Spero Therapeutics, Inc. · NASDAQ:SPRO
Spero Therapeutics — Investor Presentation (July 2026)
28 slides from Spero Therapeutics's investor presentation, Jul 14, 2026
Slide 1: Corporate Presentation July 2026
Corporate Presentation July 2026 Exhibit 99.3
Slide 2: Forward-looking statements
This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the Company; the ability to successfully achieve and execute on the Company’s goals, priorit
Slide 3: Developing Novel Medicines for Immune-Mediated Diseases
Developing Novel Medicines for Immune-Mediated Diseases Established operational and public company infrastructure SP001, a third-generation Fc-silent anti-CD40L mAb with potential for development across a range of immune-mediated diseases Cash runway into 2H 2029 Lead indication in IgG4-related dise
Slide 4: Key Investment Highlights: SP001
Key Investment Highlights: SP001 Sjögren’s disease, additional rheumatological applications, and applications in non-rheumatological therapeutic areas Target with human proof-of-concept in several autoimmune diseases Differentiated mechanism compared to other B-cell targeting agents Preclinical data
Slide 5: SP001 Development Plan for Rheumatological Disorders
Indication Exploratory Phase 1 Phase 2 Phase 3 Catalyst / Expected timing IgG4-RD Phase 2 initiation Q2 2027 Sjögren’s disease (Innovent)* Phase 2 initiation by early 2027 * Development in greater China SP001 Development Plan for Rheumatological Disorders
Slide 6: CD40-CD40L System: A Master Regulator of Immunity
Adapted from Laman JD, Molloy M, Noelle RJ. Switching off autoimmunity. Science. 2024 Aug 23;385(6711):827-829. CD28/CD80–CD86 T-cell co-stimulation not shown for clarity CD40-CD40L System: A Master Regulator of Immunity Antigen presentation: CD4 T cells present a CD40L “go” signal to antigen presen
Slide 7: CD40L Mechanism Provides Multiple Development Opportunities
Sources: Wallace ZS et al. Ann Rheum Dis 2023; Stone JH et al. NEJM 2012; Lanzillotta M. et al. Rheumatology 2020.; De IgG4-RD DelveInsight Epidemiology, 2024. CD40L Mechanism Provides Multiple Development Opportunities Phase 2 ready in Sjögren's disease Additional rheumatological diseases Explorato
Slide 8: Selected Indications Offer Attractive Competitive Dynamics
SP001 1,2. Lists may not be all inclusive. 2. Initiated by other industry sponsors developing CD40L targeting agents. Preliminary Indications Selected Offer Attractive Competitive Dynamics Spero’s Potential Development1 Ongoing Clinical Trials in Additional Indications2 IgG4-related disease – Sjögre
Slide 9: SP001 Overview
SP001 Overview SPER@®
Slide 10: SP001 Is a Third-Generation, Fully Humanized, Fc-silent CD40L mAb
SP001 is an IgG1 mAb designed to be Fc-silent (ΔP-LALA) No detectible Fc receptor and complement binding, eliminating platelet activation Normal FcRn interactions are preserved à IgG-like half-life Constant fragment (Fc) domain interacted w/ FcgRIIa on platelets, the putative MOA for the increased r
Slide 11: SP001 Presents Potent Immune Suppression In Vivo
SP001 demonstrated superior immune suppression in anti-KLH immunization model compared to leading Phase 3 mAb Anti-KLH (keyhole limpet hemocyanin) antibody evaluates immune function by measuring IgM (early response) and IgG (later response) antibodies following vaccination. Saghari M, Gal P, Ziagkos
Slide 12: Phase 1b Characterized Safety/Tolerability, PK, and Efficacy Signals
1. Phase 1b MAD in Sjögren’s disease patients completed in China. *Sponsor unblinded. N=10/cohort | Ratio 8:2 (active: placebo) within each cohort; two parallel placebo slots per cohort pooled as N=6. Poster presentation dated June 5, 2026, presented at the European Alliance of Associations for Rheu
Slide 13: Safety Data Was Generally Benign
Safety Parameter SP001 7.5 mg/kg (N=8) SP001 15 mg/kg (N=8) SP001 30 mg/kg (N=8) SP001 Total (N=24) Placebo (N=6) Any Adverse Event (%) 75.0 87.5 75.0 79.2 100.0 Upper Respiratory Tract Infection (%) 50.0 50.0 50.0 50.0 33.3 Hyperlipidemia (%) 37.5 12.5 0.0 16.7 16.7 Serious Adverse Events None repo
Slide 14: Improvements in Disease Activity and B-cell Biomarkers
Source: 2026 EULAR poster, Efficacy section Demonstrated Improvements in Disease Activity and B-cell Biomarkers Rheumatoid factor, a classical autoantibody marker EULAR Sjögren's Syndrome Patient Reported Index EULAR Sjögren's Syndrome Disease Activity Index ESSDAI ESSPRI RF% 7.5 mg/kg N=7 15 mg/kg
Slide 15: Ph1b Trial Demonstrates Favorable Efficacy over Competitor Candidates
*Study performed in China 1. 2026 EULAR poster, Efficacy section. SP001 PBO group had 3 patients w/ ESSDAI ≥5; LS mean change from week 0 to week 24 = -0.67 2. Xu et al. Rheumatology (Oxford). 2024;63:698–705 3. St. Clair et al. Nat Med. 2024;30:1583–1592 4. Bowman et al. Lancet. 2022;399:161–171. T
Slide 16: Data to Date Support Continued Development
Data to Date Support Continued Development Low rate of anti-drug antibodies (ADA) SP001 well-tolerated across doses over the course of Phase 1b trial Preclinical toxicology and Phase 1 studies support continued development Chronic preclinical toxicology study currently underway to support longer dur
Slide 17: IgG4-Related Disease
IgG4-Related Disease
Slide 18: IgG4-Related Disease: Chronic, Immune-Mediated Fibroinflammatory Condition
Source: UpToDate; DelveInsight; Wallace ZS, et al. Ann Rheum Dis 2023;82:957–962 IgG4-Related Disease: Chronic, Immune-Mediated Fibroinflammatory Condition Back Abdominal Cavity Thyroid & Pituitary Gland Chest Cavity Pancreas Lungs Kidneys Liver and Biliary Tract Heart & Aorta Meninges Eye Sockets S
Slide 19: Current IgG4-RD Treatment Paradigm Results in Cycles of Relapse
IgG4-RD Diagnosed Source: Syneos Health analysis. 1. Peyronel et al, Nature 2025. IgG4-related disease and other fibro-inflammatory conditions | Nature Reviews Rheumatology 2. Khosroshahi et al, A&R 20215 International Consensus Guidance Statement on the Management and Treatment of IgG4‐Related Dise
Slide 20: IgG4-RD Development Landscape Leaves Room for Differentiated Mechanism
Asset Name Company Target Mechanism of Action Route of Administration Development Status SP001 CD40L T–B cell co-stimulation Intravenous Phase 2 planned Uplizna CD19 B-cell depletion Intravenous Launched Obexelimab CD19+FcgRIIb B-cell inhibition Subcutaneous Phase 3 Rilzabrutinib BTK B-cell inhibiti
Slide 21: Biological Rationale for CD40L Inhibition in IgG4-RD
1. Borges T, Silva S. IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? Mod Rheumatol. 2020 Jul;30(4):609-616.; 2. Kudo-Tanaka E, et al., A case of Mikulicz's disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren's s
Slide 22: Phase 2 Study Designed to Establish Proof of Concept
* Patient is flaring despite steroids Phase 2 Study Designed to Establish Proof of Concept Phase 2 Open Label Treatment (24 weeks) Optional Long-term Extension (to 52 weeks) SP001 Dose 1 N=15 SP001 Dose 2 N=15 R Population: IgG4-RD patients with >1 organ involved over time and active in at least one
Slide 23: Expansion Opportunities
Expansion Opportunities
Slide 24: Sjögren's Disease Is a Complex Disorder with Limited Treatments Available
Neurological Problems concentration, memory loss (brain fog) Dry nose, recurrent sinusitis, nose bleeds Dry mouth, mouth sores dental decay, difficulty chewing, speech, taste Dry eyes, corneal ulceration and infections Difficulty swallowing, heartburn, reflux esophagitis Recurrent bronchitis pneumon
Slide 25: Sjögren's Disease: US Epidemiology and Unmet Needs
Epidemiology 1-4 *Potential to capture additional patients as market evolves with new and improved therapies. Sources: 1.Sjögren’s Foundation website – fast facts accessed 8 June 2026 (affecting as many as 4m Americans); 2. Willey C, Ali S, Alten R. Prevalence of Physician-Diagnosed versus Clinicall
Slide 26: The Biological Rationale for CD40L in Sjögren's Disease Is Well Established
The Biological Rationale for CD40L in Sjögren’s Disease Is Well Established 1. Dimitriou et al. Clin Exp Immunol. 2002;127:386–392 2. Nakamura et al. Lab Invest. 1999;79:261–269 3. Goules et al. J Autoimmun. 2006;26:165–171 4. Belkhir et al. Scand J Immunol. 2014;79:37–42. 5. Wieczorek et al. Ann Rh
Slide 27: Key Investment Highlights: SP001
Key Investment Highlights: SP001 Sjögren’s disease + applications in cardiology and endocrine disorders Target with human proof-of-concept in several autoimmune diseases Differentiated mechanism compared to other B-cell targeting agents Preclinical data show high potency compared to key competitors
Slide 28: Thank You
Thank You Spero Therapeutics www.sperotx.com
Spero Therapeutics — Investor Presentation (July 2026) on 6ix