Iovance Biotherapeutics : August 2020.pdf

Investigating the Power of Tumor Infiltrating Lymphocytes for Treatment of Cancer

August 2020

Forward Looking Statements

Certain matters discussed in this presentation are "forward-looking statements" of Iovance Biotherapeutics, Inc. (hereinafter referred to as the "Company," "we," "us," or "our") within the meaning of the Private Securities Litigation Reform Act of 1995 (the "PSLRA"). All such written or oral statements made in this presentation, press releases, filings with the Securities and Exchange Commission ("SEC"), reports to stockholders and in meetings with investors and analysts, other than statements of historical fact, are forward-looking statements and are intended to be covered by the safe harbor for forward-looking statements provided by the PSLRA. Without limiting the foregoing, we may, in some cases, use terms such as "predicts," "believes," "potential," "continue," "estimates," "anticipates," "expects," "plans," "intends," "forecast," "guidance," "outlook," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes and are intended to identify forward-looking statements. These forward-looking statements include, but are not limited to, statements regarding the success, timing, projected enrollment, manufacturing and production capabilities, and cost of our ongoing clinical trials and anticipated clinical 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 of initiation and completion of these trials; the strength of the Company's product pipeline; and the guidance provided for the Company's future cash, cash equivalents, short term investment and restricted cash balances, as well as forecasted operating expenses. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance, achievements and developments to be materially different from those expressed in or implied by these forward-looking statements, including, without limitation, the following substantial known and unknown risks and uncertainties inherent in the Company's business: the COVID-19 pandemic may have an adverse effect on the Company and its clinical trials, including potential slower patient recruitment, inability of clinical trial sites to collect data, inability of the Company or its contract research organizations to monitor patients, as well as U.S. Food and Drug Administration ("FDA") availability due to competing priorities; our ability to achieve long-term profitability and successfully commercialize our products alone or with third parties, as well as our history of operating losses and our expectations that we will continue to incur significant operating losses; our business plan or the likelihood of our successfully implementing such business plan; risks related to the timing of and our ability to successfully develop, submit, obtain and maintain FDA or other regulatory authority approval of, or other action with respect to, our product candidates (including with respect to lifileucel for the treatment of metastatic melanoma, for which we expect to submit a biologics licensing application to the FDA during 2020), and our ability to successfully commercialize any product candidates for which we obtain FDA approval; our clinical trial plans; our need to rely on third parties, including contract research organizations, contract manufacturing organizations and consultants, in connection with the conduct, supervision and monitoring of our clinical trials for our product candidates; preliminary and interim clinical results, which may include efficacy and safety results, from ongoing Phase 2 studies may not be reflected in the final analyses of our ongoing clinical trials or subgroups within these trials; the risk that a slower rate of enrollment may delay the Company's clinical trial timelines or otherwise adversely impact our clinical development activities; the risk that enrollment may need to be adjusted for the Company's trials and cohorts within those trials based on FDA and other regulatory agency input; the new version of the protocol which further defines the patient population to include more advanced patients in the Company's cervical cancer trial may have an adverse effect on the results reported to date; the risk that the results obtained in our ongoing clinical trials may not be indicative of results obtained in future clinical trials or that data within these trials may not be supportive of product approval, including that later developments with the FDA may be inconsistent with already completed FDA meetings; the risk that the FDA may not agree with our approach to expand our cervical cancer trial to include Cohort 2 of the C-145-04 trial; the risk that changes in patient populations may result in changes in preliminary clinical results; the Company's ability or inability to address FDA or other regulatory authority requirements relating to its clinical programs and registrational plans, such requirements including, but not limited to, clinical, safety, manufacturing and control requirements; the risk that regulatory authorities may potentially delay the timing of FDA or other regulatory approval of, or other action with respect to, our product candidates, or that we may be required to conduct additional clinical trials or modify ongoing or future clinical trials based on feedback from the FDA or other regulatory authorities; the risk that the Company's interpretation of the results of its clinical trials or communications with the FDA may differ from the interpretation of such results or communications by the FDA; our ability to obtain and maintain intellectual property rights related to our product pipeline; our ability to successfully implement our research and development programs and collaborations; the acceptance by the market of our product candidates and their potential reimbursement by payors, if approved; our ability to obtain tax incentives and credits and the risk that our existing net operating loss carryforwards and research tax credits may expire or otherwise be limited in use; the success of our manufacturing, license or development agreements; risks related to the Company's ability to maintain and benefit from accelerated FDA review designations, including breakthrough therapy designation or regenerative medicine advanced therapy designation, which may not result in a faster development process or review of the Company's product candidates (and which may later be rescinded by the FDA), and which does not assure approval of such product candidates by the FDA or the ability of the Company to obtain FDA approval in time to benefit from commercial opportunities; the ability or inability of the Company to manufacture its therapies using third party manufacturers or its own facility may adversely affect the Company's potential commercial launch; the results of clinical trials with collaborators using different manufacturing processes may not be reflected in the Company's sponsored trials; our dependence on additional financing to fund our operations and complete the development and commercialization of our product candidates, and the risks that raising such additional capital may restrict our operations or require us to relinquish rights to our technologies or product candidates; the risk that additional expenses may decrease our estimated cash balances and increase our estimated capital requirements; and other factors, including general economic conditions and regulatory developments, not within the Company's control. A further list and description of the Company's risks, uncertainties and other factors can be found in the Company's most recent Annual Report on Form 10-K and the Company's subsequent reports that we file or furnish with the SEC from time to time. Copies of these reports are available online at www.sec.gov or www.iovance.com. The forward-looking statements in this presentation should be considered in light of these risks and uncertainties. All forward-looking statements made in this presentation are based solely on information available to us as of the date of this presentation and the Company undertakes no obligation to publicly update or revise such forward-looking statements, whether as a result of subsequent events, changed circumstances, new information or otherwise.

© 2020, Iovance Biotherapeutics

2

2020 Updates

2020 Recent Updates

Data flow:

Updated Cohort 2 at ASCO

Early pivotal Cohort 4 data in melanoma by investigator

Data showing effect of Moffitt TIL in NSCLC presented at AACR 2020

• 90% manufacturing success rate in over 300 patients

© 2020, Iovance Biotherapeutics

3

TIL: Platform Therapy for Treatment of Solid Tumors

Tumor-Infiltrating

Lymphocytes (TIL) -

Unique Mechanism in

Immuno-oncology

• Highly personalized therapy
• Our own immune system amplified and rejuvenated

Reinfuse Post-	Excise
Lymphodepletion	Tumor

Culture & Expand

with IL-2

© 2020, Iovance Biotherapeutics

4

Iovance Proprietary Centralized, Scalable, and Efficient GMP Manufacturing

1	2	3	4	5	6
Patient Intake	Surgical Resection	NMA-LD	TIL Infusion	IL-2 Infusions	Recovery/Discharge

TIL were generated from skin, lymph nodes, liver, lung, peritoneal, musculo-skeletal, breast, and other organs.

2

Gen 2 Process Time: 22 Days

© 2020, Iovance Biotherapeutics

5

TIL Mechanism of Action

Infusion of	Circulation	Migration
tumor-infiltrating
lymphocytes (TIL)
		Tumor
	TIL	bed

	TIL
Tumor
Peripheral	Blood
blood	vessel

Chemokine Chemokine receptor

© 2020, Iovance Biotherapeutics

Recognition

TIL

Tumor

cell

T-cell Tumor MHC-I receptor antigen

peptide

Lysis

TIL

Lysing

tumor

cell

TIL

Granzyme

Perforin

Lysing

tumor cell

6

Leveraging Tumor Infiltrating Lymphocyte (TIL) to Address Unmet Need

Discovery

Manufacturing Development, Clinical Program Establishment

Pre-Commercialization

2011	2015	2016	2017	2018
TIL therapy conducted	FDA Orphan	First patient dosed	Head & Neck	FDA RMAT
by Steven	Drug Designation	for Gen 1 lifileucel	and Cervical	designation for
Rosenberg/NCI	for lifileucel in	in melanoma	studies began	lifileucel in advanced
published results	malignant melanoma	Gen 2 manufacturing	FDA Fast Track	melanoma received
showing: 56% ORR(1)
and 24% CR rate in		developed and	designation for	FDA EOP2 meeting
melanoma patients,		transferred to CMOs	lifileucel in	for lifileucel held
with durable CRs as			melanoma received	Lifileucel Cohort 2
an early line therapy(2)
			clinical data showed
				38% ORR in 47
				patients, patients
				with average 3.3
				prior lines of therapy
				Two rounds of
				financing conducted:
				over $425 mil raised

2019

First patient dosed for melanoma registrational trial

FDA Fast Track, BTD in cervical

FDA EOP 2 held for lifileucel for cervical

File IND for PBL

in chronic lymphocytic leukemia (CLL), IND cleared and first patient dosed

Clinical IRC data from Cohort 2 of melanoma at SITC shows 35% ORR

2020

TIL manufactured by Moffitt shows 2 durable CRs in post-PD1 NSCLC

Data presentation by investigator for: Cohort 2 at ASCO, early data in Cohort 4 pivotal melanoma

Complete enrollment for registrational program in cervical

Start a registration- directed NSCLC program

Hold pre-BLA meeting with FDA

Submit BLA

for lifileucel for melanoma

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

© 2020, Iovance Biotherapeutics

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Key Highlights for Melanoma Cohort 2 Data

2019: Melanoma Data update at SITC(8 Nov 2019)(1)

Melanoma Cohort 2 showed

36.4% ORR

by investigator and

34.8% ORR

as read by independent review committee (IRC) (N=66)

(1)Sarnaik et al., SITC 2019, P865

(2)Sarnaik et al., ASCO 2020, 10006

2020: Updated Melanoma Data cut

ASCO20

Median DOR not reached at 18.7 months of median study follow up

(investigator assessed) (2)

© 2020, Iovance Biotherapeutics

8

Investment Highlights

Leading cell therapy company focused on treatment of solid tumors

	Potential to be
	the first cell therapy
Large market	approved for solid	Efficient and
opportunity and	tumors in melanoma	scalable proprietary
strong unmet need	and cervical	manufacturing

Broad platform

and wide applications explored through partnerships

• Initial focus in post-checkpoint solid tumors
• Expansion into combinations and earlier lines of therapy
• Five company-sponsored programs in melanoma, cervical, head & neck, non-small cell lung cancer (NSCLC), and CLL indications

• Accelerated path to approval in melanoma and cervical cancer
• Last patient dosed in pivotal trial for melanoma and BLA filing expected 2H 2020
• Melanoma: RMAT, Orphan Drug, and Fast Track
• Cervical: BTD, Orphan Drug and Fast Track

• U.S. and E.U. capacity with contract manufacturers
• Building Iovance 136,000 sq. ft. manufacturing facility in Philadelphia
• Rapid 22-day Gen 2 manufacturing with 90%+ success rate
• 300+ patients treated with Iovance proprietary process

• Investigator-ledprograms to evaluate additional solid tumors or new combinations
• Data from Moffitt TIL in NSCLC as a new indication for Iovance
• Touch points with institutions including NIH/NCI, Moffitt Cancer Center, MD Anderson, Yale, and University of Montreal (CHUM)

© 2020, Iovance Biotherapeutics

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Highly Individualized, Specific & Potent Attack Against Cancer

Leverages and enhances the body's natural defense against cancer using a patient's own Tumor Infiltrating Lymphocytes, or TIL

• Polyclonal: Can recognize multiple neoantigens
• • Effective in heterogeneous solid tumors
  • Data in melanoma, cervical, head & neck, and lung cancers
• Individualized: TIL of each patient is specific and private with little overlap of uCDR3 between patients(1)
• Persistence: 100% of patients had TIL persisting at Day 42(1)
• Immunological memory: No additional maintenance therapy after infusion
• • Responses in treatment naïve and refractory melanoma; including checkpoint refractory
  • Durable complete responses in cervical cancer patients, maintained at 53 and 67 months(2)
  • Durable CRs observed in NSCLC patients beyond one-yearpost-TIL(3)

1. Gontcharova, et al., Persistence of cryopreserved tumor-infiltrating lymphocyte product lifileucel (LN-144) in C-144-01 study of advanced metastatic melanoma, AACR 2019, Abstract #LB-069
2. Stevanovic, et al., Treatment of Metastatic Human Papillomavirus-Associated Epithelial Cancers with Adoptive Transfer of Tumor-Infiltrating T Cells, ASCO 2018, Abstract #3004
3. Creelan, et. al., Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): a phase I trial, AACR 2020, Abstract #20-LB-10617

© 2020, Iovance Biotherapeutics

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Competitive Advantages of TIL in Solid Tumors

Checkpoints	TCR	CAR-T	TIL
(Liquid tumors)	(Solid tumors)
Target multiple	Target only single	Mainly target only single/	Target multiple tumor antigens
tumor antigens	tumor antigen	surface tumor antigen
Long maintenance period	One-time treatment	One-time treatment	One-time treatment
Utility in several	Few solid tumors	No examples of successful	Available data in: melanoma, cervical,
solid tumors	treated so far	utility in solid tumors	head & neck, and lung cancers
Potential long-term	Potential on-target,	Potentially immunogenic:	No unexpected off-tissue
irreversible toxicities	off-tissue effects	cytokine release syndrome	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

© 2020, Iovance Biotherapeutics

11

Broad, Iovance-Owned IP Around TIL Therapy

Manufacturing

Twelve granted U.S. patents for compositions and methods of treatment

in a broad range of cancers relating to Gen 2 manufacturing process including combinations with PD-1 antibodies

Advanced Technologies

Patent applications filed for a wide range of TIL technologies including:

• Marrow infiltrating (MIL) and peripheral blood lymphocyte therapies (PBL)
• Novel manufacturing processes including selected TIL process
• Use of costimulatory molecules in TIL therapy
• Stable and transient genetically-modified TIL therapies
• Patient subpopulations for TIL therapies

© 2020, Iovance Biotherapeutics

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Iovance Cell Therapy Center (iCTC)

• Build-to-suitcustom facility located in the Navy Yard, Philadelphia, PA
• ~136,000 sq. feet, $85 mil investment
• Clean room build initiated April 2020
• Commercial GMP production is expected to commence in 2022
• Significant reduction in COGS expected

© 2020, Iovance Biotherapeutics

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Significant Market Potential in Solid Tumors

90%

of all cancer cases are solid tumors

1.6M

New cases of solid tumors in the U.S.(1)

1. https://seer.cancer.gov

Expand into other indications

Move into earlier line of therapy

Solid Tumor Indication	Deaths(1)	New Cases(1)
Melanoma	7,230	96,480
Cervix Uteri	4,250	13,170
Lung & Bronchus	142,670	228,150
Oral Cavity, Pharynx & Larynx	10,860	53,000
Breast	41,760	268,600
Pancreatic	45,750	56,770
Brain & Other Nervous System	17,760	23,820
	Potential to	Potential market
	address unmet	for early lines in
	need in late lines	combo with
	of treatment	standard of care

© 2020, Iovance Biotherapeutics

14

Current Clinical Pipeline and Select Collaboration Studies

	Regimen	Trial	Indication	N	Partner	Phase 1	Phase 2	Pivotal
	Lifileucel	C-144-01	Melanoma	178	-
	Lifileucel	C-145-04	Cervical cancer	138	-
	LN-145/LN-145-S1	C-145-03	Head & neck cancer	55	-
Company	Lifileucel + pembrolizumab		Melanoma
sponsored	LN-145-S1		Melanoma
studies	LN-145 + pembrolizumab	IOV-COM-202	Head & neck	~75	-
	LN-145 + pembrolizumab		Non-small cell lung
	LN-145		Non-small cell lung
			Chronic
	IOV-2001	IOV-CLL-01	lymphocytic	~70	-
			leukemia
	MDA TIL	NCT03610490	Ovarian, colorectal,	~54
	pancreatic
Select investigator
sponsored
proof-of-concept	LN-145	NCT03449108	Ovarian, sarcomas	~54
studies
	Moffitt TIL + nivolumab	NCT03215810	Non-small cell lung	20
		© 2020, Iovance Biotherapeutics					15

Metastatic Melanoma

© 2020, Iovance Biotherapeutics

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Potential Market for Metastatic Melanoma

• Estimated 7,230(1) U.S. patient deaths due to melanoma
• Limited options after progression on checkpoint and BRAF/MEK inhibitors

Nature has selected TIL to recognize features unique to the tumor not present on normal tissues, which helps make a TIL therapy approach effective compared to other cell therapy strategies for solid tumors. Iovance TIL treatment has a novel mechanism of action, completely separate from those of other treatment options, and has resulted in highly durable responses in patients that have progressed on prior FDA-approved treatment for their metastatic melanoma."

- Dr. Amod Sarnaik

Department of Cutaneous Oncology,

the Immunology Program and the Melanoma

Center of Excellence at Moffitt Cancer Center

Metastatic Melanoma Facts

309k	each year(3)		62k	each year(3)
	New Cases WW			Deaths WW
96k	Diagnoses in U.S.		7k	Deaths in U.S.
each year(1)		each year(1)
1st line:	BRAF/MEK		Chemotherapy
inhibitors for
Immuno		ORR 4-10%(2)
BRAF
-therapy		OS ~7-8 mons(4)
positive

1. in 2019,https://seer.cancer.gov;
2. CheckMate-37Trial Results (ICC 10%), Keytruda label (4%);
3. JAMA Oncol. 2019; 5(12):1749-1768. doi:10.1001/jamaoncol.2019.2996;
4. Eur J Cancer. 2016; 65:182-184. J Clin Oncol. 2018; 36 (suppl: abstr e21588)

© 2020, Iovance Biotherapeutics

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C-144-01: Phase 2 Study Design

Unresectable or metastatic melanoma treated with 1 systemic prior therapy including a PD-1 blocking antibody and if BRAF V600 mutation positive,

a BRAF or

BRAF/MEK

Cohort 1:

Non-cryopreserved TIL product (Gen 1) N=30

Closed to enrollment

Cohort 2:

Cryopreserved

TIL product (Gen 2) N=60

Closed to enrollment

Cohort 4:

Pivotal

Cryopreserved

TIL product (Gen 2) N=75

Closed to enrollment

Cohort 3:

TIL re-treatment

N=10

Endpoints

• Primary: Efficacy defined as IRC ORR

Study Updates

• Mar 2019: Cohort 4 (pivotal trial) FPI
• Jun 2019: Full Cohort 2 data on 66 patients presented at ASCO
• Nov 2019: IRC Cohort 2 data presented at SITC
• Nov 2019: Investigator read of
  Cohort 2 sub-analysis for primary refractory to PD-1 presented
• Jan 2020: last patient dosed
• May 2020: Cohort 4 early data show 32.4% ORR at 5.3 months of median study follow up
• May 2020 ASCO oral: Cohort 2 median DOR not reached at 18.7 months of median study follow up

© 2020, Iovance Biotherapeutics

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COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01: Cohort 2 Patient Characteristics at ASCO 2020

CHARACTERISTIC	Cohort 2, N=66, (%)
Gender, n (%)
Female	27 (41)
Male	39 (59)
Age, years
Median	55
Min, Max	20, 79
Prior therapies, n (%)
Mean # prior therapies	3.3
Anti-PD-1	66 (100)
Anti-CTLA-4	53 (80)
BRAF/MEK	15 (23)
Progressive Disease for at least 1 prior therapy
Anti-PD-1	65 (99)
Anti-CTLA-4	41 (77(1))
Baseline ECOG score, n (%)
0	37 (56)
1	29 (44)

CHARACTERISTIC	Cohort 2, N=66, (%)
BRAF Status, n (%)
Mutated V600	17	(26)
Wild Type	45	(68)
Unknown	3	(5)
Other	1	(2)
Baseline LDH (U/L)
Median	244
1-2 times ULN	19	(29)
> 2 times ULN	8 (12)
Target Lesions Sum of Diameter (mm)
Mean (SD)	106 (71)
Min, Max	11, 343
Number of Target and Non-Target Lesions (at Baseline)
>3	51	(77)
Mean (SD)	6 (2.7)
Patients with Baseline Liver and/or Brain	28	(42)
Lesions

Cohort 2 patients have:

• 3.3 mean prior therapies, ranging from 1-9
• High tumor burden at baseline: 106 mm mean sum of diameters of the target lesions

(1)The denominator is the 53 patients who received prior anti-CTLA-4

© 2020, Iovance Biotherapeutics

19

COHORT 2 BY INVESTIGATOR (ASCO 2020)

Adverse Events Tend to be Expected, Early and Transient

• Adverse event profile consistent with underlying advanced disease and safety profile of lymphodepletion and IL-2 regimens
• Median number of 6 IL-2 doses administered
• Decreasing frequency of AEs over time reflective of potential benefit of one-time treatment with lifileucel

Treatment Emergent Adverse Events (≥ 30%)

	Cohort 2 (N=66)
Preferred term	Any Grade, Grade 3/4,	Grade 5,
n (%)	n (%)	n (%)
Number of patients
reporting at least one	66 (100)	64	(97.0)	2 (3.0)
Treatment-Emergent AE
Thrombocytopenia	59 (89.4)	54	(81.8)	0
Chills	53 (80.3)	4 ( 6.1)	0
Anemia	45 (68.2)	37	(56.1)	0
Pyrexia	39 (59.1)	11	(16.7)	0
Neutropenia	37 (56.1)	26	(39.4)	0
Febrile neutropenia	36 (54.5)	36	(54.5)	0
Hypophosphatemia	30 (45.5)	23	(34.8)	0
Leukopenia	28 (42.4)	23	(34.8)	0
Fatigue	26 (39.4)	1 ( 1.5)	0
Hypotension	24 (36.4)	7	(10.6)	0
Lymphopenia	23 (34.8)	21	(31.8)	0
Tachycardia	23 (34.8)	1 ( 1.5)	0

*The number of AEs is cumulative and represent the total number of patients dosed

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 term. Safety terms which describe the same medical condition were combined.

© 2020, Iovance Biotherapeutics

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COHORT 2 BY INVESTIGATOR (ASCO 2020)

Potentially Efficacious Treatment for Patients with Limited Options

In heavily pretreated metastatic melanoma patients (3.3 mean prior therapies)

• ORR 36%
• DCR 80%
• Median DOR has not been reached at 18.7 mons of study follow up
• Mean TIL cells infused: 27.3 x 109
• Median number of IL-2 doses: 5.5

Response	Patients, N=66
	n (%)
Objective Response Rate	24	(36.4)
Complete Response		2 (3.0)
Partial Response	22	(33.3)
Stable Disease	29	(43.9)
Progressive Disease	9	(13.6)
Non-Evaluable(1)		4 (6.1)
Disease Control Rate	53	(80.3)
Median Duration of Response	Not Reached
Min, Max (months)	2.2, 26.9+

18% attrition in patients harvested (6% manufacturing failure)

© 2020, Iovance Biotherapeutics

21

COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01 Cohort 2 Efficacy: Best Overall Response

79% of responders had received prior ipilimumab. Responses deepen over time.

1. BOR is best overall response on prior anti-PD-1 immunotherapy. (2) U: unknown. (3) Patient 22 BOR is PR.

© 2020, Iovance Biotherapeutics

22

COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01 Cohort 2 Efficacy: Best Overall Response

81% (50/62) of patients had a reduction in tumor burden

• Mean Time to response 1.9 months (range 1.3-5.6)
• Responses are deep - nearly all responders are >30%

*Patients with BRAF mutations

Three subjects had no post TIL disease assessment due to early death, and one due to start of new anti-cancer therapy.

© 2020, Iovance Biotherapeutics

23

COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01 Cohort 2 ORR By Subgroup

Responses were demonstrated:

• Across a wide age range

• Even in patients who have progressed on prior anti-CTLA-4 or prior BRAF

• Regardless of the BRAF mutational status

• Equally in patients with PD-L1 low or high levels

CI, Confidence interval.

95% CI is calculated using the Clopper-Pearson Exact test.

© 2020, Iovance Biotherapeutics

24

COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01 Cohort 2 ORR By Subgroup

Responses were demonstrated:

• In patients with elevated LDH (1-2x)

• In patients with bulky disease at baseline

• Patients with lesions in liver and/or brain

• Patients post anti-PD-1 regardless of duration of time from the patient's last anti-PD-1/L1

ULN, Upper Limit Normal; CI, Confidence interval.

95% CI is calculated using the Clopper-Pearson Exact test.

© 2020, Iovance Biotherapeutics

25

COHORT 2 BY INVESTIGATOR (ASCO 2020)

C-144-01 Cohort 2: Conclusions

• In heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD-1 and BRAF/MEK inhibitors, if BRAFV600 mutant, lifileucel treatment results in:
• • 36.4% ORR
  • 80.3% DCR
  • Median DOR was still not reached at 18.7 months of median study follow up
• Responses deepen over time

Lifileucel has demonstrated potential efficacy and durability of response for patients with metastatic melanoma regardless of prior therapy with immune checkpoint therapies, or BRAF status

© 2020, Iovance Biotherapeutics

26

Late Stage (2L/3L) Melanoma Treatment Development Efforts

2L/3L melanoma treatment has no current standard of care

Combination with Anti-PD-1

Single Agent

Agent	ORR % (N)	Current Development Status	Prior Lines of Tx	Patient Characteristics
Checkpoints
			1+	All comers, ECOG ≤2
LAG-3 + nivo (BMS)	12% (N=61)(1)	Multiple 1L studies	• LAG-3 expression ≥1% (N=33) ORR=18%;
				• LAG-3 expression <1% (N=22) ORR=5%
TLR9 agonists, HDAC
IMO-2125 (Idera) + ipi	22% (N=49)(2)	Phase 3, post-PD-1 melanoma	1-3	ECOG ≤1, intratumoral injection
ILLUMINATE 204	Median DOR was 11.4 months
CMP-001 (CheckMate) + pembro	25% (N=82)(3)	Phase 1b	1+	ECOG ≤1, intratumoral injection
SD-101 (Dynavax) + pembro	19% (N=31)	Phase 1b/2 (abandoned)(8)	1+	2mg, 1-4 lesions, 8 mg 1 lesion
13% (N=30)(4)	ECOG ≤1 intratumoral injection
Entinostat (Syndax) + pembro	19% (N=53)(5)	ENCORE 601	1+	ECOG ≤1
Checkpoints
TIGIT, TIM-3	Unknown	Phase 1/2
Cytokines
HD IL-2	8% (N=9)(6)		1+	HD IL-2 post anti-PD1
Other
TIL	36.4% (N=66)(7)	Phase 2, continuing to	3.3	All post anti-PD1
enroll pivotal trial

1. Ascierto P et al., ESMO 2017; (2) Idera Pharmaceuticals Press Release April 21, 2020; (3) Milhem M et al., SITC 2019; (4) Amin et al., ASCO 2019, Abstract 9555;

1. Ramalingam et al., AACR 2019; (6) Buchbinder EI et al., JCO 2017; (7) Sarnaik et al., SITC 2019; (8) DVAX press release May 23, 2019

© 2020, Iovance Biotherapeutics

27

Cervical Cancer

© 2020, Iovance Biotherapeutics

28

Potential Market for Cervical Cancer

TIL immunotherapy with lifileucel 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

Cervical Cancer Facts

601k	each year(1)	260k	each year(1)
	New Cases WW		Deaths WW
13k	Diagnoses in	4k	Deaths in U.S.
U.S. each year(2)	each year(2)

potentially life extending new treatment. This is the most exciting news in this field in decades."

- Amir Jazaeri, M.D.

Available care:

Chemo -therapy

as first line option

For PD-L1 + patients, post- chemo receiving

Keytruda(3)

ORR 14.3%

Available Care

for chemotherapy in 2L metastatic cervical patients

4.5-13%(4)(5)

Director of the Gynecologic Cancer

Immunotherapy Program in the

Department of Gynecologic Oncology and

Reproductive Medicine at MD Anderson

1. JAMA Oncol. 2019;5(12):1749-1768. doi:10.1001/jamaoncol.2019.2996;
2. https://seer.cancer.gov/
3. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
4. Schilder et al., Gynecologic Oncology2005;
5. Weiss, et al., A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: A Southwest Oncology Group Study

© 2020, Iovance Biotherapeutics

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C-145-04: Pivotal Phase 2 Trial in Cervical Cancer

Phase 2, multicenter study to evaluate the efficacy and safety of autologous TIL (lifileucel, formerly LN-145) in patients with recurrent, metastatic or persistent cervical carcinoma (NCT03108495)

Cervical Cancer		Cohort 1
progressed on at least 1		Pivotal
prior systemic therapy		TIL
excluding checkpoint		N=75
Cervical Cancer progressed		Cohort 2
	TIL
on prior anti-PD-1/PD-L1
	N=24
Cervical Cancer with		Cohort 3
	TIL + pembro
no prior systemic therapy
	N=24
		Cohort 4
		TIL
		previously enrolled pts e.g., Gen 1 TIL
		Cohort 5
		TIL
		Retreatment

Endpoints

• Primary: ORR as determined by IRC
• Secondary: safety and efficacy

Study Updates

• March 2019: Fast Track designation
• May 2019: Breakthrough Therapy Designation
• June 2019: ASCO data presentation
• June 2019: FDA EOP2 held-existing study may be sufficient to support registration of lifileucel
• July 2019: Study expanded to enroll a total of 75 patients
• November 2019: Additional cohorts added (Cohorts 2-5)

© 2020, Iovance Biotherapeutics

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Lifileucel in Cervical Cancer Interim Update at ASCO 2019

Key Inclusion Criteria

• Recurrent, metastatic or persistent cervical carcinoma with at least 1 prior therapy
• Age ≥ 18

Endpoints

• Primary: efficacy defined as ORR by IRC per RECIST 1.1
• Secondary: safety and efficacy

Study Updates

• Fast Track and BTD received
• EOP2 meeting held with FDA

Baseline Demographics	N=27 (%)
Prior therapies
Mean # prior therapies		2.4
Platinum-based	27 (100)
Taxane	26	(96)
Anti-VEGF	22	(82)
PD-1/PD-L-1	4 (15%)
Target lesions sum of diameter (mm)
Mean (SD)	61	(38)
Min, Max	10, 165
Histologic Cell Type, n (%)
Squamous Cell Carcinoma	12	(44)
Adenocarcinoma	12	(44)
Adenosquamous Carcinoma	3 (11)
Number of target & non-target lesions (at baseline)
>3	17	(63)
Mean (min,max)	4 (1,9)

© 2020, Iovance Biotherapeutics

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Adverse Events Tend to be Early and Transient

Frequency of AEs over time is reflective of potential benefit of one-time treatment with TIL (lifileucel)

	N=27
	Any Grade,	Grade 3/4,	Grade 5,
Preferred Term		n (%)		n (%)	n (%)
Number of patients reporting at	27 (100)	26	(96.3)	0
least one Treatment-Emergent AE**
Chills	21	(77.8)		0	0
Anemia	15	(55.6)	15	(55.6)	0
Diarrhea	14	(51.9)		2 (7.4)	0
Pyrexia	14	(51.9)		1 (3.7)	0
Thrombocytopenia	14	(51.9)	12	(44.4)	0
Neutropenia	11	(40.7)	8	(29.6)	0
Vomiting	11	(40.7)		1 (3.7)	0
Hypotension	10	(37.0)	4	(14.8)	0
Dyspnea	9	(33.3)		1 (3.7)	0
Febrile neutropenia	9	(33.3)	8	(29.6)	0
Hypoxia	9	(33.3)	3	(11.1)	0
Leukopenia	9	(33.3)	6	(22.2)	0
Hypomagnesemia	8	(29.6)		0	0
Sinus tachycardia	8	(29.6)		0	0

Adverse Events Over Time

*The number of AEs is cumulative and represent the total number of patients dosed

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 term. Safety terms which describe the same medical condition were combined;

© 2020, Iovance Biotherapeutics

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Significant Response Observed in Patients with Limited Options

In heavily pretreated cervical cancer patients (2.4 mean prior therapies)

• CR 11%
• ORR 44%
• DCR 85%
• Median DOR has not been reached
  • Median follow-up 7.4 months
• Mean TIL cells infused: 28 x 109
• Median number of IL-2 doses: 6.0

Responses	N=27 (%)
Objective Response Rate	12	(44%)
Complete Response	3 (11%)
Partial Response	9	(33%)
Stable Disease	11	(41%)
Progressive Disease	4	(15%)
Non-Evaluable		0
Disease Control Rate	23	(85%)

© 2020, Iovance Biotherapeutics

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Responses Observed Early On and Consistent with Melanoma

Lifileucel time to response and current duration for evaluable patients (partial response or better)

• Mean time to first response 1.9 months

• Mean time to best response 2.4 months

© 2020, Iovance Biotherapeutics

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Three Complete Responses Observed with Lifileucel

Lifileucel best overall response rate

• 78% of patients had a reduction in tumor burden

• Mean time to response 1.9 months

• All assessments are by RECIST 1.1

• Responses are deep with majority of responders are over 30%

© 2020, Iovance Biotherapeutics

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Development Efforts in Recurrent, Metastatic or Persistent Cervical Carcinoma

Recurrent, metastatic, or persistent cervical carcinoma has no current standard of care

Agent	ORR % (N)	Current Dev Status	Prior Line of Tx	Patient Characteristics
Antibody-drug conjugate
tisotumab vedotin (TV)				Recurrent or metastatic cervical cancer
24%			that progressed on standard therapy
(Genmab/Seattle	Phase 2	1+
(N=101)(1)	(most had received at least two prior therapies),
Genetics)
			median DOR=8.3 months
Anti-PD-1
AGEN2034	11.4%			Patients must have relapsed after a
Phase 2	1+	platinum-containing doublet administered for treatment
(Agenus)	(N=44)(2)
		of advanced disease
cemiplimab	10% (N=10)(3)	Phase 3	2+	Recurrent or metastatic cervical cancer resistant to, or
(Regeneron)	intolerant of, platinum therapy
TKI
neratinib	27% (N=11)(4)	Phase 2	2	Metastatic HER2-positive cervical cancer (percentage
(Puma Biotechnology)	of HER2+ in cervical cancer is ~3.9%)(5)
Cell therapies
				All patients progressed on or after chemo; median
TIL (lifileucel)	44% (N=27)	Phase 2	2.4 (mean)	DOR not reached (median follow-up 7.4 months)

1. Seattle Genetics Press Release, 6/29/20; (2) Drescher, et al. ESMO 2018; (3) Rischin, D. et al. ESMO 2018; (4) D'Souza et al. SGO 2019; (5) Yan, et al. Cancer Metastasis Rev. 2015

© 2020, Iovance Biotherapeutics

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Additional Solid Tumor Studies

© 2020, Iovance Biotherapeutics

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Non-Small Cell Lung Cancer (NSCLC)

© 2020, Iovance Biotherapeutics

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Moffitt NSCLC TIL plus Nivo (AACR 2020)

Efficacy Data Post Moffitt TIL Infusion

Responses	N=12 (%)
Objective Response Rate	3 (25%)
Complete Response	2 (17%)
Partial Response	1 (8%)

• ORR 25%;
• • 1 CR is noted in EGFRΔEx19 post afatinib, osimertinib, nivolumab
  • 1 additional uPR may confirm to increase the ORR to 33%
• Median DOR not reached;
• • All 3 responders on TIL were relapsed or refractory to monotherapy Nivo
  • The TIL CR responses were ongoing
  • 2/3 responders were PD-L1 low (TPS<5%)

© 2020, Iovance Biotherapeutics

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Moffitt NSCLC TIL plus Nivo (AACR 2020)

Moffitt TIL in Post-Nivolumab NSCLC

Nivolumab and Tumor Infiltrating Lymphocytes (TIL) in Advanced Non-Small Cell Lung Cancer (NCT03215810)

Post-TIL

SD

PD Unconfirmed PR

PR

CR

	change vs. preTIL baseline	60					n=12 evaluable
Best Overall Response	40	**
20
0
-20
-40
-60
-80
	%	-100
	Subject ID	14	32	07	01	04 31 05 08	16	02	25	09

Last RR PD PD PD* PD PD PD PD SD PS PS PS PD* on Prior Nivo

In 12 evaluable patients with advanced

NSCLC who received nivolumab and TIL:

• Two CRs out to one year
• • (PD-L1low=1, EGFR mutation=1)
• ORR 25% (or 33% if a uPR confirms)

1. Creelan, et. al., Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): a phase I trial, AACR 2020, Abstract #20-LB-10617

© 2020, Iovance Biotherapeutics

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IOV-COM-202

TIL in Earlier Lines of Therapy in Combination with SOC

• prospective, open-label,multi-cohort,non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144(Lifileucel)/LN-145 in combination with pembrolizumab or TIL LN-145/LN-145-S1 as a single therapy (NCT03645928)

Melanoma: PD-1/PDL-1 Naïve

Melanoma: ≥ 1 Prior Systemic Therapy (including anti-PD1 and BRAF)

Head & Neck: PD-1/PDL-1 Naïve

NSCLC: PD-1/PDL-1 Naïve

NSCLC: 1-3 Prior Systemic Therapies (including CPI and TKI)

Melanoma	Cohort 1A:
	TIL+ pembro, N=12
Melanoma
Cohort 1B:
	TIL (LN-145-S1), N up to 27
Head & Neck
Cohort 2A:
	TIL+ pembro, N=12
NSCLC	Cohort 3A:
	TIL+ pembro, N=12
NSCLC	Cohort 3B:
	TIL, N=12

Endpoints

• Primary: ORR and safety
• Secondary: CR rate

Study Updates

• 28 sites are activated globally
• Sites in the U.S., Canada and Europe

© 2020, Iovance Biotherapeutics

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Research Focus into Next Generation TIL

Expand the TIL platform into new indications/regimens

• First patient dosed in Phase 1/2 study for PBL in CLL
• IOV-3001IL-2 analog licensed from Novartis

Select more potent TIL

• PD-1positive selected TIL by Iovance
• PD-1positive selected TIL also through collaboration with CHUM

Genetically modify to make a more tumor-reactive TIL

• Cellectis TALEN® collaboration agreement in place to support a clinical program

Process optimization

• Gen 3 (16-day) process
• Core biopsy

© 2020, Iovance Biotherapeutics

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Iovance Biotherapeutics Global Reach and Scale

San Carlos, CA

Iovance Biotherapeutics has >200 employees

• Headquartered in San Carlos, CA
• 3 additional offices
• Iovance commercial manufacturing facility in Philadelphia, PA
  (under construction)

Corporate Headquarters

Business Office or Subsidiary

Iovance Manufacturing Site

New York City, NY

Philadelphia, PA

Tampa, FL

Zug, CH

© 2020, Iovance Biotherapeutics

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Well Capitalized in Pursuit of TIL Commercialization

June 30, 2020	In millions
(unaudited)
Common shares outstanding	146(1)
Preferred shares	4(2)
Options	12
Cash, cash equivalents, short-term investments, restricted cash	$777.4(3)
Anticipated year-end cash balance	>$630(3)
Debt

1. Includes May 2020 offering of 19,475,806 shares of common stock
2. Preferred shares are shown on an as-converted basis
3. Includes Restricted Cash of $5.5 million

© 2020, Iovance Biotherapeutics

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Milestones 2020

• Last patient dosed in Cohort 4 for lifileucel in support of registration in melanoma
• Data presentation at ASCO for long term follow up of melanoma Cohort 2
• Early cohort 4 data from melanoma

Last patient dosed in pivotal program of lifileucel for cervical cancer

Hold a pre-BLA meeting with FDA

Submit BLA for melanoma

Initiate NSCLC registration-supporting study

© 2020, Iovance Biotherapeutics

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Thank You