Captor Therapeutics Sa · GPW:CTX
Captor Therapeutics Sa — Investor Presentation (September 2023)
56 slides from Captor Therapeutics Sa's investor presentation, Sep 1, 2023
Slide 1: Corporate Overview Q3 2023
Corporate Overview Q3 2023 1 September 2023 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 2: Legal notice
Legal notice This document and the information contained herein (unless otherwise indicated) have been prepared by Captor Therapeutics S.A. (the “Issuer”) solely for informational purposes. For this notice, the presentation that follows shall mean and include the slides that follow, the oral present
Slide 3: Advanced therapies from targeted protein degradation
Advanced therapies from targeted protein degradation Captor Therapeutics: Warsaw Exchange listed biotech (WSE: CTX): ~110 FTEs dedicated to targeted protein degradation (TPD) with facilities in Poland and Switzerland $2 billion innovation support program in Poland allows a capital sparing R&D model:
Slide 4: Fully owned pipeline
Fully owned pipeline Programme Target Indications Modality Discovery Preclinical* IND Filing Phase IA / IB Phase II GSPT1, Hepatocellular carcinoma, CT-01 NEK7, Lung cancer, NET tumours MG SALL4 Autoimmunity, CNS, CT-02 NEK7 Metabolism, Oncology MG CT-03 MCL1 Liquid & solid tumours BIFD Autoimmunity
Slide 5: An experienced leadership team
An experienced leadership team LEADERSHIP TEAM Tom Shepherd, Ph.D. Michal Walczak, Ph.D. Radoslaw Krawczyk Sylvain Cottens, Ph.D. Chief Executive Officer Chief Scientific Officer Chief Financial Officer Co-founder – SVP Chemistry Andrew Saunders Paweł Dobrzański, Ph.D. Michał Biśta, Ph.D. Robert Dyj
Slide 6: Optigrade Targeted Protein Degradation Platform
Optigrade™ Targeted Protein Degradation Platform Molecular glues/ Bifunctional Degraders/ Novel E3 ligases 66 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 7: Targeted Protein Degradation (TPD) – a revolutionary approach
Targeted Protein Degradation (TPD) – a revolutionary approach • TPD involves attaching ubiquitin to the target protein, marking it for degradation in the proteasome, the cell's waste disposal system • Ubiquitin serves as a molecular tag in this process and its attachment is facilitated by a cascade
Slide 8: Optigrade discovery platform – importance of structure
Optigrade™ discovery platform – importance of structure OptigradeTM – addressing Molecular Glues, Bifunctional Degraders and novel Ubiquitin E3 Ligases • Industry leading capability in protein engineering and structural biology • Unique structure-guided lead optimization paradigm gives high potency
Slide 9: Attractive features of KLHDC2 E3 ligase
Attractive features of KLHDC2 E3 ligase CRL2 are validated with highly Cullin 2-type E3 ligase Human tissue expression effective VHL-based degraders engaged in protein quality versatility by targeting a wide control via DesCEND pathway range of proteins for degradation localized in nucleus and allow
Slide 10: Captor ligands for KLHDC2
Captor ligands for KLHDC2 Hit-to-lead process Known exit vectors ▪ 5 different EVs identified ▪ 3 chemotypes identified ▪ potential for modulation of ▪ over 30 X-ray structures TCF with different proteins solved ▪ regulation of selectivity and ▪ low nanomolar affinity efficiency of degradation In ce
Slide 11: Bifunctional compound X degrades BRD4 via KLHDC2
Bifunctional compound X degrades BRD4 via KLHDC2 ± KLHDC2 competitive ligand ± Proteasome inhibitor ± Neddylation inhibitor BIFDcompound BID compound X X++ ligand ligand BIFD BID compound compound X X+ +MG-132 MG-132 BIFD BID compoundXX++MLN4924 compound MLN4924 150 150 150 Normalized data [%] Norma
Slide 12: Collaborative opportunities using Optigrade
Collaborative opportunities using OptigradeTM • Captor is interested in leveraging its TPD platform against new targets of interest to potential partners through collaboration • All three pillars of the OptigradeTM platform can be usefully applied to find high quality degrader drugs against new targ
Slide 13: CT-01: First-in-Class GSPT1 Degraders for HCC
CT-01: First-in-Class GSPT1 Degraders for Hepatocellular Carcinoma (HCC) 13 13 October 2023 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 14: CPT-6281 – first-in-class MG degrader of GSPT1, NEK7 & SALL4
CPT-6281 – first-in-class MG degrader of GSPT1, NEK7 & SALL4 Lung cancer GSPT1 degradation leads to an Integrated Stress Response and induction of apoptosis in HCC cells SALL4 is expressed in fetal liver, silenced in adults, but often re- expressed in HCC and correlates with poor prognosis NEK7 degr
Slide 15: CPT-6281 triggers ISR-dependent cell death in Hep3B cells
CPT-6281 triggers ISR-dependent cell death in Hep3B cells Densitometry results of WB WB analysis of ISR markers during ABS-752 treatment analysis of GSPT1 degradation DMSO CPT-6281 0.1 µM 4 4 8 16 24 32 48 72 96 Time of treatment CPT-6281 kDa [hrs] 50 ATF-4 [% of DMSO ctrl normalized vs -Actin] 100
Slide 16: CPT-6281 impaired the ability of single HCC cells to form colonies
CPT-6281 impaired the ability of single HCC cells to form colonies Colony count Colony formation at 1 nM compounds (colony = ca. 50 cells) vehicle 300 vehicle CPT-6281 ABS-752 CC-90009 colonies # 200 CPT-6281 100 CC-90009* 0 0 1 10 100 degrader [nM] HCC clonogenic assay – 8 days treatment with 1, 10
Slide 17: Highly potent CPT-6281 regresses tumors in mice
Highly potent CPT-6281 regresses tumors in mice NSG_Hep3B kDa CPT-5170* CPT-6281 1250 CPT-6281, PO, BID Vehicle 10 mg/kg 10 mg/kg kDa 75 Tumor volume [mm3] 1000 75 Vehicle GSPT1 750 37 37 500 1 mg/kg NEK7 150 250 3 mg/kg 150 10 mg/kg 0 Vinculin 0 2 4 6 8 10 12 14 Day of treatment Regression of large
Slide 18: Convincing tumor growth inhibition in HCC PDX models
Convincing tumor growth inhibition in HCC PDX models Tumor Growth Inhibition 111 Tumor regression 97 %Δ Inhibition 75 62 10 randomly selected HCC models 42 35 CPT-6281, 100mg/kg, BID 31 22 3 animals per vehicle & treatment groups LI-1 LI-2 LI-3 LI-4 LI-5 LI-6 LI-7 LI-8 LI-9 LI-10 Model ID Efficacy d
Slide 19: Combination with an approved drug is synergistic
Combination with an approved drug is synergistic in less sensitive tumors HUH-7 Xenograft Model LI1097 HCC PDX 2000 1200 1000 Tumor volume [mm3] Tumor volume [mm3] 1500 800 1000 Vehicle 600 Vehicle CPT-6281, 30 mg/kg, BID 400 CPT-6281, 100 mg/kg, BID 500 Compound X, 5 mg/kg, QD 200 Compound X, 5 mg/
Slide 20: Status of preclinical development of CPT-6281
Status of preclinical development of CPT-6281 In vitro and in vivo pharmacology studies Drug Substance synthesis optimization and manufacture for tox MTD/DRF tox studies in rats and NHP DMPK studies GLP tox studies In-life phase complete GLP tox studies Ongoing Histopathology, TK, safety pharmacolog
Slide 21: Development timeline – CPT-6281
Development timeline – CPT-6281 Initial indication: Expected milestones: Hepatocellular carcinoma CTA submission for initiation of clinical trials in Q4 2023 Degradation profile Initial phase I top-line data to be reported by the end of 2024 Molecular GSPT1, SALL4, NEK7 Combination study data in 202
Slide 22: Summary
Summary CPT-6281 first-in-class MG degrader of GSPT1, NEK7 & SALL4 with target tissue pro-drug activation for liver, lung and neuroendocrine cancers • CPT-6281 degrades GSPT-1, NEK7 and SALL4 and is cytotoxic in cancer cell lines in vitro & in vivo • CPT-6281 potently inhibits tumor growth in Hep3B
Slide 23: CT-03: First-in-Class MCL-1 Degraders
CT-03: First-in-Class MCL-1 Degraders for Liquid & Solid Tumours 23 23 October 2023 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 24: MCL-1 as a target in numerous cancers
MCL-1 as a target in numerous cancers MCL-1 is a key mechanism of drug resistance in cancer cells Highly attractive target serving as a major survival signal in numerous cancers Haematological malignancies Multiple Myeloma (MM) Acute Myeloid Leukaemia (AML) Non-Hodgkin Lymphoma (NHL) Selected solid
Slide 25: MCL-1 degraders offer pharmacology distinct from inhibitors
MCL-1 degraders offer pharmacology distinct from inhibitors • MCL-1 degraders reduce MCL-1 protein levels, unlike inhibitors that accumulate MCL-1 • Reduction of MCL-1 by ca. 70% results in apoptosis induction in cancer cells • Monoallelic KO of MCL-1 in mice is viable and without phenotype • CPT-90
Slide 26: Potent degradation of MCL-1 across different in vitro models
Potent degradation of MCL-1 across different in vitro models SK-MEL-2 DMS 114 CPT-2036 CPT-908 CPT-2036 0.001 DC50/Dmax kDa 0.01 Conc. [µM] Cell line CPT-2036 CPT-908 0.1 0.1 0.1 10 10 10 0 0 1 1 1 MCL-1 37 MV4-11 79 nM / 96% 1 nM / 99% 25 hsPBMC 26 nM / 87% 1 nM / 88% 100 PARP SK-MEL-2 1 uM/ 50% 56
Slide 27: Cell line and PBMCs sensitivity to CPT-2036 & CPT-908
Cell line and PBMCs sensitivity to CPT-2036 & CPT-908 120 pIC50 100 Cell line CPT-2036 CPT-908 Viability (%) 80 MV-4-11 6.5 ± 0.1 8.5 ± 0.2 60 MV-4-11 Ven-resistant - 11.5 (N=1) MV-4-11 Ven-resistant + 40 - 12.0 (N=1) Venetoclax WSU-DLCL-2 5.4 ± 0.2 7.6 ± 0.1 20 DMS 114 6.2 ± 0.3 7.8 ± 0.1 0 -10 -9
Slide 28: CPT-2036 in combination with chemotherapeutic agents
CPT-2036 in combination with chemotherapeutic agents CPT-2036 ABS-836 100 Bliss synergy score MV-4-11 75 Co-treatment with CPT-2036 and different chemotherapeutic agents 50 in MV4-11 and DMS 114 for 72 h. Viability assessed by CTG assay. DMS 114 25 i i Ki i i i i ne EK FR T3 L2 R FR BT TO i BC tid F
Slide 29: CPT-2036 effective in-vivo in AML and lung cancer models
CPT-2036 effective in-vivo in AML and lung cancer models Strong tumor growth inhibition in intermittent dosing (every 3 days) Potent MCL-1 degradation and apoptosis activation in SCLC xenograft model kDa Vehicle CPT-2036 50 37 MCL-1 150 PARP FL 100 PARP CL 75 20 15 CC3 50 Stain Free blot 37 Mice wit
Slide 30: High potency of CPT-908 in AML ex vivo models
High potency of CPT-908 in AML ex vivo models pIC50 values of tested CPT-908 is more potent than ABS-994 in compounds in each of the ABU-098 is more potent than ABS-994 in most of the most oftested the tested models models 30 AML ex vivo models 10 10 CTG-3950 CTG-4044 CTG-3950 CTG-4044 9 9 TP53_muta
Slide 31: Strong PD effect of CPT-908 & CPT-2036 in vivo
Strong PD effect of both CPT-908 & CPT-2036 in vivo (NHP PBMCs) Internal control CPT-2036 0.1 mg/kg 1 mg/kg 10 mg/kg kDa -24 3 6 -24 3 6 -24 3 6 Treatment time [h] 50 37 MCL-1 CPT-2036 0.1 mg/ml 50 37 Total protein CPT-2036 1 mg/ml CPT-2036 10 mg/ml Internal control CPT-908 0.1 mg/ml CPT-908 CPT-908
Slide 32: Development timeline – CT-03
Development timeline – CT-03 Partnering: Open to partnering now Initial indications: Blood cancers, subsequently solid tumours Expected milestones: Bifunctional Degrader Degrader profile • Candidate selection planned for Oct 2023 Selective first-in-class MCL1 degraders, • GLP tox start Nov 2023 (Com
Slide 33: Summary
Summary Two MCL-1 bifunctional degraders have been developed with in vitro potency (DC50) of <1 nM & 100 nM • CPT-2036 & CPT-908 selectively degrade MCL-1 and are cytotoxic in cancer cell lines in vitro & in vivo • Both CPT-908 & CPT-2036 potently inhibit tumor growth in MV4-11 xenograft models • CP
Slide 34: CT-02: First-in-Class NEK7 degraders
CT-02: First-in-Class NEK7 degraders for autoimmune & neurodegenerative diseases 34 34 September 2023 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 35: CT-02: Vast market potential for inflammasome modulators
CT-02: Vast market potential for inflammasome modulators Neuroinflammation Allergy Asthma (AD, PD, MS, ALS) Myocardial infarction Fibrotic diseases Diabetic cardiomyopathy Inflammasome: NEK7 complex Lupus Inflammatory nephritis Bowel Disease Caspase 1 Gout Psoriasis Rheumatoid Arthritis IL-1𝛽 IL-18
Slide 36: Development of NLRP3/NEK7 inhibitors is growing rapidly
Development of NLRP3/NEK7 inhibitors is growing rapidly PHASE I PHASE II PHASE III INDICATIONS Olatec Therapeutics OLT1177 (Dapansutrile) Knee OA; Gout Novartis DFV890 (IFM-2427) Knee OA; FCAS Zydus Lifesciences ZYIL1 CAPS NLRP3 Ventyx Biosciences VTX2735 CAPS INHIBITORS Roche IZD174; IZD334 CAPS Ro
Slide 37: Intervention in NLRP3 pathway via NEK7 degradation
Intervention in NLRP3 pathway via NEK7 degradation Aberrant activation of NLRP3 INCREASED INFECTIONS via REDUCED IMMUNITY NLRP3 inhibition COMPLETE INACTIVATION OF NLRP3 PARTIAL INACTIVATION OF NLRP3 NEK7 degradation MAINTAINED NLRP3 inflammasome NEK7 IMMUNITY 37 CT-02 (NEK7) Business Use Only | Do
Slide 38: Captor has developed two series of NEK7 degraders
Captor Therapeutics has developed two series of NEK7 degraders CPT-764/CPT-513 CPT-565 systemic therapy for therapy of the treatment of inflammatory autoimmune neurodegenerative disorders disorders cross the blood-brain barrier CPT-513 is an optimized lead compound of CPT-764 with improved NEK7 degr
Slide 39: CPT-764, CPT-513 & CPT-565 do not affect viability of human PBMC
CPT-764, CPT-513 & CPT-565 do not affect viability of human PBMC in vitro CPT-764 ABS-674 CPT-513 ABU-153 CPT-565 ABX-011 150 150 150 100% - DMSO 100% - DMSO 100% - DMSO 0% - no cells 0% - no cells 0% - no cells 100 100 100 % Viability % Viability % Viability 50 50 50 0 0 0 -4 -3 -2 -1 0 1 2 -4 -3 -
Slide 40: Potent degradation of NEK7 in human macrophages in vitro
Potent degradation of NEK7 in human macrophages in vitro CPT-513 CPT-565 CPT-764 0.003 0.003 0.003 Conc. [µM] 0.03 0.03 0.03 0.01 0.01 0.01 0.1 0.1 0.1 10 10 10 Nigericin [5 µM] 1 1 1 kDa - - + + + + + + + + + + + + + + + + + + + + + 40 35 NEK7 55 ß-actin 40 180 Vinculin 130 CPT-513, CPT-764 and CPT
Slide 41: Lead compounds decrease levels of IL-1β and IL-18 in vitro
Lead compounds decrease levels of IL-1𝛽 and IL-18 in vitro ELISA analysis of cytokines IL-1ß and IL-18 produced by human macrophages treated with CPT-764, CPT-513 & CPT-565 (24h treatment) IL-1𝛽 IL-18 150 150 (normalized to DMSO Ctrl) (normalized to DMSO Ctrl) %of IL-1 release %of IL-18 release…
Slide 42: In vivo PoC in peritonitis model & brain penetration
In vivo PoC in peritonitis model & brain penetration -24h 0h 2h 4h 6h Plasma and brain concentration of CPT-565 Concentration [ng/g] Brain 1000 Single MSU Terminal Plasma dose of induction bleeding & CPT-764 LPS In-life collection 100 challenge bleeding 10 IL-1β levels 1 400 Plasma 4h Plasma 6h Peri
Slide 43: Summary
Summary • Two NEK7 degrader series - potential in autoimmune diseases (CPT-513) and neurodegenerative disorders (CPT-565, brain-penetrant series) • Dose-dependent nanomolar degradation of NEK7 in HiBiT assay and Western blot (human PBMCs) • CPT-764, CPT-513 and CPT-565: o are non-cytotoxic to human,
Slide 44: CT-05: First-in-Class PKCθ degraders
CT-05: First-in-Class PKCӨ degraders for autoimmune disorders 44 44 September 2023 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 45: PKCθ: an undrugged high value target
PKCӨ: an undrugged high value target TCR Multiple sclerosis Allergy Asthma CD3 CD28 T-cell membrane Cytoplasm Myocarditis Breast cancer PKCӨ IL-2 Kidney injury IL-17 Gastrointestinal cancer Nucleus Inflammatory Bowel Psoriasis Disease 45 CT-05 (PKCӨ) Business Use Only | Do not use without written co
Slide 46: Rationale for targeted degradation of PKCθ
Rationale for targeted degradation of PKCӨ Multiple PKCӨ inhibitors evaluated in clinical trials: 1st generation (e.g. pan-PKC Sotrastaurin) – many side effects 2nd generation (e.g. Astellas, AbbVie, Celgene) - PKCӨ-selective but showed side effects due to unknown off-target(s) or poor target engage
Slide 47: Clonogenic assay – reported PKCθ inhibitors in GIST-T1
Clonogenic assay – reported PKCӨ inhibitors in GIST-T1 Clonogenic assay - A570 Clonogenic GIST-T1assay Other PKCӨ non-selective inhibitors, developed in the 150 past tested in Clonogenic assay control ctrl 0.1 µM 0.5 µM DMSO 0.5% 100 VTX-27 % of DMSO (Vertex) %DMSO Darovasertib 50 (Ideaya Bioscience
Slide 48: CPT-763 & CPT-308 degrade PKCθ in a human T cell line
CPT-763 & CPT-308 degrade PKCӨ in a human T cell line PKCӨ PKCδ stimulated Jurkat cells Protein remaining [%] Protein remaining [%] -log(conc.[M]) -log(conc.[M]) CPT-763 CPT-308 Compound DC50 Dmax CPT-763 & CPT-308 degrade PKCӨ efficiently, with no effect on PKCδ CPT-763 29 nM 75 % (the isoform shar
Slide 49: CPT-763 & CPT-308 inhibit IL-2 production in a human T cell line
CPT-763 & CPT-308 inhibit IL-2 production in a human T cell line ELISA analysis of IL-2 secretion upon PKCӨ CPT-763 CPT-308 degradation by CPT-763 & CPT-308, 7h Normalized IL-2 level [%] Normalized IL-2 level [%] Normalized IL-2 level [%} Normalized PKCӨ level [%] Normalized PKCӨ level [%] 0.0003 µM
Slide 50: CPT-763 is highly selective in a panel of assays
CPT-763 is highly selective in a panel of assays KinomeScan results Inhibitor shows significant effects on non-immune cells TREEspot™ Interaction Map Degrader has no effect in non-immune cells panel of ca. 450 kinases CPT-763 @ 10000nM 0.1 µM 0.5 µM Astellas compound CPT-191 Inadequate Selectivity C
Slide 51: CPT-308 degrades PKCθ in vivo
CPT-308 degrades PKCӨ in vivo a-CD3-stimulated, CPT-308 20mpk-treated PKCӨ CPT-308 Efficient PKCθ degradation is observed in CPT-308-treated animals Efficient degradation of PKCӨ in C57BL/6 mouse splenocytes is observed 6h after CPT-308 application 51 CT-05 (PKCӨ) Business Use Only | Do not use with
Slide 52: Summary
Summary • Established a screening workflow that allows for discovery of PKCƟ degraders superior to existing inhibitors • Early stage of lead optimisation with 2 compounds has demonstrated: • In vitro: degradation of PKCƟ in mouse & human T-cells & inhibition of IL-2 in human T-cells • In vivo: degra
Slide 53: Finance highlights
Finance highlights 53 53 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 54: Strong balance sheet and cash position
Strong balance sheet and cash position Consolidated statement of financial position (US$, M) Cash position Available funding secured (US$ M; as of June 30,2023): 24.7 23.5 Total : US$ 33.5 M US$ 14.3 16.7 cash, short-term bonds 14.3 13.5 33.5 19.2 US$ 19.2 available grants (NCBR; ABM) 5.0 2.8 3.3 2.
Slide 55: Captor Therapeutics contact details
Captor Therapeutics S.A ul. Duńska 11 54-427 Wrocław, Poland Captor Therapeutics GmbH Hegenheimermattweg 167A 4123 Allschwil, Switzerland Contact: [email protected] 55 Business Use Only | Do not use without written consent of Captor Therapeutics Inc. © 2023
Slide 56: Projects co-financed by the European Regional Development Fund
Projects co-financed by the European Regional Development Fund: Discovery and development of a new clinical drug candidate for the eradication of cancer stem cell in the treatment of hepatocellular carcinoma, through degradation of oncofetal transcription factor (POIR.01.01.01-00-0740/19-00) Discove
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