Gene, Cell, + RNA Therapy Landscape Report

Q1 2024 Quarterly Data ReportAbout the authors
The American Society of Gene & Cell Therapy (ASGCT) is the primary professional
membership organization for scientists, physicians, patient advocates, and otherprofessionals with interest in gene and cell therapy.
Our members work in a wide range of settings including universities, hospitals,
government agencies, foundations, biotechnology, and pharmaceuticalcompanies. ASGCT advances knowledge, awareness, and education leading to thediscovery and clinical application of gene and cell therapies to alleviate human disease
to benefit patients and society.
Citeline, a Norstella company, powers a full suite of complementary businessintelligence offerings to meet the evolving needs of life science professionals toaccelerate the connection of treatments to patients and patients to treatments.
These patient-focused solutions and services deliver and analyze data used to drive
clinical, commercial, and regulatory-related decisions and create real-world
opportunities for growth.
Our global teams of analysts, journalists, and consultants keep their fingers on thepulse of the pharmaceutical, biomedical, and medtech industries, covering it all withexpert insights: key diseases, clinical trials, drug R&D and approvals, market
forecasts, and more. For more information on one of the world’s most trusted life
science partners, visit Citeline.

Table of contents
4

Introduction

5

Key takeaways from Q1 2024

6

Key highlights in Q1 2024

16

Pipeline overview

18

Gene therapy pipeline26

Non-genetically modified cell therapy
pipeline

31

RNA therapy pipeline

37

Overview of dealmaking

40

Start-up funding

44

Upcoming catalysts

46

AppendixIntroduction
Following a landmark close to 2023, the cell and gene therapy field has continued its impressive momentum in the firstquarter of 2024 with several notable approvals and strong growth in all stages of clinical development.
The field earned the approval of three new therapies—a CAR-T therapy for myeloma in China, an AAV gene therapy forhemophilia B in Canada, and an autologous cell therapy for melanoma in the United States.
Excitingly, there are now more than 4,000 gene, cell, and RNA therapies in development. We also recorded significant
increases in the number of therapies across all three phases of development in the clinical pipeline, with notable
growth (11 percent) in Phase I programs.
While overall dealmaking rebounded with a 34 percent increase in transactions, the start-up financing landscapecontinued to face challenges. Both the number and total value of seed and Series A rounds declined in Q1.
Nevertheless, the breadth of progress across approvals, clinical development, and the broader ecosystem underscores
the progress, promise, and vitality of cell and gene therapy.
David Barrett, JD
CEO, ASGCT

4 / Q1 2024

Key takeaways from Q1 2024
Three new approvals headline Q1 2024 in the advanced therapy landscape••Two new gene therapies were approved: CT-053 (zevorcabtagene autoleucel), a CAR-T therapy
developed by CARsgen, was approved for myeloma in China; and Beqvez, an AAV gene therapy
developed by Pfizer, was approved for hemophilia B in Canada
Amtagvi, an autologous cell therapy developed by Iovance Biotherapeutics, was approved formelanoma in the US

The past quarter was one of growth at the clinical development stage (Phase I–III), in particular forgene therapies••

The number of therapies at all three phases of clinical pipeline development has increased since theend of 2023
Phase I therapy numbers in particular saw their greatest growth (11%) since prior to Q4 2022

Overall dealmaking rebounded for advanced molecular therapy companies, but start-up financing
continued to slow•••

5 / Q1 2024

The sector saw a 34% increase in total deals in Q1 2024, reaching 125 transactions, up from 93 in theprevious quarter
Driving this increase was a substantial jump in total financings; however, start-ups raising seed or
Series A funds continued the downward trend seen in previous quarters
Start-up volume declined by 33% to eight transactions in Q1 2024, and had a nearly 3x decrease invalue to $240.1m

Q1 2024

Key highlights in Q1 2024

Approved gene, cell, and RNA therapies
Globally, for clinical use:
• 32 gene therapies have been approved(including genetically modified cell therapies)

Approved gene, cell, RNA therapies• In Q1 2024, CT-053 (CARsgen) was approved for
myeloma in China, and Beqvez (Pfizer) was approvedfor hemophilia B in Canada• 28 RNA therapies have been approved• 68 non-genetically modified cell therapies have been
approved• In Q1 2024, Amtagvi was approved in the US for thetreatment of melanoma

Gene therapies

Source: Pharmaprojects | Citeline, April 2024
7 / Q1 2024

RNA therapies

Cell therapies (non-genetically modified)Approved gene therapies as of Q1 2024 (1/3)
Product name

Generic nameYear first approved Disease(s)Locations approved

Originator company

Gendicine

recombinant p53 gene

2004

Head and neck cancer

China

Shenzhen SiBiono GeneTech

Oncorine

E1B/E3 deficient adenovirus

2005

Head and neck cancer; nasopharyngeal
cancerChina

Shanghai Sunway Biotech

Rexin-Gmutant cyclin-G1 gene

2006

Solid tumors

Philippines

Epeius Biotechnologies

Neovasculgenvascular endothelial growth
factor gene

2011

Peripheral vascular disease; limb ischemia

Russian Federation, Ukraine

Human Stem Cells Institute

Imlygic

talimogene laherparepvec

2015

Melanoma

US, EU, UK, Australia

Amgen

Strimvelis

autologous CD34+ enriched cells

2016

Adenosine deaminase deficiency

EU, UK

Orchard Therapeutics

US, EU, UK, Japan, Australia,
Canada, South Korea,
Switzerland

Novartis

Kymriahtisagenlecleucel-t

2017

Acute lymphocytic leukemia; diffuse large
B-cell lymphoma; follicular lymphoma

Luxturna

voretigene neparvovec

2017

Leber’s congenital amaurosis; retinitis
pigmentosa

US, EU, UK, Australia, Canada,South Korea, Japan

Spark Therapeutics (Roche)

Yescarta

axicabtagene ciloleucel

2017

Diffuse large B-cell lymphoma; nonHodgkin’s lymphoma; follicular lymphoma

US, EU, UK, Japan, Canada,
China, Australia

Kite Pharma (Gilead)

Collategene

beperminogene perplasmid

2019

Critical limb ischemia

Japan

AnGes

Zolgensma

onasemnogene abeparvovec

2019

Spinal muscular atrophy

US, EU, UK, Japan, Australia,
Canada, Brazil, Israel, Taiwan,
South Korea

Novartis

Zynteglo

betibeglogene autotemcel

2019Transfusion-dependent beta thalassemia

US

bluebird bio

Source: Pharmaprojects | Citeline, April 2024
8 / Q1 2024

Text highlighted in yellow represents new approvals during Q1 2024

Approved gene therapies as of Q1 2024 (2/3)
Product name

Generic nameYear first approved

Disease(s)Tecartus

brexucabtagene autoleucel

2020

Libmeldy

atidarsagene autotemcel

2020

Breyanzi

lisocabtagene maraleucel2021

Abecmaidecabtagene vicleucel

2021

Multiple myeloma

Delytact

teserpaturev

2021

Malignant glioma

Relma-celrelmacabtagene autoleucel

2021

Diffuse large B-cell lymphoma; follicularlymphoma

China

JW Therapeutics

Skysonaelivaldogene autotemcel

2021

Early cerebral adrenoleukodystrophy(CALD)

US

bluebird bio

Carvykti

ciltacabtagene autoleucel

2022

Multiple myeloma

US, EU, UK, Japan, Australia,
China

Legend Biotech

Upstazaeladocagene exuparvovec

2022

Aromatic L-amino acid decarboxylase(AADC) deficiency

EU, UKPTC Therapeutics

Roctavianvaloctocogene roxaparvovec

2022

Hemophilia A

EU, UK, US

BioMarin

Hemgenixetranacogene dezaparvovec

2022

Hemophilia B

US, EU, UK, Canada,
Switzerland

uniQureAdstiladrin

nadofaragene firadenovec

2022

Bladder cancer

US

Merck & Co.

Elevidysdelandistrogene
moxeparvovec

2023

Duchenne muscular dystrophy

US

Sarepta Therapeutics

Vyjuvek

beremagene geperpavec

2023

Dystrophic epidermolysis bullosa

US

Krystal Biotech

Fucasoequecabtagene autoleucel

2023

Multiple myeloma

China

Nanjing IASO Biotechnology

Mantle cell lymphoma; acutelymphocytic leukemia
Metachromatic leukodystrophy
Diffuse large B-cell lymphoma; follicularlymphoma; chronic lymphocytic
leukemia

Locations approved

Originator company

US, EU, UK, Australia

Kite Pharma (Gilead)

EU, UK, Switzerland, US

Orchard Therapeutics

US, Japan, EU, Switzerland,
UK, Canada

Celgene (Bristol Myers Squibb)

US, Canada, EU, UK, Japan,
Israel, Switzerland
Japan

Source: Pharmaprojects | Citeline, April 2024
9 / Q1 2024

Text highlighted in yellow represents new approvals during Q1 2024

bluebird bio
Daiichi Sankyo

Approved gene therapies as of Q1 2024 (3/3)
Product name

Generic nameYear first approved

Disease(s)Locations approved

Originator company

Casgevy

exagamglogene autotemcel

2023

Sickle cell anemia; thalassemia

US, UK, Bahrain, Saudi
Arabia, EU

CRISPR Therapeutics

inaticabtagene
autoleucel

inaticabtagene autoleucel2023

Acute lymphocytic leukemia

China

Juventas Cell Therapy

Lyfgenia

lovotibeglogene autotemcel

2023

Sickle cell anemia

USbluebird bio

zevorcabtagene
autoleucel

zevorcabtagene autoleucel2024

Relapsed or refractory multiple myeloma China

CARsgen Therapeutics

Beqvezfidanacogene elaparvovec

2024

Hemophilia B

PfizerCanadaSource: Pharmaprojects | Citeline, April 2024
10 / Q1 2024

Text highlighted in yellow represents new approvals during Q1 2024

Approved RNA therapies as of Q1 2024 (1/3)
Product name

Generic nameYear first
approved

Disease(s)Locations approved*

Originator company

Kynamromipomersen sodium

2013

Homozygous familial hypercholesterolemia

US, Mexico, Argentina, South Korea

Ionis Pharmaceuticals

Exondys 51

eteplirsen

2016

Dystrophy, Duchenne muscular

US

Sarepta Therapeutics

Spinrazanusinersen

2016

Muscular atrophy, spinal

Ampligenrintatolimod

2016

Chronic fatigue syndrome

US, EU, UK, Canada, Japan, Brazil, Switzerland,
Australia, South Korea, China, Argentina,
Ionis Pharmaceuticals
Colombia, Taiwan, Turkey, Hong Kong, Israel
Argentina
AIM ImmunoTech

Tegsediinotersen

2018

Amyloidosis, transthyretin-related hereditary

EU, UK, Canada, US, Brazil

Onpattro

patisiran

2018

Amyloidosis, transthyretin-related hereditary

US, EU, UK, Japan, Canada, Switzerland, Brazil,
AlnylamTaiwan, Israel, Turkey, Australia

Vyondys 53

golodirsen

2019

Dystrophy, Duchenne muscular

US

Sarepta Therapeutics

Waylivra

volanesorsen

2019

Hypertriglyceridemia; lipoprotein lipase
deficiency

EU, UK, Brazil, Canada

Ionis Pharmaceuticals

Comirnaty

tozinameran

Moderna COVID-19 vaccine COVID-19 vaccine, Moderna

2020

Infection, coronavirus, novel coronavirus
prophylaxis

2020

Infection, coronavirus, novel coronavirus
prophylaxis

Source: Pharmaprojects | Citeline, April 2024
11 / Q1 2024

Text highlighted in yellow represents new approvals during Q1 2024

Ionis Pharmaceuticals

UK, Bahrain, Israel, Canada, US, Rwanda,
Serbia, United Arab Emirates, Macao, Taiwan,
Mexico, Kuwait, Singapore, Saudi Arabia,
Chile, Switzerland, EU, Ghana, Colombia,
BioNTechPhilippines, Indonesia, Australia, Hong Kong,
Peru, South Korea, New Zealand, Japan, Brazil,
Sri Lanka, Vietnam, South Africa, Thailand,Oman, Egypt, Malaysia
US, Canada, Israel, EU, Switzerland, Singapore,
Qatar, Vietnam, UK, Philippines, Thailand,
Japan, South Korea, Brunei, Paraguay, Taiwan, Moderna Therapeutics
Botswana, India, Indonesia, Saudi Arabia,
Mexico, Australia, Nigeria, Colombia

Approved RNA therapies as of Q1 2024 (2/3)
Product name

Generic nameYear first
approved

Disease(s)Locations approved*

Originator company

Givlaari

givosiran

2020

Porphyria

US, EU, UK, Canada, Switzerland,Brazil, Israel, Japan

AlnylamOxlumolumasiran2020

Hyperoxaluria

EU, UK, US, Brazil

AlnylamViltepso

viltolarsen

2020

inclisiran2020

Amondys 45

casimersen

2021

US, Japan
EU, UK, Australia, Canada, Israel,
US, Saudi Arabia, Japan, ChinaUSNS Pharma

LeqvioDystrophy, Duchenne muscular
Atherosclerosis; heterozygous familial
hypercholesterolemia; hypercholesterolemia
Dystrophy, Duchenne muscular

Nulibry
Gennova COVID-19
vaccineAmvuttrafosdenopterin
COVID-19 vaccine, Gennova
Biopharmaceuticals
vutrisiran

2021

Molybdenum cofactor deficiency

US, EU, UK, Israel

2022

Infection, coronavirus, novel coronavirus prophylaxis

India

2022

Amyloidosis, transthyretin-related hereditary

US, EU, UK

Orphatec
Gennova
Biopharmaceuticals
Alnylam

2022

Infection, coronavirus, novel coronavirus prophylaxis

2022

Infection, coronavirus, novel coronavirus prophylaxis

2022

Infection, coronavirus, novel coronavirus prophylaxis

US, UK

BioNTech2023

Infection, coronavirus, novel coronavirus prophylaxis

China

CSPC Pharmaceutical

2023

Infection, coronavirus, novel coronavirus prophylaxis

China, UAE, US

SinoCellTech

Moderna Spikevax
COVID-19 bivalent
Bivalent Original/Omicron original/Omicron vaccine,
vaccineModerna
COVID-19 vaccine, Suzhou
ARCoV
Abogen Biosciences
Pfizer & BioNTech’s
Omicron BA.4/BA.5Omicron BA.4/BA.5-adapted
adapted bivalent booster bivalent booster vaccine
vaccineCSPC Pharmaceutical
COVID-19 vaccine, CSPCCOVID-19 vaccine
Pharmaceutical
COVID-19
Sinocelltech COVID-19
alpha/beta/delta/Omicron
vaccinevariants S-trimer quadrivalent
recombinant protein vaccine

Sarepta Therapeutics

UK, Canada, Taiwan, Switzerland,
Japan, EU, Australia, South Korea, Moderna Therapeutics
Singapore, US
Suzhou Abogen
Indonesia
Biosciences

12 / Q1 2024

Source: Pharmaprojects | Citeline, April 2024

Alnylam

Text highlighted in yellow represents new approvals during Q1 2024

Approved RNA therapies as of Q1 2024 (3/3)
Product name

Generic nameYear first
approved

Disease(s)Locations approved*

Originator company

Qalsody

tofersen

2023

Amyotrophic lateral sclerosis

US

Ionis Pharmaceuticals

ARCT-154

COVID-19 mRNA vaccine, Arcturus

2023

Infection, coronavirus, novel coronavirus prophylaxis

Japan

Arcturus Therapeutics

Daichirona

COVID-19 vaccine, Daiichi Sankyo

2023

Infection, coronavirus, novel coronavirus prophylaxis

Japan

Daiichi Sankyo

Wainuaeplontersen

2023

Transthyretin-related hereditary amyloidosis

US

Ionis Pharmaceuticals

Rivfloza

nedosiran

2023

Hyperoxaluria

US

Dicerna Pharmaceuticals

SYS-6006.32

Bivalent COVID-19 mRNA vaccine,
CSPC Pharmaceutical

2023

Infection, coronavirus, novel coronavirus prophylaxis

China

CSPC Pharmaceutical*For COVID-19 vaccines, this includes emergency use authorization and full approvals
Note that molnupiravir was previously included in this list; however, it has now been removed as it is no longer considered to fall under the category of RNA therapeutics

Source: Pharmaprojects | Citeline, April 2024
13 / Q1 2024

Text highlighted in yellow represents new approvals during Q1 2024

Key highlights in Q1 2024 (1/2)
Drug
DOC1021
Carteyva
CABA-201
CABA-201
Casgevy
SER-155
Casgevy
SGT-003
Hemgenix
Casgevy
ATSN-101
Revascor

Event Type
Orphan Drug Designation (U.S.)
Filing for Approval (China)
Fast Track Status
Fast Track Status
Approval (Emerging Markets)
Fast Track Status
Approval (Emerging Markets)
Orphan Drug Designation (U.S.)
Approval (Europe) - Individual Country
Approval (U.S.)
Rare Pediatric Disease (RPD) Designation
Rare Pediatric Disease (RPD) Designation

RZ001

Orphan Drug Designation (U.S.)KYV-101
4D-710
FT-002
Breyanzi
Breyanzi
ACDN-01

Fast Track Status
Fast Track Status
PRIME Designation (Europe)
Conditional Marketing Authorisation (Europe)
Conditional Marketing Authorisation (Europe)
Fast Track Status

BST02

Orphan Drug Designation (U.S.)

CABA-201
Amtagvi
WainuaGTX-102 (GeneTx)

Orphan Drug Designation (U.S.)
Accelerated/Conditional Approval (U.S.)
Rare Pediatric Disease (RPD) Designation
Fast Track Status

Casgevy

Breakthrough Therapy Designation (U.S.)

Source: Biomedtracker | Citeline, April 2024
14 / Q1 2024

Noteworthy events that happened in Q1 2024

Indication
Molecule
Brain Cancer (Malignant Glioma; AA and glioblastoma (GBM))
Cellular
Mantle Cell Lymphoma - NHLCellular
Systemic Sclerosis
Cellular
Dermatomyositis
CellularSickle Cell Anemia
Non-Viral Gene Therapy
Graft vs. Host Disease (GVHD) - Treatment
Cellular
Thalassemia
Non-Viral Gene Therapy
Duchenne Muscular Dystrophy (DMD)
Viral Gene Therapy
Hemophilia B
Viral Gene Therapy
Thalassemia
Non-Viral Gene Therapy
Leber's Congenital Amaurosis (Ophthalmology)
Viral Gene Therapy
Chronic Heart Failure - Reduced Ejection Fraction (Chronic HFrEF) Cellular
Hepatocellular (Liver) Cancer (HCC) (Including Secondary
Non-Viral Gene Therapy
Metastases)
Multiple Sclerosis (MS)Cellular
Hepatitis B (HBV) Treatment (Antiviral)
Antisense
Fabry's Disease
Viral Gene Therapy
Thalassemia
Non-Viral Gene Therapy
Sickle Cell Anemia
Non-Viral Gene Therapy
Lung Cancer - Unspecified
Viral Gene Therapy
Familial Chylomicronemia Syndrome (FCS)/Lipoprotein Lipase
Antisense
Deficiency (LPLD)
Chronic Heart Failure - Reduced Ejection Fraction (Chronic HFrEF) Cellular
Melanoma
CellularDuchenne Muscular Dystrophy (DMD)siRNA/RNAi
Myotonic Muscular Dystrophy
Oligonucleotide
Familial Chylomicronemia Syndrome (FCS)/Lipoprotein Lipase
Antisense
Deficiency (LPLD)

Event Date
02 January 2024
04 January 2024
08 January 2024
08 January 2024
09 January 2024
09 January 2024
09 January 2024
11 January 2024
15 January 2024
16 January 2024
16 January 2024
18 January 2024
18 January 2024
19 January 2024
12 February 2024
12 February 2024
13 February 2024
13 February 2024
13 February 2024
14 February 2024
14 February 2024
16 February 2024
20 February 2024
20 February 2024
21 February 2024

Key highlights in Q1 2024 (2/2)
Drug
Event Type
KB707
Orphan Drug Designation (Europe)
Bepirovirsen
Fast Track Status
Isaralgagene
Fast Track Status
Civaparvovec
Revascor
Orphan Drug Designation (Europe)
Casgevy
Fast Track Status
Olezarsen
Orphan Drug Designation (U.S.)
AOC 1044
Fast Track Status
PGN-EDODM1
Fast Track Status
ION356
Approval (China)
IONIS-TMPRSS6-LRx Orphan Drug Designation (U.S.)
Donidalorsen
Orphan Drug Designation (U.S.)
AlloNK
Regenerative Medicine Advanced Therapy (RMAT) Designation
Olezarsen
Rare Pediatric Disease (RPD) Designation
LUNAR-CF
Approval (U.S.)
CT053
Orphan Drug Designation (U.S.)
IDP-023
Innovative Licensing and Access Pathway (ILAP) (U.K.)
IDP-023
NDA/BLA Filing
Dilanubicel
Regenerative Medicine Advanced Therapy (RMAT) Designation

Source: Biomedtracker | Citeline, April 2024
15 / Q1 2024

Noteworthy events that happened in Q1 2024

Indication
Hereditary Angioedema (HAE)
Polycythemia Vera (PV)

Molecule
Antisense
Antisense

Event Date
21 February 2024
21 February 2024

Pelizaeus-Merzbacher Disease (PMD)

Antisense

21 February 2024

Cystic Fibrosis (CF)
Lupus Nephritis
Acute Myelogenous Leukemia (AML)
Non-Hodgkin's Lymphoma (NHL)Multiple Myeloma (MM)Multiple Myeloma (MM)Duchenne Muscular Dystrophy (DMD)
Multiple Myeloma (MM)Osteoarthritis
Duchenne Muscular Dystrophy (DMD)
Metachromatic Leukodystrophy
Systemic Sclerosis
Krabbe Disease (Globoid Cell Leukodystrophy)
Neurology - Other
Acute Myelogenous Leukemia (AML)siRNA/RNAi
Cellular
Cellular
Cellular
Cellular
Cellular
Oligonucleotide
Cellular
Viral Gene Therapy
Oligonucleotide
Viral Gene Therapy
Cellular
Viral Gene Therapy
Viral Gene Therapy
Cellular

22 February 2024
22 February 2024
26 February 2024
29 February 2024
29 February 2024
01 March 2024
07 March 2024
12 March 2024
13 March 2024
13 March 2024
18 March 2024
19 March 2024
19 March 2024
19 March 2024
19 March 2024

Q1 2024

Pipeline overview

Pipeline of gene, cell, and RNA therapies

Pipeline therapies by category

4,002 therapies are in development,
ranging from preclinical throughpre-registration• 2,093 gene therapies (including geneticallymodified cell therapies such as CAR-T celltherapies) are in development, accountingfor 52% of gene, cell, and RNA therapies• 885 non-genetically modified cell therapies
are in development, accounting for 22% ofgene, cell, and RNA therapies

22%
52%
26%

Gene therapies

Source: Pharmaprojects | Citeline, April 2024
17 / Q1 2024

RNA therapies

Cell therapies (non-genetically modified)Gene therapy and genetically modified cell therapies

Q1 2024

Gene therapy pipeline

Gene therapy pipeline: quarterly comparison•••

Q1 2024 saw an increase in the number of therapies at eachpipeline stage of development except pre-registration
The number of gene therapies at pre-registration is the lowest it
has been since prior to Q4 2022, while Phase I development has
seen the largest percentage increase in over a year (11%)
between Q4 2023 and Q1 2024

Global Status

Q1
2023

Q2
2023

Q3
2023

Q4
2023

Q1
2024

Preclinical

1,493

1,539

1,522

1,528

1,471

Phase I

245

240

256

270

301

Phase II

247

260

267

274

282

Phase III

30

30

30

33

35

Preregistration

7

6

7

6

4

Total

2,022

2,075

2,082

2,111

2,093

Therapies currently in pre-registration:•

In the US•

RP-L201 (Rocket Pharmaceuticals)•

EB-101 (Abeona Therapeutics)•

afami-cel (Adaptimmune Therapeutics)•

obe-cel (Autolus Therapeutics)

Source: Pharmaprojects | Citeline, April 2024

19 / Q1 2024

Genetic modification: In vivo vs. Ex vivo

• Ex vivo genetic modification is more
widely used for gene therapies inpipeline development

In vivo vs. Ex vivo genetic modification• In Q1 2024, in vivo delivery techniques
were used in 42% of gene therapies

In Vivo

Source: Cell and Gene Therapy dashboard | Citeline, April 2024
20 / Q1 2024

Ex Vivo

Gene therapy breakdown: CAR-Ts continue to dominate the pipeline• CAR-T cell therapies remained the most common technology used in the pipeline of genetically modified celltherapies (preclinical through to pre-registration), representing 52%, followed by the “other” category at 27%,
which includes a list of less commonly used technologies such as TCR-NK, CAR-M, and TAC-T• 97% of CAR-T cell therapies were in development for cancer indications. The remaining non-oncology
indications included scleroderma, HIV/AIDS, and autoimmune disease (unspecified)
Genetically modified cell therapy breakdown

CAR-T breakdown

7%
27%
52%

14%

CAR-NK

CAR-T

TCR-T

Other

Source: Cell and Gene Therapy dashboard | Citeline, April 2024
21 / Q1 2024

Oncology

Non-oncology

Gene therapy pipeline: most commonly targeted therapeutic areas• Oncology and rare diseases remained the top areas of gene therapy development in both the overall pipeline(preclinical to pre-registration) and in the clinic (Phase I to pre-registration)• Development for rare diseases most commonly occurred in oncology, representing a majority of 54% compared
to non-oncology rare disease gene therapy pipeline development, one percentage point lower than theprevious quarter
Number of therapies from preclinical through pre-registration

Therapies in the clinic (excludes preclinical development)

Number of therapies
Anticancer
Rare Diseases
NeurologicalSensory
Alimentary/Metabolic
Musculoskeletal
Immunological
NA/Unspecified
Blood and Clotting
Cardiovascular
Anti-infective
Respiratory
Dermatological
Genitourinary (including sex hormones)
Miscellaneous
Hormonal (excluding sex hormones)

1123

Rare Diseases

1035

213
198
154
92
87
80
66
65
42
32
21
10
4
2

Source: Pharmaprojects | Citeline, April 2024
22 / Q1 2024

Number of therapies
429

Anticancer

411

Sensory

Rare diseases

46% 54%

Oncology

Non-oncology

48

Alimentary/Metabolic

36

Neurological

34

Blood and Clotting

31

Immunological

21

Musculoskeletal

20

Cardiovascular18

Anti-infective

12

Dermatological

6

Respiratory

5

Genitourinary (including sex hormones)

1

Hormonal (excluding sex hormones)

1

Miscellaneous1

NA/Unspecified

1

Note: Figures based on indications in pipeline development only for each therapy

Gene therapy pipeline: most common rare diseases targeted••

For the 1,035 pipeline (preclinical to preregistration) gene therapies being
developed for rare diseases, eight out of
the top 10 rare diseases were oncological,
a trend seen throughout 2022 and 2023
In the same order as the previous quarter,
the top five rare diseases for which genetherapies are being developed are:Number of therapies
Cancer, myeloma

99

Cancer, leukemia, acute myelogenous

85

Cancer, lymphoma, non-Hodgkin's

84

Cancer, lymphoma, B-cell70

Cancer, ovarian

67

Cancer, liver

53

Cancer, pancreatic

50

Cancer, gastrointestinal, stomach

42

Amyotrophic lateral sclerosis

34

Retinitis pigmentosa

1.
2.
3.
4.
5.

MyelomaAcute myelogenous leukemia
Non-Hodgkin’s lymphoma
B-cell lymphoma
Ovarian cancer

Source: Pharmaprojects | Citeline, April 2024
23 / Q1 2024

29

Dystrophy, Duchenne's muscular

25

Cancer, lymphoma, B-cell, diffuse large

23

Cancer, renal

23

Hemophilia A

22

Cancer, lymphoma, T-cell21

Cancer, leukemia, chronic lymphocytic

19

Cystic fibrosis

16

Thalassemia

16

Cancer, mesothelioma

12

Myelodysplastic syndrome

12

Note: Figures based on indications in pipeline development only for each therapy

Gene therapy pipeline: most common targets
Of the gene therapies in preclinical trials through pre-registration for which targets were disclosed:•

CD19, B-cell maturation antigen (BCMA), also known as TNF receptor superfamily member 17, and CD22 molecule continued
to be the top three most common targets for oncology indications•

CD19 molecule was the most common target for non-oncology indications, while coagulation factor VIII remained the second
most common in Q1 2024, as seen in the previous two quarters
Non-oncology targets

Oncology

Number of therapies

Number of therapies
CD19 molecule
TNF receptor superfamily member 17
CD22 molecule
membrane spanning 4-domains A1
mesothelin
erb-b2 receptor tyrosine kinase 2
glypican 3
claudin 18
KRAS proto-oncogene, GTPase
CD70 molecule
cancer/testis antigen 1B
CD33 moleculeCD7 molecule
programmed cell death 1
CD276 moleculeC-type lectin domain family 12 member A
G protein-coupled receptor class C group 5 member D
epidermal growth factor receptor
mucin 1, cell surface associatedtumor protein p53

Source: Pharmaprojects | Citeline, April 2024
24 / Q1 2024

147
56

34
25
25
23
23
22
20
16
15
14
14
14
13
11
11
10
9
9

CD19 molecule
coagulation factor VIII
dystrophin
glucosylceramidase beta
vascular endothelial growth factor A
gap junction protein beta 2
hemoglobin subunit beta
ATP binding cassette subfamily A member 4
C9orf72-SMCR8 complex subunit
CF transmembrane conductance regulator
granulin precursor
membrane spanning 4-domains A1
otoferlin
TAR DNA binding protein
TNF receptor superfamily member 17
apolipoprotein E
coagulation factor IX
glucosidase alpha, acidmethyl-CpG binding protein 2
N-sulfoglucosamine sulfohydrolase
proprotein convertase subtilisin/kexin type 9
retinoid isomerohydrolase RPE65
superoxide dismutase 1
survival of motor neuron 1, telomeric
telomerase reverse transcriptase

27

12
10
8
8
6
6
5
5
5
5
5
5
5
5
4
4
4
4
4
4
4
4
4
4

Gene therapy clinical trial activity• The proportion of gene therapy trials for non-oncology indications has increased by four percentage points since theprevious quarter, to 43%, continuing the trend of an increasing proportion of non-oncology gene therapy trials• 61 gene therapy trials were initiated in Q1 2024
Q2 2023: Oncology vs. Non-oncology Q3 2023: Oncology vs. Non-oncology
Number of trials initiated by phase
40

32%

38%

35

68%

30

62%

25
20

Oncology

Non-oncology

Oncology

Non-oncology

15

Q4 2023: Oncology vs. Non-oncology Q1 2024: Oncology vs. Non-oncology

10
5
0
I

I/II
Q2 2023

II

II/IIIIII

Q3 2023

Q4 2023

Q1 2024

Other

43%

39%
61%
Oncology

Source: Trialtrove | Citeline, April 2024
25 / Q1 2024

Non-oncology

57%
Oncology

Non-oncology

Q1 2024

Non-genetically modified celltherapy pipelineNon-genetically modified cell therapy pipeline: most commonly targeted
therapeutic areas
Of the cell therapies in development (preclinical through pre-registration):• Oncology and rare diseases remained the top areas of non-genetically modified cell therapy development• Of the non-genetically modified cell therapies in preclinical to pre-registration stages for rare diseases, 64% were indevelopment for non-oncology rare diseases, as found in the previous three quarters
Number of therapies

Rare diseases

Anticancer

292

Rare Diseases

275

Neurological

127

Alimentary/Metabolic

111

Musculoskeletal

108

Cardiovascular76

Immunological

Oncology

Non-oncology

59

Sensory

50

Respiratory

48

Dermatological

46

Genitourinary (including sex hormones)

41

Blood and Clotting

37

Miscellaneous

34

Anti-infective

25

NA/Unspecified
Hormonal (excluding sex hormones)

Source: Pharmaprojects | Citeline, April 2024
27 / Q1 2024

16
4

Note: Figures based on indications in pipeline development only for each therapy

Non-genetically modified cell therapy pipeline: most common diseases
targeted
Number of therapies

Of the therapies for which indications are
specified, Parkinson’s disease is the mosttargeted disease, while type 1 diabetes has
overtaken acute respiratory distresssyndrome to become the third mosttargeted:
1.
2.
3.

Parkinson’s disease
Osteoarthritis
Type 1 diabetes

Source: Pharmaprojects | Citeline, April 2024
28 / Q1 2024

Cancer, solid, unspecified

108

Cancer, unspecified

39

Parkinson's disease

39

Arthritis, osteo

38

Diabetes, Type 1

34

Respiratory distress syndrome, acute32

COVID-19 complications

28

Cancer, lung, non-small cell

24

Cancer, brain

22

Cancer, liver

22

Ischemia, cerebral

22

Alzheimer's disease

21

Graft-versus-host disease

21

Heart failure

21

Cancer, leukemia, acute myelogenous

20

Cancer, melanoma

20

Cancer, breast

18

Spinal cord injury

18

Cancer, pancreatic

17

Cancer, ovarian

16

Hepatic dysfunction, unspecified

16

Note: Figures based on indications in pipeline development only for each therapy

Non-genetically modified cell therapy pipeline: most common rare diseases
targeted
Number of therapies
Respiratory distress syndrome, acuteOf the therapies in development(preclinical through preregistration) for rare diseases:

Cancer, liver

21

Cancer, leukemia, acute myelogenous

20

Spinal cord injury• The top three non-oncology
indications were acuterespiratory distress syndrome,
graft-versus-host disease, andspinal cord injury

29 / Q1 2024

22

Graft-versus-host disease• The top three oncology
indications were liver cancer,
acute myelogenous leukemia,
and pancreatic cancer

Source: Pharmaprojects | Citeline, April 2024

32

18

Cancer, pancreatic

17

Cancer, ovarian

16

Cancer, gastrointestinal, stomach

14

Amyotrophic lateral sclerosis

12

Cancer, myeloma

12

Myelodysplastic syndrome

11

Cancer, lymphoma, non-Hodgkin's

9

Retinitis pigmentosa

9

Fibrosis, pulmonary, idiopathic

7

Thalassemia

6

Anal fistula

5

Cancer, renal

5

Dystrophy, Duchenne's muscular5

Epidermolysis bullosa

5

Huntington's disease5

Note: Figures based on indications in pipeline development only for each therapy

Non-genetically modified cell therapy trial activity• 42 trials were initiated for non-genetically modified cell therapies in Q1 2024, two fewer than in the previous quarter• Of these 42, 55% were for non-oncology indications
Q2 2023: Oncology vs. Non-oncology

Q3 2023: Oncology vs. Non-oncology

Number of trials initiated by phase
18
16
14
12

10

Oncology8Non-oncology

Q4 2023: Oncology vs. Non-oncology

6

Oncology

Non-oncology

Q1 2024: Oncology vs. Non-oncology

4
2
0
I

I/II
Q2 2023

II
Q3 2023

II/III
Q4 2023

III

IV

Q1 2024

Oncology

Source: Trialtrove | Citeline, April 2024
30 / Q1 2024

Non-oncology

Oncology

Non-oncology

Q1 2024

RNA therapy pipelineRNA therapy pipeline: most common modalities• Of RNA therapies in the pipeline, messenger RNA (mRNA) and RNA interference (RNAi) continued to be thepreferred RNA modalities for research

500
450
400

Number of therapies

350
300
250
200
150
100
50
0
April 2021

July 2021

October 2021 January 2022
RNA interference

Source: Pharmaprojects | Citeline, April 2024
32 / Q1 2024

April 2022

July 2022

Antisense therapy

October 2022 January 2023
Messenger RNA

April 2023

July 2023

October 2023 January 2024

Oligonucleotide, non-antisense, non-RNAi

April 2024

RNAi, mRNA, and antisense oligonucleotides: preclinical vs. clinical• The majority of RNAi, mRNA, and antisense therapies in development were in the preclinical stage,
representing 73%, 67%, and 71% of their respective pipelines

RNAi Therapies

mRNA Therapies

27%

33%
73%

Preclinical

Clinical

Source: Pharmaprojects | Citeline, April 2024
33 / Q1 2024

Antisense Therapies

29%
67%

Preclinical

Clinical

71%

Preclinical

ClinicalRNA therapies: most commonly targeted therapeutic areas
Of the 1,072 RNA therapies currently in the pipeline (from preclinical through pre-registration):• Rare diseases remained the top targeted therapeutic area by RNA therapies, while anti-infective indications
remained the second most commonly targeted, above oncology indications• Non-oncology indications continued to be the most targeted rare diseases by RNA therapies, representing amajority of 80%
Number of therapies
Rare Disease
Anti-infective
Anticancer
Neurological
Alimentary/Metabolic
Musculoskeletal
NA/Unspecified
Cardiovascular
Respiratory
Sensory
Immunological
Blood and Clotting
Dermatological
Genitourinary (including sex hormones)
Miscellaneous
Antiparasitic
Hormonal (excluding sex hormones)

Source: Pharmaprojects | Citeline, April 2024
34 / Q1 2024

329

Rare Diseases

264

224
152

118
77
67
61
42
37
35
21
21
17
10
8
2

Oncology

Note: Figures based on indications in pipeline development only for each therapy

Non-oncology

RNA therapies: most common rare diseases targeted
Of the RNA therapies currently in thepipeline (from preclinical through preregistration):• Top specified rare oncology indications
were pancreatic, liver, and ovariancancer• For non-oncology rare diseases,
Duchenne muscular dystrophy,
amyotrophic lateral sclerosis, andHuntington’s disease were the mosttargeted indications

Source: Pharmaprojects | Citeline, April 2024
35 / Q1 2024

Number of therapies
Dystrophy, Duchenne's muscular
Amyotrophic lateral sclerosis
Cancer, pancreatic
Cancer, liver
Huntington's disease
Fibrosis, pulmonary, idiopathic
Dementia, frontotemporal
Respiratory distress syndrome, acute
Cystic fibrosis
Cancer, ovarian
Dystrophy, myotonic muscular
Infection, malaria prophylaxis
Primary ciliary dyskinesia
Infection, rabies prophylaxis
Angioedema, hereditary
Hyperphenylalaninemia
Infection, hepatitis-D virus
Cancer, gastrointestinal, stomach
Cancer, leukemia, acute myelogenous
Charcot–Marie–Tooth disease
Dystrophy, facioscapulohumeral muscular
Infection, dengue virus prophylaxis
Infection, monkeypox virus prophylaxis
Myelodysplastic syndrome
Retinitis pigmentosa

30
22
22
18
15
11
10
10
9
8
7
7
7
6
5
5
5
4
4
4
4
4
4
4
4

Note: Figures based on indications in pipeline development only for each therapy

RNA therapy pipeline: clinical trial activity• 30 RNA trials were initiated in Q1 2024, compared to 24 in Q4 2023, 90% of which were for non-oncology indications

Number of trials initiated by phase
14
12
10
8
6
4
2
0
I

I/II

II
Q2 2023

Source: Trialtrove | Citeline, April 2024
36 / Q1 2024

II/III
Q3 2023

Q4 2023

III
Q1 2024

IV

Other

Q1 2024

Overview of dealmaking for gene, cell,and RNA therapy companies

Alliance, acquisition, and financing in gene, cell, and RNA therapy•

Advanced molecular companies signed a total of 125 deals in Q1 2024, a 34% increase over the previous quarter’s aggregate of 93
Q1 2024’s total was not only 14% ahead of the 110 deals seen during the same quarter of 2023, but also represents a single-quarterhigh within the last year
Driving the increase in 2024’s opening quarter was financing volume, which rose by 74% from 49 to 85 transactions

Total number of deals by type, most recent five quarters

Number of deals

•
•

90
80
70
60
50
40
30
20
10
0

85
68
54

*Financing

49

Alliance

49

40

40
34

7

9

Q1 2023

Q2 2023

Source: Biomedtracker | Citeline, BioSciDB | Evaluate, April 2024
38 / Q1 2024

67

9

Q3 202310

Q4 202334
6

Q1 2024*Financings include public financings (IPOs and follow-ons) plus privately raised funding
through venture rounds, debt offerings, or private investment in public equity

Acquisition

Q1 2024 acquisitions in gene, cell, and RNA therapy•••

Acquisition volume continues to trend downward quarter by quarter; Q1 2024’s six total deals was down from Q4 2023’s total of 10,
and is also the lowest quarterly volume seen in the last year
In Q1 2024’s largest deal, Novo Nordisk is paying up to €1bn ($1.1bn) up front plus earn-outs for Cardior, which targets non-coding
RNAs in cardiac diseases, focusing on a lead candidate in heart failure patients with reduced ejection fraction
Regeneron created a new entity called Regeneron Cell Medicines by acquiring 2seventy bio’s immune cell therapy pipeline for $5m

Deal date

Deal title

2 January 2024

Tome Biosciences Acquires Replace Therapeutics

185,000,000

23 January 2024

NAYA Biosciences to Acquire Florida Biotechnologies

25,000,000

30 January 2024

Regeneron to Acquire 2seventy bio's Platforms and Clinical Programs

5,000,000

28 February 2024

Ginkgo Bioworks Acquires Patch Biosciences

Undisclosed

29 February 2024

StemCell Technologies Acquires SQZ Biotechnologies Company

11,800,000

25 March 2024

Novo Nordisk to Acquire Cardior Pharmaceuticals for €1B

1,107,697,000

Source: Biomedtracker | Citeline, BioSciDB | Evaluate, April 2024
39 / Q1 2024

Potential deal value (USD $)Q1 2024

Start-up funding for gene, cell, andRNA therapy companies

Start-up financing for gene, cell, and RNA therapy companies•

The volume of start-up financing continues to decrease, with eight seed and Series A financings completed in Q1 2024, a 33%
decline from Q4 2023’s 12 transactions
Total value from seed and Series A financings was also down in Q1 2024, totaling $240.1m, a nearly 3x decrease from theprevious quarterQ1 2024’s figures also represent declines compared with the opening quarter of 2023••

Volume and dollar value of Series A and seed financings for gene, cell, & RNA therapy
companies, most recent five quarters
21

Total raised ($M)

$1,200.0$1,000.0

17

25
20

17

15

12

$800.0$600.08$400.0$200.0$-5$615.2$1,331.4$348.2$683.0$240.1Q1 2023

Q2 2023

Q3 2023

Q4 2023

Q1 2024

Total raised ($M)
Source: Biomedtracker | Citeline, Evaluate, April 2024
41 / Q1 2024

10

Number of financings0

Number of financings$1,400.0

Q1 2024 start-up financing for gene, cell, and RNA therapy companies
Deal date

Deal title

4 January 2024

Resalis Therapeutics Raises €10M Series A to Complete AntisenseFirst Clinical Trial for RES-010 in Obesity
oligonucleotides

17 January 2024

Bolden Therapeutics Closes $1.5M Pre-Seed Financing

Exon-skipping antisense
oligonucleotides

17 January 2024

Tr1x Raises $75M in Series A Round

Allogeneic cell therapy

23 January 2024

GenEdit Brings in $24M in Series A1 Round

20 February 2024

MIP Discovery Raises £7M Series A Round

29 February 2024

Kenai Therapeutics Raises $82M in Series A Round

14 March 2024

Asgard Therapeutics Closes $32.8M Series A Round

19 March 2024

Portal Biotechnologies Gets $5M in Pre-Seed RoundSource: Biomedtracker | Citeline, Evaluate, April 2024
42 / Q1 2024

Modality typeNon-viral genetic
delivery
Reagents fordownstream
bioprocessing
Allogeneic cell therapy
In vivo cell
reprogramming
Intracellular delivery ingene editing and gene
expression modulation

Company location

Academic source

Potential deal
value ($M)

Italy / Torino

Aalborg University; Harvard Medical
School10.9

Brown University

1.5

Stanford University

75.0

UC Berkeley

24.0

United Kingdom /Bedfordshire

Newcastle University

8.8

United States / California /San Diego

n/a – established by Cure Parkinson's

82.0

Sweden / Lund

University of Coimbra; Lund University

32.8

United States /Massachusetts / Watertown

n/a – established by former leadershipof SQZ Biotechnologies

5.0

United States /Massachusetts / Boston
United States / California /San Diego
United States / California /San Francisco

Notable Q1 2024 start-up gene, cell, and RNA therapy companies
Company details

Off-the-shelf dopamine neuron
replacement therapies using
induced pluripotent stem cell
technology

Type 1 regulatory T-celltherapies

Gene therapies for in vivo
reprogramming of cancer cells
into antigen-presenting
dendritic cells

Academic
sourcen/a - establishedby CureParkinson'sSeries A/$82M

Lead investor(s)Therapy areas ofinterest

Alaska Permanent Fund
Corporation; Cure Ventures; The
Column Group

Parkinson’s disease(moderate-to-severe,
mild-to-severe rapid
progressing, and young
onset forms)

Stanford
University

Series A/$75M

The Column Group

Autoimmune andinflammatory diseases
including IBD, GvHD,
and multiple B-cellmediated AID

University of
Coimbra; Lund
University

Series A/$32.8M

RV Invest; Johnson & Johnson
Innovation – JJDC, Inc.

Oncology

Source: Biomedtracker | Citeline, Evaluate, April 2024
43 / Q1 2024

Financing type/amount raised

Q1 2024

Upcoming catalysts

Upcoming Catalysts
Below are noteworthy catalysts (forward-looking events) expected in Q2 2024
Therapy

Generic name

DiseaseCatalyst

Catalyst datemRNA-1345

n/aRespiratory Syncytial Virus (RSV) Prevention

PDUFA/Approval Decision (U.S.)

10 May 2024 - 10 May 2024

Breyanzi

lisocabtagene maraleucel

Follicular Lymphoma (FL)PDUFA for sNDA/sBLA

23 May 2024 - 23 May 2024

EB-101n/a

Epidermolysis Bullosa

PDUFA/Approval Decision (U.S.)

25 May 2024 - 25 May 2024

HPC-cord blood therapyn/aIschemic Stroke

PDUFA/Approval Decision (U.S.)19 Mar 2024 - 31 May 2024

Breyanzi

lisocabtagene maraleucel

Mantle Cell Lymphoma - NHL

PDUFA for sNDA/sBLA

31 May 2024 - 31 May 2024

Ryteloimetelstat

Myelodysplastic Syndrome (MDS)PDUFA/Approval Decision (U.S.)

14 Jun 2024 - 14 Jun 2024

Beqvezfidanacogene elaparvovec
leukocyte adhesion deficiency-1
gene therapy

Hemophilia B

PDUFA/Approval Decision (U.S.)

01 Apr 2024 - 30 Jun 2024

Autoimmune Disorders

PDUFA/Approval Decision (U.S.)

30 Jun 2024 - 30 Jun 2024

Beqvezfidanacogene elaparvovec

Hemophilia B

CHMP (European Panel) Results

01 Mar 2024 - 30 Sep 2024

Izervay

avacincaptad pegol

Dry Age-Related Macular Degeneration (DryAMD)/Geographic Atrophy (Ophthalmology)

CHMP (European Panel) Results

01 May 2024 - 30 Nov 2024

Beqvezfidanacogene elaparvovec

Hemophilia B

Approval Decision (Europe)

01 May 2024 - 30 Nov 2024

QALSODY

tofersenAmyotrophic Lateral Sclerosis (ALS)

Approval Decision (Europe)

08 Jan 2024 - 31 Dec 2024

Ryteloimetelstat

Myelodysplastic Syndrome (MDS)

CHMP (European Panel) Results

01 Jun 2024 - 31 Dec 2024

mRNA-1345

n/aApproval Decision (Europe)

01 Jun 2024 - 31 Dec 2024

Wainuaeplontersen

Approval Decision (Europe)

08 Jan 2024 - 31 Dec 2024

Breyanzi

lisocabtagene maraleucel

Respiratory Syncytial Virus (RSV) Prevention
Hereditary Transthyretin (hATTR) Amyloidosis With
Polyneuropathy (Familial Amyloid Polyneuropathy)
Indolent Non-Hodgkin's Lymphoma - iNHLPDUFA for sNDA/sBLA

01 Jan 2024 - 31 Dec 2024

OxlumolumasiranHyperoxaluria

Supplemental Approval (Europe)

29 Jan 2024 - 31 Jan 2025

Kresladi

Source: Biomedtracker | Citeline, April 2024
45 / Q1 2024

Methodology, sources, and glossary of key terms

Q1 2024

AppendixMethodology: sources and scope of therapies
Sources for all data come from Citeline
Pipeline and trial data••

Data derived from Pharmaprojects and Trialtrove
Therapeutic classes included in report categorizations:• Gene therapies: gene therapy; cellular therapy, chimeric antigen receptor; cellular therapy, T-cell
receptor; lytic virus• Cell therapies: cellular therapy, other; cellular therapy, stem cell; cellular therapy, tumor-infiltrating
lymphocyte• RNA therapies: messenger RNA; oligonucleotide, non-antisense, non-RNAi; RNA interference;
antisense therapy

Deal, financing, and catalyst data••

Data derived from Biomedtracker. The following industry categorizations of deals are included: genetherapy, cell therapy; antisense, oligonucleotides
Additional alliance and acquisition deals data from BioSciDB, part of Evaluate Ltd. The following industry
categorizations of deals are included: cell therapy – stem cells/factors, oligonucleotides, antisense/triple
helix, gene therapy, RNAi

47 / Q1 2024

Glossary of Key Terms
Therapy type definitions
Gene therapy is the use of genetic material to treat or prevent disease.
For the purpose of this report, the following terms shall mean the following:

Gene therapy

Therapies containing an active ingredient synthesized following vector-mediated introduction of a genetic sequence into
target cells in- or ex-vivo. Used to replace defective or missing genes (as in cystic fibrosis) as well as to introduce broadly
acting genetic sequences for the treatment of multifactorial diseases (e.g., cancer). Direct administration ofoligonucleotides without using vectors is covered separately in the antisense therapy class; RNA interference class; oroligonucleotide, non-antisense, non-RNAi class. Platform technologies for gene delivery are covered separately in thegene delivery vector class

Cellular therapy, chimeric antigen receptor(falls under gene therapy in this report)

Cellular therapy consisting of T cells that have been modified to express a chimeric antigen receptor (CAR) – this is a cellsurface receptor that gives the T cells the ability to target a specific protein and fight the targeted cells

Cellular therapy, T cell receptor(falls under gene therapy in this report)

Cellular therapies whereby natural T cells collected for the patient are engineered to express artificial receptors (usually
through viral transfections) that would target specific intracellular antigens (as peptides bound to proteins encoded by
the major histocompatibility complex, MHC)

Lytic virus(falls under gene therapy in this report)

48 / Q1 2024

Therapies that have a replication-competent virus, that lyse pathogenic cells directly. These are normally geneticallymodified to render them harmless to normal tissues. Examples include oncolytic viruses that specifically attack cancer
cellsGlossary of Key Terms
Therapy type definitions, cont.
Cell therapy includes the following therapeutic classes:
Cellular therapy, stem cell

Regenerative therapy which promotes the repair response of injured tissue using stem cells (cells from which all otherspecialized cells would originate)

Cellular therapy, tumor-infiltrating lymphocyte

Adoptive cellular transfer of tumor-resident T cells from tumor material, their expansion ex vivo, and transfer back into
the same patient after a lymphodepleting preparative regimen

Cellular therapy, other

Cellular therapies that do not fall under the categories of cellular therapy, stem cell; cellular therapy, CAR; cellulartherapy, TIL; cellular therapy, TCR; or the specific cellular therapy are unspecified

49 / Q1 2024

Glossary of Key Terms
Therapy type definitions, cont.
RNA therapy includes the following therapeutic classes:
Messenger RNA

Therapies that carry the desired mRNA code to overcome genetic mutations. The mRNA sequence will replace thedefective mRNA in a patient and start producing the desired protein

Oligonucleotide, non-antisense, non-RNAi

Synthetic therapeutic oligonucleotides which operate by a mechanism other than antisense or RNA interference (RNAi).
This includes ribozymes, aptamers, decoys, CpGs, and mismatched and immunostimulant oligonucleotides. Sequencesdelivered using vectors (gene therapy) are covered separately in “gene therapy.” Antisense and RNAi oligonucleotides
are covered separately in “antisense therapy” and “RNA interference,” respectively

RNA interference

Includes products which act therapeutically via an RNA interference (RNAi) mechanism, including small interfering RNAs(siRNAs). These may be synthetic oligonucleotides, or RNAi sequences may be expressed from a vector as a form of genetherapy (see “gene therapy” therapeutic class). In vivo, these sequences block the expression of a specific protein byforming an RNA-induced silencing complex, which then specifically binds to and degrades a complementary mRNA
encoding the target protein. The use of RNAi purely as a drug discovery tool (e.g., in transgenic animal model production
or in target validation) is not covered in this section

Antisense therapy

Antisense compounds under development as potential therapeutics. These may be synthetic oligonucleotides, orantisense RNA may be expressed from a vector as a form of gene therapy. They may prevent the expression of a specificprotein in vivo by binding to and inhibiting the action of mRNA, since they have a specific oligonucleotide sequencewhich is complementary to the DNA or RNA sequence that codes for the protein

50 / Q1 2024

Glossary of Key Terms
Development status definitions

Deal type categories

Pipeline

Drugs that are in active development

Alliances

PreclinicalNot yet tested in humans

Phase I

Early trials, usually in volunteers, safety, PK, PD

Co-marketing, co-promotion, disease management,
joint venture, manufacturing or supply, marketinglicensing, product or technology swap, productpurchase, R&D and marketing-licensing, reverse
licensing, trial collaborations

Phase IIFirst efficacy trials in small numbers of patients

Financing

Phase III

Large-scale trials for registrational data

Pre-registration

Filing for approval made to regulatory authorities

Convertible debt, FOPO, IPO, nonconvertible debt,
financing/other, private investment in public equity,
private placement, royalty sale, special-purpose
financing vehicle, spin-off

Approved

Approval from relevant regulatory authorities forhuman use

Acquisitions

Buy-out, divestiture, spin-out, full acquisition, partial
acquisition, reverse acquisition

Unspecified indications
Cancer, unspecified

Indications for which the specific tumor type is not
specifiedCancer, hematological,
unspecified

Indications for which the specific hematological cancer
is not specified

Cancer, solid, unspecified

Indications for which the specific solid tumor is not
specified

51 / Q1 2024

Report Contributors
David Barrett, JD
CEOAmerican Society of Gene + Cell Therapy

Shardha Millington
Consultant
Citeline

Alex Wendland, MSJ
Director of Communications
American Society of Gene + Cell Therapy

Amanda Micklus, MSc
Senior Manager, Consulting & Analytics
Citeline

Devin Rose
Communications Manager
American Society of Gene + Cell Therapy

52 / Q1 2024

Usage Guidelines
The Gene, Cell, + RNA Therapy Landscape Report, created by the American Society of Gene & Cell Therapy andCiteline, provides helpful overview graphics and data on cell and gene therapy trends. Readers are welcome tocite and share images and data from the report as-is with appropriate citations. When using any graphics ordata, please include a citation stating "Data source: Gene, Cell, + RNA Therapy Landscape Report, American
Society of Gene & Cell Therapy and Citeline, [year]" and link back to the original report source at
https://asgct.org/publications/landscape-report to allow others to access the full context.
Data should not be modified or recreated in any way or suggest endorsement by ASGCT or Citeline. Contact
ASGCT at media@asgct.org for any usage questions.

53 / Q1 2024

Contact: David Barrett, JD at
info@asgct.org

Contact:clientservices@citeline.com