EX-99.1 2 d269001dex991.htm EX-99.1

CATALYST BIOSCIENCES Corporate Overview 12 January 2022 Exhibit 99.1

© 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 statements of historical facts, are forward-looking statements. This press release contains forward-looking statements that involve substantial risks and uncertainties. Forward-looking statements include, without limitation, our plans for CB 4332 and the rest of our complement programs, our plans to continue to support Biogen in the development of CB 2782-PEG, the statement that complement has broad potential, can be combined with conventional therapies and will open opportunities in multiple disease settings, as well as statements about the benefits of our protease engineering platform. 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 clinical trials and preclinical studies may be delayed as a result of COVID-19, competitive products, and other factors, that Biogen could terminate our agreement for the development of CB 2782-PEG, that our complement degraders are not yet in human clinical trials and will require additional manufacturing validation and preclinical testing before entering human clinical trials, that we may need to raise additional capital, and other risks described in the "Risk Factors" section of our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on March 4, 2021, the Quarterly Report on Form 10-Q filed with the SEC on November 12, 2021, and in other filings filed from time to time with the SEC. We do not assume any obligation to update any forward-looking statements, except as required by law.

Modulating Biological Systems with Nature’s Regulatory Proteins Proteases are nature’s key regulatory proteins Innovative engineered molecules to degrade or activate therapeutic targets Applicable across multiple disease areas We harness the regulatory power of proteases

Catalyst’s protease platform in complement Validated across three programs CB 2782-PEG Best-in-class profile for dry AMD Extended pharmacodynamics Novel C3-degrader for dry AMD CB 4332 PK extended CFI Restoring balance to complement where CFI activity is insufficient Protease platforms tailored to improve C3b & C4b regulation © Catalyst Biosciences

Unique targeted approach to complement regulation Classical pathway Lectin pathway Alternative pathway C3a C5a C5b C3 C5 CB 2782-PEG MASP C4 C2 C1r C1s C3b FD FB CB 4332 (CFI) C4b Degrader C3b Degrader FD FB Cascade initiation Cascade regulation Terminal complement C5a Degrader C3a Degrader C4b Degraders C3b Degraders CB 2782-PEG CB 4332 C3 (H2O) C3b C4b C3b © Catalyst Biosciences Inflammation Terminal Pathway

Catalyst protease and protein degrader discovery platform Distinct expertise enables design of optimal therapeutic candidates Controlled target engagement Fast elimination of difficult targets Tunable for high potency & affinity Modulate instead of inactivating Can be combined with conventional therapies Protease engineering © Catalyst Biosciences

A platform based on the natural braking mechanisms of complement Nature’s way to regulate complement Rebalances complement using the natural brakes (CFI) Safely regulate complement without broad immunosuppression Multiple diseases driven by C3b/C4b deposition & immune activation Differentiated mechanisms to regulate at or around C3 & C5 Uses the natural regulatory protein to modulate the complement system © Catalyst Biosciences Nature’s Regulator of Complement at C3b/C4b Complement Factor I Nature’s Regulator of Complement at C3a/C5a CB 6000

A platform based on the natural braking mechanisms of complement Nature’s way to regulate complement Complement Activation Classical – Lectin - Alternative C5b C5a C3a C3b C4b C3 C5 © Catalyst Biosciences CFI CB 6000 Inflammation Proinflammatory Anaphylatoxins Membrane Attack Complex Cell Lysis Opsonization (Alternative) Targeted Destruction Opsonization (Classical/Lectin) Targeted Destruction Nature’s Regulator of Complement at C3b/C4b Complement Factor I Nature’s Regulator of Complement at C3a/C5a CB 6000

Our protease platforms are tailored to specific indications​ Tuning functionality to restore complement homeostasis & immunoregulation​ ImmunoTUNE™ C3a/C5a ProTUNE™ C3b/C4b Specific inhibition of complement components at different sites of the complement cascade allows a personalized approach to treating complement disorders © Catalyst Biosciences Immunology Autoimmune Neurology Nephrology Hematology oncology

CB 4332 Half-Life Extended Complement Factor I to rebalance the complement system © Catalyst Biosciences

CB 4332: Extended half-life Complement Factor I Development candidate to restore regulation 1Bienaime et al. Kidney Int. (2010); 2Ferreira et al. Nefrologia. (2016); Note: CFI = Complement factor I; Structural model based on PDB 2XRC. Engineered for an extended half-life Potential for once weekly SQ therapy In vitro & ex vivo activity comparable to native CFI Classical & alternative pathway regulation High yield production process Safe GLP toxicology with a high dosing window Entering the clinic in 2022 Rebalance the complement system in patients with insufficient complement regulation No specific therapies exist to correct complement dysregulation using natural proteases Potentially targets a population with no treatment or who respond poorly to current treatments1,2 HSA Fusion Technology © Catalyst Biosciences

Systemic & ocular CFI to rebalance the complement system CB 4332 has potential to address a breadth of mechanistically related diseases *Patient population estimate does not include age-related macular degeneration US population with rare CFI variants AMD: Age-Related Macular Degeneration, aHUS: atypical Hemolytic Uremic Syndrome, C3G: C3 Glomerulonephropathy, SLE: Systemic Lupus Erythematosus, LN: Lupus Nephritis, AIHA: Autoimmune Hemolytic Anemia, ANCA: ANCA-associated Vasculitis, ITP: Immune Thrombocytopenia, HAE: Hereditary Angioedema, APS: Antiphospholipid Antibody Syndrome ~4,000 U.S. Patients ~2.3M U.S. patients aHUS C3G SLE AIHA ANCA LN ITP APS CFID IC-MPGN CFI Replacement Complete CFI Deficiency Life-threatening recurrent infections & immune disorders Partial CFI Deficiency Kidney disorders CFI Intervention Re-Balancing Complement Disorders of Complement dry AMD Ocular CFI Re-Balancing Complement Disorders of the eye ~200,000 U.S. Patients

CB 4332 may target diseases of excessive C3b and C4b deposition Deposition of C4b & C3b in AIHA lead to hemolysis & cellular destruction C5a C5b C3a C3b C4b C3 C5 Membrane Attack Complex Cell Lysis © Catalyst Biosciences C5 Convertase C3b C3b Intravascular Hemolysis Extravascular Hemolysis C3d MAC-mediated lysis Phagocytosis Inflammation Proinflammatory Anaphylatoxins Degradation of C3b to C3d leads to cellular survival Complement Activation Classical – Lectin - Alternative

C3b & C4b Degraders Broad applications in complement-mediated disorders © Catalyst Biosciences

Tuned C3b/C4b Degrader Augmented Catalytic Activity Desired Functionality Modified C3b/C4b Specificity Improved catalytic power & specificity for CFI variants ProTUNE™ platform has been used to generate specific C3b/C4b degraders to complement toward C3b & C4b to restore balance to the complement cascade by sparing cascade leading to MAC formation SPECIFICITY ProTUNE™ PLATFORM C4b C3b © Catalyst Biosciences

Using ProTUNETM Platform to tune C3b & C4b cleaving capabilities Rational Design EC50= 77 nM EC50= 41 nM EC50= 15 nM EC50= 5.8 nM EC50= 15.6 nM EC50= 1.8 nM © Catalyst Biosciences

© Catalyst Biosciences Cofactor independent CFI may target patient subpopulations ProTUNE™ platform has generated degraders that work without cofactors Cofactor independent molecules broaden the scope of addressable patients

C3b & C4b degraders significantly reduce inflammation in vivo Inflammatory markers in IgA nephropathy Reduction of IFNγ, TNF⍺, and RANTES that are chemokines involved in kidney damage and proteinuria in IgA nephropathy patients IFNγ (pg/mL) TNF⍺ (pg/mL) RANTES (pg/mL) Concomitant reduction of inflammatory markers and complement C3 cleavage Rat sepsis model of complement activation % C3b formation % C3b formation % C3b formation © Catalyst Biosciences

Healthy IgAN Example: C3b/C4b degraders for IgA nephropathy patients Disease in which both lectin & alternative pathways drive pathogenesis Most common form of glomerulopathy with accumulation & deposition of IgA immune complexes deteriorating renal function patients with rapidly progressive glomerulonephritis of IgAN patients develop end stage renal disease over 20 years & need dialysis/renal transplant in order to survive will modulate the alternative & lectin pathways to address complement dysregulation with low off-target effects Significant burden on healthcare resources with an estimated cost of in 2020 in the US High unmet need – current treatments only address symptoms © Catalyst Biosciences

Example: C3b/C4b degraders for IgA nephropathy Dual targeting of alternative & lectin pathways Classical pathway C4 C2 C1r C1s MASPs C1q MBL C4b 2b C3 Alternative pathway CFB C3(H2O) CFD C3b Bb Dual targeting mode of action: pathways Both pathways are involved in IgA nephropathy & correlate with severe clinical manifestation 1, 2, 3 Inhibition of only MASP2 or Factor B to reduce proteinuria in IgA nephropathy patients Clinically validated target for IgAN 1Medjeral-Thomas et al. Kidney International Reports (2018); 2Bi et al. BMC Nephrology (2019); 3Roos et al. J Am Soc Nephrol (2006) Clinically validated target for IgAN © Catalyst Biosciences

C3a & C5a Degraders For inflammatory disorders © Catalyst Biosciences

Tuned C3a/C5a Degrader Augmented Catalytic Activity Desired Functionality Modified C3a/C5a Specificity Dialing catalytic power & specificity to restore immunoregulation Using the ImmunoTUNE™ engineering platform to tune C3a/C5a degraders to control dysregulatedcomplement toward C3a & C5a to restore balance to the complement cascade ImmunoTUNE™ PLATFORM C3a C5a SPECIFICITY © Catalyst Biosciences

C3a/C5a degraders: Efficacy in acute LPS-induced ARDS model Improves respiratory function & reduces cell infiltrates in an acute setting CFx 7-fold lower dose vs. anti-C5 Respiratory functions & cell infiltration at 24 h CB 6000 outperforms anti-C5 antibody1 in reducing inflammatory cell infiltration CB 6000 compares well on respiratory functions with anti-C5 antibody​ Mouse LPS model of lung inflammation CB6000 CB6000 1Mouse surrogate of Solaris (BB5.1) © Catalyst Biosciences

Example: C3a/C5a degraders: Potential for ANCA Vasculitis patients Autoimmune disease where anaphylatoxins play a role in the pathogenesis 1S. Moiseev et al. British Society for Immunology, Clinical and Experimental Immunology (2020); 2Gou et al. Kidney International (2012). High unmet need – current treatments only addressing symptoms Autoimmune disorder characterized by inflammation & destruction of small blood vessels Clinical signs vary & affect several organs with frequent involvement of upper respiratory track & kidneys Severe pain due to neuropathy, pulmonary hemorrhages, failure of kidneys of patients die within the 1st year of treatment with conventional therapies (immunosuppressant & steroids) The only treatments available are to manage the symptoms © Catalyst Biosciences

Example: C3a/C5a degraders: Potential for ANCA Vasculitis patients Dual targeting of both C3a & C5a with one protease medicine C3b C3 C5 C3a C5a C5b C3 convertase C3 convertase C3aR C5aR Clinically validated targets for ANCA Both levels are elevated in active ANCA associated vascuiltis patients 1, 2 Degrade activation products of C3 (C3a) & C5 (C5a) that are inflammatory mediators Unlike Avacopan, may provide beneficial function via blocking the Inhibition of to increase remission rates in ANCA associated vasculitis patients Classical pathway Alternate pathway 1S. Moiseev et al. British Society for Immunology, Clinical and Experimental Immunology (2020); 2Gou et al. Kidney International (2012). © Catalyst Biosciences

CB 2782-PEG Novel engineered C3 degrader Partnered with © Catalyst Biosciences

© Catalyst Biosciences Complement inhibition is a validated approach in dry AMD Drug Category Route Dose level Frequency Inhibition GA growth GT005 CFI gene therapy Subretinal 2E11 vg Once Unknown Pegcetacoplan PEGylated amino acid cyclic peptide Intravitreal 15 mg 1-2 months 20-30% NGM621 Antibody anti-C3 Intravitreal 15 mg 1-2 months Unknown Zimura pegylated RNA aptamer Intravitreal 2 mg 1-2 months 20-30% CB 2782-PEG (Preclinical) PEGylated anti-C3 protease Intravitreal Low undisclosed 2-3 months Model of NHP data Unknown Inflammation Proinflammatory Anaphylatoxins C5b C5a C3a C3b C4b C3 C5 Membrane attack complex Cell Lysis GT005 Zimura Pegcetacoplan NGM621 CB 2782-PEG Complement Activation Classical – Lectin - Alternative

CB 2782-PEG: Best-in-class C3 degrader for dry AMD The protease advantage demonstrated in vivo 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 CB 2782-PEG (nM) Days C3 Concentration (nM) © Catalyst Biosciences

Building on nature’s way of regulating key processes in health & disease Catalyst Biosciences protease platform has broad potential Catalyst develops enhanced natural core proteases & protease degraders targeting complement regulation Catalyst has designed optimized, next-generation complement degrader candidates Complement dysregulation serves as driver for many diseases with unmet needs Catalyst has protease programs designed to take advantage of nature’s natural complement regulators that restore complement homeostasis & potentially treat other complement-mediated disorders Application of Catalyst's protease & protein degrader technology could unlock treatments in immunology, nephrology, hematology, ocular diseases, and beyond © Catalyst Biosciences

Overview of complement portfolio Multiple value generating events in 2022 & 2023 Clinical Development Preclinical Preclinical Clinical Development of Initial Indication 2022 2023 C3b-C4b C3a-C5a ProTUNE™ ImmunoTUNE™ Platform Technology CFI-HSA Intervention CB 4332 Discovery Discovery Preclinical

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