Complement R&D Day Presentation

Nasdaq: CBIO

CATALYST BIOSCIENCES

Complement R&D Day 14 December 2020

CatalystBiosciences.com

12:00 pm – 12:10 pm ET 12:25 pm – 12:45 pm ET Nassim Usman, Ph.D. – President and CEO Grant Blouse, Ph.D. – SVP, Translational Research + Company vision + Protease engineering platform + Protease engineering platform overview + CBIO complement pipeline update + Complement program strategy . First development candidate – CB 4332 . Pipeline plans 12:10 pm – 12:25 pm ET Ron Taylor, Ph.D. – Professor Emeritus, 12:45 pm – 1:00 pm ET Biochemistry and Molecular Genetics, University of Clinton Musil – Chief Financial Officer Virginia School of Medicine + Milestones & closing remarks + Complement pathways; the role of proteases + Q&A + Diseases associated with uncontrolled complement activation + Current therapies and unmet needs

Certain information contained in this presentation and studies may be delayed as a result of COVID-19 and other statements made orally during this presentation include factors, that trials may not have satisfactory outcomes, that forward-looking statements that involve substantial risks and human trials will not replicate the results from earlier trials, the uncertainties. All statements included in this presentation, other risk that costs required to develop or manufacture the than statement of historical facts, are forward-looking Company’s products will be higher than anticipated, including statements. Forward-looking statements include, without as a result of delays in development and manufacturing limitation, statements about Catalyst’s product candidates and resulting from COVID-19 and other factors, the risk that Biogen the benefits of its protease engineering platform, projected will terminate Catalyst’s agreement, competition and other risks complement market opportunity, solution to fundamental described in the “Risk Factors” section of the Company’s shortcomings in current treatment options, plans to enroll the Annual Report on Form 10-K filed with the Securities and CB 4332 observational trial in the Company's complement Exchange Commission (the "SEC") on February 20, 2020, program in mid 2021, and ongoing updates on CB 4322 and Quarterly Report on Form 10-Q filed with the SEC on November the C4b degrader. Actual results or events could differ 5, 2020, and in other filings with the SEC. The forward-looking materially from the plans, intentions, expectations and statements in this presentation represent the Company's projections disclosed in the forward-looking statements. Various views as of the date of this presentation and the Company does important factors could cause actual results or events to differ not assume any obligation to update any forward-looking materially, including, but not limited to, the risk that trials and statements, except as required by law.

Nature’s biological regulators

Control key biological mechanisms

Activate or inactivate biological pathways

Can be tuned for high specificity and functionality

Deficiencies often cause severe disease

© Catalyst Biosciences 5 Structural model based on PDB 1AVW Catalyst’s protease platform generates differentiated therapeutics Unique expertise in protease biology enables design of optimized protease therapeutics

Discovery Platform

Structure guided Our Proteases Protease design Therapeutic scaffold protease + Functionally enhanced natural proteases in Molecular evolution biological pathways + Modulate biological activation & inactivation Engineered pathways regulation + Engineered novel protein degraders Pharmacokinetic improvement

Therapeutic modalities The protease advantage Address root cause of disease Monoclonal antibodies caused by cascade dysregulation

Small molecule inhibitors One molecule regulates 1000s – Optimal for high abundancy and Protease therapies undruggable targets

RNA interference Can be engineered to specifically degrade novel targets

Marzeptacog alfa Dalcinonacog alfa CB 2782-PEG (activated) 90% reduction Achieved sustained Best-in-class profile for dry AMD in annualized bleed rate & high target levels of FIX Extended pharmacodynamics

Normal clotting levels

50% Mild Hemophilia

5% Moderate Hemophilia 1% Severe Hemophilia Before treatment On treatment

Engineered Engineered Novel rFVIIa protease rFIX protease C3 degrader

Cascade Central point of Terminal initiation regulation complement

C2 Classical C1r C4b C3a pathway C1s C4 Immune response inflammation

Lectin MASP C3 C3b C5a pathway CB 2782-PEG C5

Alternative C3 FB FD C3b C5b pathway (H2O) Membrane attack complex (MAC)

Grant E. Blouse, Ph.D. SVP, Translational Research

CP LP AP

Damaged/altered/foreign cells and debris Exacerbation Exacerbation

Neoepitopes/ ? FP autoepitopes MBL Fcn CL DAMP NAb AAb Immune Tick-over C1qR C1q MASP1 MASP2 ? modulation C1r C1s MASP3 C3* C3 C3b C1-INH pFD FD FB

C2 C4 FD FB FP C4a C3*Bb Circulation C4BP C4b2b FH turnover

Extrinsic C3 C3bBb % FP protease

Immune FD FP C3aR C3a C3bBb modulation C3 convertase Amplification FB C3a-dR C3b CPN CD55 FH 80 of the complement FP CR1 CR1 Adhesion C4b2b3b C3bBb3b Immune C5a-dR C5 convertase CR46 C3b modulation cascade is regulated CPN CD46 Chemotaxis, Extrinsic C5 FH FB inflammatory C5aR2 proteases by proteases signaling and C5a CR1 cell C5aR1 CR4 Phagocytosis activation C5b iC3b Trafficking CR3 Signaling C6

C7 CR1 FI C9n C8

Lysis, cell Adaptive MAC CD59 C3dg CR2 damage signaling

Terminal Breakdown pathway pathway

Reference: Figure adapted from Mastellos et al., Clinical promise of next-generation complement therapeutics. Nature Reviews. 2019 © Catalyst Biosciences 34 Complement plays a critical role in many diseases Late-stage complement therapies projected to achieve net sales over $12B by 2026

Nephrology Infectious Disease

Hematology/Oncology Dermatology

Neurology Immunology

Pulmonology Gastroenterology

Endocrine/Metabolism Musculoskeletal

Cardiovascular Ophthalmology References: Globaldata consensus net sales forecast 2020

eculizumab approval (2007)

2000 2005 2010 2015 2020

2000 - 2015 2015 - 2020 187 252 Clinical trials Clinical trials

Discovery Platform

Structure guided Our Proteases Protease design Therapeutic scaffold + Functionally enhanced protease natural proteases in biological pathways Molecular evolution + Modulate biological activation & inactivation pathways Engineered Engineered novel protein regulation + degraders - designed for almost any target or cascade Pharmacokinetic improvement

© Catalyst Biosciences 37 Structural model based on PDB 1AVW Proteases are ideal for high abundancy targets & cascades A better way to regulate biological processes compared with antibodies & small molecules

Protease Therapeutic target neutralization

Efficient regulation at low concentrations of therapeutic protease

Antibodies Requires high antibody concentrations in excess of the target

Small molecules / peptides Requires high concentrations & frequent dosing

CB 2782-PEG Designed for a best-in-class anti-C3 profile in dry AMD

CB 2782-PEG degrades C3 levels in the eye for Catalytic Advantage of Proteases at least 28 days in a non-human primate model

+ One therapeutic molecule neutralizes 1000s

+ Fast & potent response

+ Extended pharmacodynamic effect

+ Can activate or degrade therapeutic targets

+ Engineered novel protein degraders “sweep away” difficult to drug targets

C2 Classical C1r C4b pathway C1s C4

+ CFI normally acts to downregulate C4b and C3b Normal CFI CFI + Inhibition of C4b and C3b prevents overactivation of the complement responses that can cause disease

Alternative C3 FB FD C3b pathway (H2O)

C2 Classical C1r C4b C3a pathway C1s C4 Immune response inflammation

Defective CFI CFI C3 C3b C5 C5a

Alternative C3 FB FD C3b C5b pathway (H2O) Membrane attack complex (MAC)

+ In patients with CFI mutations, C4b and C3b cannot be sufficiently regulated + Dysregulation leads to overactivation of the complement pathway and damaging immune responses

C2 Classical C1r C4b C3a pathway C1s C4 Immune response inflammation

Defective CFI CFI C3 C3b C5 C5a

Alternative C3 FB FD C3b C5b pathway (H2O) Membrane attack Other Treatments complex (MAC)

+ Current C5 blockade therapies do not address disease root cause leading to inadequate disease control + Small molecules and peptides are unable to fully block complement

C2 Classical C1r C4b pathway C1s C4

CB 4332: Enhanced CFI

Alternative C3 FB FD C3b pathway (H2O)

Unmet needs in CB 4332 CFI deficiency Designed to address

Blocks complement-initiated cell destruction in the circulation  Directly addresses root cause of disease  Addresses extravascular hemolysis  Preserves normal immune functions, eg. to fight off infections  Convenient weekly SQ administration 

+ Restores normal complement system in patients with dysregulated CFI + No specific therapies exist to correct CFI dysregulation + Targets population with no treatment or who respond poorly to current Half-Life Extension 1,2 Technology treatments + Engineered for an extended half-life + Genetically defined patient population . Once weekly SQ therapy + Full activity comparable to native CFI . Classical and alternative pathway regulation + Efficient high yield production process References: 1Bienaime et al. Kidney Int. 2010; 2Ferreira et al. Nefrologia. 2016 Note: CFH = Complement factor H © Catalyst Biosciences Structural model based on PDB 2XRC 46 CB 4332 nonhuman primate pharmacokinetics predicts weekly SQ Systemic single-dose PK in nonhuman primates

CB 4332 Dosed at 1 mg/kg SQ

Engineered Functional Improvements Plasma Concentration Plasma

Plasma CFI Dosed at 1 mg/kg SQ

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Days) © Catalyst Biosciences 47 CB 4332 & plasma CFI perform similarly in human serum

100 Classical pathway 100 Alternative pathway

75 75

50 25 Inhibition of hemolysis (%) Inhibition of hemolysis (%) Plasma CFI Plasma CFI CB 4332 CB 4332 25 0 10 100 1000 10000 100000 1 10 100 1000 Concentration of test article (nM) Concentration of test article (nM)

© Catalyst Biosciences 48 CB 4332 - CFI dysregulation observational study Observational trial to identify CFI deficient patients for further CB 4332 clinical development Screening Objectives Total ≥ 24 Subjects (male/female) ≥ 12 years of age ● Primary Objective Demonstrate the prevalence, distribution and phenotypic manifestation of CFI mutations in aHUS, C3G, IC-MPGN Study / Observational Period (6 mo) subjects requiring treatment to identify patients for a future Phase 1 study

Cohort 1: aHUS ● Secondary Objectives Cohort 2: C3G / IC-MPGN Monitor efficacy / disease status over time during SOC Monitor safety and tolerability of SOC Record dosing and compliance with SOC Follow-up Monitor QoL measures End of Study Timeline Observational stage to start enrollment mid-2021 Global phase 1 expected in 2022 Planned Phase 1 Study Intend to pursue an accelerated regulatory path

© Catalyst Biosciences Note: aHUS = atypical Hemolytic Uremic Syndrome, C3G = Complement 3 Glomerulopathy, IC-MPGN = Immune-Complex Membranoproliferative Glomerulonephritis 49 CB 4332 market opportunity

US / EU5 market opportunity Unmet needs Significant opportunity for patients with Additional opportunity in CFI mutations CFI Deficiency outside nephrology Specific systemic therapies in development 0 for patients with dysregulated CFI IC-MPGN $500M 0 Therapies addressing the root cause of disease Market opportunity in Approved treatments for C3G, IC-MPGN, CFID C3G CFI deficient 0 aHUS, C3G, IC-MPGN CFI mutations are significant drivers of disease aHUS

Note: aHUS = atypical Hemolytic Uremic Syndrome, C3G = Complement 3 Glomerulopathy, IC-MPGN = Immune-Complex Membranoproliferative Glomerulonephritis, CFID = Complement Factor I Deficiency References: Bresin et al. JASN. 2005; Fremeaux-Bacchi et al. ASN. 2013; Rui-Ru et al. Jour Rare Dis Res. 2018; Servais et al. Kidney Int. 2012; Iatropoulous et al. Mol Immunol. 2016; Hou et al. Kidney Int. 2014; Alba-Domiguez et al. J rare Dis. 2012. El Sissy et al. Front. Immunol. 2019; Shields et al. Front Immunol. 2019; Naesens et al. Jour Allergy and Clin Immunol. 2020. Yan et al. Clin Epi 2020; Smith et al. Nature Reviews. 2020; Noris et al. Clin J Am Soc Nephrol. 2010; CBIO KOL interviews © Catalyst Biosciences 50 Nonfunctional CFI increasingly identified as genomic initiatives grow

References: World Economic Forum. 2019

C4b Degrader

C2 Classical C1r C4b pathway C1s C4

Lectin MASP pathway

Selective & potent + Catalyst’s protease platform allows for tuning specificity to individual targets + Leverages CB 4332 protease scaffold + efficient high yield production process + No competitors specifically targeting C4b

ALS 32K LN GBS 130K 13K Nephrology

Immunology SLE C4b gMG 370K Degrader 130K Hematology

Neurology wAIHA MMN 75K 4K Note: ALS = Amyotrophic lateral sclerosis, GBS = Guillain-Barré syndrome, CAD gMG = Generalized Myasthenia Gravis, MMN = multifocal motor neuropathy, CAD = Cold agglutinin disease, wAIHA = warm Autoimmune hemolytic 22K anemia, SLE = Systemic lupus erythematosus, LN = Lupus Nephritis, References: Data on file

Potent and specific C4b degrader Engineering specificity

1.00 CB 4473 CB 4473 (-) cofactor

0.75

Parent Parent molecule molecule 0.50 (+) cofactor C4b degradationC4b

0.25 Parent molecule

(-) cofactor activity change inagainst C4b Fold

0.00 10 -8 10 -7 10 -6 10 -5 Concentration of test article (M) Fold change in activity against C3b

100 Engineering Specificity Classical pathway specific regulators >10x specificity for C4b over C3b

10 Alternative pathway specific regulators >10X specificity for C3b over C4b

1 Central pathway regulators Variants with increased activity on both C3b & C4b 0.1 Fold change in activitychange inagainst C4b Fold

0.01 0.01 0.1 1 10 Fold change in activity against C3b

NextGen CB 2782 CB 4332 C4b Degraders 1 2 3 4 Degraders

CB 2782 Novel engineered C3 CB 4332 Leads Catalyst’s degrader established expansion into systemic Catalyst in complement complement in CFI Next generation of dysregulation specific and potent C4b degraders targets Future classical complement complement disorders with large degraders broaden market potential Catalyst’s footprint

Enrollment to Observational trial for CB 4332 start mid-2021

Updates on C4b degrader 2021 and additional programs

Progress CB 2782 2021 in collaboration with Biogen

CB 4332 in the clinic globally 2022