Protease medicines to catalyse change in complement ...
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ADVERTISEMENT FEATURE ADVERTISER RETAINS SOLE RESPONSIBILITY FOR CONTENT www.nature.com/biopharmdeal | June 2021 | B31 Catalyst Biosciences, Inc. www.catalystbiosciences.com Protease medicines to catalyse change in complement-targeting therapies Catalyst Biosciences has built a protease medicines platform for engineering protease therapeutics designed to correct disease-causing imbalances in biological cascades. The company currently focuses on disorders in 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 on rare disorders of the complement or coagulation systems. Catalyst’s approach builds on the com- pany’s unique protease engineering platform, which can generate improved or novel molecules to help correct disease-causing imbalances in the comple- ment and coagulation systems (Fig. 1). Proteases cleave or degrade proteins with high specificity. Because one protease molecule can act on thousands of target proteins, even at low concentrations proteases can be major regulatory factors of complex biological processes. Using its protease engineering platform, Catalyst has advanced two engineered coagulation factors, marzeptacog alfa (activated) and dalcinonacog alfa, to late clinical stages for the subcutaneous treatment of bleeding in patients with rare bleeding disorders. Catalyst’s complement-targeting preclinical pro- grams include CB 2782-PEG, licensed to Biogen for dry age-related macular degeneration (AMD), and CB 4332, a wholly-owned first-in-class engineered complement factor I (CFI) for systemic prophylaxis in individuals with complete CFI deficiency. CFI defi- ciency can result in disorders including recurrent inva- sive infections, autoimmune and immune-complex diseases such as chronic inflammation of blood ves- sels in the brain, spinal cord, heart, or the kidneys and when localized to the eye, dry-AMD. CFI deficiency can also manifest in renal conditions such as atypical hemolytic uremic syndrome, complement 3 glomeru- lopathy, or immune-complex membranoproliferative glomerulonephritis. The company’s protease engi- neering platform is also powering a pipeline of addi- tional complement programs, including a portfolio of complement factor 4b degraders targeting disorders of the classical and lectin complement pathways, that are all in advanced discovery phases. “We have built a robust protease engineering plat- form that allows us to harness the catalytic power of nature’s key biological regulators through optimiza- tion and tuning of their specificity, potency and func- tionality,” said Grant Blouse, senior vice president of translational research at Catalyst. “We are excited to see our efforts translating into optimized prote- ase therapeutics that have the potential to change patient lives. Our protease engineering platform can be applied to the treatment of disorders associated with complement dysregulation and could bring us first-in-class therapeutics to address conditions ranging from renal and hematological diseases to ophthalmological and neurological disorders.” Catalyst continues to expand its pipeline of prote- ase-based therapeutics through focused in-house research and strategic outside collaborations and is open to further partnerships—from early discovery to late-stage clinical and commercialization. Tuning proteases in complement The human complement system is a complex defense system that helps protect the body from pathogens. Similar to the coagulation system, the complement system consists of a cascade of pro- teases that is triggered by particular extracellular signals and leads to membrane attack complexes and systemic immune and inflammatory response signals targeting pathogens. Deficient or excessive activation of the complement system may lead to severe disorders, including micro- thrombotic, autoimmune, and neurological diseases that can have severe or even fatal consequences. Current complement-targeting therapies often do not address the root cause of disease, resulting in incomplete blockade and inadequate disease control. Catalyst has built its complement strategy around the concept of tuning proteases in the complement cascade to target key regulatory components that can help reset the regulatory balance by controlling central nodes of the regulatory network while also reconstituting positive and negative feedback loops. Advancing complement therapies through partnerships Catalyst is building a robust pipeline of engineered complement proteases that leverages the company’s proven expertise with developing therapeutics tar- geting the coagulation system. The platform enables the generation of novel or improved proteases and allows the optimization of their functional properties, including longer half-life, enhanced specificity, higher potency and increased bioavailability. As a result, Catalyst’s product candidates enable subcutaneous administration and a less frequent dosing regimen. Catalyst is planning to initiate a natural his- tory study in mid-2021 supporting CB 4332, its enhanced CFI product candidate, in patients with CFI deficiency–related conditions. A phase 1 clinical study is planned for 2022. CB 2782-PEG, Catalyst’s novel anti-C3 protease for the treatment of dry AMD, achieved a higher than 99% reduction of C3 in preclinical non-human primate models. Catalyst and Biogen continue to progress the molecule towards clinical studies. “Backed by an experienced leadership team of protease engineers, advisors, and collaborators, Catalyst continues to expand its robust intellectual property estate to advance the therapeutic potential of targeting the complement system,” said Tom Knudsen, vice president of corporate development at Catalyst. “We are now poised to further acceler- ate our complement programs with partners looking to improve the lives of patients with large unmet needs worldwide.” Fig. 1 | Catalyst’s protease engineering platform. Catalyst’s expertise enables it to develop differentiated therapeutics based on optimized protease designs. By using protease engineering, Catalyst can enhance natural proteases, engineer protein degraders, and modulate or target biological activation or inactivation. Tom Knudsen, Vice President of Corporate Development Catalyst Biosciences, Inc. South San Francisco, CA, USA Tel: +1-650-871-0761 Email: [email protected] CONTACT
Transcript of Protease medicines to catalyse change in complement ...
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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