What is ADOPTIVECell Therapy?Adoptive cell therapy is a living treatment:A type of immunotherapy in which T cells are given to apatient to help the body fight diseases. In cancertherapy, T cells are usually taken from the patient’s ownblood or tumor tissue, grown in large numbers in thelaboratory, and then given back to the patient to helpthe immune system fight the cancer.

ADOPTIVE CELL THERAPYCiteline recently introduced a new Therapeutic Class called "Adoptive cell therapy", enabling more granular searching capabilities to hone in on this exciting cancer immunotherapy that is expanding the horizon of personalized medicine

DNA

Modified gene

Genetic modification of T cells

T cells are removed from patient

Patient received modified T cells

T CELLS

1

2

3

Enhanced immuneresponse

4

Adoptive T Cell therapyHow does it work?

Currently, Citeline classifies adoptive cell therapy (ACT) into three types with their own mechanism of action, namely:

ACT with chimeric antigen receptor modified T cells (CART-T)

ACT with tumor-infiltrating lymphocytes (TIL)

ACT using T cell receptor (TCR) gene therapy

Continuous global rise in research investigating ACT

0

50

100

150

200

250

300TIL

TCR

CAR-T

Tria

l cou

nt

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

Trial per therapy type that started in the last 10 years

457

517

67

10

568

77

18

98

30

10

10

60

4

17

113

14

33

154

16

32

183

15

43

196

Total number of industry vs non-industry sponsored trials

INDUSTRY SPONSORED NON-INDUSTRY SPONSORED

0 100 200 300 400 500

TIL

TCR

CAR-T

Top industry sponsors by ACT type

Celgene/JunoInnovation Cellular TherapeuticsNovartisBellicum TherapeuticsCARsgen Therapeutics

AdaptimmuneGlaxoSmithKlineTakara BioUnum TherapeuticsCell Medica

IovanceBristol-Myers SquibbPrometheus BioscienceWindMil TherapeuticsMerck & Co.

CAR-T cell therapy is the more extensively studied ACT treatment type

The leading diseases for CAR-T therapies are non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL), which are also the indications with two ACTs currently approved: Kymriah (tisgeniecleucel-t) for the treatment of ALL and NHL and Yescarta (axicabtagene ciloleucel) for NHL. Both are CAR-T therapies, launched in the United States and registered in many EU countries.

Alternatively, TIL and TCR therapies have been mostly studied in solid tumor cancers, with the most trials in melanoma.

CAR-T72%

TCR17%

TIL11%

0 50 100 150 200 250 300 350 400

CAR-T

Gastric cancer

Chromic myelogeneous leukemia

Colorectal cancer

Breast cancer

Non-small cell lung cancer

Glioblastoma

Liver cancer

Pancreatic cancer

Hodgkin's leukemia

Acute myelogenous leukemia

Melanoma

Multiple Myeloma

Chronic lymphocytic leukemia

Acute lymphocytic leukemia

Non-Hodgkin's lymphoma

0 10 20 30 40 50

TCR

Myelodysplastic Syndrome

Breast cancer

Colorectal cancer

Esophageal cancer

Non-Hodgkin's lymphoma

Renal cancer

Gastric cancer

Head and neck cancer

Liver cancer

Ovarian cancer

Acute myelogenous leukemia

Solid tumors

Soft tissue sarcoma

Non-small cell lung cancer

Melanoma

0 10 20 30 40 50 60 70 80

TIL

Esophageal cancer

Solid tumors

Glioblastoma

Liver cancer

Gastric cancer

Multiple Myeloma

Soft tissue sarcoma

Pancreatic cancer

Renal cancer

Head and neck cancer

Colorectal cancer

Non-small cell lung cancer

Ovarian cancer

Breast cancer

Melanoma

Source for all figures: Trialtrove®, Pharmaprojects® November 2019

Trial count

Trial count Trial count Trial count

China and the United States hold the leading positions in the ACT pipeline

China has become the top country with the largest number of ACT clinical trials, outpacing the US in recent years primarily due to non-industry trial sponsor activity.

The UK, Germany, France, and Japan follow, but with much lower levels of activity.

>500401 to 50051 to 40031 to 505 to 30<5

*Note: No countries have ACT trial activity that fall into the category of 51 to 400

Geographic distribution of ACT trials