2020 Annual Report

TIL CELL THERAPY

DEDICATED TO THE FIGHT

AGAINST SOLID TUMORS

2020 ANNUAL REPORT

IOVANCE'S

DEDICATION

TO PURSUING

THERAPIES FOR

CANCER PATIENTS

LIKE ME GIVES ME

GREAT HOPE."

LARRY S.

IOVANCE TIL STUDY

PARTICIPANT

TIL therapy is an investigational therapy and has not been approved for any indication by the United States Food and Drug Administration (USFDA) or any other regulatory agency. The safety and efficacy of this therapy has not been determined.

IN THE FIVE YEARS SINCE I JOINED IOVANCE, WE HAVE TRANSFORMED TIL FROM A LENGTHY ACADEMIC PROCESS TO A POTENTIALLY COMMERCIALIZABLE PRODUCT USING

• CENTRALIZED, SHORTER, AND SCALABLE GMP PROCESS YIELDING
• CRYOPRESERVED PRODUCT."

WE REMAIN FOCUSED ON OUR EFFORTS

IN BRINGING NOVEL THERAPIES TO PATIENTS IN NEED."

LETTER FROM THE PRESIDENT & CEO

DEAR IOVANCE BIOTHERAPEUTICS

STOCKHOLDERS,

2020 WAS A SIGNIFICANT YEAR FOR IOVANCE. We expanded our leadership in Tumor Infiltrating Lymphocyte (TIL) cell therapy development, manufacturing and planned commercialization. We continued to advance Iovance TIL in pivotal programs in melanoma and cervical cancers, while making great strides to broaden our TIL pipeline into additional indications and earlier lines of therapy. We also introduced new TIL products in clinical studies, including selected TIL and third generation (Gen 3) TIL products. Despite the COVID-19pandemic and its significant impact, the resilience and dedication of our Iovance team allowed us to continue many of our clinical and manufacturing activities with minimal interruption. We adapted to the virtual way of work and continued with our drug development activities.

TIL is a first-in-class cell therapy product. As

such, we are establishing new pathways with regulators in defining TIL. I've spent decades developing new classes of drugs and bringing them to market. I know from experience that the road to a successful approval is rarely straightforward. At Iovance we are currently navigating some of these challenges. During a Type B meeting with the FDA to discuss our planned biologics license application (BLA) for lifileucel in metastatic melanoma, we reached agreement with the FDA on the duration of clinical follow up needed to support the BLA submission. We did not reach agreement on the required potency assays to fully define the TIL product. Our top priority is to refine our current potency assays and simultaneously develop additional assays to address the outstanding questions in support of a BLA. I am very pleased with the progress that the Iovance team has made to date toward this important goal.

Defining our regulatory pathway forward is

important for our lead program, lifileucel in metastatic melanoma, as well as for the future of TIL in additional indications and treatment settings. We are steadfast in our commitment of defining patient populations with unmet need and developing new TIL therapies that may offer benefits to patients. During 2020 we made significant progress in development, manufacturing and pre-commercial activities.

TIL PIVOTAL PROGRAMS IN METASTATIC MELANOMA & ADVANCED CERVICAL CANCER

We completed patient dosing in our pivotal cohort

• from our C-144-01 clinical study in metastatic melanoma in January 2020. In May 2020 we reported early pivotal Cohort 4 data which was comparable to Cohort 2 data at approximately similar follow up of six months. At ASCO 2020, we presented updated Cohort 2 data showing a 36.4% overall response rate (ORR) and duration of response had not been reached in 66 patients as assessed by investigators. In an Iovance corporate update provided in January 2021, the DOR was still not reached at 28.1 months of median study follow up. Published data shows median overall survival in late-stage melanoma patients may reach seven to eight months. Therefore, these results with lifileucel are highly encouraging.

Despite the COVID-19 pandemic, we also completed enrollment in the C-145-04 study in cervical cancer in our pivotal cohort of patients who progressed

on or after chemotherapy, as well as a second cohort of patients previously treated with anti-PD-1 therapy. Resolution of the potency assay in melanoma is an important next step for our cervical cancer program, after which we intend to meet with the FDA to discuss the next steps toward a potential BLA submission in that indication.

TIL DEVELOPMENT IN NEW INDICATIONS & EARLIER TREATMENT SETTINGS

In non-small cell lung cancer (NSCLC) we believe that the proof of concept for TIL efficacy was well established through the Moffitt TIL data presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting 2020, showing an overall response rate of 25%, including two durable complete responses, and one confirmed durable partial response in 12 evaluable patients. Despite significant advances in first line treatment for NSCLC, patients who progress after anti-PD-1 and chemotherapy

are expected to achieve overall response rate to docetaxel that is approximately 9%. We also initiated a registration-supporting clinical study (IOV-LUN-202) of Iovance TIL in second line NSCLC, a new indication for Iovance. We defined an unmet need patient population without driver mutations who progressed on one prior checkpoint inhibitor and chemotherapy, and separated cohorts according to PD-L1 status.

In head and neck cancer, we presented initial data for TIL in combination with an anti-PD-1 therapy at the Society for the Immunotherapy of Cancer (SITC) 2020 meeting. This cohort is part of a broader strategy to investigate TIL in combination with anti-PD-1 in earlier lines of therapy across multiple solid tumors.

In our ongoing IOV-COM-202 basket study in solid tumors, Cohort 2A is evaluating LN-145 in combination with pembrolizumab in head and neck squamous cell carcinoma (HNSCC). The SITC poster highlighted nine patients with HNSCC who had not previously received treatment with anti-PD-1 but may have received prior chemotherapy. Following LN-145 in combination with pembrolizumab, ORR was 44% and median duration of response had not been reached at 8.6 months of median study follow up. While the data is early, we find the results to be very promising. ORR with anti-PD-1 monotherapy in anti-PD-1-naive head and neck cancer patients ranges from 15-18 percent in the literature. We have since expanded Cohort 2A to include up to 19 patients with HNSCC, and we look forward to gathering additional data to present at an upcoming conference in the future.

Our IOV-COM-202 basket study actively enrolled patients throughout 2020. The COVID-19 pandemic had some impact on our enrollment, primarily cohorts enrolling patients in earlier line treatment settings. IOV- COM-202 now includes seven total cohorts of various TIL products alone or in combination with anti-PD-1 therapy across melanoma, head and neck, and non- small cell lung cancers.

TIL MANUFACTURING &

IOVANCE CELL THERAPY CENTER (iCTC)

More than 450 patients have received Iovance TIL and our manufacturing success rate remains above 90%. In the five years since I joined Iovance, we have transformed TIL from a lengthy academic process to a potentially commercializable product using

a centralized, shorter, and scalable GMP process

yielding a cryopreserved product. These efforts have culminated in the successful construction of our Iovance Cell Therapy Center (iCTC), which is expected to become one of the largest cell therapy manufacturing facilities in the U.S. Less than two years ago we broke ground on this state-of-the-art, 136,000 square foot commercial-scale production facility in Philadelphia. The core and shell of the building and our first set of clean rooms are complete. The iCTC is expected to be operational to produce clinical supply in 2021 and to support commercial supply in 2022, to meet demand for thousands of patients with multiple types of cancers.

TOWARD TIL COMMERCIALIZATION

In anticipation of the launch of lifileucel, our main area of focus remains ensuring a positive patient experience with our product. The Iovance team is currently focused on KOL engagement, site activation and training, TIL education and awareness, patient access, and other readiness activities. Our priority is to ensure launch success while taking a gated approach to commercial readiness expenses and headcount prior to BLA submission.

Our medical affairs team works with a network of treating healthcare professionals (HCPs) and patient advocacy groups to ensure that information about TIL is available to interested organizations. A core commercial team continues to partner with the leading U.S. cancer centers to build their TIL service line capabilities. In addition, our market access team engages with private payers and the Centers for Medicare and Medicaid Services (CMS) to ensure patients may have appropriate and timely access to lifileucel. We believe that HCPs, CMS and payers recognize the unmet need and clinical value of lifileucel, as well as the potential benefits for patients with metastatic melanoma.

ORGANIZATIONAL GROWTH

Our Iovance team totals over 250 employees, of which an impressive 76% have at least a year of cell therapy experience. We have a diverse Board of Directors and management team: 43% of our executives are female, as are 56% of our total employees. In addition, 35% of our executives and 50% of our employees are people of color. I believe that a diverse team of world-class leaders is paramount to success, and I am quite pleased with our highly diverse and competent Iovance team.

We remain focused on our efforts in bringing novel therapies to patients in need. We are closer than ever to delivering the value of TIL to many people with cancer thanks to the valuable contribution of many individuals, including committed shareholders, hardworking employees, clinical investigators, collaboration partners, and patients and patient families who motivate us. We look forward to realizing the shared vision of these individuals in bringing this first in class

cell therapy to patients with solid tumors.

Maria Fardis, Ph.D., M.B.A.

PRESIDENT & CHIEF EXECUTIVE OFFICER

IOVANCE IS COMMITTED TO DEVELOPING COMMERCIALLY AVAILABLE CELL THERAPIES FOR PATIENTS WITH SOLID TUMORS AND HEMATOLOGIC MALIGNANCIES UTILIZING AUTOLOGOUS TUMOR INFILTRATING LYMPHOCYTES (TIL) THAT AMPLIFY AND REJUVENATE THE BODY'S OWN IMMUNE RESPONSE TO ERADICATE CANCER.

OUR UNIQUE TIL TECHNOLOGY PLATFORM HAS ENABLED US TO GENERATE SCALABLE, PERSONALIZED, CELL THERAPIES THAT ARE CURRENTLY IN CLINICAL STUDIES FOR MULTIPLE CANCERS INCLUDING METASTATIC MELANOMA, CERVICAL CANCER, HEAD AND NECK CANCER, NON-SMALL CELL LUNG CANCER, AND CLL.

ESTABLISHED LEADERSHIP IN TIL THERAPY

DEVELOPMENT, MANUFACTURING & POTENTIAL COMMERCIALIZATION

450+

Patients Treated with Iovance TIL

>90%

Manufacturing Success Rate

2

Pivotal Programs

4

Solid Tumor

Indications in Clinic

5

Academic &

Research Collaborations

1 1

BTD RMAT

FOSTERING DIVERSITY IN OUR GROWTH & SUCCESS:

250+

Iovance Employees

2

Female Board Members

43%

Female Executives

56%

Female Employees

35%

Executives of Color

50%

Employees of Color

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

Form 10-K

(Mark One)

• ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2020

• TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transaction period from __________ to __________
  Commission file number: 001-36860

IOVANCE BIOTHERAPEUTICS, INC.

(Exact Name of Registrant as Specified in Its Charter)

Delaware		75-3254381
(State or Other Jurisdiction of			(I.R.S. Employer
Incorporation or Organization)			Identification No.)
999 Skyway Road, Suite 150, San Carlos, California	94070
(Address of Principal Executive Offices)		(Zip Code)
		[phone]
		(Registrant's Telephone Number, Including Area Code)
		Securities registered pursuant to Section 12(b) of the Act:
				Name Of Each Exchange
Title of Each Class	Trading Symbol(s)		On Which Registered
Common Stock, $ 0.000041666 Par Value per Share		IOVA		The Nasdaq Global Market

Securities registered pursuant to Section 12(g) of the Act:

None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes  No 

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes  No 

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes  No 

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes  No 

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule 12b-2 of the Exchange Act.

Large accelerated filer		Accelerated filer 
Non-accelerated filer		Smaller reporting company ☐
		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. 

Indicate by check mark whether the registrant has filed a report on and attestation to its management's assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. 

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common stock, par value $0.000041666 per value		IOVA		The Nasdaq Stock Market, LLC

The aggregate market value of the registrant's common stock held by non-affiliates on June 30, 2020, the last business day of the registrant's most recently completed second fiscal quarter, was approximately $3.7 billion. Shares of common stock held by directors and executive officers and any ten percent or greater stockholders and their respective affiliates have been excluded from this calculation, because such stockholders may be deemed to be "affiliates" of the Registrant. This is not necessarily determinative of affiliate status of other purposes. As of February 17, 2021, there were 146,979,253 shares of the registrant's common stock outstanding.

Documents Incorporated By Reference

Portions of registrant's proxy statement relating to registrant's 2021 Annual Meeting of Stockholders (the "Proxy Statement") to be filed with the Securities and Exchange Commission pursuant to Regulation 14A, not later than 120 days after the close of the registrant's fiscal year, are incorporated by reference in Part III of this Annual Report on Form 10-K. Except with respect to information specifically incorporated by reference in this Annual Report on Form 10-K, the Proxy Statement is not deemed to be filed as part of this Annual Report on Form 10-K.