EX-99.1 2 d92742dex991.htm EX-99.1

Catalyst Biosciences © Catalyst Biosciences Complement R&D Day 14 December 2020 Exhibit 99.1

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

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

Nassim Usman, Ph.D. © Catalyst Biosciences President and CEO

© Catalyst Biosciences 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 Harnessing the catalytic power of proteases Structural model based on PDB 1AVW

© Catalyst Biosciences Catalyst’s protease platform generates differentiated therapeutics Unique expertise in protease biology enables design of optimized protease therapeutics Functionally enhanced natural proteases in biological pathways Modulate biological activation & inactivation pathways Engineered novel protein degraders Protease scaffold Therapeutic protease Structure guided design Pharmacokinetic improvement Molecular evolution Our Proteases Discovery Platform Engineered regulation

© Catalyst Biosciences Protease therapeutics Protease therapies Address root cause of disease caused by cascade dysregulation One molecule regulates 1000s – Optimal for high abundancy and undruggable targets Can be engineered to specifically degrade novel targets Monoclonal antibodies Therapeutic modalities The protease advantage RNA interference Small molecule inhibitors

© Catalyst Biosciences Clinical & partnering success of the CBIO protease platform Before treatment On treatment Marzeptacog alfa (activated) Dalcinonacog alfa CB 2782-PEG Engineered rFVIIa protease 50% 5% 1% Mild Hemophilia Normal clotting levels Severe Hemophilia Moderate Hemophilia 90% reduction in annualized bleed rate Achieved sustained & high target levels of FIX Best-in-class profile for dry AMD Extended pharmacodynamics Engineered rFIX protease Novel C3 degrader

© Catalyst Biosciences Catalyst is taking a targeted approach to complement regulation Classical pathway Lectin pathway Alternative pathway Membrane attack complex (MAC) Immune response inflammation Cascade initiation Central point of regulation Terminal complement C3a C5a C5b C3 C5 C3b CB 2782-PEG C4b MASP C4 C2 C1r C1s C3b C3 (H2O) FD FB 80% of the complement system is regulated by proteases

Grant E. Blouse, Ph.D. © Catalyst Biosciences SVP, Translational Research

© Catalyst Biosciences Complement is a perfect fit to develop protease therapeutics The complement pathway is driven by a protease cascade of the complement cascade is regulated by proteases 80 % Exacerbation Immune modulation Immune modulation C1qR C3aR C1s C1r AAb NAb Neoepitopes/ autoepitopes Damaged/altered/foreign cells and debris C1-INH C2 C4 C4a C4BP C4b2b C3 Extrinsic protease C3a C3a-dR CPN C3b C4b2b3b C3bBb3b C5 convertase C5 C5b C5a Chemotaxis, inflammatory signaling and cell activation C5aR2 C5aR1 C5a-dR CPN MAC C6 C7 C8 C9n Extrinsic proteases CD59 MBL Fcn CL MASP1 MASP2 C1q Tick-over C3*Bb C3bBb pFD FP FP FD FB FH FP MASP3 C3* C3 C3b FP ? ? FB FD C3bBb C3 convertase FP FD FB FH CD55 CR1 C3b iC3b CD46 FH FB CR1 C3dg FI CR1 CR2 CR4 CR3 CR1 CR46 Exacerbation DAMP Amplification Immune modulation Adhesion Phagocytosis Trafficking Signaling Adaptive signaling Lysis, cell damage Terminal pathway Breakdown pathway CP LP AP Circulation turnover Reference: Figure adapted from Mastellos et al., Clinical promise of next-generation complement therapeutics. Nature Reviews. 2019

© Catalyst Biosciences Complement plays a critical role in many diseases Late-stage complement therapies projected to achieve net sales over $12B by 2026 Nephrology Hematology/Oncology Endocrine/Metabolism Infectious Disease Cardiovascular Dermatology Neurology Musculoskeletal Immunology Ophthalmology Pulmonology Gastroenterology References: Globaldata consensus net sales forecast 2020​

© Catalyst Biosciences Investment in complement is driven by an evolving biology Scientific advancements facilitate increased interest in complement indications 2000 2005 2010 2015 2020 2000 - 2015 187 2015 - 2020 252 Clinical trials Clinical trials eculizumab approval (2007)

© Catalyst Biosciences Catalyst’s protease platform generates differentiated therapeutics Unique expertise in protease biology enables design of optimized protease therapeutics Functionally enhanced natural proteases in biological pathways Modulate biological activation & inactivation pathways Engineered novel protein degraders - designed for almost any target or cascade Protease scaffold Therapeutic protease Structure guided design Pharmacokinetic improvement Molecular evolution Our Proteases Discovery Platform Engineered regulation Structural model based on PDB 1AVW

© Catalyst Biosciences Proteases are ideal for high abundancy targets & cascades A better way to regulate biological processes compared with antibodies & small molecules Efficient regulation at low concentrations of therapeutic protease Requires high antibody concentrations in excess of the target Requires high concentrations & frequent dosing Protease Antibodies Small molecules / peptides Therapeutic target neutralization

© Catalyst Biosciences Protease advantage demonstrated in vivo 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 at least 28 days in a non-human primate model Catalytic Advantage of Proteases 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

© Catalyst Biosciences CB 4332: Enhanced Complement Factor I CBIO’s Next Development Candidate Structural model based on PDB 2XRC

Classical pathway Alternative pathway © Catalyst Biosciences Normal CFI: Key central regulator of complement activation C4 C2 C1r C1s C3b C3 (H2O) FD FB CFI CFI normally acts to downregulate C4b and C3b Inhibition of C4b and C3b prevents overactivation of the complement responses that can cause disease Normal CFI C4b

Classical pathway Alternative pathway Membrane attack complex (MAC) Immune response inflammation © Catalyst Biosciences CFI dysregulation: Lack of proteolytic CFI activity causes disease C3a C5a C5b C3 C5 C3b C4b C4 C2 C1r C1s C3b C3 (H2O) FD FB CFI Defective CFI In patients with CFI mutations, C4b and C3b cannot be sufficiently regulated Dysregulation leads to overactivation of the complement pathway and damaging immune responses

Classical pathway Alternative pathway Membrane attack complex (MAC) Immune response inflammation © Catalyst Biosciences Other treatments do not directly address CFI dysregulation C3a C5a C5b C3 C5 C3b C4b C4 C2 C1r C1s C3b C3 (H2O) FD FB CFI Defective CFI Other Treatments 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

Classical pathway Alternative pathway © Catalyst Biosciences CB 4332 - Catalyst’s enhanced CFI Specifically addresses the problem by restoring CFI regulation of the system C4 C2 C1r C1s C3b C3 (H2O) FD FB CB 4332: Enhanced CFI C4b

CB 4332 designed to provide unique advantages © Catalyst Biosciences CB 4332 to address CFI deficiency at the root cause​ Unmet needs in ​ CFI deficiency CB 4332 Designed to address Blocks complement-initiated cell destruction in the circulation​ ü Directly addresses root cause of disease​ ü Addresses extravascular hemolysis​ ü Preserves normal immune functions, eg. to fight off infections​ ü Convenient weekly SQ administration​ ü

© Catalyst Biosciences CB 4332: Enhanced Complement Factor I CBIO’s next SQ development candidate to restore CFI regulation References: 1Bienaime et al. Kidney Int. 2010; 2Ferreira et al. Nefrologia. 2016 ​ Note: CFH = Complement factor H 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 treatments1,2 Genetically defined patient population Rationale & unmet need Engineered for an extended half-life Once weekly SQ therapy Full activity comparable to native CFI Classical and alternative pathway regulation Efficient high yield production process Structural model based on PDB 2XRC Half-Life Extension Technology

© Catalyst Biosciences Time (Days) CB 4332 Dosed at 1 mg/kg SQ Plasma CFI Dosed at 1 mg/kg SQ Engineered Functional Improvements Systemic single-dose PK in nonhuman primates Plasma Concentration CB 4332 nonhuman primate pharmacokinetics predicts weekly SQ

© Catalyst Biosciences CB 4332 & plasma CFI perform similarly in human serum Inhibition of hemolysis (%) Concentration of test article (nM) Concentration of test article (nM) Inhibition of hemolysis (%) Classical pathway Alternative pathway

© Catalyst Biosciences Cohort 1: aHUS Cohort 2: C3G / IC-MPGN End of Study Total ≥ 24 Subjects (male/female) ≥ 12 years of age Screening Study / Observational Period (6 mo) Follow-up Planned Phase 1 Study Objectives Primary Objective Demonstrate the prevalence, distribution and phenotypic manifestation of CFI mutations in aHUS, C3G, IC-MPGN subjects requiring treatment to identify patients for a future Phase 1 study Secondary Objectives Monitor efficacy / disease status over time during SOC Monitor safety and tolerability of SOC Record dosing and compliance with SOC Monitor QoL measures Timeline Observational trial to identify CFI deficient patients for further CB 4332 clinical development Note: aHUS = atypical Hemolytic Uremic Syndrome, C3G = Complement 3 Glomerulopathy, IC-MPGN = Immune-Complex Membranoproliferative Glomerulonephritis CB 4332 - CFI dysregulation observational study Observational stage to start enrollment mid-2021 Global phase 1 expected in 2022 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, 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 aHUS C3G IC-MPGN US / EU5 market opportunity Market opportunity in CFI deficient aHUS, C3G, IC-MPGN $500M Additional opportunity in CFI Deficiency outside nephrology Significant opportunity for patients with CFI mutations 0 Specific systemic therapies in development for patients with dysregulated CFI 0 Approved treatments for C3G, IC-MPGN, CFID 0 Therapies addressing the root cause of disease Unmet needs CFI mutations are significant drivers of disease CB 4332 market opportunity 27

© Catalyst Biosciences Nonfunctional CFI increasingly identified as genomic initiatives grow References: World Economic Forum. 2019

© Catalyst Biosciences C4b Degraders Expanding into Classical Complement Disorders Structural model based on PDB 2XRC

© Catalyst Biosciences Catalyst C4b degrader complement therapy Classical pathway C4b C4 C2 C1r C1s C4b Degrader Lectin pathway MASP 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

© Catalyst Biosciences C4b degraders target multiple high unmet need diseases US & EU5 patient opportunity Note: ALS = Amyotrophic lateral sclerosis, GBS = Guillain-Barré syndrome, gMG = Generalized Myasthenia Gravis, MMN = multifocal motor neuropathy, CAD = Cold agglutinin disease, wAIHA = warm Autoimmune hemolytic anemia, SLE = Systemic lupus erythematosus, LN = Lupus Nephritis, References: Data on file ALS 32K LN 130K SLE 370K wAIHA 75K GBS 13K gMG 130K MMN 4K CAD 22K C4b Degrader Nephrology Immunology Hematology Neurology

© Catalyst Biosciences Concentration of test article (M) CB 4473 (-) cofactor Potent and specific C4b degrader Engineering specificity Fold change in activity against C4b Fold change in activity against C3b CB 4473 Parent molecule (-) cofactor Parent molecule (+) cofactor C4b degradation Parent molecule CB 4473 demonstrates engineered C4b potency & specificity

© Catalyst Biosciences Classical pathway specific regulators >10x specificity for C4b over C3b Alternative pathway specific regulators >10X specificity for C3b over C4b Central pathway regulators Variants with increased activity on both C3b & C4b Tuning potency and selectivity to the therapeutic indication Engineering Specificity Fold change in activity against C4b Fold change in activity against C3b Catalyst is developing a portfolio of C3b and C4b degraders based on CB 4332

© Catalyst Biosciences Catalyst’s complement pipeline CB 2782 Novel engineered C3 degrader established Catalyst in complement CB 4332 Leads Catalyst’s expansion into systemic complement in CFI dysregulation Next generation of specific and potent C4b degraders targets classical complement disorders with large market potential Future complement degraders broaden Catalyst’s footprint 2 3 4 1 CB 4332 C4b Degraders NextGen Degraders CB 2782

Clinton Musil © Catalyst Biosciences CFO Closing Remarks, Q&A

© Catalyst Biosciences CBIO’s complement program next steps Observational trial for CB 4332 Updates on C4b degrader and additional programs Progress CB 2782 in collaboration with Biogen CB 4332 in the clinic globally Enrollment to start mid-2021 2021 2021 2022