Leveraging the natural strengths of humanity and our collective - PowerPoint PPT Presentation

KIADIS PHARMA | COMPANY PRESENTATION | NOVEMBER 2019 EURONEXT: KDS Leveraging the natural strengths of humanity and our collective immune systems to source the best cells for life Cell therapy to treat cancer, combining innate and adaptive immune system

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Kiadis: Proprietary K-NK cell cancer immunotherapy K-NK cell therapy: K-NK pipeline: K-NK platform: Treatments across all Blood cancer and solid Off-the-shelf potent, high modalities, combining tumor cell-therapy dose NK cells based on strengths of innate and programs universal donor and haplo adaptive immune system donor • Salvage therapy: stand alone • K-NK002: Phase 1/2 as adjunctive • Off-the-shelf: mature universal • Front line therapy: adjunctive to to haplo HSCT with PTCy (2020) donor optimal for all patients • K-NK003: phase 1/2a to treat AML • PM21 particle platform : expansion surgery, chemo, MAbs, PARP • Preventive therapy R/R (2020) & activation with IL21 and 41bbL • K-NK00X: preclinical solid tumor programs HSCT: hematopoietic stem cell transplantation; Haplo: haploidentical (genetically half matched); allodepleted T-cells: T-cells without patient specific T-cells that could cause GVHD; GVHD: Graft versus Host disease; RMAT: Regenerative Medicine Advanced Therapy (‘breakthrough designation’); PTCy: post transplant cyclophosphamide KIADIS PHARMA | www.kiadis.com 3

Kiadis K-NK Pipeline: Blood tumors and solid tumors, entering Phase 1/2 in 2020 PRE RE- PHAS ASE CATALYSTS IN PROOF OF F PR PROD ODUCT INDI DICATION SET SETTING CLI LINICAL PoC oC 1/2 1/2 2020 2020 CONCEPT Adjunctive to Phase 1/2 (63 25 patients: standard of care patients) start reduction of K-NK002 02 Blood cancer 2020 HSCT-PTCy with US BMT- relapse from (chemo) CTN 45% to 8% 13 patients: Stand alone K-NK003 03 AML R/R 2020 Phase 1/2a start 69% complete salvage therapy remission Combo with front Preclinical data; Preclinical data K-NK00X Solid tumors line therapy initiation new and literature (Mabs, chemo) trials KIADIS PHARMA | www.kiadis.com 4

Combine innate and adaptive immunity Adaptive (IFN g ) MHC restricted Killing T cells killing (+receptors) NK cell Targeting CD8 Killing (ADCC) Tumor Ags Adaptive Antigen CD4 presentation DC B cell DC maturation selection and DC maturation Abs B cells KIADIS PHARMA | www.kiadis.com 5

No need for CAR-engineering, NK cells naturally potent Issues CAR Issue CTL engineering HLA-1 down-regulation Toxicity and by tumor to escape mAb limited to single T-cells target CAR-T CD16 TCR NK-cell T-cell KIRXDSX GITR Stress/viral ligands (HLA independent) Activation Single antigen via HLA-1 or CAR-T ‘Self protection’ by recognition of HLA -1 Inhibition Checkpoints (HLA-1 independent) KIADIS PHARMA | www.kiadis.com 6

Clinical benefit of combining NK-cells with antibody (ADCC) Outcomes for patients with high affinity CD16 (polymorphism in 10-15% of population) KIADIS PHARMA | www.kiadis.com 7

Clinical benefit of giving NK cells after chemo CHEMO SENSITIZES TUMOR TO NK- PATIENT’S OWN NK CELLS NOT CHEMO INHIBITS NK CELL KILLING CELLS PRESENT OR P0TENT • Bortezomib (proteasome • Bortezomib leads to upregulation of • Lower numbers of NK cells in Multiple peripheral blood of patients 1, 2 myeloma inhibitor), inhibits NK cell killing NK cell receptor ligands, MICA and PVR, on tumor cells 1,6 and may interfere with NK cell – • Patient NK cells have low based immunotherapy 5 • Bortezomib and carfilzomib expression activating receptors and • Dexamethasone decrease inhibitory ligands, MHC, elevated expression of PD-1, a NK on tumor cells 7,8 inhibitory receptor 3,1 (glucocorticoid, often given with proteasome inhibitors), • NK activity and numbers is suppresses NK cell activity 14 associated with low tumor burden 4 • Paclitaxel and docetaxel • Docetaxel enhances NK mediated • Patients with large and locally Breast cancer (antimicrotubule drugs), may killing of tumor cells by advanced disease have lower interfere with NK cell – based upregulating activating ligands on absolute numbers of NK cells and immunotherapy by inhibiting tumor cell surface such as MICA, increased proportions of immature NK cell function 5 ULBP1-3 13 and non-cytotoxic NK cells 9,10 Multiple myeloma: 1. Mohyuddin et al, 2018 Advances in Cell and Gene Therapy; 2. Famularo et al, 1992 Journal of Clinical and Laboratory Immunology; 3. Fauriat et al, 2006 Leukemia; 4. Osterborg et al, 1996 European Journal of Hematology; 5. Markasz et al, 2007 Molecular Cancer Therapeutics; 6.Sorani et al, 2009 Immunobiology; 7. Shi et al, 2008 Immunobiology; 14. Chen et al, 2018 Inflammapharmacology Breast cancer: 8. Zang et al, 2015 Oncotarget; 9. Verma et al, 2015 Journal of Translational Medicine; 10.Mamessier et al, 2013 Journal of Immunology; 11.Chagollan-Garcia et al, 2018 Technology in Cancer Research and Treatment; 12. Zingoni et al, 2018 Frontiers in Immunology; 13. Acebes-Huerta et al, 2016 Oncoimmunology KIADIS PHARMA | www.kiadis.com 8

Kiadis K-NK platform: addressing all NK critical attributes KIADIS PLATFORM BENEFITS • Hyperactive phenotype with high cytotoxicity 4-1bbL PM21 Potent, safe and antitumor IFNγ and TNF release (not (mbIL-21 and and persistent engineered) 41bbL particles) mbIL-21 • In vivo persistence (no senescence) • Fully licensed and mature NK cells Universal adult • Off-the-shelf Activating/inhibiting receptor profile optimized donor for all patients (HLA-KIR mismatch) • PM21 High yield/long culture allow high dosing and low Large scale (mbIL-21and COGS (>1000 doses/batch feasible) industrial • 41bbL Cryopreserved manufacturing • particles) No feeder/tumor cell materials in final product KIADIS PHARMA | www.kiadis.com 9

K-NK cell industrial manufacturing platform with PM21 particles Day 0 - 7 Day 7 - 13 Day 14 Day 14 Xuri Acquisition Prodigy/Clinimacs+ Hollow fiber/Lovo ViaFreeze of donor GRex Expansion in a Harvest and Cryo- bioreactor cells from NK cell enrichment; concentration preservation the clinic Stimulation using Formulation in cryo- PM21 particles preservative PM21: mbIL-21 and 41bbL particles Native membrane particles presenting mbIL21 and 41bbL No intact tumor cells (regulatory) KIADIS PHARMA | www.kiadis.com 10

Kiadis K-NK Clinical development outline PRODUCT INDICATION CLINICAL STUDIES Phase 1/2 BMT CTN Ph 2/3 Adaptive Design Blood K-NK002 (add-on bridge to OTS) versus PTCy cancer Ph 2/3 Adaptive Phase 1/2a K-NK003 AML R/R Design Phase 1 Phase 2a dose finding expansion & safety Phase 2 basket Phase 3 K-NK00X Solid tumors study indications Signal Activity studies 2024 KIADIS PHARMA | www.kiadis.com 11