Tumor Antigens in the Age of Engineered T cell Therapies

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1 Tumor Antigens in the Age of Engineered T cell Therapies September 30 th 2016 ESMO Preceptorship Course Amsterdam Carsten Linnemann, PhD Senior Scientist Kite Pharma EU B.V. Amsterdam

2 Forward Looking Statements/Safe Harbor To the extent statements contained in this presentation are not descriptions of historical facts regarding Kite Pharma, Inc. ( Kite, we, us, or our ), they are forward-looking statements reflecting management s current beliefs and expectations. 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. You can identify forward-looking statements by words such as anticipate, believe, could, estimate, expect, intend, may, plan, potential, predict, project, should, will, would or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding: (i) the success and timing of our product development activities and clinical trials; (ii) the ability and willingness of the National Cancer Institute (NCI) to continue research and development activities relating to our product candidates; (iii) our ability to obtain and maintain regulatory approval of KTE-C19 and any other product candidates; (iv) our ability to further develop and commercialize our product candidates; (v) our plans to research, discover and develop additional product candidates, including through our subsidiary Kite Pharma EU, and next generation product candidates, including a next-generation CAR with an on/off switch; (vi) our and our partners ability to develop, manufacture and commercialize our product candidates and to improve the manufacturing process; (vii) the size and growth potential of the markets for our product candidates, and our ability to serve those markets; (viii) the rate and degree of market acceptance of our product candidates; (ix) our ability to attract and retain key scientific or management personnel; (x) the anticipated timing of clinical data availability; (xi) the anticipated timing of commercial launch of KTE-C19; (xii) our plans to expand geographically; (xiii) our ability to meet the milestones set forth herein and (xiv) our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates. Various factors may cause differences between Kite's expectations and actual results as discussed in greater detail in Kite's filings with the Securities and Exchange Commission (SEC), including without limitation in its Quarterly Report on Form 10Q filed with the SEC on August 8, Except as required by law, we undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. 2

3 Disclosure I am an employee at Kite Pharma EU B.V. with ownership of stock and stock options in Kite Pharma, Inc. (NASDAQ: KITE) 3

4 Overview of content Tumor antigens: 1. Concept & therapeutic relevance 2. Targeting tumor antigens with genetically engineered T cells Take-home message: Engineered T cell therapies against tumor antigens mark a new age of cancer treatment 4

5 Tumor antigens Concept & therapeutic relevance

6 Tumor antigens make tumors visible to the immune system Definition (one of many): component generated by tumor cells that can be targeted by an immune response Types of possible immune response: innate (Macrophages, NK cells, Neutrophils, etc.), antibody-mediated or T cell mediated Immune response against tumor antigen may be naturally occurring or induced therapeutically Focus for today: tumor antigens in the context of engineered T cell therapies 6

7 Discovery of the first tumor antigen recognized by T cells in humans Science 1991 Van der Bruggen et al provided a conceptual basis for immunotherapy: Autologous T cells recognize a gene product found on melanoma cells The novel gene family is shared between different tumors The gene is not found in normal tissue 7 Recognition of autologous tumor lines and engineered targets by autologous T cells Van der Bruggen et al., Science 1991 Vision: T cell based therapies eradicate tumor cells with high specificity and are applicable to large patient groups

8 T cells recognize different classes of tumorantigens Tumor antigen class Cell Lineage antigens Example MART-1 protein in melanoma Example references Kawakami et al. Proc Natl Acad Sci USA 1994 Coulie et al. J Exp Med 1994 Overexpressed antigens WT-1 in hematological cancers Bellantuono et al. Blood 2002 Cancer/Germline antigens NY-ESO-1 expression in melanoma Jäger et al. J Exp Med 1998 Gnjatic et al. Proc Natl Acad Sci USA Oncogenic virus proteins HPV E6/E7 proteins expressed in cervical and H&N cancer Altered proteins arising from tumor-specific mutations Recognition of patientspecific mutations in various cancers Nakagawa et al. J Infect Dis 1997 De Jong et al. Cancer Res 2004 Lennerz et al. Proc Natl Acad Sci USA 2005 Robbins et al. Nat Med 2013

9 Tumor antigens can be classified by 3 parameters Ideal tumor antigen for therapy Kvistborg et al., Curr Opin Immunol

10 Mobilizing patient T cells against tumor-antigens can be highly effective in advanced cancer stages Example: Treatment of metastatic melanoma with Tumorinfiltrating lymphocyte (TIL) therapy Rosenberg et al., Nat Rev Cancer

11 Mobilizing patient T cells against tumor-antigens can be highly effective in advanced cancer stages Example: Treatment of metastatic melanoma with a combination therapy of anti-pd1 and anti- CTLA-4 antibodies Larkin et al., N Engl J Med Drake et al. Nat Rev Clin Oncol 2014

12 Which tumor-antigens mediate cancer regression? Example: Monitoring of T cell responses against 145 melanoma-associated T cell epitopes in patients receiving anti-ctla4 therapy 12 Kvistborg et al., Sci Transl Med 2014

13 Which tumor-antigens mediate cancer regression? Example: Detection of a tumor mutation-specific T cell response in a melanoma patient receiving anti-ctla4 therapy van Rooij et al. J Clin Oncol

14 Which tumor-antigens mediate cancer regression? Conclusion: Tumors are immunogenic and visible for T cells (at least in a number of cases) T cell responses against different classes of tumor antigens are frequently induced by immunotherapeutic interventions Perspective: Can we learn which tumor-antigens are truly driving cancer regression to develop even more effective therapies? 14

15 Mobilization of endogenous tumor reactive T cells is not always effective Global manipulation Endogenous T cell compartment Possible reasons for treatment failure Anti-tumor T cell response Absence of tumorspecific T cells Dysfunction of tumor-specific T cells Side-effects too strong 15 Can we develop even better T cell therapies by engineering Designer T cell responses against tumor antigens?

16 Tumor antigens Targeting tumor antigens with genetically engineered T cells

17 Engineering T cell responses by receptor transfer Introduction of a new T cell receptor can redirect T cells against any antigen of interest Offringa Science

18 Targeting solid tumors with engineered T cells Example: Treatment of metastatic melanoma using T cells engineered with a NY- ESO-1 specific TCR gene 18 Robbins et al. Clin Cancer Res 2015 Robbins et al. J Clin Oncol 2011

19 Natural and designer receptors allow re-direction of T cells T Cell Receptor (TCR) Intracellular Targets Chimeric Antigen Receptor (CAR) Cell surface targets 19

20 Targeting B cell malignancies with engineered T cells Example: Treatment of B cell Chronic lymphocytic leukemia (B-CLL) using T cells modified with anti-cd19 specific CAR Bone marrow Blood Kochenderfer& Rosenberg Nat Rev Clin Oncol 2013 Kochenderferet al. Blood

21 Kite Pharma Anti-CD19-CAR therapy in ongoing clinical trials Study Phase Indication Status ZUMA-1 Phase 2 Pivotal (N=112) DLBCL PMBCL TFL Enrollment Complete Interim Data * 2016 Primary Data 2017 ZUMA-2 Phase 2 Pivotal (N=70) MCL Enrolling Data 2017 ZUMA-3 Phase 1/2 Pivotal (N=75) Adult ALL Phase 1/2 Enrolling P2 Data 2017 ZUMA-4 Phase 1/2 Pivotal (N=75) Pediatric ALL Phase 1/2 Enrolling P2 Data 2017 Additional studies in FL, CLL, earlier lines of DLBCL, and combination studies starting in *If supported by data, plan to file Biologics License Application based on interim data

22 22 4 ongoing registration studies in >40 centers in the US

23 KTE-C19 to be provided through a state-of-the-art manufacturing facility In-house clinical manufacturing in full operation Commercial facility in close proximity to LAX airport Capacity to produce 4,000-5,000 patient therapies per year Modular design is scalable and cost effective Site to produce KTE-C19 and all TCR products 23

24 The future of engineered T cell therapies has started! Thank you very much for your attention Kite Pharma at ESMO Congress 2016 Ongoing Complete Remissions in Phase 1 of ZUMA-1: A Phase 1-2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 (Anti- CD19 CAR T Cells) in Patients with Refractory Aggressive B Cell Non- Hodgkin Lymphoma (NHL) (F. Locke) Trials in Progress: ZUMA-1: A Phase 2 Multicenter Study Evaluating KTE- C19 (Anti-CD19 CAR T Cells) In Patients with Refractory Aggressive Non- Hodgkin Lymphoma (NHL) (Neelapu) Trials in Progress: ZUMA-2: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-CD19 (Anti-CD19 CAR T Cells) in Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) (M. Wang) Trials in Progress: ZUMA-3: A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 (Anti-CD19 CAR T Cells) in Adult Patients with Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia (R/R ALL) (B. Shah) OralPresentation # /7/16: 4:00-5:30 PM Trials in Progress Poster # /8/16 1:00 2:00 PM Trials in Progress Poster # /8/16 1:00 2:00 PM Trials in Progress Poster # /8/16 1:00 2:00 PM 24