A D V E R T I S E M E N T F E A T U R E
A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T www.nature.com/biopharmdeal | June 2021 | B31
Catalyst Biosciences, Inc.www.catalystbiosciences.com
Protease medicines to catalyse changein complement-targeting therapiesCatalyst Biosciences has built a protease medicines platform for engineering protease therapeutics designedto correct disease-causing imbalances in biological cascades. The company currently focuses on disordersin the complement or coagulation systems, but has the potential to address additional diseases.
Catalyst Biosciences is a research and clinical devel-opment biopharmaceutical company focusing onrare disorders of the complement or coagulationsystems. Catalyst’s approach builds on the com-pany’s unique protease engineering platform, whichcan generate improved or novel molecules to helpcorrect disease-causing imbalances in the comple-ment and coagulation systems (Fig. 1).
Proteases cleave or degrade proteins with highspecificity. Because one protease molecule canact on thousands of target proteins, even at lowconcentrations proteases can be major regulatoryfactors of complex biological processes.
Using its protease engineering platform, Catalysthas advanced two engineered coagulation factors,marzeptacog alfa (activated) and dalcinonacog alfa,to late clinical stages for the subcutaneous treatmentof bleeding in patients with rare bleeding disorders.Catalyst’s complement-targeting preclinical pro-grams include CB 2782-PEG, licensed to Biogen fordry age-related macular degeneration (AMD), andCB 4332, a wholly-owned first-in-class engineeredcomplement factor I (CFI) for systemic prophylaxisin individuals with complete CFI deficiency. CFI defi-ciency can result in disorders including recurrent inva-sive infections, autoimmune and immune-complexdiseases such as chronic inflammation of blood ves-sels in the brain, spinal cord, heart, or the kidneys andwhen localized to the eye, dry-AMD. CFI deficiencycan also manifest in renal conditions such as atypicalhemolytic uremic syndrome, complement 3 glomeru-lopathy, or immune-complex membranoproliferativeglomerulonephritis. The company’s protease engi-neering platform is also powering a pipeline of addi-tional complement programs, including a portfolio ofcomplement factor 4b degraders targeting disordersof the classical and lectin complement pathways, thatare all in advanced discovery phases.
“We have built a robust protease engineering plat-form that allows us to harness the catalytic power ofnature’s key biological regulators through optimiza-tion and tuning of their specificity, potency and func-tionality,” said Grant Blouse, senior vice president oftranslational research at Catalyst. “We are excitedto see our efforts translating into optimized prote-ase therapeutics that have the potential to changepatient lives. Our protease engineering platform canbe applied to the treatment of disorders associatedwith complement dysregulation and could bringus first-in-class therapeutics to address conditionsranging from renal and hematological diseases toophthalmological and neurological disorders.”
Catalyst continues to expand its pipeline of prote-ase-based therapeutics through focused in-houseresearch and strategic outside collaborations and isopen to further partnerships—from early discoveryto late-stage clinical and commercialization.
Tuning proteases in complementThe human complement system is a complexdefense system that helps protect the body frompathogens. Similar to the coagulation system, thecomplement system consists of a cascade of pro-teases that is triggered by particular extracellularsignals and leads to membrane attack complexesand systemic immune and inflammatory responsesignals targeting pathogens.
Deficient or excessive activation of the complementsystem may lead to severe disorders, including micro-thrombotic, autoimmune, and neurological diseasesthat can have severe or even fatal consequences.Current complement-targeting therapies often donot address the root cause of disease, resulting inincomplete blockade and inadequate disease control.
Catalyst has built its complement strategy aroundthe concept of tuning proteases in the complementcascade to target key regulatory components thatcan help reset the regulatory balance by controllingcentral nodes of the regulatory network while alsoreconstituting positive and negative feedback loops.
Advancing complement therapiesthrough partnershipsCatalyst is building a robust pipeline of engineeredcomplement proteases that leverages the company’sproven expertise with developing therapeutics tar-geting the coagulation system. The platform enables
the generation of novel or improved proteases andallows the optimization of their functional properties,including longer half-life, enhanced specificity, higherpotency and increased bioavailability. As a result,Catalyst’s product candidates enable subcutaneousadministration and a less frequent dosing regimen.
Catalyst is planning to initiate a natural his-tory study in mid-2021 supporting CB 4332, itsenhanced CFI product candidate, in patients withCFI deficiency–related conditions. A phase 1 clinicalstudy is planned for 2022.
CB 2782-PEG, Catalyst’s novel anti-C3 proteasefor the treatment of dry AMD, achieved a higherthan 99% reduction of C3 in preclinical non-humanprimate models. Catalyst and Biogen continue toprogress the molecule towards clinical studies.
“Backed by an experienced leadership team ofprotease engineers, advisors, and collaborators,Catalyst continues to expand its robust intellectualproperty estate to advance the therapeutic potentialof targeting the complement system,” said TomKnudsen, vice president of corporate developmentat Catalyst. “We are now poised to further acceler-ate our complement programs with partners lookingto improve the lives of patients with large unmetneeds worldwide.”
Fig. 1 | Catalyst’s protease engineering platform. Catalyst’s expertise enables it to develop differentiatedtherapeutics based on optimized protease designs. By using protease engineering, Catalyst can enhancenatural proteases, engineer protein degraders, and modulate or target biological activation or inactivation.
Tom Knudsen, Vice President ofCorporate DevelopmentCatalyst Biosciences, Inc.South San Francisco, CA, USATel: +1-650-871-0761Email: [email protected]
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