Corporate Overview September 2024
The material in this presentation regarding Tourmaline Bio, Inc. (“we,” “us” or the “Company”) is for informational purposes only. This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the timing of initiation, progress and results of the Company’s current and future preclinical and clinical trials for its product candidates, including pacibekitug (also referred to as TOUR006); the therapeutic potential of pacibekitug; the timing and likelihood of seeking regulatory approval for the Company’s product candidates, including pacibekitug; the timing of submitting investigational new drug applications and other regulatory documents; the Company’s ability to achieve planned milestones; the competitive landscape for the Company’s product candidates; and the Company’s estimates regarding expenses, future revenue, capital requirements, cash runway and needs for additional financing. The words “may,” “will,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Many factors may cause differences between current expectations and actual results, including, but not limited to, unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in the regulatory environment, changes in expected or existing competition, unexpected litigation or other disputes, and other risks and uncertainties, including those described in the section titled “Risk Factors” in the Company’s most recent filings with the Securities and Exchange Commission. The forward-looking statements included in this presentation represent the Company’s views as of the date of this presentation. The Company undertakes no obligation to update the information contained in this presentation to reflect new events or circumstances, except as required by law. In addition, certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. This presentation contains trademarks, services marks, trade names and copyrights of the Company and other companies, which are the property of their respective owners. The use or display of third parties’ trademarks, service marks, trade name or products in this presentation is not intended to, and does not, imply a relationship with the Company, or an endorsement of sponsorship by the Company. Solely for convenience, the trademarks, service marks and trade names referred to in this presentation may appear without the ®, TM or SM symbols, but such references are not intended to indicate, in any way, that the Company will not assert, to the fullest extent under applicable law, their rights or the right of the applicable licensor to these trademarks, service marks and trade name. Disclaimer 2
Our mission 3 We are driven by our mission to develop transformative medicines that dramatically improve the lives of patients with life-altering immune and inflammatory diseases
Emil deGoma, MD Senior Vice President, Medical Research Gerhard Hagn Senior Vice President, Head of Commercial & BD Kevin Johnson, PhD Chief Regulatory Officer Experienced leadership team 4 Ryan Robinson, CPA Chief Financial Officer Sandeep Kulkarni, MD Co-founder and Chief Executive Officer Brad Middlekauff, JD Chief Business Officer and General Counsel Yung Chyung, MD Chief Medical Officer Susan Dana Jones, PhD Chief Technology Officer Dora Rau Senior Vice President, Head of Quality Management Team Board of Directors Clay Siegall, PhD Chairman Caley Castelein, MD Aaron Kantoff Mark McDade Sapna Srivastava, PhD Parvinder Thiara Sandeep Kulkarni, MD Don Fitch Senior Vice President, Product Development
Pacibekitug (also referred to as TOUR006) has demonstrated best-in class potential: long-acting, low immunogenicity, and low-volume subcutaneous administration observed in clinical trials to date Two strategic paths to significant value creation: (1) FcRn+ and (2) cardiovascular inflammation Key highlights 5 An IL-6 renaissance is underway: new insights emerging about a broad range of indications where IL-6 may be clinically validated A late-stage clinical company: pivotal Phase 2b spiriTED TED trial and Phase 2 TRANQUILITY CV trial ongoing, pivotal Phase 3 TED trial also expected to commence in 2H 2024 Accomplished leadership team: extensive experience developing and commercializing antibodies for immune and inflammatory diseases Well-financed: cash expected to fund operations into 2027, enabling the delivery of key anticipated milestones for both strategic paths
Second wave of IL-6 Inhibition: driven by emerging insights 2024: Late-stage programs 2024+: Large body of potential indications We are in an IL-6 renaissance 6 AAA: Abdominal aortic aneurysm; AAV: ANCA-associated vasculitis; AE: Autoimmune encephalitis; AM: Acute myocarditis; AMI: Acute myocardial infarction; ASCVD: Atherosclerotic cardiovascular disease; BP: Bullous pemphigoid; CD: Crohn's disease; CHP: Chronic hypersensitivity pneumonitis; CIDP: Chronic inflammatory demyelinating polyneuropathy; COVID19: Coronavirus disease 2019; CRS: Cytokine release syndrome; DMD: Duchenne muscular dystrophy; DME: Diabetic macular edema; GCA: Giant cell arteritis; FcRn: neonatal Fc receptor; HFpEF: Heart failure with preserved ejection fraction; IBM: Inclusion body myositis; IgAN: IgA nephropathy; IgG4-RD: IgG4 related disease; IPF: Idiopathic pulmonary fibrosis; ITP: Idiopathic thrombocytopenic purpura; MCD: Multicentric castleman’s disease; MG: Myasthenia gravis; MN: Membranous nephropathy; MOGAD: Myelin oligodendrocyte glycoprotein antibody-associated disease; MS: Multiple sclerosis; NIU: Non-infectious uveitis; NMOSD: Neuromyelitis optica spectrum disorder; PAP: Pulmonary alveolar proteinosis; pJIA: Polyarticular juvenile idiopathic arthritis; PMR: Polymyalgia rheumatica; PV: Pemphigus vulgaris; RA: Rheumatoid arthritis; Sarcoid: Sarcoidosis; sJIA: Systemic juvenile idiopathic arthritis; SjS: Sjögren's syndrome; SSc-ILD: Systemic sclerosis interstitial lung disease; TED: Thyroid eye disease; TTP: Thrombotic thrombocytopenic purpura; UC: Ulcerative colitis; UME: Uveitic macular edema First wave of IL-6 inhibition: focus on rheumatology 2010 – 2023 RA sJIA pJIA PMR SSc-ILD COVID19 MCD GCA NMOSD CRS NIU Hem: GI: Neph: Resp: Neuro: Rheum: Ophth: Endo: Derm: AAV IgG4-RD SjS CHP IPF PAP Sarcoid DME CIDP IBM MG MS IgAN MN ITP TTP CD UC Graves’ BP PV Cardio: AAA AM Stroke Sustained academic and investigator enthusiasm for IL-6 Hypothesis-generating success from off-label experimentation Human translational data: genetic, biomarker, epidemiologic Sources of emerging insights: Tourmaline-Selected Indications Key Cardiovascular Inflammation FcRn+ UME AE ASCVD MOGAD HFpEF TED AMI DMD
Pacibekitug: an anti-IL-6 antibody with the potential to deliver significant value to patients Pacibekitug attributes observed to date Potential value to patients 1Across six clinical trials in healthy volunteers and RA, SLE, and CD patients. 2Data on file; single intravenous 10mg dose in Ph1 MAD study in RA patients; as measured by C-reactive protein (CRP), a pharmacodynamic marker of IL-6 signaling. 3Generated from Medarex transgenic mouse platform; across 448 subjects dosed with pacibekitug, only 2 subjects generated anti-drug antibodies (ADAs) following treatment. 4Data on file. 5To be assessed based on data from prior Phase 2 trials. 6To be evaluated in CV Phase 2 trial. Long-acting with terminal half-life of ~7 weeks1 >90% pathway inhibition after single 10mg dose2 Fully human with ADAs in only 0.5% of pt3 High affinity to IL-64 Existing data from 448 study participants1 Dosing every 8 weeks5 or quarterly6 Fast, deep, and durable impact across diseases Durable benefit without need to increase dose Volume of ≤1ml for SC injection5 Generally well-tolerated safety profile observed to date 7
The timing of regulatory and clinical trial milestones are subject to change and additional discussion with the FDA AMI: acute myocardial infarction; ASCVD: atherosclerotic cardiovascular disease; CKD: chronic kidney disease; Satra: satralizumab; Zilti: ziltivekimab Two strategic paths to unlock major value creation 8 FcRn+ Cardiovascular Inflammation IL-6 Renaissance Emerging insights implicating IL-6 in a wide range of rare & large diseases Pacibekitug ✓ Long-acting ✓ Low immunogenicity ✓ Low volume, SC Pacibekitug has the potential to be a superior therapy for a wide range of autoantibody- driven diseases vs. FcRn inhibitors Pacibekitug has the potential to transform the care of high- risk patients by targeting key inflammatory pathways driving cardiovascular disease + ❑ H1 2025: TRANQUILITY Phase 2 topline data ➢ 2025: Zilti ASCVD in CKD Phase 3 (ZEUS) topline data ❑ 2025: spiriTED Phase 2b topline data ➢ 2025: Satra TED Phase 3 (Satra-GO) topline data ➢ 2026: Zilti AMI Phase 3 (ARTEMIS) topline data Key expected readouts Key expected readouts Milestones key: ❑ Internal ➢ External ❑ 2026: TED Phase 3 topline data
Strategy Indication Preclinical Phase 1 Phase 2 Phase 3 Expected key milestones FcRn+ Thyroid Eye Disease (TED) Phase 2b topline data expected in 2025 Phase 3 expected to begin in H2 2024 Cardiovascular Inflammation Atherosclerotic Cardiovascular Disease (ASCVD) Phase 2 topline data expected in H1 2025 Clinical development plan for pacibekitug 9 Note: Hatched bars represent trials that have not yet commenced. The timing of regulatory submissions and clinical trial milestones are subject to change and additional discussion with the FDA Expect to announce at least one additional indication in 2024
FcRn+
1Pyzik et al., Nat Rev Immunol (2023). 2Chronic inflammatory demyelinating polyneuropathy (CIDP): ARGX, “argenx Reports Posit Topline Data from ADHERE study...” July 17, 2023. 3Rheumatoid arthritis (RA): Taylor et al., presentation at ACR Convergence (2023). 4Thyroid eye disease (TED): Kahaly et al., J Clin Endocrinol Metab (2023). 5ARGX company reports and filings. 6FactSet as of 12/29/23; assumes Momenta acquisition for $6.5B, UCB market capitalization not included. 7VYVGART, VYVGART HYTRULO, and RYSTIGGO FDA labels. FcRn inhibition has garnered substantial attention to date, however significant unmet need persists 11 • Neonatal Fc receptor (FcRn) inhibition observed to lower IgG antibodies • Mechanism relevant in disorders mediated by pathogenic IgG autoantibodies • Two anti-FcRn therapies approved for myasthenia gravis with additional supportive data in CIDP, RA, and TED2,3,4 What is FcRn?1 • Efficacy limitations: incomplete clinical response observed • Lack of durable efficacy: clinical worsening occurs soon after cessation of therapy • High burden dosing profile: burdensome weekly or biweekly IV or high-volume SC infusions/injections • Unknown long-term safety profile: uncertain rate of infectious or other complications from sustained non-specific reduction of total IgG Key limitations of FcRn inhibition7FcRn market adoption • First approved FcRn inhibitor annualizing ~$1.5B sales in 2nd year of launch in MG5 • FcRn companies account for >$30B in market capitalization6
1Cabezas et al., Front Immunol (2022). 2Dienz et al., J Exp Med (2009). 3Tourmaline PK/PD modelling. 4Howard et al., Lancet Neurol (2021). 5Patel and Bussel, J Allergy Clin Immunol (2020). 6VYVGART, VYVGART HYTRULO, and RYSTIGGO FDA labels. Pacibekitug has broad potential beyond autoantibody reduction An FcRn+ opportunity 12 Potential benefits of IL-6 inhibition versus FcRn inhibitionModes of action for IL-6 inhibition1,2 IL-6 inhibition1,2,3 FcRn inhibition4,5,6 Autoantibody reductions Inhibition of autoantibody production Anti-inflammatory effects beyond autoantibody reduction Durability of effect Low administration burden Favorable long-term safety profile observed to date ? Pathogenic B-cell and plasma cell proliferation Pathogenic Th17 and Tfh cell proliferation and differentiation Acute phase proinflammatory signaling Circulation of pathogenic autoantibodies IL-6 inhibition impacts:
1Lazarus, Best Pract. Res. Clin. Endocrinol. Metab. (2012). 2Bartalena et al., Front. Endocrinol. (2020). 3Horizon Q3 2022 earnings call. 4Tourmaline market research. TED: our beachhead indication designed to validate pacibekitug’s FcRn+ potential in autoantibody-driven diseases 13 High unmet medical need with significant market opportunity • TED patients experience significant disease burden driven by inflammation, proptosis, double-vision, and pain • ~30k new patients each year in the U.S. (average age at diagnosis is ~45)1,2 • ~80%3 of moderate-to-severe TED patients not receiving an FDA-approved treatment, which we believe may be related to significant limitations such as risk of permanent hearing impairment / loss: • Vast majority of US treaters report unmet need across all aspects of treatment (efficacy, safety, administration)4 Extensive third-party clinical support that IL-6 inhibition may address key unmet needs • 50+ publications with 350+ patients demonstrate the therapeutic potential of IL-6 pathway inhibition in TED • IL-6 may play a more central and upstream role in TED pathogenesis than IGF-1R or FcRn • Many TED treaters already routinely utilize IL-6 inhibition in their practice4 Pacibekitug has best-in-disease potential in TED • Deep inhibition of IL-6 pathway observed to date offers potential for durable efficacy across many endpoints • Existing clinical database supports the potential for a well-tolerated profile at selected doses • Q8W dosing would allow for a patient-friendly, low burden treatment course 1 2 3
1. Safety issues: Risk of potentially permanent hearing loss2 2. Limited durability: Growing real-world effectiveness data reveals larger than anticipated number of non-responders / high relapse rate3,4 3. High level of inconvenience & complexity: – IV Q3W (n=8)2 but limited access to infusion centers5 – Numerous visits and high time commitment (HCPs and patients)5 – Need for serial audiograms, as per label2,6 – Burdensome reimbursement approval process7 1Horizon and Amgen company reports and filings. 2TEPEZZA FDA label. 3Kahaly et al., Thyroid (2021) (ATA 2021 presentation). 4Rosenblatt et al., Ophthalmic Plast Reconstr Surg (2023). 5Tourmaline market research. 6Chow and Silkiss, BMJ Case Rep (2022). 7Horizon Therapeutics Public Ltd. Co. Q2 2023 Form 10-Q. IGF-1R class limitations present a significant opportunity for novel therapeutic approaches in TED 14 Sales ($M)1 TEPEZZA U.S. revenues have been stagnating since 2021… …believed to be due to real-world experience $24 $166 $287 $344 $2 $453 $616 $590 $502 $480 $491 $494 $405 $446 $453 $467 $424 $479 -- $100 $200 $300 $400 $500 $600 $700 Q1 2020 Q2 2020 Q3 2020 Q4 2020 Q1 2021 Q2 2021 Q3 2021 Q4 2021 Q1 2022 Q2 2022 Q3 2022 Q4 2022 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Q1 2024 Q2 2024
1Horizon Q3 2022 earnings call; LTM = last twelve months. 2Tourmaline market research; endo = endocrinologist; ophth = ophthalmologist. 3AAMC 2022 Physician Specialty Data Report. 4Hussey and Tao, Orbit (2022). Despite an FDA-approved medicine, the vast majority of moderate-to-severe TED patients remain untreated Most TED patients are not receiving TEPEZZA… …or only get it relatively late in the treatment journey2 Endo (~8.2k3) monitors thyroid levels, treats mainly mild TED Ophth (~18.9k3) manages moderate-severe ocular symptoms Oculoplastic Surgeons (~1.2k4) manages severe disease and/or inadequate response to steroids Mild Moderate Severe / Sight-Threatening TEPEZZA 15 Surgery 0% 20% 40% 60% 80% 100% High Proptosis, High CAS TED Patients % o f P a ti e n ts Untreated 16,000 80% Treated with Tepezza 4,000 20% Simplified Treatment Journey2TEPEZZA US LTM penetration1 Most refer out to other specialists today but many indicate interest in treating as new advanced therapies become available
Adapted from Huang et al., Eye (2018); Hodgson and Rajaii, Ophthalmol Ther (2020); Fang et al, Front Endocrinol (2021); Smith et al., Eye (2019); and Cabezas et al., Front. Immunol. (2022) IL-6 inhibition has the potential to address a central and upstream driver of TED Adipocytes MyofibroblastsHyaluronan 3) Inhibits orbital fibroblast signaling and differentiation Inflammation: • Pain • Redness • Swelling Orbital tissue expansion: • Proptosis • Diplopia • Eyelid retraction • Optic nerve compression Anti-TSHR/IGF-1R autoantibodies IL-6 Orbital fibroblasts 2) Inhibits T-cell driven inflammation1) Inhibits formation of autoantibodies CD4 T-cell TFhMemory B-cell B-cell IL-6 + IL-6 + IL-6 + Survival Plasma cell IL-21 Th17 CD4 T-cell TGF-β IL-6 + IL-17A IL-22 TNFα IL-1β Anti-FcRn Anti-IGF-1R Anti-IL-6 1 3 2 16
Over 50 publications support the therapeutic potential of IL-6 pathway inhibition in TED • 350+ mostly steroid- refractory patients • Late IL-6 inhibition (>9 months post symptom onset) when disease may have exited active phase • Exposure to IL-6 inhibition may have been suboptimal (<6 months) • Tourmaline market research with over 100 TED treaters suggests many HCPs already routinely utilize IL-6 inhibition in their practice We believe many of these reports may underestimate the true efficacy of IL-6 inhibition Proptosis response rate is generally defined in the data outlined here as a ≥2 mm proptosis improvement in the worse eye at baseline without any worsening in the other eye. CAS response rate is generally defined in the data outlined here as a CAS of 0 or 1. Studies referenced in this table represent investigator-led studies and were not designed with the intent of generating evidence for an approval of tocilizumab or sarilumab in TED. The majority of these studies were not designed with power to detect statistical significance. Retro: retrospective. Obs: observational. Prosp: prospective. RCT: randomized controlled trial. CS: case series. CR: case report. NR: not reported. NS: not significant. CI: clear improvement. Tepro: teprotumumab. Publications available upon request 17 Study Details Key Endpoints First author Year Study type N treated Proptosis response rate CAS response rate % autoantibody reduction Pérez-Moreiras 2021 Retro 54 78 89 75 Sánchez-Bilbao 2020 Obs 48 NR NR NR Atienza-Mateo 2018 Retro 29 NR NR NR Lee 2024 Prosp 19 11 47 56 Pérez-Moreiras 2014 Prosp 18 72 100 76 Pérez-Moreiras 2018 RCT 15 93 60 NS de la Fuente Bursón 2020 Retro 15 NR NR NR Pereira 2023 Retro 14 NR NR NR Habroosh 2024 Prosp 13 100 31 68 Boutzios 2023 Obs 12 NR NR 84 Pampín-Sánchez 2022 Retro 11 75 73 NR Moi 2022 Retro 10 CI 80 75 Cortez 2022 Prosp 10 10 100 81 Silkiss 2020 CS 9 CI 56 74 Smith 2021 Retro 9 78 100 54 Bielefeld 2019 Obs 8 NR NR NR Ceballos-Marcias Jose 2020 CS 8 NR 75 41 Bennedjai 2020 Retro 7 NR NR 73 Moás 2022 Obs 7 NR NR 92 Toro-Tobon 2023 Retro 6 50 NR NR de Pablo Gomez 2018 CS 5 NR 60 NR Navarrete 2022 Retro 5 NR NR NR Ribi 2017 CS 3 33 67 NR Maldiney 2020 CS 3 67 NR NR Stevens 2022 Retro 3 100 67 NR Russell 2017 CS 2 NR 0 NR Sy 2017 CS 2 CI 50 69 Study Details Key Endpoints First author Year Study type N treated Proptosis response rate CAS response rate % autoantibody reduction Copperman 2019 CS 2 100 0 NR Coy 2019 CS 2 NR 50 NR Sierra Osorio 2020 CS 2 100 100 NR Park 2021 CS 2 100 100 NR Abeillon-du Payrat 2022 CS 2 100 50 NR Butnaru 2013 CR 1 NR 100 NR Gómez Rodríguez 2014 CR 1 NR 100 NR Bielefeld 2017 CR 1 CI NR NR Canas 2018 CR 1 100 NR NR Pascual-Camps 2018 CR 1 NR NR NR Garreta Fontelles 2019 CR 1 NR NR 93 Mehmet 2020 CR 1 0 NR NR Kaplan 2020 CR 1 NR 0 85 Cayon-Blanco 2020 CR 1 NR 100 NR Tran 2020 CS 1 NR NR NR Ruiz 2021 CR 1 NR NR NR Albrashdi 2022 CR 1 100 NR NR Cezara 2022 CR 1 NR 0 NR Mohamed 2022 CS 1 0 0 NR Moleiro 2022 CR 1 100 NR 86 Almazrouei 2023 CR 1 NR NR NR Cuculescu 2023 CR 1 CI 0 NR Nirmalan 2023 CS 1 NR NR NR Pramono 2023 CR 1 NR NR NR Rymuza 2024 CR 1 100 0 8 Weighted Mean 68% 72% 71% Smith 2017 (tepro Phase 2) 71% 69% N/A Douglas 2020 (tepro Phase 3) 83% 59% N/A
18 Deep & broad efficacy • Meaningful reduction of proptosis • Important improvement of CAS and diplopia Durable • Inhibition of production of anti-TSHR auto-antibodies • Durable response, in part due to low immunogenicity Patient-friendly • SC, ≤1ml injections, every 8 weeks • Finite treatment for most of patients with flexibility where needed Well-tolerated • Well-tolerated safety profile, manageable with routine monitoring • Lack of permanent or irreversible side effects Potential target profile of pacibekitug Market research indicates pacibekitug’s potential to become an optimal first-line therapy and market leader in TED The characteristics presented reflect outcomes that may not be representative of pacibekitug. The results of past clinical trials may not be indicative of future results, and the results of future or ongoing clinical trials may not demonstrate some or any of the characteristics presented.
Inactive phase characterized by fibrosis Active phase (up to 36 months) characterized by inflammation 1Adapted from Bartley, Arch Ophthalmol. (2011). 2Tourmaline market research. Pacibekitug offers the potential to stop disease progression in the inflammatory active phase 19 D is e a s e S e v e ri ty 1 Pacibekitug Expected to be prescribed as 1L Tx T E P E Z Z A U s e 2 Limited TEPEZZA use Majority of TEPEZZA use Symptom onset Treatment of ~2/3 moderate to severe patients Referral of ~1/3 moderate to severe patients P a ti e n t J o u rn e y 2 OphthEndo Oculoplastic surgeon Acute Chronic
24 weeks24 weeks24 weeks pivotal trial in first-line TED n = 81 (27 / arm) Pacibekitug 50 mg SC Q8W x 3 Pacibekitug 20 mg SC Q8W x 3 Period A: Primary efficacy Study population: • Moderate-to-severe TED, with proptosis ≥ 3mm above normal (based on race and gender) • Active phase, with symptom onset ≤ 15 months, CAS ≥ 4 and positive TSI • First-line setting, with cap on prior corticosteroid use (< 1g methylprednisolone or equivalent) Primary efficacy endpoint: • Proptosis response rate at week 20 Additional endpoints: • CAS • Diplopia • QoL, safety, PK/PD/ADA Double-masked, placebo-controlled Phase 2b trial (NCT06088979) Placebo R 20 *Any patient who receives rescue therapy/intervention in Period A will not receive pacibekitug in Period B and will instead undergo follow-up only Pacibekitug 50 mg SC Q8W x 3 Follow-up Period B: Extension Proptosis non- responders* Proptosis responders Open label Study drug dosed at Day 1, Week 8, & Week 16; primary efficacy assessed at Week 20 Follow-up
Cardiovascular Inflammation
Pacibekitug could address a critical but poorly-addressed risk factor in cardiovascular diseases 22 IL-6 driven inflammation has increasingly been validated as a critical modifiable risk factor driving residual cardiovascular risk The potential of IL-6 inhibition spans a broad range of cardiovascular indications, affecting tens of millions of patients globally Pacibekitug’s potentially best-in-class profile, including quarterly subcutaneous administration, is being evaluated in the Phase 2 TRANQUILITY study and is anticipated to be Phase 3-ready in 2025 Converging lines of human evidence across multiple settings support the transformative potential of IL- 6 inhibition IL-6 inhibition is being evaluated in multiple cardiovascular outcomes trials, and Tourmaline is well- positioned to capitalize on emerging clinical enthusiasm
1Tsao et al., Circulation (2023). *Includes coronary heart disease, heart failure and stoke; excludes hypertension CVD: Cardiovascular disease. Cardiovascular disease continues to be the largest area of unmet medical need in the US1 23 >28M CVD patients* ~10% of adults over age 20 >7.5M emergency room visits per year >5M inpatient hospitalizations per year #1 cause of death >900K annual deaths High prevalence High treatment burden Significant mortality
1Adapted from Ridker, Eur Heart J (2016). 2Vrints et al., Eur Heart J (2024). Many patients suffering from cardiovascular diseases continue to experience residual inflammatory risk 24 Known cardiovascular disease LDL 3.8 mmol/L (150 mg/dL) hs-CRP 4.5 mg/L High-intensity statin “Residual cholesterol risk” LDL 2.8 mmol/L (110 mg/dL) hs-CRP 1.8 mg/L Additional LDL reduction “Residual inflammatory risk” LDL 1.15 mmol/L (45 mg/dL) hs-CRP 3.8 mg/L Additional inflammation reduction Differential secondary prevention treatment options for statin-treated patients1 “Lower is better” • A growing body of evidence supports addressing residual inflammatory risk in cardiovascular disease patients whose inflammation is not well- controlled on existing therapies, such as statins. • As of August 2024, the European Society of Cardiology guidelines recommend hs-CRP screening for patients with suspected chronic coronary syndrome2
Conrad et al., Lancet (2022). ASCVD: atherosclerotic cardiovascular disease Inflammation is a strong predictor of risk across several cardiovascular indications 25 • Landmark study of >440,000 patients with chronic inflammatory disorders • Each of the 19 most common autoimmune diseases showed increased CV risk • Excess risk reflected in a wide range of cardiovascular diseases beyond ASCVD • Risk elevation was not explained by traditional risk factors such as cholesterol, body-mass index, and diabetes OtherArrythmiasThrombotic diseasesAtherosclerotic diseases
ACEI: angiotensin-converting enzyme inhibitor, ANGPTL3: angiopoietin-like protein 3, ApoB: apolipoprotein B, ARB: angiotensin receptor blocker, GLP-1: glucagon-like peptide-1, MTP: microsomal triglyceride transfer protein, NPC1L1: Niemann-Pick C1-Like 1, PAR: protease-activated receptors, PCSK9: proprotein convertase subtilisin/ kexin type 9, SGLT2: sodium-glucose cotransporter 2 Significant unmet need for targeted anti-inflammatory therapies for cardiovascular diseases 26 Thrombosis Hypertension Atherogenic lipoproteins Diabetes, Insulin resistance, Obesity Inflammation None readily available Blood pressure ApoB, Non-HDL-C, LDL-C, Triglycerides, Lipoprotein(a) HbA1c, Fasting glucose, Weight C-reactive protein Aspirin P2Y12R inhibitors Factor Xa inhibitor PAR-1 antagonist ACEI/ARB Calcium channel blocker Thiazide diuretic Renin inhibitor Beta-blocker Mineralocorticoid antagonist Statins PCSK9 inhibitors Icosapent ethyl NPC1L1 inhibitor ACL inhibitor Bile acid sequestrants MTP inhibitor ANGPTL3 inhibitor Apheresis SGLT2 inhibitors GLP-1 agonists GIP/GLP-1 agonist Colchicine Atherothrombotic Pathways Biomarkers Approved Therapies Factor XI/XIa inhibitors Angiotensinogen inhibitor Aldosterone synthase inhibitors Endothelin antagonist Renal denervation Baroreceptor activation CEPT inhibitor Lipoprotein(a) inhibitors ApoC3 inhibitor Fibrates CRISPR PCSK9 base editing GIP/GLP-1/glucagon agonists Amylin agonists GIP-1/amylin agonists IL-6 inhibitors NLRP3 inhibitors Therapies in Development
Research increasingly highlights inflammation as a driver of CV risk and supports therapeutic potential of IL-6 inhibition 27
1Publications available upon request. *Annual incidence AAA: abdominal aortic aneurysm. ASCVD: atherosclerotic cardiovascular disease. CAD: coronary artery disease. CKD: chronic kidney disease. HF: heart failure. HFmrEF: Heart Failure with Mid-Range Ejection Fraction. HFpEF: heart failure with preserved ejection fraction. HFrEF: heart failure with reduced ejection fraction. MI: myocardial infarction. PAD: peripheral artery disease. IL-6 inhibition has the potential to address millions of patients across a wide range of inflammation mediated CV conditions 28 ~55% ~55% ~60% ~55% ~55% 100% ~55% ~60% ~60% ~60% ~60% ~75% ~75% ~75% 25M 18M 8.5M 5.5M 3.7M 900K 800K 7.0M 3.2M 3.2M 600K 1.3M 2.5M 900K ASCVD – Total CAD Ischemic stroke ASCVD + CKD 3/4 PAD Acute MI* Acute ischemic stroke* HF - Total HFpEF HFrEF HFmrEF Acute HF* AAA - Total AAA 3.5 to <5.0 cm Estimated US prevalence (2024)1 Populations are not mutually exclusive AS otal CAD I i stroke ASCVD + CKD G3/4 PAD cute MI* Acut i ic stroke* - otal FpEF FrEF F rEF cute HF* A - otal . t <5.0 cm Key Elevated hs-CRP Normal hs-CRP
ASCVD: atherosclerotic cardiovascular disease Convergence of human evidence supports therapeutic potential of IL-6 inhibition for ASCVD 29 Evidence suggests IL-6 may drive ASCVD risk Human genetic evidence Epidemiological evidence Clinical trial evidence
1Ference et al., J. Am. Coll. Cardiol. (2012). 2Casula et al., Pharm. Res. (2019). 3Zhao et al., Ann Rheum Dis (2022). 4Spiera eta al. N Engl Med (2023). 5Wan et al., Hypertension (2021). 6The Blood Pressure Lowering Treatment Trialists’ Collaboration, Lancet (2021). 7Voight et al., Lancet (2012). 8Keene et al., BMJ (2014). 9Gregson et al., Eur J Prev Cardiol. (2017). 10Fras et al., Arch Med Sci. (2021). 11Kang et al., Neurology (2021). 12Lenercept Multiple Sclerosis Study Group, Neurology (1999). 13Levin et al, Circulation Research (2021). 14Minikel et al., Nature (2024). Human genetic studies provide initial support for IL-6 pathway inhibition to lower ASCVD risk 30 Concordance between results of human genetic studies and randomized clinical trials Therapeutic target Genetic Result RCT Result Lowering LDL-C to lower ASCVD risk1,2 Positive Positive Inhibiting IL-6 to treat polymyalgia rheumatica3,4 Positive Positive Lowering blood pressure to lower ASCVD risk5,6 Positive Positive Raising HDL-C to lower ASCVD risk7,8 Negative Negative Inhibiting LpPLA2 to lower ASCVD risk9,10 Negative Negative Inhibiting TNFα to treat multiple sclerosis11,12 Negative (harm) Negative (harm) Inhibiting IL-6 to lower ASCVD risk13 Positive Trials Ongoing “Probability of success for drug mechanisms with genetic support is 2.6 times greater than those without.”14
Hazard ratios shown. Major adverse cardiovascular events (MACE) include myocardial infarction, stroke, coronary revascularization, cardiovascular (CV) death. CKD: chronic kidney disease. hs-CRP: high-sensitivity C-reactive protein. LDL: low-density lipoprotein cholesterol. Certain data in this presentation are based on a cross-trial comparison and are not based on head-to-head clinical trials. Cross trial comparisons are inherently limited and may suggest misleading similarities or differences in outcomes. Results of head-to-head comparisons may differ significantly from those set forth herein. 1Ridker et al., Lancet (2023). 2Ridker et al., Circulation (2023). 3Ridker et al., Eur Heart J (2022). Multiple observational studies show inflammation predicts future MACE even better than cholesterol in high-risk populations 31 0.8 1.0 1.2 1.4 1.6 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 LDL-C hs-CRP Risk of Major Adverse CV Events ASCVD or high risk of ASCVD1 (n=31,245) LDL-C hs-CRP LDL-C hs-CRP 0.8 1.3 1.8 2.3 2.8 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Risk of CV Death (downstream biomarker of IL-6 activity) CANTOS CKD Subgroup3 (n=9,151) CLEAR-Outcomes2 (n=13,970) 1 2 3 41 2 3 4 1 2 3 41 2 3 4 1 2 3 41 2 3 4 1 2 3 41 2 3 4 1 2 3 41 2 3 4 1 2 3 41 2 3 4 uartile uartile uartile uartile uartile uartile Quartile Quartile Quartile Quartile Quartile Quartile hs-CRP LDL-C
1Women’s Health Study. MACE: CV death, MI, stroke, coronary revascularization. Increased risk defined as 1-relative risk, compared to lowest quintile of Lp(a) and hs-CRP population, adjusted for age, initial randomization treatment group, smoking (current, past, never), presence of diabetes, and Framingham blood pressure categories. Table 2. Ridker et al, NEJM (2024). Emerging evidence suggests that hs-CRP is more strongly associated with MACE than both LDL and Lp(a) 32 1.00 1.01 0.94 1.04 1.33 1.00 1.00 1.07 1.23 1.36 1.00 1.11 1.19 1.38 1.70 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5 Lp(a) LDL-C hs-CRP Risk of MACE (95% CI) 30-year longitudinal data from the Women’s Health Study1 (n=27,929) Late breaking data presented at European Society of Cardiology 2024 Congress and simultaneously published in the New England Journal of Medicine
1Ridker et al., N. Engl. J. Med. (2017). 2Adapted from Ridker et al., Circ. Res. (2016), Arnold et al., Eur. J. Cardiol. (2021) and Muller et al., J Lipid Res (2015) Analysis of CANTOS implicates IL-6 as a key ASCVD risk factor Greater IL-6 pathway inhibition associated with greater CV benefit 33 10,061 patients • Stable CAD (post MI) • On Statin, ACE/ARB, BB, ASA • hs-CRP ≥2 mg/L Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) Trial Design1 Primary endpoint: Time to the first occurrence of MACE (CV death, non-fatal MI, or non-fatal stroke) On-treatment analysis: • Reduction in MACE & CV death stratified by on treatment hs- CRP reduction (pre-specified) • Reduction in MACE & CV death stratified by on treatment IL-6 reduction Canakinumab 50 mg Q3M n = 2,170 Placebo Q3M n = 3,344 Canakinumab 150 mg Q3M n = 2,284 Canakinumab 300 mg Q3M n = 2,263 IL-1β is upstream of IL-62 NLRP3 Inflammasome IL-6 IL-1β canakinumab pacibekitug ziltivekimab clazakizumab C-reactive protein (marker of inflammation) PAI-1 Anti- fibrinolytic Pro- clotting Fibrinogen + - NLRP inflammasome inhibitors colchicine Lipoprotein(a)
Reduction in MACE shown as 1-Hazard Ratio. ITT: intent to treat. MACE: major adverse cardiovascular events including CV death, myocardial infarction (MI), stroke. n.s.: not statistically significant. ITT CANTOS analysis presents data for 150mg dose group; values for CANTOS subanalyses combine all doses (50, 150, 300 mg). Ridker et al., NEJM (2017). Ridker et al., Lancet (2018). Adjusted for age, gender, smoking, hypertension, diabetes, BMI, baseline hs-CRP, baseline LDL-C. Ridker et al., Eur Heart J (2018). Adjusted for age, gender, smoking, hypertension, diabetes, BMI, baseline IL-6, baseline LDL-C. Ridker et al., JACC (2018). Lessons from canakinumab (anti-IL-1β mAb): “Lower is better” for downstream biomarkers of IL-6 activity 34 On-treatment On-treatment -15% -25% -30% -35% -60% -50% -40% -30% -20% -10% 0% R e d u c ti o n i n M A C E IL-6 low tertile hs-CRP <2 mg/L CKD ITT hs-CRP <2 mg/L R e d u c ti o n i n C V D e a th IL-6 low tertile hs-CRP <2 mg/L hs-CRP <2 mg/L -12% -31% -34% -59% -60% -50% -40% -30% -20% -10% 0% ITT CKD n.s.
Reduction in MACE shown as 1-Hazard Ratio. MACE: major adverse cardiovascular events including CV death, myocardial infarction (MI), stroke except for: ODYSSEY OUTCOMES (all death, MI, ischemic stroke); COLCOT (CV death, MI, stroke, resuscitated cardiac arrest); LoDoCo2 (CV death, MI, ischemic stroke); main CANTOS analysis presents data for 150mg dose group; values for CANTOS subanalyses combine all doses (50, 150, 300mg); control arms were placebo + background SoC. Certain data in this slide are based on a cross-trial comparison and are not based on head-to-head clinical trials. Cross-trial comparisons are inherently limited and may suggest misleading similarities or differences in outcomes. Results of head-to-head comparisons may differ significantly from those set forth herein. NNT (number needed to treat) values obtained from absolute risk extracted from Kaplan-Meier figures via webplotdigitizer, unless directly reported. NNT for IL-6 < median shown; not reported for IL-6 low tertile. The information on this slide is based on Tourmaline-generated analysis of third-party data and is being presented for hypothesis generating purposes only. As a result, the actual MACE risk reduction hypothesized may be more or less than the data presented in this slide. Publications available upon request. Lessons from canakinumab (anti-IL-1β mAb): Robust inhibition of IL-6 pathway has transformative potential in ASCVD 35 -30% -35% -14% -15% -15% -20% -20% -26% -28% -50% -40% -30% -20% -10% 0% R e d u c ti o n i n M A C E IL-6 low tertile hs-CRP <2 mg/L CKD Alirocumab ODYSSEY Bempedoic acid CLEAR Colchicine COLCOT Evolocumab FOURIER Semaglutide SELECT Icosapent ethyl REDUCE-IT Colchicine LoDoCo2 3-year estimates for NNT (number needed to treat) support transformative potential and efficient Phase 3 study designs 14 20 63 CANTOS: On-treatment 57368350nr85
-17% -47% -59% -68% -4% -76% -88% -91% 19% -86% -90% -92%-100% -80% -60% -40% -20% 0% 20% PBO 50 mg 150 mg 300 mg PBO 7.5 mg 15 mg 30 mg PBO 2.5 mg 5 mg 10 mg 1Ridker et al., NEJM (2017). 2Ridker et al., Lancet (2021). 3Chertow, Nature (2024). Certain data in this presentation are based on a cross-trial comparison and are not based on head-to-head clinical trials. Cross trial comparisons are inherently limited and may suggest misleading similarities or differences in outcomes. Results of head-to-head comparisons may differ significantly from those set forth herein. In independent studies, direct IL-6 inhibition lowered hs-CRP more than upstream IL-1β blockade 36 M e d ia n % r e d u c ti o n i n h s -C R P (W e e k 1 2 ) Ziltivekimab Monthly (Phase 2 RESCUE)2 Canakinumab Quarterly (Phase 3 CANTOS)1 Direct IL-6 inhibition achieved ~2x placebo-adjusted reductions in hs-CRP compared to upstream IL-1β Clazakizumab Monthly (Phase 2b)3
The timing of clinical trial milestones are subject to change. ASCVD: atherosclerotic cardiovascular disease. CKD: chronic kidney disease. CVOT: cardiovascular outcome trial. ESKD: End Stage Kidney Disease. HFpEF: heart failure with preserved ejection fraction. MACE: major adverse cardiovascular event. MI: myocardial infarction. 1Clinicaltrials.gov: NCT05021835. 2Clinicaltrials.gov: NCT06118281. 3Clinicaltrials.gov: NCT06200207 4Clinicaltrials.gov: NCT05636176 5Clinicaltrials.gov: NCT05485961 (Phase 3 portion only) Five Phase 3 CVOTs enrolling >24,000 patients 37 Ziltivekimab 15 mg QM + Standard of Care Placebo QM + Standard of Care 6,200 patients • ASCVD • CKD stage 3-4 • hs-CRP ≥2 mg/L 1:1 ZEUS: ASCVD w/CKD1 Primary endpoint: Time to the first occurrence of MACE (CV death, non-fatal MI, or non-fatal stroke) Secondary endpoints: • Time to first occurrence of expanded MACE (above plus urgent coronary revascularization) • Number of hospitalizations for HF or urgent HF visits • Time to occurrence of CV death • Time to first occurrence of composite CKD endpoint ATHENA: HFpEF3 Primary endpoint: Change in KCCQ-CSS at 1 year Secondary endpoints: • Participant achieving threshold for clinically meaningful within- participant change in KCCQ CSS • Participant achieving threshold for clinically meaningful within- participant change in 6-minute walk distance (6MWD) • Participants improving 5 points or more in KCCQ-CSS ARTEMIS: acute MI2 Ziltivekimab loading dose 1 followed by dose 2 QM + Standard of Care Placebo QM + Standard of Care 10,000 patients • Acute MI • First dose within 24 or 48 hrs 1:1 Primary endpoint: Time to the first occurrence of MACE (CV death, non-fatal MI, or non-fatal stroke) Secondary endpoints: • Number of CV death, non-fatal MI, non-fatal stroke • Time to first occurrence of composite MACE consisting of: all- cause mortality, non-fatal MI, and non-fatal stroke • Time to first occurrence of MI (fatal and non-fatal) • Time to occurrence of CV death Ziltivekimab QM + Standard of Care Placebo QM + Standard of Care 680 patients • HF Class II-III • hs-CRP ≥2 mg/L 1:1 Topline data readouts expected 2025 2026 2026 HERMES: HFpEF4 Primary endpoint: Time to first occurrence of a composite HF endpoint (CV death, HF hospitalization, or urgent HF visit) Secondary endpoints: • Time to first occurrence of 4-point composite HF endpoint (CV death, HF hospitalization or urgent HF visit, non-fatal MI, non-fatal stroke) • Number of CV deaths, HF hospitalizations or urgent HF visits • Time to occurrence of CV death Ziltivekimab 15 mg QM + Standard of Care Placebo QM + Standard of Care 5,600 patients • HF Class II-IV • hs-CRP ≥2 mg/L 1:1 2027 POSIBIL6: ESKD5 Primary endpoint: Time to first occurrence of CV death or MI Secondary endpoints: • Time to first occurrence of all- cause death or MI • Time to first occurrence of CV death, MI, or ischemic stroke • Time to first occurrence of CV death Clazakizumab 5 mg Q4W + Standard of Care Placebo Q4W + Standard of Care 2,310 patients • ESKD • Diabetes or ASCVD • hs-CRP ≥2 mg/L 1:1 2028
CD: Crohn’s disease, CKD: chronic kidney disease, HD: hemodialysis, NDD: non-dialysis dependent, SLE: systemic lupus erythematosus. 1Incidence of ADAs in repeat-dose studies calculated as reported per dosing arm. 2Route of administration in planned or ongoing studies in patients with or at high-risk of ASCVD. 3Clinicaltrials.gov NCT03926117. 4Pergola et al., JASN (2021). 5Ridker et al., Lancet (2021). 6Wada et al., J Cardiol (2023). 7Clinicaltrials.gov NCT01490450. 8Clinicaltrials.gov NCT01545050. 9Weinblatt et al., Arthritis Rheum (2015). 10Clinicaltrials.gov NCT05485961. Data reported in publications or on clinicaltrials.gov as detailed above. No head-to-head studies have been conducted between the mabs shown here, which have each been evaluated in different populations. Pacibekitug designed to offer best-in-class potential profile in cardiovascular diseases 38 Pacibekitug Ziltivekimab Clazakizumab Company Monoclonal antibody fully human (IgG2) Medarex UltiMAb platform fully human (IgG1k, YTE mutation) humanized rabbit (IgG1k) Anti-drug antibodies1 0-1% 6-13%3,4 0-10%7-9 Route of administration2 SC 0.6 mL SC5,6 1.0 mL IV10 Longest dosing intervals in completed studies Q8W (SLE, CD) Q4W (NDD-CKD)5,6 Q4W10 (HD-CKD) Targeted dosing intervals Quarterly Monthly Monthly
CRP: C-reactive protein, CD: Crohn’s disease, OLE: open-label extension, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus. Rheumatoid arthritis: B0151002 study report. Table 14.4.7.1.1. Median baseline CRP 9.0 mg/L. Key eligibility: active disease, background methotrexate. Crohn’s disease: B0151003 study report. Table 14.2.4.1.3. Median baseline hs-CRP 21.1 mg/L. Key eligibility: active disease, failed/intolerant to anti-TNFα. CD OLE B0151005 study report. Table 14.2.4.1. Median pre-baseline hs-CRP 16.4 mg/L, baseline hs-CRP 4.0 mg/L. Systemic lupus erythematosus: B0151006 study report. Table 14.3.4.1.5. Median baseline hs-CRP 2.2 mg/L. Pacibekitug achieved robust and durable suppression of CRP in patients with high-grade inflammatory autoimmune disorders 39 Dosing: 0 2 4 6 8 10 0 4 8 12 16 20 0 5 10 15 20 0 4 8 12 Phase 1 RA IV 10 mg (n=6) Phase 2 CD SC 50 mg (n=71) M e d ia n C -r e a c ti v e p ro te in ( m g /L ) Weeks Weeks 0 5 10 15 20 -8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Phase 2 CD OLE SC 50 mg or 50→100 mg (n=91; n=100) Pre Weeks 0 2 4 6 8 10 0 4 8 12 16 20 24 Phase 2 SLE SC 50 mg (n=47) Weeks
ASCVD: atherosclerotic cardiovascular disease, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, CD: Crohn’s disease. The PK and PK/PD models for pacibekitug were developed based on the data from 5 clinical studies (two phase 1 studies in healthy volunteers, one phase 1 study in RA, one phase 2 study in SLE, and one phase 2 study in CD). A two-compartment model with first-order absorption and linear elimination and a mechanism-based indirect response model (in a relationship on CRP) adequately described the PK and PK/PD relationships, respectively. Simulations were performed assuming an RA-like population with baseline CRP >2 mg/L to 10 mg/L. Results at Day 90 are shown. 1Ridker et al., Lancet (2021). 2Chertow, Nature (2024). Results after 12 weeks of treatment are shown. Certain data in this slide are based on a cross-trial comparison and are not based on head-to-head clinical trials. Cross-trial comparisons are inherently limited and may suggest misleading similarities or differences in outcomes. Results of head-to-head comparisons may differ significantly from those set forth herein. PK/PD modeling supports potential for quarterly dosing of pacibekitug SC in ASCVD 40 Median % reduction in hs-CRP 15 mg50 mg 25 mg % achieving hs-CRP <2 mg/L % achieving ↓hs-CRP >50% Quarterly Monthly Results of PK/PD model developed from five studies in patients with RA, SLE, CD and healthy volunteers Ziltivekimab 15 mg monthly1 median % reduction: 88% % achieving hs-CRP<2 mg/L: 82% % achieving ↓hs-CRP>50%: 89% 15 mg50 mg 25 mg Quarterly Monthly 15 mg50 mg 25 mg Quarterly Monthly >85% >80% >90%-100% 0% >90% >85% >90% 0% 100% >90% >90% >90% 0% 100% Clazakizumab 5 mg monthly2 median % reduction: 90% % achieving hs-CRP<2 mg/L: 82% % achieving ↓hs-CRP>50%: 92%
6 months Safety follow-up period 6 months Treatment period n = 120 (30 / arm) Phase 2 trial supporting development in ASCVD 41 Pacibekitug 50 mg SC quarterly Pacibekitug 25 mg SC quarterly Pacibekitug 15 mg SC monthly Study population: • CKD stage G3-4 (eGFR 15-59 ml/min/1.73m2) • hs-CRP ≥2 mg/L and <15 mg/L • Exclude patients at higher risk for safety complications (e.g., immunocompromised patients) Primary efficacy endpoint: • Change from baseline in hs-CRP Additional endpoints: • Other pharmacodynamic markers: serum amyloid A, fibrinogen, lipoprotein(a), and other biomarkers • Safety and tolerability R Placebo Double-blinded, placebo-controlled Phase 2 trial (NCT06362759) Follow-up
The timing of regulatory and clinical trial milestones are subject to change and additional discussion with the FDA AE: autoimmune encephalitis; AMI: acute myocardial infarction; ASCVD: atherosclerotic cardiovascular disease; HFpEF: heart failure with preserved ejection fraction. MOGAD: myelin oligodendrocyte glycoprotein antibody-associated disease; Satra: satralizumab; TED: thyroid eye disease; Zilti: ziltivekimab Key milestones expected through 2026 42 ❑ H1 2024: Initiate CV Phase 2 trial ❑ H1 2025: CV Phase 2 topline data Cash runway expected into 2027 FcRn+ Cardiovascular Inflammation ❑ H2 2024: Initiate pivotal TED Phase 3 trial ❑ 2026: TED Phase 3 topline data❑ 2025: spiriTED Phase 2b topline data ➢ 2026: Zilti AMI Phase 3 (ARTEMIS) topline data ➢ 2026: Satra AE Phase 3 (CIELO) topline data ➢ 2025: Satra TED Phase 3 (Satra- GO) topline data ➢ 2025: Zilti ASCVD in CKD Phase 3 (ZEUS) topline data 2024 2025 2026 ➢ 2026: Zilti HFpEF Phase 3 (ATHENA) topline data ➢ 2026: Satra MOGAD Phase 3 (METEOROID) topline data Expect to announce at least one additional indication in 2024 Milestones key: ❑ Internal ➢ External
