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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

 

Washington, D.C. 20549

 

FORM 8-K
Current Report

 

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

 

Date of Report (date of earliest event reported): January 7, 2019

 

IOVANCE BIOTHERAPEUTICS, INC.
(Exact Name of Registrant as Specified in Charter)

 

Delaware
(State of Incorporation)
 
001-36860   75-3254381
Commission File Number   (I.R.S. Employer Identification No.)
     
999 Skyway Road, Suite 150    
San Carlos, California   94070
(Address of Principal Executive Offices)   (Zip Code)
     
(650) 260-7120
(Registrant’s Telephone Number, Including Area Code)
 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425).

 

¨Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12).

 

¨Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)).

 

¨Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)).

 

Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company ¨

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

 

 

 

 

 

Item 2.02.Results of Operations and Financial Condition.

 

Iovance Biotherapeutics, Inc. (the “Company”) is currently in the process of finalizing its financial results for the fiscal year ended December 31, 2018. Based on information currently available, the Company estimates that as of December 31, 2018, cash, cash equivalents, and short-term investments were approximately $469 million.

 

These estimates are preliminary and actual results may differ from these estimates due to the completion of the Company’s closing procedures with respect to the fiscal year ended December 31, 2018, final adjustments and other developments that may arise between now and the time the financial results for the 2018 fiscal year are finalized. As such, these estimates should not be viewed as a substitute for the full audited financial statements prepared in accordance with U.S. generally accepted accounting principles. These expected results could change materially and are not necessarily indicative of the results to be achieved for the 2018 fiscal year or any future period. As a result of the foregoing considerations and the other limitations described herein, investors are cautioned not to place undue reliance on this preliminary financial information. The Company does not undertake any obligation to publicly update or revise this estimate, except as required by law.

 

The information in this Item 2.02 shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 2.02 shall not be incorporated by reference into any registration statement or other document filed by the Company with the Securities and Exchange Commission, whether made before or after the date of this Current Report on Form 8-K, regardless of any general incorporation language in such filing (or any reference to this Current Report on Form 8-K generally), except as shall be expressly set forth by specific reference in such filing.

 

Item 8.01.Other Events.

 

The Company from time to time makes presentations at healthcare conferences and to analysts, current stockholders, and others. A copy of the Company’s presentation that it intends to use at such events is filed as Exhibit 99.1 to this Current Report on Form 8-K and incorporated by reference herein.

 

Item 9.01.Financial Statements and Exhibits.

 

(d)Exhibits

 

Exhibit No.   Description
99.1   Iovance Biotherapeutics, Inc., Corporate Presentation - January 2019.

  

 1 

 

 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this Report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: January 7, 2019 IOVANCE BIOTHERAPEUTICS, INC.
   
  By: /s/ MARIA FARDIS
    Maria Fardis, Chief Executive Officer

 

 

 

 

Exhibit 99.1

 

 

 

Corporate Presentation January 2019

 

 

This presentation contains “forward - looking statements” of Iovance Biotherapeutics, Inc. (hereinafter referred to as the “Compan y,” “we,” “us,” or “our”). We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “ma y,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward - looking statements. The forward - looking statements include, b ut are not limited to, risks and uncertainties relating to the success, timing, projected enrollment, manufacturing capabilities, and cost of our ongoing clinical trials and anticipate d c linical trials for our current product candidates (including both Company - sponsored and collaborator - sponsored trials in both the U.S. and Europe), such as statements regarding the timing o f initiation and completion of these trials; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration or other regulatory authority approval of, or oth er action with respect to, our product candidates; the strength of Company’s product pipeline; the successful implementation of the Company’s research and development programs and col laborations; the success of the Company’s manufacturing, license or development agreements; the acceptance by the market of the Company’s product candidates, if approv ed; and other factors, including general economic conditions and regulatory developments, not within the Company’s control. This presentation also contains certain preliminary fi nancial numbers and estimates for the most recently completed financial period. These numbers are good faith estimates based on currently available information and do not presen t a ll necessary information for an understanding of our financial condition as of the most recently completed financial period. Readers are cautioned not to place undue reliance on th ese estimates, which are unaudited and remain subject to review and adjustment by our auditors. As we complete our quarter - end financial close process and finalize the results for our most recently completed financial period, we may be required to make significant judgments in a number of areas. The preliminary financial information presented herein has been pre pared by and is the responsibility of our management. The factors discussed herein could cause actual results and developments to be materially different from those expressed in o r i mplied by such statements. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in the Company’s business, including, withou t l imitation: the FDA may not agree with the Company’s interpretation of the results of its clinical trials; later developments with the FDA that may be inconsistent with already c omp leted FDA meetings; the preliminary clinical results, including efficacy and safety results, from ongoing Phase 2 studies described above may not be reflected in the final analyses of these tr ials including new cohorts within these trials; the results obtained in the Company’s ongoing clinical trials, such as the studies and trials referred to in this release, may not be ind ica tive of results obtained in future clinical trials or supportive of product approval; regulatory authorities may potentially delay the timing of FDA or other regulatory authority approval of, o r o ther action with respect to, the Company’s product candidates (specifically, the Company’s description of FDA interactions are subject to FDA’s interpretation, as well as FDA’s au thority to request new or additional information); the Company may not be able to obtain or maintain FDA or other regulatory authority approval of its product candidates; the Compa ny’ s ability to address FDA or other regulatory authority requirements relating to its clinical programs and registrational plans, such requirements including, but not limited to, cli nic al and safety requirements as well as manufacturing and control requirements; risks related to the Company’s accelerated FDA review designations; the ability of the Company to obtai n a nd maintain intellectual property rights relating to its product pipeline; and the acceptance by the market of the Company’s product candidates and their potential reimbursement by p ayo rs, if approved. For more detailed information about the risks and uncertainties that could cause actual results to differ materially from tho se implied by, or anticipated in, these forward - looking statements, please refer to the Risk Factors section of the Company’s Annual Report on Form 10 - K and subsequent updates that may be contained in the Company’s Quarterly Reports on Form 10 - Q and current reports on Form 8 - K on file with the SEC. Forward - looking statements speak only as to the date they are m ade. Except as required by law, the Company does not undertake to update forward - looking statements to reflect circumstances or events that occur after the date the forward looking statements are made. This presentation does not constitute an offer to sell or buy securities, and no offer or sale will be made in any state or jurisdiction in which such o ffe r or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. © 2019, Iovance Biotherapeutics , Inc. 2 Forward Looking Statements

 

 

Manufacturing Development, Clinical Program Establishment Commercialization (1) Rosenberg, S. A., et al . Clinical Cancer Research, 2011, 17, 4550 (2) Goff, S. L. et al. Journal of Clinical Oncology , 2016, 34(20), 2389 - 2397 FDA Orphan Drug Designation for l ifileucel in malignant melanoma 2015 First patient dosed for Gen 1 l ifileucel in melanoma Gen 2 manufacturing developed and transferred to CMOs 2016 Efficacy d ata from Gen 2 proprietary, centralized and commercial process presented Head & Neck and Cervical studies began FDA Fast Track Status for l ifileucel in melanoma received Partnership with MD Anderson on multiple solid tumors executed Partnership with Ohio State University for PBL in hematological malignancies initiated 2017 European sites activated for Melanoma & Cervical FDA RMAT designation for l ifileucel in advanced melanoma received FDA End - of - Phase 2 Meeting for l ifileucel held L ifileucel Cohort 2 clinical data showed 38% ORR in 47 patients , Median DOR: 6.4 months, DCR: 77% in with average 3.3 prior lines of therapy 2018 Complete enrollment for registrational cohort in melanoma BLA submission for l ifileucel 2020 Discovery 2011 TIL therapy conducted by Steven Rosenberg/NCI published results showing: 56% ORR (1) and 24% CR rate in melanoma patients, with durable CRs as an early line therapy (2) 2019 Begin enrollment for melanoma registrational cohort Discuss registration path for cervical Initiate building US manufacturing facility for commercial supply Move TIL into earlier lines of therapy by combining with anti - PD/L - 1 antibodies in CPI - naïve population File IND for PBL in CLL © 2019, Iovance Biotherapeutics , Inc. Leveraging Tumor Infiltrating Lymphocyte (TIL) to Address Unmet Need 3

 

 

Commercialization (1) Rosenberg, S. A., et al . Clinical Cancer Research, 2011, 17, 4550 (2) Goff, S. L. et al. Journal of Clinical Oncology , 2016, 34(20), 2389 - 2397 FDA Orphan Drug Designation for l ifileucel in malignant melanoma 2015 First patient dosed for Gen 1 l ifileucel in melanoma/ Gen 2 manufacturing developed and transferred to CMOs 2016 Data from Gen 2 proprietary, centralized and commercial process demonstrated at SITC Head & Neck and Cervical studies begin FDA Fast Track Status for l ifileucel in melanoma received Partnership with MD Anderson on multiple solid tumors Partnership with Ohio State University for PBL in hematological malignancies 2017 European sites activated for Melanoma & Cervical FDA RMAT designation for l ifileucel in advanced melanoma FDA End - of - Phase 2 Meeting for l ifileucel L ifileucel Cohort 2 SITC presentation showing 38% ORR in 47 patients , Median DOR: 6.4 months, DCR: 77% in with average 3.3 prior lines of therapy 2018 Complete enrollment for registrational cohort in melanoma BLA submission for l ifileucel 2020 Discovery 2011 History of use includes data from National Cancer Institute with 200+ patients treated TIL therapy conducted by Steven Rosenberg/NCI published results showing: 56% ORR (1) and 24% CR rate in 101 melanoma patients, durable CRs as an early line therapy (2) 2019 Begin enrollment for melanoma registrational cohort Discuss registration path for cervical Initiate building US manufacturing facility for commercial supply Move TIL into earlier lines of therapy by combining with anti - PD/L - 1 antibodies in CPI - naïve populations File IND for PBL in CLL © 2019, Iovance Biotherapeutics, Inc. 4 2017: Efficacy d ata from Gen 2 proprietary, centralized and commercial process generated and presented Key Highlights 2018: Lifileucel Cohort 2 data showed 38% ORR in 47 patients , Median DOR: 6.4 months, DCR: 77% in patients with average 3.3 prior lines of therapy 2019: Begin enrollment for melanoma registrational cohort (fast to market registration plan) FDA End - of - Phase 2 Meeting for lifileucel held FDA agreed with the single arm r egistration plan Leveraging Tumor Infiltrating Lymphocyte (TIL) to Address Unmet Need

 

 

© 2019, Iovance Biotherapeutics, Inc. Leading cell therapy company focused on treatment of solid tumors Investment Highlights 5 Large market opportunity starting in solid tumors Accelerated path to approval in melanoma confirmed with FDA Efficient and scalable proprietary manufacturing • Initial focus in post - checkpoint solid tumors • Expansion into combinations and earlier lines of therapy • Five company - sponsored programs in melanoma, cervical, head & neck, NSCLC • Single arm registrational cohort commencing in 2019 • BLA submission in melanoma expected in 2H 2020 • RMAT, Orphan Drug, and Fast Track Designations in melanoma • Demonstrated U.S. and E.U. manufacturing capacity • Rapid 22 day manufacturing with >90% success rate • 100+ patients treated with proprietary Gen 2 process • Investigator - led programs to evaluate additional solid tumors or new combinations • Touch points with institutions including NIH/NCI, Moffitt Cancer Center, MD Anderson, Roswell Park, and Ohio State University Broad platform: proof - of - concept applications are explored through partnerships

 

 

© 2019, Iovance Biotherapeutics, Inc. TIL Therapy Elicits a Highly Individualized, Specific and Potent Attack Against Solid Tumors 6 • 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 single treatment • Potential to establish immunological memory, requiring no additional maintenance therapy after infusion – Responses seen both in treatment naïve and refractory melanoma patients who have failed other options, including checkpoint inhibitors – Complete responses observed in cervical cancer patients, maintained at 53 and 67 months (1) (1) Stevanovic , et al., Treatment of Metastatic Human Papiliomavirus - Associated Epithelial Cancers with Adoptive Transfer of Tumor - Infiltrating T Cells, ASCO 2018, Abstract #3004

 

 

© 2019, Iovance Biotherapeutics , Inc. Competitive Advantages of TIL in Solid Tumors 7 CHECKPOINTS TCR CAR - T (LIQUID TUMORS) TIL (SOLID TUMORS) Target multiple tumor antigens Target only single tumor antigen Mainly target only single/ surface tumor antigen Target multiple tumor antigens Long maintenance period One - time treatment One - time treatment One - time treatment Utility in several solid tumors Few solid tumors treated so far No examples of successful utility in solid tumors Available data in: melanoma, head & neck lung and cervical cancers Potential l ong - term irreversible toxicities Potential o n - target, off - tissue effects Potentially immunogenic: cytokine release syndrome Minimal chance of unpredicted on - target, off - tissue effects found to date Off - the - shelf Autologous Autologous Autologous TIL target a diverse array of cancer antigens; we believe this approach represents a highly differentiated, customized, and targeted immunotherapy

 

 

EXCISE: Patient’s TIL are removed via surgical resection of a lesion EXTRACT: Tumor is fragmented and placed in media for TIL to leave the tumor and enter media EXPAND: TIL expanded via IL - 2 + OKT3 exponentially ex vivo to yield 10 9 – 10 11 TIL PREPARE & INFUSE : Patient receives non - myeloablative lymphodepletion and is infused with their expanded TIL and IL - 2 © 2019, Iovance Biotherapeutics , Inc. Developed Centralized, Scalable and Efficient GMP Manufacturing 8 Co - culture TIL and feeder cells for expansion ex vivo Courier from clinical site Courier to clinical site for infusion Harvest and cryopreserved TIL infusion product Process time: 22 days

 

 

Manufacturing Multiple layers of patent applications filed for Gen 2 TIL products • Iovance is pursuing claims covering cryopreserved TIL products, manufacturing processes and methods of treatment • Includes two recently granted U.S. patents for methods of treatment in a broad range of cancers • U.S. Patent No. 10,166,257 • U.S. Patent No. 10,130,659 Advanced technologies Patent applications filed for a wide range of TIL technologies including • Marrow infiltrating and peripheral blood lymphocyte therapies • Use of costimulatory molecules in TIL therapy • Stable and transient genetically - modified TIL therapies • Patient subpopulations for TIL therapies © 2019, Iovance Biotherapeutics, Inc. Broad, Iovance - Owned IP Around TIL Therapy 9

 

 

(1) https://seer.cancer.gov Solid Tumor Indication Deaths (1) New Cases (1) Melanoma 9,320 91,270 Cervix Uteri 4,170 13,240 Oral Cavity, Pharynx & Larynx 13,740 64,690 Lung & Bronchus 154,050 234,030 Bladder 17,240 81,190 Breast 41,400 268,670 Pancreatic 44,330 55,440 Brain & Other Nervous System 16,830 23,880 90% of all cancer cases are solid tumors 1.6M New cases of solid tumors in the U.S. (1) Potential market for early lines in combo with standard of care Potential to address unmet need in late lines of treatment Expand into other indications Move into earlier line of therapy © 2019, Iovance Biotherapeutics, Inc. Significant Market Potential in Solid Tumors 10

 

 

Company sponsored studies Select investigator sponsored proof - of - concept studies Lifileucel C - 144 - 01 Melanoma 164 — LN - 145 C - 145 - 04 Cervical cancer 47 — LN - 145 C - 145 - 03 Head & neck cancer 47 — Lifileucel + pembrolizumab LN - 145 + pembrolizumab LN - 145 IOV - COM - 202 Melanoma Head & neck Non - small cell lung 36 — LN - 145 + durvalumab IOV - LUN - 201 Non - small cell lung 12 Regimen Trial MDA TIL NCT03610490 Ovarian, sarcomas, pancreatic ~54 LN - 145 NCT03449108 Ovarian, sarcomas ~54 Indication N Partner Phase 1 Phase 2 Pivotal © 2019, Iovance Biotherapeutics , Inc. Current Clinical Pipeline and Select Collaboration Studies 11

 

 

Metastatic Melanoma

 

 

• Estimated 9,320 U.S. patients deaths due to melanoma in 2018 (1) • Limited options after progression on checkpoint and BRAF/MEK inhibitors • 4,950 U.S. patients are on 3 rd and 4 th line of therapy (2) • 6,282 U.S. patients are on 2 nd line therapy (2) • TIL is available as a 2 nd line for those who are BRAF WT (3 rd line if BRAF mutant) Metastatic Melanoma Facts ORR 4 - 10 % Retreatment with checkpoint inhibitors or chemotherapy post progression on anti - PD1 and BRAF/MEK (3) Available care: immuno - therapy as first line option 91k Diagnoses in U.S. each year (1) 9k Deaths in U.S. each year (1) (1) https://seer.cancer.gov (2) Decision Resources Group – Disease Landscape and Forecast for Malignant Melanoma - Reprinted with permission. © 2018 DR/Decision Resources, LLC (3) Keynote - 37 Trial Results BRAF positive patients treated with BRAF/MEK inhibitors © 2019, Iovance Biotherapeutics, Inc. Potential Market for Metastatic Melanoma 13

 

 

Key inclusion criteria • Measurable metastatic melanoma and ≥ 1 lesion resectable for TIL generation • Progression on at least one prior line of systemic therapy including immune checkpoint inhibitor or a BRAF or BRAF/MEK • Age ≥ 18 • ECOG PS 0 - 1 Endpoints • Primary: efficacy defined as ORR by investigator per RECIST 1.1 • Secondary: safety and efficacy Study updates • Cohort 2 fully enrolled • Data readout on 47 patients at SITC • Cohort 4 (registrational) will enroll in 2019 CHARACTERISTIC N= 47 (%) Prior therapies Mean # prior therapies (min, max) 3.3 (1 - 9) Anti - PD - 1 47 (100) Anti - CTLA - 4 37 (79) BRAF/MEK 12 (26) Target lesions sum of diameter (mm) Mean (SD) 112 (73) Min, Max 17, 343 Baseline LDH (U/L) Median 246 1 - 2 times ULN 12 (26) > 2 times ULN 7 (15) Number of target & non - target lesions (at baseline) >3 37 (79) Mean 6 COHORT 2 © 2019, Iovance Biotherapeutics , Inc. Cohort 2, Phase 2 Trial in Metastatic Melanoma (C - 144 - 01) 14 “This is a heavily pre - treated cohort. There are usually pre - treated patients with only 1 line of therapy, but these patients in cohort 2 have on average 3.3 prior lines. Given there are no 2L/3L standard of care treatments, these patients got every treatment, and then some.” Dr. Diwakar Davar , Assistant Professor, Hillman Cancer Center

 

 

© 2019, Iovance Biotherapeutics , Inc. Frequency of AEs over time is reflective of potential benefit of one time treatment with TIL (lifileucel) Adverse Events Tend to be Early and Transient 15 COHORT 2 (1) Treatment - Emergent Adverse Events refer to all AEs starting on or after the first dose date of TIL up to 30 days Patients with multiple events for a given preferred term are counted only once using the maximum grade under each preferred t erm . Safety terms which describe the same medical condition were combined. PREFERRED TERM Cohort 2 (N=47) Any Grade n (%) Grade 3/4 n (%) Grade 5 n (%) Patients reporting at least one Treatment - Emergent Adverse Events (1) 47(100) 45 (95.7) 2 (4.3) Thrombocytopenia 42 (89.4) 38 (80.9) 0 Chills 36 (76.6) 3 ( 6.4) 0 Neutropenia 29 (61.7) 25 (53.2) 0 Febrile neutropenia 28 (59.6) 25 (53.2) 0 Anemia 27 (57.4) 22 (46.8) 0 Pyrexia 25 (53.2) 7 (14.9) 0 Hypophosphatemia 23 (48.9) 17 (36.2) 0 Leukopenia 21 (44.7) 20 (42.6) 0 Fatigue 17 (36.2) 0 0 Hypotension 17 (36.2) 4 ( 8.5) 0 Lymphopenia 17 (36.2) 17 (36.2) 0 Tachycardia 15 (31.9) 1 ( 2.1) 0 Lifileucel Treatment - Emergent Adverse Events (≥ 30%) Adverse Events Over Time

 

 

• In heavily pretreated metastatic melanoma patients, preliminary efficacy is notable for: • ORR 38% (3.3 prior lines of therapy) vs. standard of care chemotherapy has ~10% ORR (in 2 nd line) • Median DOR is 6.4 months , range 1.3+ to 14+ • Single treatment of TIL led to DCR of 77% in late stage metastatic patients • Mean number of TIL cells infused: 26 x 10 9 • Median number of IL - 2 doses administered was 6.0 as per protocol RESPONSE N=47 (%) Objective Response Rate 18 (38%) Complete Response 1 (2%) Partial Response (PR + uPR (1) ) 17 (36%) Stable Disease 18 (38%) Progressive Disease 7 (15%) Non - Evaluable 4 (9%) Disease Control Rate 36 ( 77%) COHORT 2 (1) Only one patient is uPR due to not having reached the follow on assessment as of end Dec 2018 © 2019, Iovance Biotherapeutics , Inc. Lifileucel is Potentially an Efficacious Treatment for Patients with Limited Options 16

 

 

© 2019, Iovance Biotherapeutics , Inc. Lifileucel time to response and current duration of for evaluable patients (partial response or better) Responders from TIL Therapy had Progressed on Checkpoint Inhibitors 17 COHORT 2 (1) BOR is best overall response on prior anti - PD - 1 immunotherapy (2) U: unknown best overall response on prior anti - PD - 1 immunotherapy Time (months) since CY/FLU ( lymphodepletion )

 

 

© 2019, Iovance Biotherapeutics , Inc. Lifileucel best overall response rate (1) TIL Therapy Provides Deep Responses 18 COHORT 2 (1) Per RECIST 1.1, two patients (31,33) had BOR of SD: met PR criteria at Day 42 and PD at Day 84 due to new lesions • 72% of patients had a reduction in tumor burden • Median study follow up is 6.0 months • All assessments are by RECIST 1.1 • Responses are deep – nearly all responders are greater than 30%

 

 

Cohort 2: Cryopreserved TIL product (Gen 2) N=60 Enrollment Closed Cohort 4: Cryopreserved TIL product (Gen2) N=75 Cohort 1: Non - cryopreserved TIL product N=30 Enrollment Closed COHORT 4 Key inclusion criteria • Measurable metastatic melanoma and ≥ 1 lesion resectable for TIL generation • Progression on at least one prior line of systemic therapy including immune checkpoint inhibitor and if BRAF V600 mutation positive, BRAF or BRAF/MEK targeted therapy • 75 patients Endpoints • Primary: efficacy defined as ORR by BIRC • Secondary: safety and efficacy Study updates • Confirmed with FDA that a randomized Phase 3 study is not feasible in advanced melanoma post - CPI • FDA has acknowledged acceptability of single - arm data for registration • Enrollment to begin early 2019 © 2019, Iovance Biotherapeutics , Inc. Lifileucel in Metastatic Melanoma Single - Arm Registrational Cohort 4 19

 

 

© 2019, Iovance Biotherapeutics , Inc. 2L/3L melanoma treatment has no current standard of care Development Efforts in Late Stage (2L/3L) Melanoma Treatment 20 Combination with anti - PD - 1 Single agent (1) Idera Pharmaceuticals Results Dec 14, 2018 (2) Milhem M et al., AACR 2018 (3) Ribas A et al., Cancer Discovery 2018 (4) Ascierto P et al ., ESMO 2017 (5) Buchbinder EI et al ., JCO 2017 (6) Agarwala et al ., ASCO 2018 Agent ORR % ( N) Current Development Status Prior Lines of Tx Patient Characteristics TLR9 agonists, HDAC IMO - 2125 ( Idera ) + ipi 29% (N=34) (1) Phase 3 , post - PD - 1 melanoma (ILLUMINATE 204) 1 - 3 ECOG ≤1, intratumoral injection CMP - 001 ( CheckMate ) + PD - 1 22% (N=69) (2) Phase 1b 1+ ECOG ≤1, intratumoral injection SD - 101 ( Dynavax ) + PD - 1 15% (N=13) (3) Phase 1b 1+ ECOG ≤1 Entinostat + pembro 18% (N=34) (6) ENCORE 601 (phase 2, ongoing) 1+ ECOG ≤1 Checkpoints LAG - 3 12% (N=61) (4) Multiple 1L studies 1+ All comers, ECOG ≤2 • LAG - 3 expression ≥1% (n=33) ORR=18%; • LAG - 3 expression <1% (n=22) ORR=5% TIGIT, TIM - 3 Unknown Phase 1/2 Cytokines HD IL - 2 8% (N=9) (5) 1+ HD IL - 2 post PD - 1 Other TIL 38% Phase 2 3 All post - anti - PD1, 79% post anti - CTLA - 4, 86% post - BRAF (if mutant)

 

 

Cervical Cancer

 

 

“TIL immunotherapy with LN - 145 is literally redefining what is treatable and potentially curable in advanced metastatic chemo - refractory cervical cancer. Patients who only two years ago would be facing hospice as their only alternative now have access to this potentially life extending new treatment. This is the most exciting news in this field in decades.” Amir Jazaeri , M.D. Director of the Gynecologic Cancer Immunotherapy Program in the Department of Gynecologic Oncology and Reproductive Medicine at MD Anderson (1) Global Burden of Disease Cancer Collaboration, Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability - Adjusted Life - years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018 Nov 1;4(11):1553 - 1568. doi : 10.1001/jamaoncol.2018.2706 (2) https://seer.cancer.gov/ (3) https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf (4) Stevanovic , et al., Treatment of Metastatic Human Papiliomavirus - Associated Epithelial Cancers with Adoptive Transfer of Tumor - Infiltrating T Cells, ASCO 2018, Abstract #3004 Cervical Cancer Facts For PD - L1 + patients, post - chemo receiving Keytruda (3) ORR 14.3 % Post - chemo, TIL ORR 28% (4) New Cases WW each year (1) 511k 13k Diagnoses in U.S. each year (2) 247k 4k Deaths WW each year (1) Deaths in U.S. each year (2) Available care: Chemo - therapy as first line option © 2019, Iovance Biotherapeutics, Inc. Potential Market for Cervical Cancer 22

 

 

Phase 2, multicenter study to evaluate the efficacy and safety of autologous Tumor Infiltrating Lymphocytes (LN - 145) in patients with recurrent, metastatic or persistent cervical carcinoma (NCT03108495) Recurrent, metastatic or persistent cervical carcinoma with 1 prior therapy Simon’s two - stage design Expanded cohort N = 47 Endpoints • Primary: ORR • Secondary: safety and efficacy Key updates • Protocol amended to enroll patients with 1 - 3 prior therapies and exclude prior immunotherapy BASELINE DEMOGRAPHICS N= 15 ( 1) (%) Prior therapies Median prior therapies (min, max) 5 (1, 8) Anti - PD - 1 8 (53) Anti - CTLA - 4 2 (13) (1) The patients reported are a combination of Gen 1 and Gen 2 manufacturing processes © 2019, Iovance Biotherapeutics , Inc. Phase 2 Trial in Cervical Cancer (C - 145 - 04) 23

 

 

(1) The patients reported are a combination of Gen 1 and Gen 2 manufacturing process (2) The composition of the relevant patient population may differ between Iovance trials and published data for CPIs (USPI used) but serves as a point of reference for assessing the overall efficacy landscap e for relevant therapies (3) Treatment - Emergent Adverse Events refer to all AEs starting on or after the first dose date of TIL up to 30 days 14% 27% Cervical Cancer • N=15 • 27% ORR • 4 PRs (all confirmed) • DOR (min, max) : 2.4, 2.5+ months Keytruda in post - chemotherapy 2) TEAE (≥40%), ANY GRADE N=15 (%) Chills 11 (73) Pyrexia 8 (53) Anaemia 7 (47) Hypotension 6 (40) Platelet count decreased 6 (40) Vomiting 6 (40) LN - 145 (1) ORR ORR © 2019, Iovance Biotherapeutics , Inc. TIL Offers a Favorable Treatment for Cervical Cancer Patients 24 Treatment - Related Adverse Events (3)

 

 

Head & Neck Cancer

 

 

(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 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018 Nov 1;4(11):1553 - 1568. doi : 10.1001/jamaoncol.2018.2706 (2) https://seer.cancer.gov/ (3) The composition of the relevant patient population may differ between Iovance trials and published data for CPIs (USPI used) but serves as a point of reference for assessing the overall efficacy landscape for relevant therapies Head & Neck Cancer Facts Anti - PD - 1 immunotherapy as second line ( Opdivo and Keytruda) ORR 13 - 16% (3) New Cases WW each year (1) 694k 65k Diagnoses in U.S. each year (2) 303k 14k Deaths WW each year (1) Deaths in U.S. each year (2) Available care in first line: Chemotherapy and Immunotherapy © 2019, Iovance Biotherapeutics, Inc. Potential Market for Head & Neck Cancer 26

 

 

BASELINE DEMOGRAPHICS N= 13 (%) Prior therapies Median prior therapies (min, max) 3 (1, 5) Anti - PD - 1 11 (85) Anti - CTLA - 4 3 (23) Number of target & non - target lesions (at baseline) >3 10 (77) 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) Incurable recurrent, metastatic, or persistent SCCHN with 1 prior therapy Simon’s two - stage design Expanded cohort N = 47 Endpoints • Primary: ORR • Secondary: safety and efficacy © 2019, Iovance Biotherapeutics , Inc. Phase 2 Trial in Head & Neck Cancer (C - 145 - 03) 27

 

 

© 2019, Iovance Biotherapeutics , Inc. TIL Offers a Favorable Treatment Option for Head & Neck Cancer in post - CPI Patients 28 • N=13 • 31% ORR • 4 PRs • DOR (min, max): 2.8, 7.6 months Head & Neck Cancer TEAE (≥40%), any grade N=13 (%) Chills 10 (77) Hypotension 8 (62) Hyponatremia 7 (54) Pyrexia 7 (54) 16% ORR 31% LN - 145 (1) ORR Keytruda in post - chemotherapy 2) Treatment - Related Adverse Events (3) (1) The patients reported are a combination of Gen 1 and Gen 2 manufacturing process (2) The composition of the relevant patient population may differ between Iovance trials and published data for CPIs (USPI used) but serves as a point of reference for assessing the overall efficacy landscape for relevant therapies (3) Treatment - Emergent Adverse Events refer to all AEs starting on or after the first dose date of TIL up to 30 days

 

 

A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN - 144 or LN - 145) in Patients with Solid Tumors (NCT03645928) Melanoma PD - 1/PDL - 1 Naïve Melanoma Head & Neck Cohort 1: TIL+ Pembro N=12 Cohort 2: TIL+ Pembro N=12 RR NSCLC NSCLC Cohort 3: TIL N=12 PD - 1/PDL - 1 Naïve Endpoints • Primary: ORR and safety • Secondary: CR rate Key updates • Six U.S. sites are activate • First ex - U.S. Health Authority has approved the CTA (UK) © 2019, Iovance Biotherapeutics , Inc. Investigation of TIL in Earlier Lines of Therapy in Combination with SOC 29

 

 

© 2019, Iovance Biotherapeutics , Inc. Research Focus into Next Generation TIL 30 Prepare or select more potent TIL • Use anti - 4 - 1BB, anti - OX40, or other co - stimulants in cocktails in ex vivo growth of TIL • License to uses of 4 - 1BB agonists obtained from Moffitt Cancer Center • Select more potent TIL Identify biomarkers to find a better TIL product or better patient population Expand the TIL platform into new indications • Heme indication (OSU collaboration) • Bladder cancer (Roswell Park Cancer Institute) Genetically modify to make a more tumor - reactive TIL • Cellectis TALEN® collaboration • Phio RNAi collaboration

 

 

• Single arm registrational trial beginning in early 2019 aiming towards BLA in 2020 • Manufacturing optimization has demonstrated scalability and is moving towards commercialization • Strong balance sheet providing three years of cash runway • Multiple shots on goal for proof - of - concept studies through collaborations on additional indications, combination and earlier lines of therapy © 2019, Iovance Biotherapeutics , Inc. Value Drivers for 2019 31

 

 

Demonstrate consistent, scalable, rapid proprietary manufacturing method x x Demonstrate activity in melanoma post - checkpoint inhibitor (difficult to treat patients) x Align on registration pathway with FDA x Demonstrate activity in post - CPI cervical, head & neck tumors x Secure new IP around TIL technology and manufacturing Explore therapeutic potential of TIL in other indications Continue the dialog with FDA for both LN - 144 and LN - 145 in support of registration x Secure adequate financing providing 3 years of runway 2018 2019 Present data from Gen 2 of cervical study File new IND for new manufacturing process and/or new indications Present updated data in cohort 2 for melanoma Initiate building Iovance manufacturing facility Enrollment into Cohort 4 for C - 144 - 01 in support of registration © 2019, Iovance Biotherapeutics , Inc. Achieved and Upcoming Milestones 32

 

 

In millions - unaudited (2) Common shares outstanding 123 Preferred shares 6 (1) Warrants/options/RSU’s 7 Cash, cash equivalents, short - term investments $469 (3) Debt 0 (1) Preferred shares are shown on an as - converted basis (2 ) As of December 31, 2018. Financial numbers presented herein are unaudited preliminary estimates based upon currently availabl e i nformation and remain subject to review and adjustment by the Company's auditors. (3 ) Based upon currently available information, there has been no material change to the liabilities of the Company since the las t f iled periodic report. © 2019, Iovance Biotherapeutics , Inc. Well Capitalized in Pursuit of TIL Commercialization 33

 

 

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