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

EURONEXT: KDS KIADIS PHARMA | COMPANY PRESENTATION | NOVEMBER 2019

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

Disclaimer

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These slides and the accompanying oral presentation contain forward-looking statements and information. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry’s actual results, levels or activity, performance or achievements to be materially different from those anticipated by such statements. The use of words such as “may”, “might”, “will”, “should”, “could”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “project”, “intend”, “future”, “potential” or “continue”, and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding (i) the initiation, timing, cost, progress and results of our preclinical and clinical studies and our research and development programs, (ii)

• ur ability to advance product candidates into, and successfully complete, clinical studies, (iii) the timing or likelihood of regulatory filings and approvals, (iv) our ability

to develop, manufacture and commercialize our product candidates and to improve the manufacturing process, (v) the rate and degree of market acceptance of our product candidates, (vi) the size and growth potential of the markets for our product candidates and our ability to serve those markets, and (vii) our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates, are forward looking. All forward-looking statements are based

• n current estimates, assumptions and expectations by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking

statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. Any forward-looking statement speaks

• nly as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new

information, future events or otherwise, except as required by law. This presentation is not, and nothing in it should be construed as, an offer, invitation or recommendation in respect of our securities, or an offer, invitation or recommendation to sell, or a solicitation of an offer to buy, any of our securities in any

• jurisdiction. Neither this presentation nor anything in it shall form the basis of any contract or commitment. This presentation is not intended to be relied upon as

advice to investors or potential investors and does not take into account the investment objectives, financial situation or needs of any investor.

KIADIS PHARMA | www.kiadis.com

Kiadis: Proprietary K-NK cell cancer immunotherapy

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K-NK cell therapy: Treatments across all modalities, combining strengths of innate and adaptive immune system K-NK pipeline: Blood cancer and solid tumor cell-therapy programs K-NK platform: Off-the-shelf potent, high dose NK cells based on universal donor and haplo donor

• Salvage therapy: stand alone
• Front line therapy: adjunctive to

surgery, chemo, MAbs, PARP

• Preventive therapy
• K-NK002: Phase 1/2 as adjunctive

to haplo HSCT with PTCy (2020)

• K-NK003: phase 1/2a to treat AML

R/R (2020)

• K-NK00X: preclinical solid tumor

programs

• Off-the-shelf: mature universal

donor optimal for all patients

• PM21 particle platform: expansion

& activation with IL21 and 41bbL

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

Kiadis K-NK Pipeline: Blood tumors and solid tumors, entering Phase 1/2 in 2020

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PR PROD ODUCT INDI DICATION SET SETTING PRE RE- CLI LINICAL PoC

• C

PHAS ASE 1/2 1/2 CATALYSTS IN 2020 2020 PROOF OF F CONCEPT K-NK002 02 Blood cancer Adjunctive to standard of care HSCT-PTCy (chemo) 2020 Phase 1/2 (63 patients) start with US BMT- CTN 25 patients: reduction of relapse from 45% to 8% K-NK003 03 AML R/R Stand alone salvage therapy 2020 Phase 1/2a start 13 patients: 69% complete remission K-NK00X Solid tumors Combo with front line therapy (Mabs, chemo) Preclinical data; initiation new trials Preclinical data and literature

KIADIS PHARMA | www.kiadis.com

Combine innate and adaptive immunity

5 KIADIS PHARMA | www.kiadis.com

DC maturation

DC DC

Killing (+receptors) MHC restricted killing B cell selection and maturation Antigen presentation CD4 Killing (ADCC) Ags

B cells Abs

Targeting Adaptive (IFNg) Adaptive

NK cell T cells

CD8

Tumor

No need for CAR-engineering, NK cells naturally potent

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Issue CTL HLA-1 down-regulation by tumor to escape T-cells Issues CAR engineering Toxicity and limited to single target

KIADIS PHARMA | www.kiadis.com

GITR KIRXDSX CD16 mAb

NK-cell

Stress/viral ligands (HLA independent) ‘Self protection’ by recognition of HLA-1

TCR

T-cell

CAR-T

Single antigen via HLA-1 or CAR-T Checkpoints (HLA-1 independent) Activation Inhibition

Clinical benefit of combining NK-cells with antibody (ADCC)

KIADIS PHARMA | www.kiadis.com 7

Outcomes for patients with high affinity CD16 (polymorphism in 10-15% of population)

Clinical benefit of giving NK cells after chemo

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CHEMO INHIBITS NK CELL KILLING CHEMO SENSITIZES TUMOR TO NK- CELLS PATIENT’S OWN NK CELLS NOT PRESENT OR P0TENT Multiple myeloma

• Bortezomib (proteasome

inhibitor), inhibits NK cell killing and may interfere with NK cell– based immunotherapy5

• Dexamethasone

(glucocorticoid, often given with proteasome inhibitors), suppresses NK cell activity14

• Bortezomib leads to upregulation of

NK cell receptor ligands, MICA and PVR, on tumor cells1,6

• Bortezomib and carfilzomib

decrease inhibitory ligands, MHC,

• n tumor cells7,8
• Lower numbers of NK cells in

peripheral blood of patients1, 2

• Patient NK cells have low

expression activating receptors and elevated expression of PD-1, a NK inhibitory receptor3,1

• NK activity and numbers is

associated with low tumor burden4 Breast cancer

• Paclitaxel and docetaxel

(antimicrotubule drugs), may interfere with NK cell–based immunotherapy by inhibiting NK cell function5

• Docetaxel enhances NK mediated

killing of tumor cells by upregulating activating ligands on tumor cell surface such as MICA, ULBP1-313

• Patients with large and locally

advanced disease have lower absolute numbers of NK cells and increased proportions of immature and non-cytotoxic NK cells9,10

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

Kiadis K-NK platform: addressing all NK critical attributes

KIADIS PHARMA | www.kiadis.com 9

KIADIS PLATFORM BENEFITS Potent, safe and persistent PM21 (mbIL-21 and 41bbL particles)

• Hyperactive phenotype with high cytotoxicity

and antitumor IFNγ and TNF release (not engineered)

• In vivo persistence (no senescence)

Off-the-shelf Universal adult donor

• Fully licensed and mature NK cells
• Activating/inhibiting receptor profile optimized

for all patients (HLA-KIR mismatch) Large scale industrial manufacturing PM21 (mbIL-21and 41bbL particles)

• High yield/long culture allow high dosing and low

COGS (>1000 doses/batch feasible)

• Cryopreserved
• No feeder/tumor cell materials in final product

mbIL-21 4-1bbL

K-NK cell industrial manufacturing platform with PM21 particles

Acquisition

• f donor

cells from the clinic Prodigy/Clinimacs+ GRex NK cell enrichment; Stimulation using PM21 particles Hollow fiber/Lovo Harvest and concentration Formulation in cryo- preservative Xuri Expansion in a bioreactor ViaFreeze Cryo- preservation

Day 0 - 7 Day 7 - 13 Day 14 Day 14

PM21: mbIL-21 and 41bbL particles

Native membrane particles presenting mbIL21 and 41bbL No intact tumor cells (regulatory)

10 KIADIS PHARMA | www.kiadis.com

Kiadis K-NK Clinical development outline

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2024

PRODUCT INDICATION CLINICAL STUDIES K-NK002 Blood cancer K-NK003 AML R/R K-NK00X Solid tumors Ph 2/3 Adaptive Design Phase 1/2a Phase 1/2 BMT CTN (add-on bridge to OTS) Ph 2/3 Adaptive Design versus PTCy Phase 1 dose finding & safety Phase 2a expansion Phase 2 basket study Phase 3 indications Signal Activity studies

KIADIS PHARMA | www.kiadis.com

K-NK002: Clinical Proof-of-concept as adjunct to haplo HSCT with PTCy (MD Anderson Cancer Center*)

1212 *NK-cells produced with feeder cells expressing mbIL21 and 41bbl, not with nanoparticles; n=13 Phase 1 dose finding (published in Blood), n=12 Phase 2 at highest dose (presented at ASCO and Haplo2018); Ciurea SO, et. al. Blood 2017, (link to paper); Ciurea SO EMBT Mar2018; Ciurea SO, Haplo2018, Nov2018

45%

SIZE DOSING SCHEDULE FOLLOW UP OUTCOMES

n=25 104 to 108 cells/kg Day -2 (after conditioning) Day +7 (after cyclo) Day +28 (booster) 28 months (0.9-48)

• Improved OS, PFS, relapse
• Reduced reactivation of CMV/BKV

8% Phas Phase 1 1 clin inic ical l tria ial l us usin ing mbI mbIL21 ex x viv ivo-expanded do donor de derived NK NK cells lls aft fter ha haplo loid identic ical l transpla lantatio ion

Ciurea et all, Blood 2017 ‘Infusion of high doses of ex vivo–expanded NK cells after haploidentical HSCT associated with significantly improved NK- cell number and function, lower viral infections, and low relapse rate posttransplant’

KIADIS PHARMA | www.kiadis.com

74% 45%

K-NK002: Phase 1/2 NK-REALM with Blood and Marrow Transplant Clinical Trials Network (BMT CTN)*

Stu Study desi design gned and and con

• nducted wi

with US S BM BMT-CT CTN (e (establi lished to

• con
• nduct

lar arge mul multi-in instit itutional l HS HSCT T tria trials ls): ):

• Single arm, open label multicenter trial
• Patients undergoing a haploidentical HSCT using PTCy protocol
• 63 patients
• High-risk AML or MDS
• First cohort to be evaluated during safety lead-in phase
• Primary endpoint: cumulative incidence of relapse at 1-year post

transplant

• K-NK002 dosing: 1 x 108 NK cells per kg on days -2, +7 and +28 after

transplant graft infusion

KIADIS PHARMA | www.kiadis.com 13 *Pending discussion with FDA

HAPLO-IDENTICAL NK-CELLS TO PREVENT POST- TRANSPLANT RELAPSE IN AML AND MDS (NK-REALM)

K-NK003: Clinical proof-of-concept* for treatment

• f AML R/R 2nd line salvage

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SIZE SIZE PATIENTS DO DOSI SING FOLL LLOW UP UP OUTCOMES MD D An Anderson Can ancer Center n=8

• 4 median prior

treatments

• 3/8 prior HSCT
• 43% median BM

blasts 6 doses (11 days) of 106 cells/kg 329 days (71-730)

• CR/CRi: 75% (day 30)
• Negative MRD: 37,5%

(PCR/flow)

• HSCT: 50%
• Survival: 37,5% (1

year) MD D An Anderson Can Cancer Ce Center An And HCPA, A, Port

• rto Ale

Alegre, Brazil N= 13

• 4 median prior

treatments

• 7/13 prior HSCT
• 45% median BM

blasts 5-6 doses (11 days) of 106 to 107 cells/kg 202 days (39-590)

• CR/CRi: 69%

*NK-cells produced with feeder cells expressing mbIL21 and 41bbl, not with nanoparticles; Ciurea SO, et. al. ASCO June2018; Ciurea SO Haplo2018. Nov2018

14 KIADIS PHARMA | www.kiadis.com

K-NK003: Treatment of AML R/R 2nd line salvage – examples

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AML, MALE, 25 25 YRS YRS (MDACC)

• 8 lines of prior treatment, incl prior failed HSCT
• Active disease, 90% BM blasts
• Treated with NK cells plus FLAG, no subsequent HSCT
• Complete response
• Ongoing Minimum Residual Disease (MRD) decrease

at 120 days

• Alive at 1 year; Relapsed/death at 2 years

AML, MALE, 22 22 YRS YRS (HCPA; Braz azil) il)

• Diagnosed at age 15
• 3rd relapse; 2nd CNS relapse
• Refractory to CNS-directed therapy
• Treated with NK cells plus FLAG
• Complete response
• Continued remission at 5 months

(returned to medical school)

1 week eek pr pret etreatmen ent 1 week eek after er last NK NK ce cell inf nfusi usion

• n

6 week eeks s after er last st NK NK ce cell inf nfusi usion

• n

Courtesy L. Silla; HCPA - UFRGS

11/13/2019 KIADIS PHARMA | www.kiadis.com

Courtesy S. Ciurea, MDACC

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Hea ead and and ne neck canc ancer: Intratumoral delivery Ovarian can ancer: Intraperitoneal delivery LOCAL DE DELI LIVERY FOR R EARL ARLY PROOF OF F MECHANISM (B (BIOPSIES, DI DIAGNOSTICS)

KIADIS PHARMA | www.kiadis.com

K-NK00X: potential solid/blood tumor programs

Approved mAb Main indications Daratumumab Elotuzumab Multiple myeloma Rituximab Non Hodgkins Lymphoma Trastuzumab Breast cancer; Ovarian cancer Avelumab Lung cancer Cetuximab Colon cancer; Head and Neck cancer COMBINE WITH AP APPROVED AN ANTIBODIES FOR R EN ENHANCED ADC ADCC Mel elanoma: Intratumoral delivery

NK-cell competitive landscape

KIADIS PHARMA | www.kiadis.com 17

CLI LINICAL STAGE OFF FF THE HE SHE HELF PLA LATF TFORM EX EXPANSI SION & & ACTIVATION PLA PLATFORM APP PPROACH TO EN ENHANCE PO POTENCY Kiad adis is

• Proof-of-concept (38 patients)
• Phase 1/2 HSCT (2020)
• Phase 1/2a AML (2020)

Universal adult donor PM21: mbIL21 and 41bbL particles (no tumor cells in final product)

• Optimal fully licensed donor
• Hyperactive cytotoxic and cytokine

release phenotype

• Co-stimulation with e.g., TGFb

Fate

• Phase 1 FT500 (10 patients

treated)

• Phase 1 FT516 (2 patients

treated)

• IND clearance FT596
• Phase 1 NK100 (donor derived;

3 programs) iPSC (stem cell line; no CD16) Feeder/tumor cells with mbIL21 for iPSC and with mbIL15 for NK100

• Genetic engineering e.g., high

affinity CD16 and CAR19 Nan Nant- kwest

• Phase 2 haNK
• Phase 1 or pre-clincal taNK

NK92 (lymphoma cell line) Tumor derived cell line Nk Nkar arta

• Preclinical

Adult donor Feeder/tumor cells with mbIL15

• Genetic engineering, e.g., co-

stimulation and CAR

Strong leadership team

KIADIS PHARMA | www.kiadis.com 18

ARTHUR LAHR Chief Executive Officer SCOTT A. HOLMES Chief Financial Officer DIRK de NAEYER Chief Operations Officer ANDREW SANDLER, MD Chief Medical Officer ROBERT FRIESEN Chief Scientific Officer MARK WEGTER, Chairman Partner LSP BERNDT MODIG Former CFO Prosensa OTTO SCHWARZ Former COO, Actelion ROBERT SOIFFER, MD Prof Harvard, Director HSCT Dana Farber, Chair CIBMTR, board member NMDP MARTIJN KLEIJWEGT Founder of LSP SUBHANU SAXENA Former head of global product strategy and commercialisation, ExCom member, Novartis

SELECT MANAGEMENT TEAM MEMBERS SUPERVISORY BOARD

AMY SULLIVAN

• Sr. VP, Corporate Affairs

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CHIARA BONINI, MD

Professor of Hematology at the Università Vita-Salute San Raffaele, Milan

MICHAEL CALIGIURI, MD

Deana and Steve Campbell Physician-in-Chief Distinguished Chair

ELAINE MARDIS, PhD

Co-executive Director of the Institute for Genomic Medicine at Nationwide Children's Hospital

HELEN HESLOP, MD, DSc

Professor at Baylor College of Medicine

TODD FEHNIGER, MD, PhD

Associate Professor at the Department of Medicine, Washington University School of Medicine in St Louis

CARL JUNE, MD

The Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine of the University of Pennsylvania

DEAN LEE, MD, PhD

Director of the Cellular Therapy and Cancer Immunotherapy Program for Nationwide Children’s Hospital’s Division of Hematology/Oncology/BMT and Center for Childhood Cancer and Blood Diseases

KRISHNA KOMANDURI, MD

Medical Director of the hematopoietic stem cell transplant program at the University of Miami Sylvester Cancer Center

Renowned Scientific Advisory Board

KIADIS PHARMA | www.kiadis.com

Kiadis news flow

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2020 2021 HSCT Start NK-REALM trial Safety lead in read out and interim data NK-REALM trial AML R/R Start AML R/R trial Interim data AML R/R trial Other solid/blood tumors Preclinical data solid/blood tumors Start clinical study solid/blood tumor (signal activity) Pharma/biotech BD partnership Interim clinical data solid/blood tumor (signal activity) Start multiple clinical studies solid/blood tumor

KIADIS PHARMA | www.kiadis.com

When it comes to life-threatening diseases, we are one family.

Kiadis is leveraging the natural strengths of humanity and our collective immune systems to source the best cells for life. Our uncompromising approach to serve patients, their families and care givers aims to minimize harm and maximize help – delivering personalized treatments for every single patient to offer hope, reduce suffering and provide new life.