; COPD, chronic obstructive pulmonary disease; HS, hidradenitis suppurativa; IL, interleukin; Q, quarter; SSc, systemic sclerosis; TSLP, thymic stromal lymphopoietin ANTICIPATED EVENTS LEGEND Tibulizumab Anticipated Events External IL-7 / TSLP Anticipated Topline Data External IL-33 Anticipated Topline Data (4Q-2024) Ph2 in AA Ph2 in AD Q32 Bio bempikibart IL-7/TSLP Clinical validation* with potential for Zura to be fast follower Nasdaq: ZURA Clinical validation* with potential for Zura to be fast follower (2Q-2025) Ph3 in COPD Sanofi/Regeneron, itepekimab IL-33 (2Q-2025) Ph3 in COPD Roche, astegolimab IL-33 7

 

 

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©2024 Zura Bio Ltd. systemic sclerosis (SSc) tibulizumab ZB-106 Anti-BAFF + IL-17 Tibulizumab, is a humanized bispecific dual antagonist antibody, and has been engineered to bind to and neutralize both BAFF and IL-17A. Our approach with tibulizumab is to inhibit both pathways with a single agent, potentially providing clinical benefits to a broader range of patients, as well as a greater level of effect.

 

 

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©2024 Zura Bio Ltd. Rationale for Phase 2 Study in Systemic Sclerosis Patients Sources: 1 Spherix Global Insights: Market Dynamix: Systemic Sclerosis (US) 2024 Acronyms: B, billion; BAFF, B cell-activating factor; IL, interleukin; SSc, systemic sclerosis; TAM, total addressable market Increased Probability of Success Through Scientific and Clinical Validation IL-17 and BAFF are both validated as key contributors to SSc progression Multiple clinical studies demonstrate that inhibiting IL-17 and targeting B cells benefits SSc treatment Simultaneously inhibiting these validated targets may improve outcomes High Unmet Need and Significant Value Rare and life-threatening condition with a 40%-60% mortality rate within 10 years Limited treatment options available, with no advanced-line agents approved specifically for SSc 96% of rheumatologists identify SSc as the highest area of patient need 1 TAM projected to exceed $2B ©2024 Zura Bio Ltd. 9

 

 

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©2024 Zura Bio Ltd. Systemic Sclerosis is a Multi-Organ Disease with No Effective Treatments 10 Systemic sclerosis is a rare & life-threatening disease ~300,000 people with SSc in US, EU and Japan 1 Zero SSc-specific * drugs approved (*) no effective treatment exists that combats the disease across organ systems Sources: 1 Clarivate/DRG. Accessed 19 August 2024. Projected Prevalence 2032. Systemic sclerosis is characterized by tissue inflammation and fibrosis Lung Skin *Two disease-modifying drugs are approved for severe lung complications of the disease (SSc-ILD) Other Organs tibulizumab | ZB-106 Multiple areas for evaluation and improvement in SSc FVC Forced Vital Capacity mRSS modified Rodnan Skin Score HAQ-DI Health Assessment Questionnaire Disability Index PtGA Patient Global Assessment CGA Clinical Global Assessment

 

 

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©2024 Zura Bio Ltd. 11 Unmet Need for New Pharmacological Treatment Options % of respondents 16% 23% 26% 33% 43% 56% 61% 96% 84% 77% 74% 67% 56% 44% 36% Systemic Sclerosis (SSc) Sjogren's Syndrome (SjS) Dermatomyositis (DM) Lupus Nephritis (LN) Systemic Lupus Erythematosus (SLE) Giant Cell Arteritis (GCA) Cutaneous Lupus Erythematosus (CLE) Ankylosing Spondylitis (AS) Little/no unmet need (1-3) Moderate unmet need (4-7) Extremely high unmet need (8-10) 42% 24% 23% 10% 8% 5% 5% Therapy that treats overall disease activity Treatment to control fibrosis Treatment for skin involvement Treatment for pulmonary manifestations Treatment for gastrointestinal manifestations Lack of new treatments Targeted therapy Unmet Need for the Treatment of SSc Coded, open-end responses 96% of respondents highlight a pressing need for new pharmacological treatments in SSc Rheumatologists Rank SSc as the Highest Area of Need, with Significant Opportunity for Greater and Broader Clinical Benefit Source: Spherix Global Insights: Market Dynamix: Systemic Sclerosis (US) 2024 tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. 12 Both IL-17A and BAFF-Mediated Inflammation Contribute to SSc Progression Selective antibody therapy may be insufficient to address the heterogeneity of SSc B cell activating factor (BAFF) is a potent B-cell activator and promotes the survival and differentiation of B-cells. - BAFF is increased in peripheral blood and correlates with skin fibrosis and incidence of pulmonary fibrosis4,5 - In pre-clinical models BAFF blockade prevents skin fibrosis & autoantibody production6,7 IL-17A is a pro-inflammatory cytokine that has been identified as a key contributor to SSc progression. - IL-17A is increased in skin lesions and peripheral blood1,2 - Neutralization of IL-17A protected against bleomycin induced fibrosis3 Sources: 1 Zhou, Q., et al. The Journal of Immunology, doi:10.4049/jimmunol.1500956; 2 Yang, X., et al. Arthritis Research & Therapy, doi:10.1186/ar4430; 3 Cipolla, E., et al. The FASEB Journal, doi:10.1096/fj.201700289r; 4 Matsushita, T. Arthritis & Rheumatism, doi:10.1002/art.21526; 5 Matsushita et al. J Rheum 2007; 6 Matsushita et al. J Invest Dermatol 2007; 7 François, A., et al. Journal of Autoimmunity, doi:10.1016/j.jaut.2014.08.003. Autoimmune Inflammation Immature B-Cell Survival and Maturation T Cell independent Antibody Responses / B Cells Regulation / Class switch recombination Plasma Cell Survival Binds to BAFF trimer and BAFF 60-mer Preventing binding to BAFF-R, TACI, and BCMA2 Binds to IL-17A preventing IL-A/A and IL-17A/F heterodimerization1 IL-17A BAFF APRIL Trimer BAFF Trimer BAFF 60-mer IL-17A / IL-17F IL-17A / IL-17A IL-17F / IL-17F IL-17RA IL-17RC BAFF-R TACI BCMA Inhibiting both IL-17A and BAFF may lead to better clinical outcomes in SSc tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. Tibulizumab Was ‘designed and engineered’ to Enable Engagement with IL-17A, BAFF, or Both Simultaneously 13 Monoclonal Antibody z May not address disease heterogeneity Targets a single, selective molecule in the body 1st Generation Bispecific Antibody activated Activation may require dual engagement Binds two different targets simultaneously 2nd Generation Dual Antagonist Bispecific Antibody Blocks two distinct ligands, potentially enhancing disease suppression Functions as a single selective agent or two independent agents NEXT GENERATION

 

 

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©2024 Zura Bio Ltd. Tibulizumab Targets IL-17A, BAFF, or Both Simultaneously 14 Tibulizumab uniquely targets BAFF for B cell regulation and IL-17A for inflammation control, offering a comprehensive approach to treating autoimmune and inflammatory diseases. IL-17A CD4+ CD8+ T Cell TH17 Inflammatory Cells IL-17A IL-17A / IL-17F IL-17F IL-17RA IL-17RC ACT1 TRAF6 NF-кB ixekizumab Anti-IL-17 scFv tabalumab Anti-Baff Ab By inhibiting BAFF, tibulizumab reduces B-cell survival and proliferation, modulating immune responses, and potentially treating autoimmune conditions with BAFF overexpression. By neutralizing IL-17A, tibulizumab reduces inflammation, aiding in the treatment of autoimmune and inflammatory conditions involving IL-17A. TACI BCMA BAFF-R CD40 CD20 LTBR B7 BCR B Cells BAFF

 

 

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©2024 Zura Bio Ltd. Pre-Clinical Evidence of Additive Benefit from Inhibiting IL-17A and Neutralizing BAFF 15 Isotype control Anti-BAFF Anti-IL 17 Anti-BAFF + Anti-IL 17 7.5 5.0 2.5 0.0 20 30 40 50 Day Cumulative disease score Histology score 70 60 ** * * * Anti-BAFF + Anti-IL 17 Isotype control Anti-BAFF Anti-IL 17 50 40 30 20 10 0 Anti-BAFF + Anti-IL 17 * 25 * 20 15 10 5 0 Isotype control Anti-BAFF Anti-IL 17 ns Anti- collagen antibody (mg/ml) Mice were injected with anti-IL-17A and/or anti-BAFF on days 22, 29, and 36 The collagen-induced arthritis (CIA) murine model is similarly characterized by increased IL-17A production and B cells that drive disease pathogenesis Rheumatoid arthritis is a prototypic autoimmune disease where individually targeting IL-17A-mediated inflammation or depleting B cells has been clinically validated Surrogate murine antibodies were used to evaluate whether neutralization of IL-17A and BAFF was superior to targeting individual pathways Blockade of both IL-17A and BAFF was associated with reduced: Disease severity Anti-collagen antibodies Inflammation in the hind paw (histology score) Sources: Zura Internal Data, Investigational New Drug (IND) Briefing Acronyms: BAFF, B cell-activating factor; IL, interleukin tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. Separately Inhibiting IL-17A or BAFF Has Demonstrated Efficacy in SSc Placebo-Controlled Studies 16 Sources: 1 Fukasawa, T., et al. Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2022-eular.2519. 2 Gordon, Jessica K., et al. Arthritis Rheumatology, doi:10.1002/art.40358. Acronyms: BAFF, B cell-activating factor; dcSSc, diffuse cutaneous systemic sclerosis; FVC, forced vital capacity; IIT, investigator-initiated trial; MMF, mycophenolate mofetil; mRSS, modified Rodnan Skin Score; QOL, quality of life; SHAQ-DI, scleroderma health assessment questionnaire – disability index; SSc, systemic sclerosis; VAS, visual analogue scale IL-17 receptor antagonist – Phase 3 Brodalumab Achieved primary and endpoints for skin (reduced mRSS) and lung (improved FVC), respectively. 1 Demonstrated therapeutic effects on lung/respiratory functions, digital ulcers, symptoms of gastroesophageal reflux disease, and QOL without noteworthy safety concerns Δ -21.2 units Δ +5.2% CLINICAL PRECEDENT Phase 3 brodalumab study (24 weeks) mRSS FVC (% predicted) BAFF antagonist – IIT Belimumab A 52-week, investigator-initiated, single-center, double-blind, placebo-controlled pilot study in 20 participants with dcSSc on MMF 2 Both treatment groups experienced improvements in mRSS, favoring belimumab (-10 vs. -3; p = NS) Secondary endpoints were met with statistical significance in two endpoints: SHAQ-DI and VAS Raynaud’s phenomenon CLINICAL PRECEDENT Phase 2 belimumab IIT study (52 weeks) mRSS FVC (% predicted) Δ -7.0 units Δ +7.0% tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. Planned Phase 2 SSc Study* is Focused on Demonstrating Benefit in Skin and Lung Endpoints 17 (*) Study design is subject to change. Sources: Zura Internal Planning Acronyms: CRISS, Composite Response Index in Systemic Sclerosis; FVC, forced vital capacity; HAQ-DI, health assessment questionnaire – disability index; ILD, interstitial lung disease; mRSS, modified Rodnan skin score; OLE, open-label extension; qHRCT, quantitative high-resolution computed tomography; SSc, systemic sclerosis Early diffuse cutaneous SSc, enriched for SSc-ILD Stable background therapy Anti-centromere antibody negative Disease duration ≤2 years: mRSS 15-45 Disease duration 2-5 years: mRSS 20-45 RNA Pol III negative, or evidence of recent progression KEY INCLUSION CRITERIA mRSS (primary) qHRCT / FVC HAQ-DI (Function) revised CRISS (rCRISS) KEY EFFICACY ENDPOINTS Efficacy Period (24 weeks treatment) Baseline image HRCT HRCT OLE (28 weeks treatment) HRCT 1:1 R tibulizumab (n = 80) tibulizumab (n = 40) placebo (n = 40) n = 80 participants (weeks) RANDOMIZED PHASE 2 STUDY* (mRSS and HRCT) 0 2 4 8 12 16 20 24 28 32 36 40 44 48 52 tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. modified Rodnan Skin Score (mRSS): Endpoint for Assessing Skin Thickness and Fibrosis 18 Severe skin thickening and tightening restricts movement and causes painful ulcers on the hands and fingers, significantly impairing daily activities and quality of life. vs Fine Wrinkles1 (0/3) Severe Thickness1 (3/3) The mRSS assesses skin thickness in systemic sclerosis patients by evaluating 17 body sites (e.g., face, chest, abdomen, arms, legs). Each site is scored from 0 to 3. The total score ranges from 0 to 51, with higher scores indicating greater skin involvement. Sources: 1 Khanna, D., et al. Journal of Scleroderma and Related Disorders, doi:10.5301/jsrd.5000231; 2 Ferreli, C., et al. Clinical Reviews in Allergy & Immunology, doi:10.1007/s12016-017-8625-4. tibulizumab | ZB-106 17 Surface Anatomic Areas of the Body 2 Moderate Thickness 1 Mild Thickness 3 Severe Thickness 0 Normal Skin Face Anterior chest Abdomen Upper arm Forearm Hand Fingers Thigh Leg Foot Upper arm Forearm Hand Fingers Thigh Leg Foot with inability to pinch the skin into a fold

 

 

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©2024 Zura Bio Ltd. In Phase 2, Lung Involvement using qHRCT will be a Key Secondary Endpoint 19 Sources: Goldin, J.., et al. Annals of the American Thoracic Society, doi:10.1513/annalsats.201802-079oc; Zura Bio internal planning Acronyms: ILD, interstitial lung disease; MMF, mycophenolate mofetil; qHRCT, quantitative high-resolution computed tomography; QILD, quantitative interstitial lung disease; QLF, Quantitative Lung Fibrosis; SSc, systemic sclerosis ILD includes various pulmonary disorders marked by inflammation and progressive lung fibrosis, resulting in restrictive lung function and impaired gas exchange. SSc often leads to ILD due to immune system dysregulation and subsequent lung interstitial fibrosis.​ vs Healthy Lung Fibrotic Lung QILD by HRCT provides a sensitive measure of lung involvement, detecting changes as small as 2%. Example of improvement after 24 months of MMF in total lung involvement The blue and red areas show QLF, while the yellow area shows quantitative ground glass. The entire colored area represents QILD. After 24 months, QLF areas decreased (arrow in B). tibulizumab | ZB-106

 

 

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zurabio.com (*) As of September 2024. Does not include trials only conducted in Japan (**) Studies on clinicaltrials.gov where the primary condition listed is systemic sclerosis (diffuse or limited cutaneous) (***) Studies on clinicaltrials.gov with the condition listed is systemic sclerosis with interstitial lung disease External Development Programs* : Key Studies and Marketed SSc-ILD Specific Products for Systemic Sclerosis SSc-ILD*** SSc** Phase 1 RO7303509 (unknown) Genentech Roche BI 685509 (sGC) avenciguat Boehringer Ingelheim ATYR1923 (neuropilin-2) Efzofitimod aTyr PRA023/MK-7240 (TL1A) tulisokibart Prometheus Biosciences/Merck RO7622888 (OSMRβ) vixarelimab Kiniksa/Genentech Orencia (CD80/CD86) abatacept Bristol Meyers Squibb IVA337 (PPAR) lanifibranor Inventiva GLPG1690 (autotaxin) ziritaxestat Galapagos SAR100842 (LPA1) Sanofi Privigen and Hizentra (IgG) 20% and 10% human IgG CSL Behring Adempas (sGC) riociguat Bayer ZB-106 (IL-17/BAFF) tibulizumab Zura SAR156597 (IL-4/IL-13) romilkimab Sanofi FT-011 (GPCR-68) Certa Therapeutics MT-7117 (MC1R) dersimelagon Mitsubishi Tanabe Pharma Vasculan (sGC) ifetroban Cumberland Pharmaceuticals Phase 2 Saphnelo (IFNAR1) Anifrolimab AstraZeneca HZN-825 (LPAR1 antagonist) fipaxalparant Amgen/Horizon Lenabasum (CB2) anabusum Corbus Pharmaceuticals CONQUEST (OX40 / PDE4B) amlitelimab / nerandomilast Sanofi / BI Benlysta (anti-BLyS) belimumab GSK Phase 3 Ofev/Vargatef (TKI) nintedanib Boehringer Ingelheim Actemra (IL-6) tocilizumab Genentech Roche Marketed Route of Administration Legend RED discontinued study PURPLE ongoing study ORAL IV SUB-Q ©2024 Zura Bio Ltd. 20

 

 

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©2024 Zura Bio Ltd. Revised CRISS Endpoint in SSc Assessment 21 If no significant SSc-related event, proceed to Step 2 STEP 1: Assess for significant SSc-related events: STEP 2: Assess each core measure for improvement / worsening: New scleroderma renal crisis New decline in percent predicted FVC≥15% in established ILD or new percent predicted FVC below 80% predicted New onset of left ventricular failure requiring treatment New onset of pulmonary arterial hypertension requiring treatment Gastrointestinal dysmotility requiring enteral or parenteral nutrition Digital ischemia with gangrene, amputation, or hospitalization requiring treatment Sources: Zura Internal Planning Acronyms: CGA, clinical global assessment; CRISS: composite response index in systemic sclerosis; FVC, forced vital capacity; HAQ-DI, health assessment questionnaire – disability index; ILD, interstitial lung disease; mRSS, modified Rodnan skin score; PtGA, patient global assessment FVC mRSS HAQ-DI PtGA CGA 25% 5% Typical Threshold RESPONDER: Improvement in ≥2 core measures with worsening in ≤1 core measure tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. ©2024 Zura Bio Ltd. 22 Phase 2 SSc Development Aims to Reduce Historical Risks in Therapeutic Area Development Acronyms: CT, computed tomography; FVC, forced vital capacity; IL, interleukin; ILD, interstitial lung disease; mRSS, modified Rodnan Skin Score Historic Drivers of SSc Study Failures: Novel and unvalidated mechanisms Inclusion/exclusion criteria oversights Challenges in balancing sample sizes for mRSS and ILD participants Increasing Probability of Success: Larger study sample size increases the probability of success (mRSS) High-resolution CT highly correlates with FVC, improving ILD read- through Sufficient sample size for ILD readouts to understand potential Phase 3 effects

 

 

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©2024 Zura Bio Ltd. hidradenitis suppurativa (HS) tibulizumab ZB-106 Anti-BAFF + IL-17 Tibulizumab, is a humanized bispecific dual antagonist antibody, and has been engineered to bind to and neutralize both BAFF and IL-17A. Our approach with tibulizumab is to inhibit both pathways with a single agent, potentially providing clinical benefits to a broader range of patients, as well as a greater level of effect.

 

 

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©2024 Zura Bio Ltd. Rationale for Phase 2 Study in Hidradenitis Suppurativa Patients Acronyms: BAFF, B cell-activating factor; HiSCR, Hidradenitis Suppurativa Clinical Response; HS, hidradenitis suppurativa; IL, interleukin; TAM, total addressable market Increased Probability of Success Through Scientific and Clinical Validation IL-17A and BAFF are clinically validated as key contributors to HS pathology Inhibiting IL-17A or disrupting B cells individually shows strong clinical support Ixekizumab shows high affinity for IL-17A and IL-17A/F Dual inhibition of these targets could improve patient outcomes Unmet Need and Growth Potential 50% to 70% of HS patients do not achieve HiSCR75 with current treatments In the chronic phase, BAFF may play a more significant role, highlighting an unmet need that tibulizumab can address The TAM is projected to grow to $3.5B - $4B by 2030 ©2024 Zura Bio Ltd. 24

 

 

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zurabio.com An Overview of Hidradenitis Suppurativa ©2024 Zura Bio Ltd. 25 DISEASE OVERVIEW Recurrent nodules and abscesses resulting in pus-like discharge Difficult-to-heal open wounds and scarring Hidradenitis suppurativa is an inflammatory follicular skin disease Increased Th1/Th17 and B cell mediated inflammation 1 - 3 Disproportionately affects women between adolescent age to 55 years of age 4, 5 Skin lesions form in the armpits, groin, and under the breasts due to inflammation and infection of the sweat glands CLINICAL OPPORTUNITY 6 ~>50% patients still left inadequately treated Average time to diagnosis is 7 years ~300K people living with HS in the U.S. Sources: 1 Moran, Barry, et al. Journal of Investigative Dermatology, doi:10.1016/j.jid.2017.05.033. 2 Banerjee, Anirban, et al. Immunological Investigations, doi:10.1080/08820139.2016.1230867. 3 Sabat, Robert, et al. Journal of Allergy and Clinical Immunology, doi:10.1016/j.jaci.2022.10.034. 4 Garg, Amit, et al. JAMA Dermatology, doi:10.1001/jamadermatol.2017.0201. 5 Ingram, John R. British Journal of Dermatology, doi:10.1111/bjd.19435. 6 Medical Literature, MEDACorp KOL Discussions

 

 

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©2024 Zura Bio Ltd. B Cell Signaling Potentiates HS Disease 26 Sources: 1 Van der Zee, H.H., et al. British Journal of Dermatology, doi:10.1111/j.1365-2133.2011.10698.x. 2 Rumberger, Beth E., et al. Inflammation Research, doi:10.1007/s00011-020-01381-7. 3 Sabat, Robert, et al. Journal of Allergy and Clinical Immunology, doi:10.1016/j.jaci.2022.10.034. 4 Gudjonsson, Johann E., et al. JCI Insight, doi:10.1172/jci.insight.139930 tibulizumab | ZB-106 Cells that express CD20 Cells that express BAFF receptors a immature B cells; b mature B cells; c activated B cells; d memory B cells Plasma Cell Expression of CD20 Expression of BAFF receptors Pro-B Pre-B IgM+ IgD+ IgM+ Ag Selected B cell a b c d IgM IgG IgA IgE Overlapping expression of CD20+ and BAFF CD20+ B cells in HS Lesions BAFF gene expression in HS BAFF is essential for B cell activation Elevated CD20+ B cells and CD138+ plasma cells in chronic HS lesions sustain inflammation. 2,3 Overlapping expression of CD20+ and BAFF. 1,4 Increased BAFF in HS lesions promotes B cell activation and inflammation. 2,3 Reducing BAFF in HS lesions decreases B cell and plasma cell gene expression, indicating a potential therapeutic approach. 1,4

 

 

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©2024 Zura Bio Ltd. Role of IL-17A and B Cells Is Clinically Validated; However, Clinical Effect Remains Modest with Single-Pathway Inhibition 27 company and drug INN >> secukinumab remibrutinib* bimekizumab sonelokimab Mechanism IL-17 A BTKi IL-17 A/F IL-17 A/F Administration SC/IV PO SC SC Phase Phase 3 Phase 2b Phase 2 Phase 2 Dosing 30mg Q2W for 16W 100 mg or 25 mg BID 320mg Q2W for 12W 120mg Q2W for 12W Total Patients n = 360 n = 77 n = 88 n = 234 Efficacy (HiSCR50) Non-Placebo Adjusted 42% - 45% 48.5% - 72.7% 63% 66% Placebo Adjusted 11% + 38% 35% 38% Efficacy (HiSCR75) Non-Placebo Adjusted N/A 27.3% - 42.4% 50% 43% Placebo Adjusted N/A 24% 29% 29% Safety Candidiasis 0% - 3%1 0 9% 10.5% (*) There have been no head-to-head clinical trials between the product candidates listed above. Study designs and protocols for each product candidate were different, and as a result, results may not be comparable between product candidates. Sources: Company Presentations, Publications and Research. 1 Represents data from psoriasis trial. 2 Represents safety data from psoriatic arthritis trial remibrutinib, 2024 AAD S026. Acronyms: BID, twice a day; BTKi, Bruton tyrosine kinase inhibitors; HiSCR, Hidradenitis Suppurativa Clinical Response; HS, hidradenitis suppurativa; IL, interleukin; INN, international non-proprietary name; IV, intravenous; PO, per os or by mouth; Q2W, every two weeks; Q4W, every four weeks; SC, subcutaneous tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. 28 Tibulizumab* IL-17A Component Has Class-Leading Binding Affinity Against IL-17A and IL-17A/F Ixekizumab is a humanized IgG4 monoclonal antibody (*) Tibulizumab was engineered from Taltz® (ixekizumab) Sources: 1 Taltz®. Prescribing Information. Lilly USA, LLC, https://taltz.lilly.com/hcp/moa-il17a-igg4 . Acronyms: IgG4, immunoglobulin G4; KD, dissociation constant; pM, picomolar IL-17F Binding Affinity N/A KD 23 pM N/A KD <3 pM KD 26 pM IL-17A/F Binding Affinity KD 1.8 pM KD 3.2 pM KD 60 pM – 90 pM IL-17A Binding Affinity Taltz® (ixekizumab) Bimzelx® (bimekizumab) Cosentyx® (secukinumab) Binding affinity, quantified by the dissociation constant (KD), reflects the strength of interaction between a drug and its target, with a lower KD indicating stronger binding. Stronger binding affinity ensures effective neutralization of the target, leading to the potential for improved clinical outcomes. KD 2400 pM tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. 29 Ongoing Novartis Phase 2b Multicenter Platform Study Offers Additional Clinical Evidence of B Cell Targeting Benefit in HS *Study started in February 2019 and is currently ongoing. BAFF-R, B-cell activating factor of the tumor necrosis alpha family receptor; b.i.d., twice daily; BTKi, Bruton’s tyrosine kinase inhibitor; CD, cluster of differentiation; D, day; EOS, end of study; HS, hidradenitis suppurativa; IL, interleukin; LTA4H, leukotriene A4 hydrolase; MoA, mechanism of action; PEA, primary endpoint analysis; R, randomization; s.c., subcutaneous; W, week. Clinicaltrials.gov NCT03827798. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT03827798 (Accessed 6 Mar 2024). Presented at the American Academy of Dermatology Annual Meeting; March 8–12, 2024; San Diego, CA. Adult patients aged 18–65 years Moderate to severe HS for ≥12months in ≥2 anatomical areas with ≤15 tunnels Cohorts A, C, and E: ≥5 inflammatory lesions Cohorts B and D: ≥3 inflammatory lesions Patients Cohorts Iscalimab s.c. 600 mg anti–CD-40 A LYS006 b.i.d. 20 mg LTA4Hi B MAS825 s.c. 300 mg anti–IL-1β/ IL-18 C Outcome Follow-up period variable length depending on MoA Investigational treatments (Cohort A–E) ~40–70 patients per cohort Screening Corresponding placebo (Cohort A–E) R W –5 D 1 W 16 PEA EOS Double-blind treatment period D Remibrutinib b.i.d. 100 mg or 25 mg BTKi E Ianalumab s.c. 300 mg anti–BAFF-R Positive ꭓ Negative Positive Positive Ongoing tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. 30 Novartis’ Interim Results Presented at ‘24 AAD: BTKi PBO-Adjusted Delta Aligns with Approved and In-Development Agents Presented at the American Academy of Dermatology Annual Meeting; March 8–12, 2024; San Diego, CA. *The sHiSCR is defined as a ≥50% reduction in the abscess and inflammatory nodule count and no increase in draining tunnels compared with baseline. †Difference refers to the difference between remibrutinib (either dose) and pooled placebo at Week 16. ‡Bayesian posterior probability of remibrutinib (either dose) being better than pooled placebo. CI, confidence interval; HiSCR, hidradenitis suppurativa clinical response; n, total number of patients with response; N, total number of patients in each treatment arm; NRI, non-responder imputation; sHiSCR, simplified hidradenitis suppurativa clinical response. The primary endpoint of this study was met for both doses of remibrutinib; patients treated with remibrutinib reported a greater rate of sHiSCR* at Week 16 compared with placebo 48.5 72.7 34.7 20 0 40 60 80 100 0 2 4 6 10 12 14 16 Proportion of patients reporting sHiSCR (%) 8 Week Remibrutinib 100 mg (N = 33) Remibrutinib 25 mg (N = 33) Pooled placebo (N = 49) Cohort D Cohort A–D Remibrutinib 25 mg (N = 33) Remibrutinib 100 mg (N = 33) Pooled Placebo (N = 49) Proportion of patients with sHiSCR*: Observed with NRI (%) 72.7 48.5 34.7 Difference† (%) (95% CI) 38.0 (21.1 to 55.0) 13.8 (–4.4 to 32.0) Bayesian estimated (%) 72.3 48.5 34.9 Difference† (%) (95% CI) 37.2 (19.7 to 53.0) 13.9 (–4.2 to 31.9) Probability of difference‡ 99.9 89.6 tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. Planned Phase 2 HS Study Design* 31 (*) Study design is subject to change. Sources: Zura Internal Planning Acronyms: DLQI, dermatology life quality index; HiSCR, Hidradenitis Suppurativa Clinical Response; HS, hidradenitis suppurativa; IHS4, international hidradenitis suppurativa severity score system; PD, pharmacodynamic; PGA, physician’s global assessment; PK, pharmacokinetic; R, randomization Moderate to Severe HS Hurley Stage II/III Total abscess and inflammatory nodule count (AN) ≥ 5 Up to 30% TNF inadequate responders KEY INCLUSION CRITERIA KEY EFFICACY ENDPOINTS HiSCR AN count IHS4 PGA DLQI PK / PD assessments KEY SAFETY ENDPOINTS General Safety and Tolerability Severe infection Efficacy Period (16 weeks treatment) DOUBLE BLIND, PLACEBO-CONTROLLED, 16-WEEK STUDY n = 120 – 180 participants tibulizumab dose 1 tibulizumab dose 2 placebo 1:1:1 R 12-week safety follow-up tibulizumab | ZB-106

 

 

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©2024 Zura Bio Ltd. 32 The Phase 2 development programs for systemic sclerosis and hidradenitis suppurativa are progressing The strategy follows validated pathways with the potential for improved outcomes, supported by related mechanism-of-action data from IL-17 and BAFF/B-cell depletion therapies We believe tibulizumab is positioned as a potential first-in-class dual-pathway biologic The next 6 to 12 months offer significant growth opportunities, with multiple key milestones anticipated Tibulizumab Summary

 

 

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©2024 Zura Bio Ltd. crebankitug ZB-168 Anti-IL-7Rα + TSLP Crebankitug is a high-affinity, fully human monoclonal antibody that neutralizes the IL-7 receptor alpha (IL-7Rα) chain, potentially blocking the immune pathways of IL-7 and thymic stromal lymphopoietin (TSLP).

 

 

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©2024 Zura Bio Ltd. Crebankitug 34 Crebankitug, a fully human IL-7Rα antibody Originally developed by Pfizer IL-7Rα inhibition has potential to inhibit two critical immune pathways (IL-7 and TSLP) Potential applicability in broad range of T-cell mediated diseases and atopic diseases. Well tolerated in Phase 1 and Phase 1b studies >90 participants dosed with crebankitug Adverse events generally mild and not treatment-related. Phase 1b data demonstrate clear evidence of impact on key T-cell compartments Only anti-IL7R program that has reported safety, PK, and PD data in participants with an auto immune disease (not just healthy volunteers) Potentially clinically relevant changes observed in memory T-cell counts and Treg : Tmemory ratios. Actively assessing Phase 2 strategy Ongoing internal planning for indications in areas with unmet needs. Will be evaluating Phase 2 IL-7Rα and TSLP competitor data readouts. creban- creating balance ki- cytokine or cytokine receptor tug- unmodified immunoglobulin crebankitug | ZB-168

 

 

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©2024 Zura Bio Ltd. 35 Crebankitug: A Multi-Functional Antibody That Blocks Signaling via IL-7 and TSLP Pathways crebankitug | ZB-168 IL-7Rα is a key receptor in immune regulation, central to the signaling of cytokines IL-7 and TSLP Positioning crebankitug for potential applications in diverse immune-related and autoimmune conditions Commonly tied to allergic responses and specific inflammatory scenarios This assembled complex initiates pathways primarily linked to type 2 immunity TSLP binds to its dedicated receptor, TSLPR. For optimal signaling, IL-7Rα joins the mix, creating a composite complex with TSLPR and TSLP TSLP IL-7Rα collaborates with the common gamma chain (γc) to establish the IL-7 receptor complex IL-7 Vital for the growth, sustenance, and balance of T-cells Triggers a sequence of cellular events, notably JAKs & STATs T-Cell JAK3 JAK1 JAK1 JAK2 IL-7Rα IL-7 TSLP

 

 

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©2024 Zura Bio Ltd. Both TSLP and IL-7 Have a Role in Activating Th1, Th2, and Th17-Driven Inflammation 36 B Cell Development T Cell Activation CD4/CDB Effector Cells B Cell Maturation T Cell B Cell DC ILC2 Mast Cell Basophil Eosinophil Keratinocytes Airway Epithelium Stromal cell IL-7Ra γC IL-7Ra γC IL-7Ra TSLPR IL-7Ra TSLPR IL-7Ra TSLPR IL-7Ra TSLPR IL-7Ra TSLPR IL-7Ra TSLPR IL-7Ra TSLPR IL-5R IL-4R IL-5R IL-4R CCL17/TARC CCL22/MDC IL-5, IL-13, Amphiregulim Th2 Differentiation Treg Development IL-7 TSLP IL-7 Mediated Allergen Virus Bacteria Pollutant TSLP Mediated 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 amplifying 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:γC 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 Teff compared to Treg, inhibition results in a 20-fold greater activity in reducing Teff, leading to an increase in Treg:Teff ratio 5, 6 IL-7 PATHWAY TSLP PATHWAY Sources: 1 Ebina-Shibuya, R. and Warren L.eonard. Nature Reviews Immunology, doi:10.1038/s41577-022-00735-y; 2 Marone, G., et al. Expert Opinion on Investigational Drugs, doi:10.1080/13543784.2019.1672657; 3 Menzies-Gow, A., et al. Respiratory Research, doi:10.1186/s12931-020-01505-x; 4 Chen, 2021. Frontiers Immunol, 5. Herold, K., et al. JCI Insight, doi:10.1172/jci.insight.126054; graphic created in BioRender; 5 Martin, M.and Badovinac P. Frontiers in Immunology, doi:10.3389/fimmu.2018.02692; 6 Waickman, A., et al. iScience, doi:10.1016/j.isci.2020.101421; 7 Marković, I. and Savvides S. Frontiers in Immunology, doi:10.3389/fimmu.2020.01557. crebankitug | ZB-168

 

 

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©2024 Zura Bio Ltd. 37 Crebankitug Is the Only mAb to Potently Inhibit Both IL-7R and TSLP tezepelumab (TSLP) bempikibart (IL-7Rα) crebankitug (IL-7Rα) TSLP mAb IL-7Rα mAb IL-7Rα mAb TSLP-Induced Signals 67 ng / ml / 0.44nM (CCL17)(3) 24 nM (CCL2)(4) 7.5 ng / ml / 0.05nM (CCL17)(1) 11 ng / ml / 0.07nM (CCL22)(1) 0.08 nM (CCL2)(4) IL-7-Induced Signals Neg 0.6 nM (IL-7 at 0.25ng/ml)(4) 2.1 nM (IL-7 at 2.5ng/ml)(4) 0.46nM (pSTAT5)(2) Inhibition of TSLP stimulated CCL17 secretion from human monocytes World Allergy Congress Poster, Dec 2023 % inhibition of TSLP stimulated CCL17 secretion from human monocytes crebankitug | ZB-168 100 50 0 -50 -4 -2 0 2 4 %Inhibition Log (ug/mL) crebankitug tezepelumab anti-TSLPR IgG anti-CD127 Source: 1 Zura Internal Data; 2 Herold, Kevan C., et al. JCI Insight, doi:10.1172/jci.insight.126054; 3 Numazaki, Mako, et al. Journal of Pharmacology and Experimental Therapeutics, doi:10.1124/jpet.121.000686; 4 Yamniuk, Aaron P., et al. Antibodies against Il-7r Alpha Subunit and Uses Thereof. 18 May 2021. Acronyms: CCL17, C-C motif chemokine ligand 17; IL, interleukin; mAb, monoclonal antibody; TSLP, thymic stromal lymphopoietin

 

 

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©2024 Zura Bio Ltd. Dual Inhibition of Th1 and Th2 May Offer Broader or Deeper Levels of Response in Atopic Dermatitis 38 crebankitug | ZB-168 TSLP and IL-25 activate Th2 cells, which are crucial in the early stages of atopic dermatitis. As the condition progresses, the influence of Th2 decreases, while Th1 and Th17 responses become more prominent. Targeting both Th2 and Th1 pathways may offer broader and more effective treatment options. Nonlesional skin Early lesions / acute Late lesions / chronic Circulating CLA+ Th2 cells Microinflammation and increased number of T cells compared to healthy skin Skin homing and expansion of type 2 response TSLP, IL-25, IL-33 direct or indirect effects Barrier defect S. aureus colonization Eczema/ spongiosis Single keratinocyte apoptosis by IFN- γ, Fas-L, TNF-α Chronic dermatitis Allergens IL-31 IL-5 IDEC IL-13 IDEC IDEC MDLC LC LC LC Th0 Th2 Th0 Th2 Th2 Th2 Th2 Th2 Th2 IFN-γ Th1 Th17 Th1 Th2 Th22 IL-22 IFN-γ FAS-L IL-4 Microbial toxins MDLC Scratching crebankitug

 

 

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©2024 Zura Bio Ltd. 39 Crebankitug Provides Optionality for Clinically Validated Development or Novel Indications Explore the potential indication space Solid biologic rationale for IL-7 / TSLP Expected Clinical Readout1 Zura Internal Evaluation of New or Orphan Indications2 Common autoimmune disease Orphan autoimmune disease atopic dermatitis & alopecia areata Ulcerative colitis (and other GI) Asthma (and other Respiratory) Internal Evaluation 2024 External Phase 2 PoC 2024 crebankitug Sources: 1 ClinicalTrials.gov database, Company Presentations; 2 Zura Internal Planning Acronyms: GI, gastrointestinal; IL, interleukin; PoC, proof-of-concept; TSLP, thymic stromal lymphopoietin crebankitug | ZB-168

 

 

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©2024 Zura Bio Ltd. 40 Crebankitug targets immune-related and autoimmune conditions linked to IL-7R or TSLP signaling In three Phase 1 and 1b studies involving 93 participants, crebankitug was well-tolerated, with most adverse events being mild and unrelated to the treatment Only anti-IL-7Rα program with clinical data showing impact on key T-cell subpopulations, indicating potential for broad T-cell mediated and atopic diseases Advancing indication planning and monitoring IL-7R and TSLP therapies to support Phase 2 strategy Crebankitug Summary

 

 

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©2024 Zura Bio Ltd. torudokimab ZB-880 Anti-IL-33 Torudokimab is a fully human, high affinity monoclonal antibody that neutralizes IL-33, preventing ST2-dependent and ST2-independent (e.g., RAGE) inflammation.

 

 

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©2024 Zura Bio Ltd. Mechanism of Action About torudokimab Initial Focus on Respiratory, Dermatologic, Gastrointestinal and Orphan Autoimmune Indications Torudokimab Asset Overview 42 Sources: 1 Cohen, S., et al. Nature Communications, doi:10.1038/ncomms9327; 2 Clinicaltrials.Gov, clinicaltrials.gov/ct2/show/NCT03913260. Accessed 26 Aug. 2024; Clinicaltrials.Gov, clinicaltrials.gov/ct2/show/NCT03343587. Accessed 26 Aug. 2024; Clinicaltrials.Gov, clinicaltrials.gov/ct2/show/NCT03831191. Accessed 26 Aug. 2024; Section 6.1, DSUR for period 23-Sep-2019 to 22-Sep-2020; 3 Laquer, V., et al. British Journal of Dermatology, doi:10.1111/bjd.21631. 4 Okragly, A., et al. Journal of Inflammation Research, doi:10.2147/jir.s320287. 5 Wechsler, M., et al. New England Journal of Medicine, doi:10.1056/nejmoa2024257. 01 IL-33 implicated in driving Th2 biology through ST2 and Th1/Th17 through alternative signaling 1 02 Well tolerated in Phase 1 and Phase 2 trials conducted by Eli Lilly 2 03 The target engagement evaluation suggested binding to IL-33 and treatment emergent ADA had no apparent impact on PK or target engagement 141 healthy volunteers in Phase 1 study 103 participants with moderate to severe atopic dermatitis in Phase 2 Analyses confirmed key biomarker reductions (IL-13, periostin and CCL17/TARC) and no ADA impact 3 Potential utility in diseases driven by epithelial inflammation 1 01 Potential for 1st-in-class opportunities 02 Validated pathways in COPD 4 and asthma 5 01 Inhibition of IL-33 blocks both ST2 and RAGE signaling 4 torudokimab | ZB-880

 

 

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©2024 Zura Bio Ltd. Torudokimab IL-33 Pathway 43 Sources: 1 Chan, B., et al. Frontiers in Immunology, doi:10.3389/fimmu.2019.00364; 2 Cayrol, C. and Girard, J.P. Cytokine, doi:10.1016/j.cyto.2022.155891. 3 Gudbjartsson, D., et al. Nature Genetics, doi:10.1038/ng.323; Ketelaar, M., et al. Journal of Allergy and Clinical Immunology, doi:10.1016/j.jaci.2020.04.051; 4 Singh, D. The Lancet Respiratory Medicine, doi:10.1016/s2213-2600(22)00005-4; Wechsler, M., et al. New England Journal of Medicine, doi:10.1056/nejmoa2024257; Chen, Yi-Ling, et al. Science Translational Medicine, doi:10.1126/scitranslmed.aax2945; 5 Zura Internal data; 6 Pei, C., et al. Immunology, doi:10.1111/imm.12174; Kurimoto, M., et al. Frontiers in Physiology, doi:10.3389/fphys.2021.781012; Dong, Y., et al. Frontiers in Medicine, doi:10.3389/fmed.2021.739489. IL-33 is a member of the IL-1 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 and itepekimab suggesting the potential for best-in-class activity 5 Emerging biology suggests expanding opportunity for IL-33 in fibrotic and autoimmune conditions 6 torudokimab | ZB-880

 

 

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©2024 Zura Bio Ltd. Torudokimab Has Potential for “Best-in-Class” Activity 44 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 Sources: Zura Internal Data Antibody kon (M-1 s-1 ) koff (s-1 ) kd (pM) Torudokimab Potency torudokimab (LY3375880) 1.7 x 106 6.7 x 10-5 39 etokimab (AnaptysBio) 9.4 x 105 1.2 x 10-4 112 2.9x itepekimab (Regeneron) 7.6 x 105 1.6 x 10-4 215 5.5x torudokimab | ZB-880

 

 

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©2024 Zura Bio Ltd. Corporate Update Team and Cash Runway

 

 

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©2024 Zura Bio Ltd. Zura’s Leadership: Driving Innovation in I&I 46 Robert Lisicki Chief Executive Officer and Director Steve Schoch Director Jennifer Jarrett Director Parvinder Thiara Director Someit Sidhu, MD Founder and Director Arnout Ploos van Amstel Director Amit Munshi Chairman Neil Graham, MBBS, MD, MPH Director Sandeep C. Kulkarni, MD Director BOARD OF DIRECTORS Ajay Nirula, MD, PhD Johann Gudjonsson, MD, PhD Michael Weinblatt, MD Dinesh Khanna, MD, MSc Steven Ziegler, PhD SAB EXECUTIVE TEAM Robert Lisicki Chief Executive Officer and Director Verender Badial Chief Financial Officer Kiran Nistala, MBBS, PhD Chief Medical Officer and Head of Development Gary Whale PhD Chief Technology Officer Kim Davis JD Chief Legal Officer and Corporate Secretary Michael Howell PhD Chief Scientific Officer And Head of Trans. Med. Nasdaq: ZURA Acronyms: I&I, inflammation and immunology; SAB, scientific advisory board

 

 

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©2024 Zura Bio Ltd. Key milestones* expected through 2026 47 2H-2024 2025 2026 tibulizumab SSc study HS study crebankitug Indication Planning Ongoing torudokimab Indication Evaluation On-going (*) The timing of regulatory and clinical trial milestones are subject to change and additional discussion with the FDA Sources: Internal Zura Planning Acronyms: AA, alopecia areata; AD, atopic dermatitis; COPD, chronic obstructive pulmonary disease; CRO, contract research organization; HS, hidradenitis suppurativa; SSc, systemic sclerosis; US FDA, United States Food & Drug Administration ▲ External Catalyst Internal Zura MILESTONE LEGEND: Cash runway expected through 2027 ▲ 4Q-2024: Phase 2a Topline Data bempikibart in AA, Q32 Bio ▲ 4Q-2024: Phase 2 Topline Data bempikibart in AD, Q32 Bio Complete internal indication planning Initiate a Phase 2 study in HS Select CRO Obtain IND from US FDA Phase 2 study recruitment Initiate a Phase 2 study in SSc Obtain IND from US FDA Select CRO SSc Topline Data HS Topline Data Select indication for future development* Pending data outcomes, Phase 3 Pending data outcomes, Phase 3 ▲ 2Q-2025: Phase 3 Study Complete itepekimab in COPD, Sanofi Complete internal indication planning ▲ 2Q-2025: Phase 3 Topline Data astegolimab in COPD, Roche ▲ 3Q-2024: Phase 3 Topline Data tezepelumab in Asthma (reducing corticosteroid), Amgen Indication selection to guide future crebankitug milestones Indication planning to guide future torudokimab milestones

 

 

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©2024 Zura Bio Ltd. 48 Source: 1 Cash includes cash and cash equivalents as of 30-June-2024; 2 S-3 dated 03-Sept-2024 Acronyms: ATM, at-the-market offering; IPO, initial public offering Nasdaq ticker: ZURA April 2024 Photo courtesy of ©Nasdaq, Inc. Our mission: Driving scientific breakthroughs by turning drug discoveries into transformative, life-saving treatments. Tibulizumab shows best-in-class potential: Introducing a tetravalent antibody therapy designed to target and potentially treat autoimmune diseases. Promising pipeline for value creation: Integrating validated biological pathways into multifunctional antibody assets to potentially improve therapeutic outcomes. Upcoming external catalysts: Anticipating near-term developments that could further expand the pipeline's potential. Proven leadership: Experienced team with a track record of contributing to over $8 billion in mergers and acquisitions in the past three years. Strong financial position: With approximately $188 million1 in cash, cash equivalents, and investments, we are funded to support our planned operations through 2027. The 3Q 2024 IPO warrant exchange has streamlined our share structure, and additional financing through ATM options remains available for future needs. As of August 29, 2024, we have 63,774,183 Class A Ordinary Shares outstanding2 .. Nasdaq: ZURA

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Cover
Sep. 09, 2024
Document Information [Line Items]  
Document Type 8-K
Amendment Flag false
Document Period End Date Sep. 09, 2024
Entity File Number 001-40598
Entity Registrant Name Zura Bio Limited
Entity Central Index Key 0001855644
Entity Tax Identification Number 98-1725736
Entity Incorporation, State or Country Code E9
Entity Address, Address Line One 1489 W. Warm Springs Rd.
Entity Address, Address Line Two #110
Entity Address, City or Town Henderson
Entity Address, State or Province NV
Entity Address, Postal Zip Code 89014
City Area Code 702
Local Phone Number 825-9872
Written Communications false
Soliciting Material false
Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Entity Emerging Growth Company true
Elected Not To Use the Extended Transition Period false
Common Class A [Member]  
Document Information [Line Items]  
Title of 12(b) Security Class A Ordinary Shares, par value $0.0001 per share
Trading Symbol ZURA
Security Exchange Name NASDAQ
Warrants [Member]  
Document Information [Line Items]  
Title of 12(b) Security Warrants, each whole warrant exercisable for one Class A Ordinary Share at an exercise price of $11.50 per share
Trading Symbol ZURAW
Security Exchange Name NASDAQ

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