Captor Therapeutics Sa · GPW:CTX
Captor Therapeutics Sa — Investor Presentation (October 2024)
58 slides from Captor Therapeutics Sa's investor presentation, October 2024
Slide 1: Pioneering targeted protein degraders for human health
Pioneering targeted protein degraders for human health Corporate Presentation October 2024
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: An experienced leadership team
An experienced leadership team LEADERSHIP TEAM Tom Shepherd, Ph.D. Michal Walczak, Ph.D. Anna Pawluk, Ph.D. Sylvain Cottens, Ph.D. Andrew Saunders DPM, FFPM Chief Executive Officer Co-founder VP Operation Co-founder Chief Medical Officer Chief Scientific Officer SVP Chemistry • 30 years in Biotech •
Slide 4: Targeted Protein Degradation expected to unlock $974 bn by 2030
Targeted Protein Degradation expected to unlock $974* bn by 2030 protein of interest PoI DEGRADER PoI PoI E3 ligase proteasome degraded protein ubiquitin Degraders Inhibitors mAbs siRNA Removing multiple pathological functions ✓✓✓ ✓✓✓ Oral bioavailability ✓✓✓ ✓✓✓ Uncoupling PK from PD = prol
Slide 5: Optigrade discovery platform – importance of structure
Optigrade discovery platform – importance of structure CRANBERRIES TULIPS OptigradeTM Platform BIFD discovery & optimization Rational Molecular Glues LILIS Novel E3 Ligases BIFD – BIFunctional Degraders OptigradeTM – addressing Molecular Glues, Bifunctional Degraders and novel E3 Ubiquitin Ligases 5
Slide 6: Fully owned pipeline
Fully owned pipeline Programme Primary Indications Modality Discovery Preclinical* IND Filing Phase IA / IB Phase II Target GSPT1 Hepatocellular carcinoma, CT-01 GSPT1 Lung cancer, NET tumours MG NEK7 Neuroinflammation CT-02B† NEK7 (Parkinson's Disease, ALS, MS) MG NEK7 CT-02S‡ NEK7 Systemic autoimm
Slide 7: CT-01: First-in-Class GSPT1 Targeted Degrader for Hepatocellular Carcinoma (HCC)
CT-01: for Hepatocellular First-in-Class Carcinoma GSPT1 Targeted (HCC) Degrader CT-01: First-in-Class GSPT1 Targeted Degrader for Hepatocellular Carcinoma (HCC) 7
Slide 8: CT-01: first-in-class molecular glue degrader of GSPT1 & NEK7
CT-01: first-in-class molecular glue degrader of GSPT1 & NEK7 Lung cancer 496k patients1,2 GSPT1 degradation leads to an Integrated Stress Response (ISR) and induction of apoptosis in HCC cells NEK7 degradation leads to reduction of IL-1𝛽 production – a well- established pro-carcinogenic factor…
Slide 9: Biology of GSPT1 supports its targeted degradation in cancer treatment
Biology of GSPT1 supports its targeted degradation in cancer treatment Target Biology and Therapeutic Rationale G1 to S phase transition 1 protein (GSPT1, eRF3a) protein is a translation termination factor that regulates mRNA translation1 GSPT1 and eRF1 form a translation termination complex that GS
Slide 10: GSPT1 degrader
GSPT1 degrader protein GSPT1 degradation leads to apoptosis via induction Integrated Stress Response (ISR) An excellent opportunity for targeting of cancer cells that require translational adaptations and efficient protein synthesis GSPT1 eRF1 CT-01 degrader is a pro-drug converted by an enzyme elev
Slide 11: HCC: current standard of care and opportunity
HCC: current standard of care and opportunity Survival Benefit vs Sorafenib Line of therapy Therapy FDA Approval [months] 1 Tecentriq + Avastin +5.81 uHCC / mHCC 1 Imfinzi + Imjudo +2.72 uHCC 1/2 Nexavar 0.03 uHCC uHCC 2 Optivo +1.74 (Post sorafenib) uHCC 2 Cabometyx +2.25 (Post sorafenib) Market Re
Slide 12: Induction of ISR-dependent cell death in Hep3B tumor cells
Induction of ISR-dependent cell death in Hep3B tumor cells Degradation of GSPT1 in the ISR markers during CT-01 treatment function of time DMS (WB densitometry) CT-01 0.1 µM O 4 4 8 16 24 32 48 72 96 Time of treatment CT-01 kDa [hrs] 50 ATF-4 [% of DMSO ctrl normalized vs -Actin] 100 37 25 ATF-3 20
Slide 13: Lack of cytotoxicity to primary human hepatocytes provides extra safety level
Lack of cytotoxicity to primary human hepatocytes provides extra safety level CT-01 CPT-ABS-752 100 80 % inhibition 60 40 20 0 -8 -7 -6 -5 -4 -20 log10C [M] IC50 (M): N.C. CTG in PHH, Eurofins CT-01 (GSPT1) CT-01 (GSPT1) 13 Business Use Only | All rights reserved
Slide 14: Highly potent CT-01 regresses tumors in mice
Highly potent CT-01 regresses tumors in mice NSG_Hep3B kDa CPT-5170* CT-01 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 tumor
Slide 15: 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 random HCC patient samples (no selection for drug target) 42 CT-01, 100mg/kg, BID 35 31 3 animals per vehicle & treatment groups 22 LI-1 LI-2 LI-3 LI-4 LI-5 LI-6 LI-7 LI-8 LI-9
Slide 16: Strong synergy of CT-01 in combination with everolimus
Strong synergy of CT-01 in combination with everolimus Everolimus is an approved anticancer drug (kidney, breast & brain cancers), and shows clear synergy with CT-01 in combination HUH-7 Xenograft Model LI1097 HCC PDX 2000 1200 1000 Tumor volume [mm3] Tumor volume [mm3] 1500 800 1000 Vehicle 600 Veh
Slide 17: CT-01 is highly differentiated among GSPT1 degraders
CT-01 is highly differentiated among GSPT1 degraders Assay CT-01 (Captor)1 CC-90009 (BMS)2 MRT-2359 (Monte Rosa)3 Selectivity (Px, WB) GSPT1, GSPT2, NEK7 GSPT1, GSPT2, SALL4, FIZ1, RNF166, ODC1 (1) GSPT1, GSPT2 CYP DDI (2B6, 1A2, 2D6, 3A4, 2C8, >50 µM CYP2C19 at 1.5 µM >30 µM 2C9, 2C19) hERG >30 µM
Slide 18: CT-01: CTA submission status
CT-01: CTA submission status In vitro and in vivo pharmacology studies Drug Substance synthesis optimization and manufacture in large scale DMPK studies Preliminary toxicology studies in 2 animal species Toxicology studies under GLP (GLP Tox) Drug Substance GMP manufacture Drug Product – capsule pre
Slide 19: Study design
Study design PART 1 – MONOTHERAPY – CT-01 Part 1a – DOSE ESCALATION Part 1a – DOSE EXPANSION DL7 RDm -1 (20 subjects) DL6 DL5 RDm (20 subjects) DL4 DL3 DL2 DL1 RDm + MTDm Parallel recruitment may start from RDc + MTDc Part 1a DL3 and Part 2a DL1 if 2 DLs of Part 1a are considered safe by SMCe DLm+2
Slide 20: Best-in-class potential of highly differentiated CT-01
Best-in-class potential of highly differentiated CT-01 • Strong differentiation from other GSPT1 degraders (BMS, Monte Rosa) • Best-in-class degradation profile • Active degrader lingers inside cancer cells after activation (poor cell penetration after prodrug conversion) • Active degrader is rapid
Slide 21: CT-03: First-in-Class MCL-1 Degraders for Liquid & Solid Tumors
CT-03: for Liquid First-in-Class Solid Tumors MCL-1 Degraders CT-03: First-in-Class MCL-1 Degraders for Liquid & Solid Tumors 21
Slide 22: CT-03: MCL-1 – a critical pathway for cancer resistance
CT-03: MCL-1 – a critical pathway for cancer resistance MCL-1 is one of the most amplified proteins in cancer† A critical resistance mechanism in hematological and solid tumors‡, cancer cells require very high levels to avoid induction of apoptosis Breast Cancer Lung cancer 919k patients1-4 Degradat
Slide 23: CT-03: MCL-1 – a critical pathway for cancer resistance
CT-03: MCL-1 – a critical pathway for cancer resistance MCL-1 biology and clinical relevance MCL-1 MCL-1 is a well-characterized oncogenic protein with a key role in MCL-1 degrader evading apoptosis and promoting the survival of cancer cells1. BAK INACTIVE Studies show cell growth dependency of MCL-
Slide 24: MCL-1 degraders advantage over inhibitors
CT-03: MCL-1 – a critical pathway for cancer resistance MCL-1 degraders advantage over inhibitors MCL-1 MCL-1 MCL-1 MCL-1 inhibition increases its stability, through its aberrant inhibitor degrader phosphorylation and consequent accumulation1. The result of MCL-1 accumulation is a cellular rewiring
Slide 25: MCL-1: a high potential cancer target
MCL-1: a high potential cancer target Highly attractive target with application in numerous cancer markets Hematological malignancies Multiple Myeloma (MM) Acute Myeloid Leukemia (AML) Non-Hodgkin Lymphoma (NHL) Est. $53B by 20301 Est. $6B by 20282 Est. $16B by 20323 Selected solid tumors Small cell
Slide 26: High potency of MCL-1 degraders in AML patient samples ex vivo & in-vivo leukemia model
High potency of MCL-1 degraders in AML patient samples ex vivo & in-vivo leukemia model 2000 Tumour volume [mm3] (mean ± SEM) MCL-1 degrader is more potent than MIK665 ABU-098 is more potent than ABS-994 in most of the 2000 (Novartis) in patient-derived AML cells Tumour volume [mm3] (mean ± SEM) tes
Slide 27: Combined MCL-1 degrader with venetoclax regresses AML tumors in mice
Combined of MCL-1 degrader with venetoclax regresses AML tumors in mice Vehicle, Q3D/IV Vehicle, QD/PO Tumor volume [mm3] Vehicle, Q3D/IV – QD/PO CT-03, 25 mpk Venetoclax, 7.5 mpk CT-03, 25 mpk + Venetoclax, 7.5 mpk Day of treatment Regression of large tumors was observed for both CT-03 and venetocl
Slide 28: Degradation of MCL-1 in NHP after single IV dose of degraders
Degradation of MCL-1 in NHP after single IV dose of degraders PK data, NHP PK data, NHP 10 6 10 6 CT-03, 33mg/kg ABS-836 mg/kg CT-03, 1010 ABS-836 mg/kg mg/kg Concentration [ng/mL] 10 5 10 5 Concentration [ng/mL] CT-03p, 3 mg/kg ABU-098 mg/kg CT-03p, 10 ABU-098 10mg/kg mg/kg ABS-836 afterCT-03p, CT-
Slide 29: Cardiotoxicity marker Troponin I in plasma of NHPs after CT-03 dosing
Cardiotoxicity marker Troponin I in plasma of NHPs after CT-03 dosing Positive Vehicle CT-03 CT-03 CT-03p CT-03p control IV 3 mpk 10 mpk 3 mpk 10 mpk CT-03 & CT-03p: no observed increase in troponin-I levels *Cardiotoxic positive control - Isoproterenol 3mg/kg, Vasopressin 0.3mg/kg CT-03 – active co
Slide 30: CT-03 candidate drug with unmatched therapeutic window
CT-03 candidate drug with unmatched therapeutic window • Strong differentiation from MCL-1 inhibitors • Pharmacology of MCL-1 degradation vs. pharmacology of accumulation (inhibitors) • No accumulation of MCL-1 protein • No cardiotoxicity observations in MTD, DRF in NHPs by any means • Very high deg
Slide 31: CT-02: First-in-Class NEK7 Degraders for Autoimmune, Neuroinflammation & Obesity
CT-02: First-in-Class Autoimmune Neuroinflammation (CT-02S), NEK7 Obesity Degraders (CT-02B)for CT-02: First-in-Class NEK7 Degraders for Autoimmune (CT-02S), Neuroinflammation & Obesity (CT-02B) 31
Slide 32: Significant market opportunities for Captor's NEK7 degraders
Significant market opportunities for Captor’s NEK7 degraders CT-02S CT-02B CPT-635(r) CPT-732(r) Peripheral autoimmunity Neurodegenerative diseases NEK7 degraders could be used in combination with Growing evidence for role of pathological activation of innate available therapeutics to manage comorbi
Slide 33: NEK7 as a new target of the NLRP3 inflammasome pathway
NEK7 as a new target of the NLRP3 inflammasome pathway NEK7 overview NEK7 is master regulator of the NLRP3 inflammasome complex TLR-L IL-1𝛽 PAMPs through its scaffolding function DAMPs NEK7 KO/KD in mouse abrogates production of IL-1 beta in TLR IL-1R Cell membrane response to stimulating factors…
Slide 34: NEK7 as a new target of the NLRP3 inflammasome pathway
NEK7 as a new target of the NLRP3 inflammasome pathway IL-1𝛽 inhibitors Differentiation (rilonacept, canakinumab) From anti-IL-1𝛽 antagonists: IL-1𝛽 receptor inhibitors Once daily oral administration instead of injection TLR-L IL-1𝛽 (anakinra) PAMPs Uncoupling pharmacokinetics from…
Slide 35: Intervention in NLRP3 pathway via NEK7 degradation
Intervention in NLRP3 pathway via NEK7 degradation Aberrant activation of NLRP3 INCREASED INFECTIONS, TOXICITY FROM NON-INFLAMMASOME FUNCTIONS OF NLRP3 NLRP3 inhibition COMPLETE INACTIVATION OF NLRP3 PARTIAL INACTIVATION OF NLRP3 NEK7 degradation NLRP3 inflammasome MAINTAINED NEK7 IMMUNITY CT-02 (NE
Slide 36: Potent degradation of NEK7 in human macrophages in vitro
Potent degradation of NEK7 in human macrophages in vitro CPT-635r CPT-732r 0.003 0.003 Conc. [µM] 0.03 0.03 0.01 0.01 0.1 0.1 10 10 Nigericin [5 µM] 1 1 kDa - - + + + + + + + + + + + + + + + 40 35 NEK7 55 ß-actin 40 180 130 Vinculin CPT-635r and CPT-732r degrade NEK7 protein dose-dependently in huma
Slide 37: High selectivity of NEK7 molecular glue degraders
High selectivity of NEK7 molecular glue degraders CPT-764* CPT-635r CPT-732r CPT-635 CPT-732 1 µM 1 µM DMSO ABX-365 vs DMSO ABX-372 vs DMSO kDa 10 10 10 Conc. [µM] NEK7 6 6 37 NEK7 NEK7 25 37 CK1α 4 4 -Log10(P-value) -Log10(P-value) -log10(P-value) -log10(P-value) 25 100 NEK1 GSPT-1 NEK6 75 NEK4 NEK
Slide 38: High selectivity of diastereoisomers against teratogenic targets
High selectivity of diastereoisomers against teratogenic targets Kelly neuroblastoma cell line High selectivity against off-targets suspected of CPT-635 CPT-732 kDa 10-5 10-4 10-3 10-2 10-1 1 10 Conc. [µM] kDa 10-5 10-4 10-3 10-2 10-1 1 10 Conc. [µM] teratogenicity: 37 NEK7 25 NEK7 SALL4, PLZF and p
Slide 39: CPT-635r efficiently covers & degrades NEK7 in NHPs after a single dose
CPT-635r efficiently covers & degrades NEK7 in NHPs after a single dose CPT-635r [3 mg/kg] CPT-635r CPT-513 NEK7 relative abundance [%0h] kDa 0h 3h 6h 24h 125 100 100 37 100 Dose: NEK7 1 mg/kg 75 3 mg/kg 25 20 50 28 24 25 150 6 4 3 2 Vinculin 0 100 0h (pre-dosing) 3h 6h 24h Time after dosing Mean Pl
Slide 40: CPT-732r efficiently covers & degrades NEK7 in NHPs after a single dose
CPT-732r efficiently covers & degrades NEK7 in NHPs after a single dose CPT-732r [3 mg/kg] CPT-732r CPT-101 NEK7 relative abundance [%0h] kDa 0h 3h 6h 24h 125 100 100 37 100 Dose: 1 mg/kg NEK7 75 3 mg/kg 25 23 20 50 9 25 11 8 150 8 5 Vinculin 0 100 0 h ( p r e - d o s in g ) 3h 6h 24h Time after dos
Slide 41: High efficacy of CPT-635r with oral dosing in EAE mouse model in vivo
High efficacy of CPT-635r with oral dosing in EAE mouse model in vivo 2.5 Disease progression in EAE model Clinical Clinical Sign Score 2.0 Clinical score [+/- SEM] 0 Normal mouse; no overt signs of disease 0.5 Tail weakness/partial tail weakness (50% of length) 1.5 1 Loss of tail tonicity (complete
Slide 42: Therapeutic potential of NEK7 degraders in Collagen-Induced Arthritis model
Therapeutic potential of NEK7 degraders in Collagen-Induced Arthritis model Clinical Clinical Sign Score Disease progression Clinical score [mean ± SEM] 10 0 No redness or swelling Sham Control Sham control 1 Slight swelling in ankle and or redness in one toe 8 Progressive swelling from ankle to mid
Slide 43: Differentiated safety profile of NEK7 degraders vs. NLRP3 inhibitors
Differentiated safety profile of NEK7 degraders vs. NLRP3 inhibitors CPT-635 CPT-732 NLRP3 inhibitors Most inhibitors based on Structural features Classical scaffold Classical scaffold sulfonamides; Anhydrases as off-targets5 Inhibition of IL-1ß Max. 80-90% Max. 80-90% 100% NEK7 NLRP3 Alternative fu
Slide 44: CT-02: Excellent degraders from two different strategies
CT-02: Excellent degraders from two different strategies Two series of potent NEK7 degraders: autoimmune diseases (CPT-635) and neurodegenerative disorders (CPT-732, brain-penetrant) Activity confirmed in vitro in mouse, monkey and human cells and in vivo in mice and monkeys Specificity-driven safet
Slide 45: CT-05: First-in-Class PKCӨ Degraders for Autoimmune Disorders
CT-05: for Autoimmune First-in-Class Disorders PKCӨ Degraders CT-05: First-in-Class PKCӨ Degraders for Autoimmune Disorders 45
Slide 46: PKCӨ: 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 CT-05 (PKC Ө) CT-05 (PKCӨ) 46 Business Use Only | All rights rese
Slide 47: PKCӨ Biology and target rationale
PKCӨ Biology and target rationale Target Biology and rationale PKCӨ Ser/Thr kinase PKCӨ has a thoroughly established role in regulatory and effector T cell functions1,2 MHCII APC PRCKQ locus was shown associated with several immune-related B7 diseases in multiple GWAS studies (type I diabetes, rheum
Slide 48: Rationale for targeted degradation of PKCӨ
Rationale for targeted degradation of PKCӨ PKCӨ Ser/Thr kinase MHCII APC B7 PKCӨ is a master regulator of T cell differentiation, proliferation and functions. TCR CD28 Drawbacks of the 1st and 2nd generation PKCӨ T cell inhibitors were related to multiple side effects due to unspecificity and insuff
Slide 49: CPT-763 is highly selective in a panel of assays
CPT-763 is highly selective in a panel of assays Inhibitor shows significant effects on GIST-T1 non-immune cells KinomeScan results Degrader has no effect in same system TREEspot Interaction Map panel of ca. 450 kinases CPT-763 @ 10000nM 0.1 µM 0.5 µM Big Pharma compound CPT-191 Inadequate Selectivi
Slide 50: Summary
Summary • Established a screening workflow that allows for discovery of PKCƟ degraders superior to existing inhibitors • Highly selective for PKCƟ with no off-target toxicity • Early stage of lead optimisation with 2 compounds has demonstrated: • In vitro: degradation of PKCƟ in mouse & human T-cell
Slide 51: Optigrade Targeted Protein Degradation Platform
Optigrade Targeted Protein Degradation Platform Molecular glues Bifunctional Degraders Novel E3 ligases 65 1 Business Use Only | All rights reserved B u s i n e s s U s e O n l y |D o n ot u s e w ith ou t written c o n s e n t of C a p t o r T h era p eu tics Inc. © 2023
Slide 52: LiLis program: developing novel E3 ligases beyond CRBN
LiLis program: developing novel E3 ligases beyond CRBN ▪ Expanding the range of targets for effective degradation ▪ CRBN down regulation-driven resistance mechanisms in cancer ▪ Crowded IP space for CRBN binders ▪ Opportunity for cell type or cell compartment specificity In-house developed E3 ligase
Slide 53: Finance Highlights
Finance Highlights Finance Highlights 53
Slide 54: Balance sheet and cash position
Balance sheet and cash position Consolidated statement of financial position (US$, M) Cash position Available funding secured 22,5 (US$ M; as of June 30, 2024): Total : - US$ M 27,9* 17,6 16,7 US$ M 14,0 cash 12,6 13,9 27,9* 14,0 US$ M 13,9 available grants (NCBR; ABM) 6,8 5,9 2,6 2,2 0,8 0,4 Fixed
Slide 55: Balance sheet and cash position
Balance sheet and cash position Consolidated statement of financial position (EUR, M) Cash position Available funding secured (EUR M; as of June 30, 2024): 20,4 Total : - EUR 26,1 M* 15,6 15,9 EUR M 13,1 cash 11,8 13,0 26,1* 13,1 EUR M 13,0 available grants (NCBR; ABM) 6,1 5,5 2,4 2,0 0,7 0,3 Fixed
Slide 56: Balance sheet and cash position
Balance sheet and cash position Consolidated statement of financial position (PLN, M) Cash position Available funding secured 88,7 (PLN M; as of June 30, 2024): Total : - PLNPLN M PLN 112,6* 67,3 69,2 PLN M 56,5 cash 50,7 56,1 112,6* 56,5 PLN M 56,1 available grants (NCBR; ABM) 26,7 23,8 10,4 8,6 3,
Slide 57: Captor Therapeutics S.A. ul. Duńska 11 54-427 Wrocław, Poland
ul. Duńska 54-427 Captor Hegenheimermattweg 4123 Contact: Allschwil, Therapeutics Wrocław, investor.relations@captortherapeutics.com 11 Switzerland Poland S.A. GmbH 167A Captor Therapeutics S.A. ul. Duńska 11 54-427 Wrocław, Poland Captor Therapeutics GmbH Hegenheimermattweg 167A 4123 Allschwil, Swi
Slide 58: Projects co-financed by the European Regional Development Fund
Projects c o - f in an c e d by the E u r o p e a n Re g io n al D e v e l o p m e n t F un d : 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” (FEN
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