Iovance Biotherapeutics, Inc. · NASDAQ:IOVA

Iovance Biotherapeutics — Investor Day (December 2017)

51 slides from Iovance Biotherapeutics's investor day presentation, Dec 13, 2017

  1. Slide 1: Analyst Day December 13, 2017

    Analyst Day December 13, 2017 © 2017, Iovance Biotherapeutics

  2. Slide 2: Forward-looking statements

    This presentation contains forward - looking statements reflecting management’s current beliefs and expectations . These forward looking statements can be identified with words such as “expects”, “plans”, “projects”, “potential”, “suggests”, “may”, or similar expressions . Such forward - looking sta

  3. Slide 3: Today's Agenda

    Today’s Agenda 3 START END AGENDA ITEM DURATION DISCUSSANT 8:30am 9:00 • Breakfast and registration 30 min 9:00 9:15 • Welcome • TIL therapy overview • Selection of Gen 2 15 min Dr. Maria Fardis 9:15 9:30 • Manufacturing Update - Gen 2 15 min Mr. Rich Gaeto 9:30 9:50 • Clinical overview • Review of

  4. Slide 4: TIL Therapy Process

    1. EXCISE 2. EXTRACT 3. EXPAND 4. PREPARE & INFUSE • EXCISION: Patient’s TIL are removed from suppressive tumor microenvironment (via surgical resection of a lesion) • EXTRACTION: Tumor is fragmented and placed in media for TIL to leave the tumor and enter media • EXPANSION: TIL expanded exponential

  5. Slide 5: Competitive Advantages of TIL in Solid Tumors

    © 2017, Iovance Biotherapeutics Competitive Advantages of TIL in Solid Tumors 5 CHECKPOINTS TCR CAR - T (LIQUID TUMORS) TIL (SOLID TUMORS) Utility in several solid tumors Few solid tumors treated so far No examples of successful utility in solid tumors Available data in melanoma and cervical cancers

  6. Slide 6: US Cancer Statistics

    US Cancer Statistics *https://seer.cancer.gov/statfacts/html/all.html © 2017, Iovance Biotherapeutics 6 ESTIMATED NEW CASES 2017    K ESTIMATED DEATHS 2017 601K* HEMATOLOGIC ~143k SOLID TUMORS 1,550K SOLID TUMORS 555k HEMATOLOGIC ~45k

  7. Slide 7: TIL Therapy: Elicits a Highly Individualized, Specific and Potent Attack Against Solid Tumors

    • Leverages and enhances the body’s natural defense against cancer using a patient’s own TIL • Polyclonal and can recognize multiple neoantigens ̶ Solid tumors are heterogeneous • Durable response with one - time treatment ̶ Potential to establish immunological memory, requiring no additional mainte

  8. Slide 8: NCI Study Survival Benefit in Second and Third Line Patients

    19/20 CR were ongoing at more than 3 to 7 years Durable remissions in melanoma regardless of prior therapies NCI Study Survival Benefit in Second and Third Line Patients Rosenberg, S.A., et al. Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T - Cell Transfer

  9. Slide 9: TIL Therapy: Single Treatment, High Response Rate

    • TIL therapy has demonstrated efficacy in melanoma and cervical cancers • Single treatment has led to durable CRs, lasting multiple years, in patients without exposure to checkpoints • Proven to work in solid tumors at multiple academic institutions as well as the NCI Rosenberg, S.A., et al. Durabl

  10. Slide 10: Iovance Biotherapeutics Today

    • Iovance Biotherapeutics has a license to the TIL technology from the NCI • Iovance has approximately ~70 employees • The company is headquartered in San Carlos, CA with offices in New York City, Tampa, and a subsidiary in Europe Iovance Biotherapeutics Today © 2017, Iovance Biotherapeutics 10 Corp

  11. Slide 11: 2017 Iovance Accomplishments

    x Establishment of manufacturing capacity x Developing a new, shorter manufacturing process, establish novel IP x Generation 2 of manufacturing was developed at Iovance, tech transferred to our CMOs and dosed in patients x Based on clinical data, this method has been selected for current and future

  12. Slide 12: TIL Therapy Manufacturing

    • Clinical and commercial manufacturing capabilities are in place in the US and EU ̶ US: Lonza, WuXi (multiple locations), Moffitt ̶ EU: LonzaNL (formerly PharmaCell) • Shorter Generation 2 manufacturing process has been selected for all current and future Iovance studies (all protocols amended) ̶ S

  13. Slide 13: Manufacturing

    Manufacturing © 2017, Iovance Biotherapeutics 13

  14. Slide 14: LN-144 and LN-145 Manufacturing Process (22 days)

    Excise tumor Express courier from clinical s ite to CMO Express courier in cryoshipper from CMO to clinical s ite Thaw and i nfuse . Follow by IL - 2 administration Cut into fragments Expansion ex vivo scale up ex vivo culture IL - 2 + OKT3 Co - culture TIL and feeder cells Rapid Expansion (REP) 11

  15. Slide 15: Gen 2 Process Improvements

    Gen 2 Process Improvements © 2017, Iovance Biotherapeutics PROCESS STEP GEN 1 GEN 2 Advantages Fragment Culture ≤ 21 days, multiple bioreactors, operator interventions 11 days, single closed bioreactor, minimal intervention Shortens culture , reduces interventions, amenable to automation TIL selecti

  16. Slide 16: Iovance Gen 2 TIL Infusion Product Benefits vs Gen 1

    © 2017, Iovance Biotherapeutics Iovance Generation 2 (Gen 2) TIL Infusion Product Benefits vs Generation 1 (Gen 1) 16 IOVANCE GEN 2 PRODUCT BENEFITS High purity TIL, comparable costimulatory molecules Comparable quality vs Gen 1 Younger cell type with higher clonal diversity Comparable or longer rel

  17. Slide 17: Gen 2 Intellectual Property

    © 2017, Iovance Biotherapeutics Gen 2 Intellectual Property • Iovance has a broad TIL - based patent portfolio ̶ Advances in TIL manufacturing implemented in the Gen 2 process • Multiple provisional patent applications have been filed • Worldwide rights will be pursued under the PCT path and US righ

  18. Slide 18: Cell Orchestration Platform (TrakCel Collaboration)

    © 2017, Iovance Biotherapeutics Cell Orchestration Platform (TrakCel Collaboration) Logistics of Each Patient’s Sample and TIL Therapy An automated process integrating scheduling, capacity and logistics throughout the supply chain: Part 11 compliant, improves communication across the stakeholders 18

  19. Slide 19: Clinical Development

    Clinical Development © 2017, Iovance Biotherapeutics 19

  20. Slide 20: Iovance Clinical Pipeline

    Iovance Clinical Pipeline INDICATION REGIMEN N PARTNER PRECLINICAL PHASE 1 PHASE 2 Melanoma TIL LN - 144 60 — Cervical Cancer TIL LN - 145 47 — Head & Neck Cancer TIL LN - 145 47 — Non - Small Cell Lung Cancer TIL LN - 145 vs TIL LN - 145 + durvalumab 24 Enrolling Enrolling Enrolling 20 Phase 2 tria

  21. Slide 21: Melanoma

    Melanoma © 2017, Iovance Biotherapeutics 21

  22. Slide 22: Metastatic Melanoma Cancer Facts

    ORR, objective response rate; TIL, tumor infiltrating lymphocytes. 1 Global Burden of Disease Cancer Collaboration, Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost , Y ears Lived With Disability, and Disability - Adjusted Life - years for 32 Cancer Groups, 1990 to 2015

  23. Slide 23: Iovance C-144-01 Phase 2 Trial in Metastatic Melanoma

    A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN - 144) for Treatment of Patients with Metastatic Melanoma (NCT02360579) Key Inclusion Criteria: • Measurable metastatic melanoma and ≥ 1 lesion resectable for TIL generation • Progression

  24. Slide 24: Patient Characteristics from Cohort 2 Update

    CHARACTERISTIC Cohort 2 N= 17 , (%) Gender, n (%) Male 8 (47) Female 9 (53) Age Median 54 Min, Max 35, 66 Prior therapies, n (%) Mean # prior systemic therapies 3.6 Anti - CTLA - 4 15 (88) Anti - PD - 1 16 (94) Target Lesion Sum of Diameter (mm) Mean (SD) 140 (93) Min, Max 38, 342 CHARACTERISTIC Coh

  25. Slide 25: Treatment Emergent Adverse Events

    Notes: Patients with multiple events for a given preferred term are counted only once using the maximum grade under each pref err ed term. Treatment - Emergent Adverse Events refer to all AEs starting on or after the first dose date of pre - treatment chemotherapy (Fludarabine and Cyclophosphamide )

  26. Slide 26: Time to Response for Evaluable Patients

    Of 10 patients in Efficacy Set, one patient (Patient 10) is not evaluable (NE) due to melanoma - related death prior to first tumor assessment not represented on figure. © 2017, Iovance Biotherapeutics Time to Response for Evaluable Patients (SD or Better) • DCR is: 80% • Time to response is similar

  27. Slide 27: Iovance C-144-01 Efficacy

    • Mean number of TIL cells infused: 34 x 10 9 • Median number of IL - 2 doses administered was 4.5 • Patients with BRAF mutation responded as well as patients with wild type BRAF One patient (Patient 10) had passed away prior to the first assessment (still considered in the Efficacy Set). * Refers t

  28. Slide 28: Iovance C-144-01 Efficacy: Evaluable Patient Data

    • All efficacy - evaluable patients had received an anti - PD - 1 and anti - CTLA - 4 checkpoint inhibitor 1 Dec 2017 Data Cut * NE due to not reaching first assessment. Iovance C - 144 - 01 Efficacy: Evaluable Patient Data © 2017, Iovance Biotherapeutics 28 RESPONSE PATIENTS, N=10 n (%) Objective R

  29. Slide 29: CT Scan for Patient with PR

    CT Scan for Patient with PR TL1: Lt low. quad. abdom. - BL: 8.8 cm / 18 wk: 3.7 cm TL2: Lt uppr quad abdom. - BL: 5.2 cm / 18 wk: 0 cm TL3: Lt renal – BL: 4.1 cm / 18 wk: 2.1 cm TL5: Rt femoral LN - 4 cm (short axis) / 18 wk: 2.3 cm © 2017, Iovance Biotherapeutics 29 Pre - Treatment 18 wks Post - Tr

  30. Slide 30: Future Plan for the Study

    Future Plan for the Study © 2017, Iovance Biotherapeutics 30 COHORT 2 CONTINUE ENROLLMENT ENROLLING PATIENTS WITH TIL PRODUCT FROM WUXI (Late - stage clinical & commercial suites) INITIATE DOSING PATIENTS IN EUROPE IN IH 2018 GEN 2 GEN 1 COHORT 1 STOP ENROLLMENT

  31. Slide 31: Head & Neck Cancer

    Head & Neck Cancer © 2017, Iovance Biotherapeutics 31

  32. Slide 32: HNSCC Cancer Facts

    Abbreviations: HPV, human papillomavirus infection; OPC, oropharyngeal cancer; ORR, objective response rate; TIL, tumor infil tra ting lymphocytes. 1 Global Burden of Disease Cancer Collaboration, Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost , Y ears Lived With Disa

  33. Slide 33: Iovance C-145-03 Phase 2 Trial in Head and Neck Cancer

    A Phase 2 Study to Evaluate the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN - 145) for the Treatment of Patients with Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (NCT03083873) N=47; Simon’s two - stage design Gen 2 manufacturing will be used going forwa

  34. Slide 34: LN-145 for Head & Neck: Stage 2 of Enrollment Triggered

    • The study will proceed with enrollment to full 47 patients • Preliminary data anticipated at an upcoming scientific conference in 2018 N=47; Simon’s two - stage design LN - 145: protocol was amended to continue enrollment with Gen 2 product Endpoints: • Primary: Efficacy defined as ORR • Secondary

  35. Slide 35: Cervical Cancer

    Cervical Cancer © 2017, Iovance Biotherapeutics 35

  36. Slide 36: NCI Cervical Cancer and TIL Treatment Data

    Stevanovic, et al. Complete Regression of Metastatic Cervical Cancer After Treatment with Human Papillomavirus - Targeted Tumor - Infiltrating T Cells, J Clin Oncol 2015, 33 (14), 1543. Hinrichs, et al. HPV - targeted Tumor - Infiltrating Lymphocytes for Cervical Cancer, J Clin Oncol , 2014, 23, 5s.

  37. Slide 37: Iovance C-145-04 Phase 2 Trial in Cervical Carcinoma

    A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety Using Autologous Tumor Infiltrating Lymphocytes (LN - 145) in Patients with Recurrent, Metastatic or Persistent Cervical Carcinoma (NCT03108495) N=47; Simon’s two - stage design LN - 145, protocol was amended to continue enrollment wit

  38. Slide 38: Non-Small Cell Lung Cancer

    Non - Small Cell Lung Cancer © 2017, Iovance Biotherapeutics 38

  39. Slide 39: Market Opportunity for TIL Therapy in US

    INDICATION NEW CASES 1 DEATHS Melanoma 87,110 9,730 Cervix Uteri 12,820 4,210 Oral Cavity, Pharynx & Larynx 63,030 13,360 Lung & Bronchus 222,500 155,870 Bladder 79,030 16,870 Breast 2 52,710 40,610 Pancreatic 53,670 4 3,090 Brain & Other Nervous System 23,800 16,700 1 https://seer.cancer.gov/ 2 htt

  40. Slide 40: Ongoing Collaborations and Partnerships

    Moffitt Cancer Center sponsored trial • TIL + anti - PD - 1, nivolumab (Opdivo ® ): An Investigator Initiated Trial (IIT), Phase 1 study with advanced NSCLC patients 1 Iovance sponsored trial in collaboration with MedImmune / AstraZeneca • TIL +/ - anti - PD - L1, durvalumab: Iovance - sponsored, Ph

  41. Slide 41: Moffitt Lung Study Phase I Clinical Trial

    Moffitt Lung Study © 2017, Iovance Biotherapeutics 41 Phase I Clinical Trial Combining Nivolumab and Tumor Infiltrating Lymphocytes (TIL) for Patients with Advanced Non - Small Cell Lung Cancer (NCT03215810) • N = 18 • First patient harvested in 4Q 2017 PD - 1/PD - L1 naïve stage IV or recurrent NSC

  42. Slide 42: NSCLC Phase 2 Study

    A Phase 2 Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN - 145) Alone and in Combination with Anti - PD - L1 Inhibitor Durvalumab (MEDI4736) in Patients with Locally Advanced or Metastatic Non - Small Cell Lung Cancer (NSCLC) NSCLC Phase 2 Study © 2017, Iova

  43. Slide 43: Sarcoma and Platinum-Resistant Ovarian Cancers

    Sarcoma and Platinum - Resistant Ovarian Cancers © 2017, Iovance Biotherapeutics 43

  44. Slide 44: MD Anderson Collaboration Program Update

    © 2017, Iovance Biotherapeutics MD Anderson Collaboration Program Update • Iovance has a collaboration with MD Anderson involving ̶ Preclinical research in expanding understanding of TIL ̶ Two clinical studies: 1. LN - 145 being provided by Iovance • Indications: sarcoma, platinum - resistant ovaria

  45. Slide 45: MD Anderson Collaboration: Clinical Study with LN-145

    PRIVILEGED AND CONFIDENTIAL © 2017, Iovance Biotherapeutics MD Anderson Collaboration Program Update Clinical Study with LN - 145 • Simon’s two - stage design • Expected first patient dosing in 1H 2018 • Iovance has capacity to support enrollment in this study. • Gen 2 manufacturing process will be

  46. Slide 46: Iovance Collaboration Pipeline

    Iovance Collaboration Pipeline © 2017, Iovance Biotherapeutics 46 INDICATION REGIMEN N PARTNER PRECLINICAL PHASE 1 PHASE 2 Melanoma Combination TIL ± TBI 101 Melanoma Combination TIL + Yervoy Melanoma Combination TIL + Keytruda 170 Melanoma Combination TIL + Opdivo 12 Ocular (Uveal) Melanoma TIL 23

  47. Slide 47: Future Indications

    Future Indications © 2017, Iovance Biotherapeutics 47

  48. Slide 48: Hematologic Malignancies

    © 2017, Iovance Biotherapeutics Hematologic Malignancies • Iovance has produced data demonstrating ̶ TIL can be grown from lymphoma with similar therapeutic potential as melanoma • Collaboration with Ohio State University to investigate power of TIL therapy in heme ̶ In patients with prior ibrutinib

  49. Slide 49: Summary of Recent Progress

    © 2017, Iovance Biotherapeutics Summary of Recent Progress • Manufacturing: ̶ Gen 2 was selected for all future TIL therapy at Iovance • IP: ̶ A broad portfolio of immuno - oncology patent applications including coverage for Gen 2 manufacturing • Clinical: ̶ Updated data in melanoma trial was provid

  50. Slide 50: Key Anticipated Milestones

    • Partner with our suppliers and vendors • Continue collaborating with new clinical sites and hospitals to assure preparation for commercialization PARTNERSHIPS • FDA interaction to define the registration path for LN - 144 • Activate melanoma and cervical studies in Europe • Continue enrollment int

  51. Slide 51: Thank you

    Thank you © 2017, Iovance Biotherapeutics

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