Patient-specific immunotherapy T-cell product ATIR

Transcription

1 Patient-specific immunotherapy T-cell product ATIR Unlock full potential of haploidentical hematopoietic stem cell transplantations (HSCT) Company presentation, October 16, 2018 Amsterdam, The Netherlands Euronext (KDS) 1

2 Disclaimer 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) our 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 on 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 only 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. 2

3 Kiadis: Patient specific immunotherapy T-cell product ATIR UNIQUE HEMATOPOIETIC STEM CELL TRANSPLANT STRONG PHASE 2, PHASE 3 ONGOING CLOSE TO MARKET WORLDWIDE RIGHTS, PREPARING EU LAUNCH LARGE TARGET POPULATION CELL THERAPY & HSCT PLATFORM T-cell product ATIR: haploidentical donor T-cells, depleted of alloreactive T-cells, given after T-cell depleted haploidentical HSCT Survival benefits over historical control in adult acute leukemia, Phase 3 for superiority over PTCy/Baltimore protocol enrolling Potential CHMP opinion 1H19; Potential first EU country launch 2H19; FDA RMAT breakthrough designation Building own commercialization infrastructure in EU (small number of transplantation sites, worldwide rights retained) ~17,000-50,000 potential patients per year for haplo-identical HSCT, of which ~85% in blood cancers and ~82% adult Leverage patient specific cell therapy and HSCT platform to expand ATIR label and suite of products HSCT: Hematopoietic Stem Cell Transplantation; GVHD: Graft Versus Host Disease; Haplo: Haploidentical; OS: Overall Survival; 3

4 Kiadis ATIR product: regulatory status (adult blood cancers) Region Phase 1 Phase 2 Phase 3 Filing Potential catalysts Commercial Rights Regulatory Status EU Orphan Drug Designation CHMP opinion (H1 2019) EU launch (H2 2019) Received EMA Day nd List of Issues (9/2018) USA Orphan Drug & RMAT Designations Phase 3 interim read out (H2 2020; 2/3 of events) RMAT breakthrough designation (9/2017; FDA access, priority review, support) 4

5 Allogeneic Hematopoietic Stem Cell Transplantations (HSCT) Potentially curative: destroy patient s blood/immune system (chemotherapy/radiation), replace with healthy system from donor Inherent risk of Graft versus Host disease (GVHD): donor immune system attacks patient Lack of donors: many patients cannot find matched donor (depending on genetic profile) Mostly blood cancers (85%) and adults (84%): potentially also for inherited disorders and autoimmune disease Expensive procedure: around $500,000 (1 year cost; US) Sources: Broder 2017; Passweg 2018; CIBMTR 2017 summary slides; Besse 2015, Gragert 2014 Maarten van der Weijden, long distance swimmer: After acute leukemia and HSCT in 2001: Olympic Gold 10 km open water (2008) UK-France-UK double Channel crossing >70km (19 hours; 2017) World distance record 103km (24 hours; 2018) Swam 163km of the Elfstedentocht to raise funds for cancer research (55 hours; 2018) 5

6 Graft Versus Host Disease (GVHD): terrible disease Subpopulation of T-cells from donor (i.e. graft) recognize patient tissue (i.e. host) as foreign and attack, mostly due to genetic differences in MHC Class II proteins (major mismatches) Disease Treatment Types & grading Impact severe GVHD Skin, eye, mouth or GI tract disease, immunodeficiency, muscle constriction, bone loss, pulmonary disease, thyroid disfunction, solid tumors, sleep deprivation, depression Immunosuppression (e.g., steroids, MMF, MTx, Cyclophosphamide) Acute (first 100 days): grade I-II (mild, moderate) and III-IV (severe) Chronic (lifelong): mild, moderate, severe With acute GVHD grade III-IV, chronic GVHD severe : 2-3x higher rate of death / lower overall survival Quality of life worse than vision impairment, MS, loss of arm/leg, diabetes (QALY loss up to 68%) 75% of patients lose 3 years of earnings, 25% permanently lose earnings The holy grail of HSCT: Give donor T-cells that protect; Remove donor T-cells that attack; Avoid immunosuppressants Sources: Jones 2016; Koreth 2013; Pidala et al 2011, Pasquini 2018, Khoury 2017, Solh

7 Severe GVHD & immunosuppression: 2-4x higher mortality Acute grade IV GVHD: 3x higher rate of death/relapse Severe chronic GVHD: 3x lower overall survival Acute GVHD grade III/IV: 2x lower overall survival Acute Grade II Acute Grade III/IV OS 95% CL p-value OS 95% CL p-value Immunosuppression: 4x higher rate of Non-Relapse Mortality (NRM) Sources: Pidala et al 2011, Pasquini 2018, Khoury 2017, Solh

8 HSCT: continued growth due to PTCy/Baltimore protocol (US) Matched Related Donors (MRD) Matched Unrelated Donor (MUD; donor registries) ~13,500 eligible patients not transplanted (2012) Haploidentical donors Cord blood Matched Related or Unrelated Donors (MRD/MUD): Between 19% (White European) and 80% (African American) cannot find a Matched Unrelated Donor Haploidentical donors, with PTCy/Baltimore protocol: Genetically half matched donors; Motivated donors almost always available (e.g., parent/child); Haploidentical enabled by Post Transplant Cyclophosphamide (PTCy or Baltimore) protocol: Trigger immediate GVHD attack by infusing all T-cells of a haploidentical (half matched) donor, then deplete allo-reactive donor T-cells with chemo (cyclophosphamide, day 3 and 5) and immunosuppression in the patient Source: CIBMTR 2017 Summary slides; Fuchs 2017; Gragert 2014; Besse

9 PTCy: benefits over MUD, yet still unmet need relapse & GVHD PTCy/Baltimore protocol and PTCy/Baltimore Matched Unrelated Donor (MUD) Matched Unrelated Donor (up to 3 yr) 53% 51% 49% 45% 38% 38% Acute GVHD II-IV 26% 27% Chronic GVHD Relapse Survival Weighted average of 5 PTCy/MUD comparison publications in the review paper by Fuchs E 2017 that reported AML/MDS/NHL/HL (Ciurea 2015; Rashidi 2016; Burroughs 2008; Kanate 2016; Garciaz 2015); n=463 PTCy and n=2647 MUD patients PTCy/Baltimore protocol (1 year) Average Overall Survival (OS) 60% Relapse 29% Relapse Related Mortality (RRM) 18% Non Relapse Mortality (NRM) 22% Acute GVHD grade III/IV 5% Chronic GVHD 24% Chronic GVHD - severe 8% Weigthed average in PTCy publications that reported >50% AML/ALL (Ciurea 2015; Piemontese 2017, Solomon 2012, Ciurea 2012; Devillier 2016; Di Stasi 2014; Esquirol 2016; Sugita 2015); n=571; Chronic GVHD confirmed with other publications PTCy/Baltimore protocol advantages over Matched Unrelated Donor: donor faster available, lower GVHD Still unmet medical need: relapse and chronic GVHD, secondary malignancies, toxicity, immunosuppression 9

10 Probability All HSCT similar GVHD-free and Relapse-Free survival (GRFS) No Events MA MRD MA MUD NMA Haplo GVHD-free and Relapse Free Survival (GRFS): Survival without: Acute GVHD grade III/IV P*=0.65 Chronic GVHD requiring systemic therapy Relapse Years Post Transplantation GVHD-free and Relapse-free Survival (GRFS) captures survival, prognosis and quality of life GRFS with Matched Related Donor (MRD), Matched Unrelated Donor (MUD) and Haploidentical donor are comparable (and less than 30%) McCurdy

11 Haploidentical HSCT: PTCy/Baltimore protocol versus ATIR Haplo HSCT plus PTCy (Baltimore protocol): (All T-cells) Conditioning of patient Apheresis of donor, graft infusion Engraftment of donor stem cells Cyclophosphamide and immunosuppression Kill attacking T-cells in the patient with cyclophosphamide & immunosuppression Haplo HSCT with T-cells (T-cell replete) Infuse chemo 3-5 days after graft infusion Haplo HSCT plus ATIR: (Subset of T- cells, depleted of allo-reactive T-cells) Apheresis of patient and donor Central ATIR production Produce ATIR 5 days (total 14 days till interim release) Conditioning of patient Apheresis of donor, graft infusion Haplo HSCT without T-cells (T-cell depleted, CD34+) Engraftment of donor stem cells ATIR Infuse ATIR ~30 days after graft infusion Kill attacking T-cells outside the patient without immunosuppression 11

12 Healthy donor donor ATIR: safe subset of T-cells, aiming to protect, not to attack ATIR TM MANUFACTURING Mix haplo donor T- PROCESS Add TH9402*, which cells with patient accumulates only in cells: allo-reactive Step 1 (Day 1 4) activated donor T- Healthy T-cells become cells (MDR pump is donor ATIR ATIR TM MANUFACTURING TM Immune cells are collected and mixed MANUFACTURING activated PROCESS (1-way PROCESS switched off in Mixed Lymphocyte activated T-cells) Step 1 (Day 1 4) Step 2 (Day 5) Step 1 (Day 1 4) Step 2 (Day ` 5) Reaction) ` donor Healthy ATIRPatient TM MANUFACTURING cells PROCESS Healthy Patient cells donor Patient cells inactivated Patient inactivated by radiation by radiation inactivated Immune cells are collected and mixed Immune cells are collected and mixed by radiation Step 1 (Day 1 4) Immune cells are collected and mixed Step 2 (Day 5) Step 2 (Day 5) Expose to green light: TH9402* induces apoptosis: activated and thus allo-reactive donor T-cells are killed Step Step 3 (Day 3 (Day 5) ` 5) FEBRUARY Step 3 (Day 5) Step 3 (Day 5) ATIR: remaining non-allo-reactive donor T-cells (2 million T-cells/kg) FEBR Final ATIR TM FEBR Final Final Step Step - Infusion - Infusion of ATIR101 of ATIR101 Healthy donor Fina Patient Patient patient Patient Patient cells inactivated by radiation Certain T-cells from the donor are activated by the TH9402 is introduced. Mixture is exposed to light. presence of the foreign patient Protect: cells. If not eliminated, Retain protective TH9402 is retained T-cells ONLY in the GvHD-causing to fight T-cells relapse and TH9402 infections is activated by light, causing the these cells would cause GvHD in the patient stained GvHD-causing T-cells to self-destruct Certain T-cells from the donor are activated by the TH9402 introduced. Mixture is exposed to light. The remaining product is infused back Certain T-cells from the donor are activated by the presence of the foreign patient & Mixture is exposed to light. cells. Not If not eliminated, attack: Reduce TH9402 is retained risk TH9402 ONLY in the of is introduced. GvHD-causing GVHD T-cellsby depleting TH9402 is activated allo-reactive by light, causing the T-cells ex The vivo remaining product is infused back presence of the foreign patient cells. If not eliminated, TH9402 is retained ONLY in the GvHD-causing T-cells TH9402 is activated by light, causing the and helps rebuild their immune system these cells would cause GvHD in the patient stained GvHD-causing T-cells to self-destruct and helps rebuild their immune system these cells would cause GvHD in the patient stained GvHD-causing T-cells to self-destruct to f ght infections and eliminate to f ght infections and eliminate remaining tumor cells remaining tumor cells Patient Pati inac by r The r and h *TH9402 proprietary selective rhodamine derivative, modified to become cytotoxic under green light MANUFACTURING 12

13 ATIR: simplified patient specific supply chain Attractive production process (as compared to CAR-T) 5 day process (total 14 days to interim product release) No genetic engineering (no viral vector production, no BL2) Cleanrooms with LAF cabinets (no bioreactors) Supply chain fits with routine HSCT procedures Ingoing (patient/donor materials): Routine apheresis and fresh shipment (formulated in hypothermosol; 42 hour hold time) Outgoing (final product): Routine frozen shipment and infusion Control over (own) manufacturing Contract manufacturing in Germany, adding capacity Own commercial manufacturing in Netherlands (2020 onwards) 13

14 Kiadis trials: haploidentical HSCT in adult blood cancers Phase 1/2 Phase 2 Phase 3 CR-GVH-001: Single dose ATIR Dose escalation (completed) 19 patients Advanced malignancies AML/ALL 5 year follow up Single site in Canada (CA) Historical controls CR-AIR-004: No ATIR Open label single arm (completed) 40 patients (29 matched to CR-AIR-007*) AML/ALL/MDS Sites in BE, CA, GE, NL, UK, US CR-AIR-006: No ATIR Observational cohort, EBMT registry (completed) 35 patients (all matched to CR-AIR-007*) AML/ALL/MDS 1 year follow up CR-AIR-007: Single dose ATIR Open label single arm (completed) 23/26 patients (MITT/ITT**) AML/ALL/MDS, median age 41 2 year follow up Sites in BE, CA, GE, UK CR-AIR-008: Single dose ATIR and two doses ATIR*** Open label single arm (enrolled, ongoing) 9/11 single dose; 6/6 patients two doses (MITT/ITT**) AML/ALL/MDS 1 year follow up Sites in CA, BE, GE, UK CR-AIR-009: Single dose ATIR Randomized/controlled (ATIR versus PTCy) 2017 (enrolling) 250 patients AML/ALL/MDS Event driven primary endpoint (GRFS) ~50 sites planned CA, Europe, US, Israel All trials: Patients: adult AML/ALL/MDS Conditioning: Myeloablative Graft source: Haplo PBMCs HSCT: T-cell depleted (CD34+) ATIR: ~30 days after HSCT No immunosuppression * Same in/exclusion criteria and HSCT and overlapping sites; control in accordance with regulatory feedback ** MITT: Modified Intent to Treat (transplanted and ATIR); ITT: Intent to Treat (transplanted) *** CR-AIR-008 was designed to test safety of second dose, but due to higher then expected GVHD it was decided to stop infusing second dose (in accordance with protocol) 14

15 ATIR: improved Overall Survival (OS; ITT, single dose; 1yr) T-cell depleted (CD34+) with ATIR (n=37)* T-cell depleted (CD34+) without ATIR (n=64)* OS 1 yr: 58% [44-77**] *ITT (intention to treat): all patients undergoing T-cell depleted CD34+ HSCT; SD: single dose; All clinical studies have similar patient characteristics and treatment sites; CR-AIR-008 status 1 June 2018 (3 patients at risk) ** 95% confidence interval [ ] OS 1 yr: 23% [14-37**] P=0.005 ( vs ) 15

16 ATIR: improved OS & NRM, low GVHD & relapse (ITT, single dose) T-cell depleted (CD34+) with ATIR (n=37)* T-cell depleted (CD34+) without ATIR (n=64)* CR-AIR-007 CR-AIR CR-AIR-006 CR-AIR single dose single dose single dose control control control 1 year post HSCT (ITT n=26) (ITT n=11) (ITT n=37) (n=35) (n=29) (n=64) Overall survival 58% [42-80] 64% [41-100] 58% [44-77] 20% [10-39] 27% [13-54] 23% [14-37] Non-relapse mortality 35% 27% 33% 66% 59% 63% Relapse-related mortality 8% 9% 8% 15% 14% 14% Relapse 8% 9% 8% NA NA NA Acute GVHD grade II-IV 19% 27% 21% 20% 18% 19% Acute GVHD grade III-IV 0% 18% 5% 6% 7% 6% Chronic GVHD 4% 0% 3% 11% 5% 8% Chronic GVHD severe 0% 0% 0% 9% 5% 7% 6 months post HSCT (MITT n=23) (MITT n=9) (MITT n=32) (n=35) (n=29) (n=64) ATIR after T-cell depleted HSCT: Improve OS and NRM, Retain low chronic GVHD & relapse No prophylactic immunosuppression P-values for vs : OS (0-12 month) p=0.005 NRM (0-6 month) p= 0.02 Non-relapse mortality 13% [0-27] 11% [0-29] 13% [0-24] 37% [19-51] 35% [15-51] 36% [23-47] Notes: NRM at 6 months primary endpoint of CR-AIR-007; Kaplan-Meier estimates for OS and NRM at 6 months; all other estimates cumulative incidence analyses; ITT: patients receiving HSCT; MITT: patients receiving HSCT and ATIR; OS: overall survival; CR-AIR-008 status 1 June 2018 (3 patients at risk) 16

17 Phase 3 (CR-AIR-009) study design: ATIR and PTCy GRFS GRFS in PTCy literature: Solh 2016 (n=126) 30-40% McCurdy 2017 (n=372) Santoro 2017 (n=208) GRFS with ATIR (ITT): 53% [39-72] Sites included Atlanta (single site) Johns Hopkins (single site) 69 EBMT sites Patients AML/ALL/MDS/ NHL/HL, CML AML/ALL/MDS/ NHL/HL, MM ALL GRFS 1-yr [95% CI] Disease risk index (DRI)* 33% [25,41] 19% low 39% intermediate 40% high/v. high 45% [40,50] 14% low 67% intermediate 19% high/v. high 33% (average) Not available 1-year estimates [95% CI]: % [38-77] 008 SD 55% [32-94] SD 53% [39-72] Normalized GRFS 1-yr* 30% 40% Not available 250 patients in CR-AIR-009: 80% power to detect 16% GRFS difference * Normalized by adjusting based on the average DRI of the CR-AIR-007/008 patient population (57% intermediate risk; 43% high/very high risk); using the hazard rates per DRI as reported in the Solh/McCurdy publications (2 patients in Solh for which DRI not known excluded); DRI is an important prognostic factor for OS,: e.g., NHL patient in CR1 is low risk, AML in CR2 is very high risk (Armand 2014); CR-AIR-008 status 1 June 2018 (3 patients at risk) 17

18 Phase 3 (CR-AIR-009): ATIR vs. PTCy/Baltimore protocol Objectives: demonstrate superior clinical benefit and collect pharmacoeconomic data Randomized Controlled (1:1) R HSCT plus ATIR: T-cell deplete CD34+ HSCT plus single dose ATIR 2 mln cells/kg at ~30 days 250 adult patients with AML, ALL or MDS PTCy/Baltimore protocol: T-cell replete HSCT with 50 mg/kg cyclophosphamide at days 3 and 5 post HSCT & prophylactic immunosuppressants Primary endpoint: GVHD-Free and Relapse- Free Survival (GRFS); Interim analysis: at 2/3 of events (17,6% GRFS treatment effect, hazard ratio 0.61) Primary analysis: at 156 events (11,4% GRFS treatment effect, hazard ratio 0.73) Secondary endpoints: Overall Survival (OS), Progression Free Survival (PFS), Relapse, Non Relapse Mortality (NRM) Other: Randomization at enrollment; Balanced conditioning regimens in ATIR/PTCy arms; Stratification for Disease Risk Index, underlying disease and treatment site ~50 sites in US, Canada, EU & Israel, to enrol 250 patients Enrolment on track (10/2018: 14 sites open and 22 patients enrolled) 18

19 Allogeneic Potential future Hematopoietic studies with Stem ATIR Cell Transplantations (HSCT) Pediatric blood cancers (EMA Pediatric Investigation Plan deferral obtained) ATIR as adjunctive after other haploidentical HSCT protocols, e.g. PTCy/Baltimore protocol α/β T-cell depleted protocol Other (RIC/MA) conditioning regimens Other HSCT indications, e.g. Inherited blood disorders (e.g. thalassemia or sickle cell anemia) Inherited immune disorders (e.g. severe combined immunodeficiency) Autoimmune disease (e.g. multiple sclerosis or lupus) 19

20 Potential haploidentical: 17,000-50,000 annual patients US/EU ~33,500 ~50,500 EU Potential continued growth ~20,000 30,800 US Grown 3x in in US 13,200 17,000 ~13, ,800 19,700 3, ,200 Haploidentical Matched Unrelated & cord blood Potential haploidentical Eligible patients not transplanted (2012)* Potential/eligible for haploidentical Note: of whih 85% blood cancers and 84% adults * US: 2012 (Besse 2015); May have declined by 40% in US by 2016, due to PTCy (Triangle market research); Includes patients not transplanted due to lack of donors, insurance issues and change in disease status; EU estimation by extrapolation from US based on population Source: CIBMTR summary slides 2017, Passweg 2017, Besse 2015; Triangle market research

21 ATIR potential adoption: > 50% of haploidentical (US, survey) ATIR benefit over PTCy: GRFS ATIR benefit over PTCy: OS ATIR share within haploidentical HSCT Profile A: GRFS benefit 18% 50% 50 HSCT KOLs/ Clinicians from 28 clinics representing 43% of US allogeneic HSCT Profile B: GRFS and OS benefit 23% 5% 61% Including Johns Hopkins, MD Anderson, Dana Farber, Fred Hutchinson, Stanford Note: consistent with two previous market surveys: 50/50 US/EU KOLs: 55%/58% (2013; based on benefit over PTCy); 9 KOLs representing 27% of US HSCT: >66% (2018; based on 18% GRFS benefit over PTCy) Source (market research): Simon Kucher (2018), Triangle (2018), Defined Health (2013) 21

22 ATIR potential: independent commercialization Europe: 63 sites in EU4 US: Top 27 sites perform 50% of HSCTs GE IT FR UK Shortened dossier to G-BA via AMNOG (until sales > 50M) L-648 (named patient basis); P&R Dossier to AIFA/CTS at MAA ATU (named patient basis); HAS/CEPS filing at MAA NICE evaluation; Interim funding potentially via Cancer Drug Fund Source: Triangle 2018 survey Preparing for launch in EU countries; Building medical affairs, market access, commercial, supply chain and manufacturing infrastructure 22

23 Protection: patents, orphan drug designation, know how Patents (owned/ licensed) Orphan drug designation Proprietary know how Methods for reducing GVHD (expiring in October 2021) Certain rhodamine derivatives (expiring in January 2024) Improved photodynamic process (expiring in February 2036 if granted) US (7 years from launch): for prevention of GVHD or TRM EU (10 years from launch): for treatment in HSCT regardless of disease, for treatment of AML, for prevention of GVHD Manufacturing critical process parameters Release assays based on critical quality attributes Cell handling, storage, formulation and shipment Patient specific supply chain with HSCT clinics (IT, relationships, service) Multiple barriers to entry for competition 23

24 Kiadis: company at a glance ORGANIZATION SHAREHOLDERS FINANCIALS (October 15, 2018) Management: track record hemato-oncology, cell therapy, orphan disease, development/commercialization (e.g., Bayer, Novartis, J&J, AstraZeneca, Merck, Medivation, Novo Nordisk, Dendreon, Iovance, Crucell, Genzyme) Supervisory board: Novartis ExCom; Actelion COO; Prosensa/Jerini CFO; Dana Farber chief of HSCT and board member of NMDP/BeTheMatch Euronext Amsterdam/Brussels, IPO in 2015 Major shareholders (>5%): Life Sciences Partners, Lenildis Holding, Esprit Market cap: ~$247M / 213M (20,4 million shares outstanding) Raised > 65M in equity & debt since June 2017, option to additional 15M in debt conditional on positive CHMP Cash 42M end H1 18; Runway into Q3 19, potential to extend into Q1 20 upon positive CHMP 24

25 Kiadis: track record late stage development and commercial Arthur Lahr (April 2017) Chief Executive Officer Scott Holmes (>January 2019) Chief Financial Officer Andrew Sandler (Oct 2017) Chief Medical Officer Jan Feijen (April 2017) Chief Operations Officer Mark Schaefer (September 2018) Chief HR Officer James Joy (July 2018) General Counsel Karl Hård (Sept 2017) Head IR comms Chief Strategy Officer Crucell Supervisory Board Sanquin McKinsey; Unilever CFO Keryx SVP finance and IR AMAG Molecular Biometrics, On- Q-ity Ernst & Young Certified accountant SVP Medical Affairs Medivation CMO Dendreon and Spectrum Pharma; Bayer; Berlex; Seattle Genetics; Board certified medical oncologist EVP Operations J&J Vaccines VP Manufacturing and Ops J&J Vaccines & Advanced Therapies VP Crucell Asia Managing Director Operations Avebe Gist-Brocades SVP HR Aenova Global HR West pharma 3M, Sony, GE Group General Counsel TomTom; VP Legal and Compliance Royal Ahold Corporate lawyer Norton Rose; Latham & Watkins; Member New York State Bar Head investor relations AstraZeneca; 10 years pharma R&D; Assistant Professor chemistry 25

26 Kiadis key milestones and upcoming catalysts EMA submission of ATIR for marketing authorization approval First patient enrolled for ATIR Phase 3 FDA Regenerative Medicine Advanced Therapy (RMAT) designation Secured own commercial manufacturing facility Completion of enrollment of second Phase 2 (CR-AIR-008) Submission of answers to EMA Day 120 questions (End Q1) Submission of answers to EMA Day 180 List of Issues (Q3) Updates Phase 2 data and Phase 3 enrollment Potential EMA CHMP opinion (H1) Potential initial commercial launch of ATIR in first EU country (H2) Initiate trial with ATIR as adjunctive to PTCy (H2) Potential reimbursement and commercial roll out across EU countries (H1) Potential interim read out Phase 3 (at 2/3 of GRFS events) (H2) 26

27 Practice two things in your dealings with disease: either help or do not harm the patient Epidemics, Book I, of the Hippocratic school I will prevent disease whenever I can but I will always look for a path to a cure for all diseases Hippocratic oath, Louis Lasagna, Academic Dean of the School of Medicine at Tufts University (1964) 27

28 Attachments 28

29 List of Abbreviations ALL AML ATIR CHMP CML EBMT EMA FDA GVHD GVL HAPLO HR HSCT ITT LAF MAA MDR acute lymphoblastic leukemia acute myeloid leukemia a donor T-lymphocyte preparation, depleted ex vivo of host alloreactive T-cells using photodynamic treatment Committee for Medicinal Products for Human Use chronic myeloid leukemia European Society of Blood and Marrow transplantation European Medicines Agency Food and Drug Administration (U.S.) graft versus host disease graft versus leukemia haploidentical (genetically half-matched) hazard ratio hematopoietic stem cell transplantation intent-to-treat population laminar air flow marketing authorization application (EU) multidrug resistant MDS MHC MITT MLR MRD MUD NRM OS PI PBMC PDT PFS PTCy QC RRM SAE TH9402 TK TRM myelodysplastic syndrome major histocompatibility complex modified intent-to-treat population mixed lymphocyte reaction matched related donor matched unrelated donor non-relapse mortality Overall survival proliferation index peripheral blood mononuclear cell photodynamic treatment progression-free survival post-transplant cyclophosphamide (Baltimore protocol) Quality control Relapse-related mortality Serious adverse event 4,5-dibromorhodamine methyl ester Thymidine kinase Transplant-related mortality 29

30 Haploidentical HSCT approaches Haplo HSCT Haplo T-cell Product (after HSCT) GVHD Treatment/ Prophylaxis Approach ATIR (Kiadis) T-cell depleted (CD34+) Subset of T-cells, depleted of alloreactive T-cells No immunosuppressant Ex-vivo ( prevent GVHD ) Zalmoxis (MolMed) BPX-501 (Bellicum) T-cell depleted (CD34+ and αβt-cell depleted) All T-cells (including allo-reactive T-cells), engineered with suicide gene Eliminate allo-reactive T-cells by infusing suicide agent, if GVHD occurs In-patient PTCy or Baltimore protocol T-cell replete (All T-cells, including alloreactive T-cells) Post Transplant Cyclophosphamide & immunosuppressants In-patient Table provided for illustrative purposes, not for direct comparison 30

31 Molmed/Bellicum: January 2018 (1 year) Patients Survival* Relapse NRM Status EMA Zalmoxis** (MolMed) Adult Approval Q BPX-501 (Bellicum) Pediatric Submission 2019 Product (Matched) Historical Control Zalmoxis pricing/dose*** (1-4 doses per patient): Germany: 163,900 Italy: 149,000 Comparison provided for illustrative purposes, based on literature comparison, NOT based on randomized controlled trials * Leukemia Free Survival for BPX-501 (BPX-501 Overall Survival is 89%, Overall Survival not reported for controls); ** CD34+ HSCT; 74% AML; 10% ALL; 16%MDS/NHL/HD; patients receiving Zalmoxis (MITT= 36 patients) *** Prices as at 16 January 2018 and 13 December 2017, respectively; subject to negotiation with GBA in Germany Source: CHMP Assessment report (Zalmoxis); Merli EHA 2017 (BPX-501); Locatelli 2017 (BPX-501) 31

32 CR-GVH-001: Overall Survival (5 years) Patients: 19 with advanced hematological malignancies (14 not in remission at transplant) ATIR101 doses: 10k cells/kg to 5 mln cells/kg; median of 31 days after HSCT Results: 67% Overall Survival at middle dose level after 5 years No acute GVHD grade III/IV related to ATIR101 at any dose 100% 80% 60% 40% 20% 0% Overall Survival (OS) 9 patients, 320k- 2M cells/kg Dose L4-L6 3 patients; 2,6-5M cells/kg) Dose L7 7 patients, 10- Dose 130k cells/kg L1-L Time after HSCT (months) Note: an unmanipulated donor lymphocyte infusion from a haploidentical donor Source: Lewalle 2003 that still contains all T-cells may cause GVHD at significantly lower doses of 10,000 cells/kg 32

33 CR-AIR-007: Outcomes (2 years, MITT) for primary and secondary efficacy endpoints in CR-AIR-007, MITT Kaplan Meijer estimates 6 months 12 months 24 months... Non Relapse Mortality 13% 32% 48%... Relapse Related Mortality 5% 10% 25%... Progression Free Survival 78% 61% 39%... Overall Survival 83% 61% 39% Outcome No. of pts Cause of death < 6 months 6-12 months months Relapse Related Mortality (RRM) 1 Non Relapse Mortality (NRM) Infections 2 Adenovirus and JC virus infections Non Relapse Mortality (NRM) Other 1 Pulmonary embolism Relapse Related Mortality (RRM) 1 Non Relapse Mortality (NRM) Infections 3 Respiratory/pulmonary infections/distress Non Relapse Mortality (NRM) Other 1 Multi-organ failure Relapse Related Mortality (RRM) 2 Non Relapse Mortality (NRM) Infections 3 * Pneumonia/sepsis/septic shock * All 3 patients immunosuppressed, subsequently contracted infections, leading to death: 2 patients who received un-manipulated DLI s in 2 nd year after HSCT and subsequently developed severe acute GVHD; 1 patient with chronic GVHD 33

34 Proliferation Index (PI) ATIR: alloreactive T-cells depleted, potency retained 12 6 Donor ATIR * Autologous Recipient 3 rd Party CD3/28 Functional release assay based on Quality Target Product Profile & Critical Quality Attributes Control: no donor reactivity Safety: depleted allo-reactivity Potency: other reactivity retained Source: Bonig ISCT

35 Healthcare costs of allogeneic HSCTs and complications (US) Total HSCT costs* $402,000 (MA) $301,000 (RIC) $549,000 (MA) $432,000 (RIC) Period / Source 100 days; Broder year; Broder 2017 $893, days; Milliman 2017** HSCT complications Cancer death $165,000 Relapse $69,000*** Hemorrhagic cystitis Chronic GVHD moderate/mild Chronic GVHD severe Costs to healthcare system $242,000***/**** $124,000 ($14,400 per year*****) $322,000 ($37,400 per year*****) * Includes Inpatient/Outpatient/pharmacy costs: MA: myeloablative conditioning; RIC: reduced intensity conditioning ** Includes different physician charges, graft procurement costs *** Cost based on Broder total cost and cost multiplier Khera **** Side effect of PTCy protocol **** 10 years, discounted Sources: Mariotto 2011; Yu 2017; Broder 2017; Khera 2014; Milliman 2017; Svan 2006; literature PTCy analysis 35

36 so that many more patients with otherwise incurable diseases will have a reasonable chance of long survival and cure Dr. E. Donnall Thomas established bone marrow transplantation as a treatment for leukemia Nobel Lecture