Cell, Gene, & RNA Therapy Landscape

Information Classification: General

Gene, Cell, & RNA Therapy Landscape

Q2 2021 Quarterly Data Report

Q2

20

21


About the authors

The American Society of Gene & Cell Therapy (ASGCT) is the primary professional membership organization for scientists, physicians, patient advocates, and other professionals with interest in gene and cell therapy.

Our members work in a wide range of settings including universities, hospitals, government agencies, foundations, biotechnology and pharmaceutical companies. ASGCT advances knowledge, awareness, and education leading to the discovery and clinical application of gene and cell therapies to alleviate human disease to benefit patients and society.

Informa Pharma Intelligence powers a full suite of analysis products – DatamonitorHealthcare™, Sitetrove™, Trialtrove™, Pharmaprojects™, Biomedtracker™, Scrip™, Pink Sheet™ and In Vivo™ – to deliver the data needed by the pharmaceutical and biomedical industry to make decisions and create real-world opportunities for growth.

With more than 400 analysts, journalists, and consultants keeping their fingers on the pulse of the industry, no key disease, clinical trial, drug approval or R&D project isn’t covered through the breadth and depth of data available to customers. For more information visit pharmaintelligence.informa.com.

https://www.globenewswire.com/Tracker?data=YeF7YZM-fHCKsB0EuxuSqHP082vqx4UHT9VY1mFfM8nNTa4BXaOrJljz_OPTSO5apDKlaCwzcRPW4ateLg6c8XRNYN8f_jLyW4eYI26xyD_PlTkkQvj_ncCxGUPwiNUS

Table of contents04 Introduction

05 Key takeaways from Q2 2021

06 Key highlights in Q2 2021

11 Gene therapy pipeline

23 Non-genetically modified cell therapy pipeline

29 RNA therapy pipeline

35 Overview of dealmaking

38 Start-up funding

43 Upcoming catalysts

45 Appendix


4 / Q2 2021

Introduction

ASGCT is pleased to provide the second in a quarterly report series with our data partner, Informa Pharma Intelligence. This series provides an iterative, detailed look at progress in the preclinical and clinical development landscape of gene and cell therapies globally, and should collectively tell a complete story of scientific achievement and clinical advancement.

Highlights in Q2 2021 include the approval of a new gene therapy in Japan, the expansion of gene therapy approvals to three new countries, continued growth in early-phase gene therapy development, and growth in studies using a herpes simplex virus.

The dollar value of start-up financing rebounded this quarter to an aggregate of $1.4 billion after a consecutive three-quarter decrease.

You will find new types of information in this quarter’s report, as well, such as new clinical trials, key regulatory events, and listings of therapies in the preregistration phase this quarter, plus changes from Q2 2020 and noteworthy upcoming approval decisions.

ASGCT is excited to continue this series of landscape reports and to tell the story of this emerging technology as it translates to clinics and improves the lives of patients worldwide.


5 / Q2 2021

Key takeaways from Q2 2021

One new gene therapy was approved, and three previously-approved gene therapies were approved in additional countries/regions

• Delytact, a new genetically engineered oncolytic herpes simplex virus type 1, was approved in Japan for malignant glioma

• Yescarta gained approval in China, Zolgensma in South Korea, and Abecma in Canada

Oncology remains the most active therapeutic area of research (preclinical through preregistration)

• More than 1,300 gene and cell therapy candidates are in development for oncology

Financing for start-ups showed a marked increase

• Seed and Series A financing volume nearly doubled in Q2, and the dollar value tripled, due to four $100M+ fundraisers

Overall dealmaking volume was down from Q1 but up from a year ago

• A total of 142 deals (financings, alliances, and acquisitions) were signed in Q2, down from 167 in Q1, but up from the 132 transactions in Q2 2020


Key highlights in Q2 2021 Q2

20

21


7 / Q2 2021

Approved gene therapies as of Q2 2021

Source: Pharmaprojects | Informa, July 2021

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 2005Head and neck cancer; nasopharyngeal cancer

China Shanghai Sunway Biotech

Rexin-G mutant cyclin-G1 gene 2006 Solid tumors Philippines Epeius Biotechnologies

Neovasculgenvascular endothelial growth factor gene

2011Peripheral vascular disease; limb ischemia

Russian Federation, Ukraine Human Stem Cells Institute

Imlygic talimogene laherparepvec 2015 Melanoma US, EU, Australia Amgen

Strimvelis autologous CD34+ enriched cells 2016 Adenosine deaminase deficiency EU Orchard Therapeutics

Kymriah tisagenlecleucel-t 2017Acute lymphocytic leukemia; diffuse large B-cell lymphoma

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

Novartis

Luxturna voretigene neparvovec 2017Leber’s congenital amaurosis; retinitis pigmentosa

US, EU, Australia, Canada Spark Therapeutics (Roche)

Yescarta axicabtagene ciloleucel 2017Diffuse large B-cell lymphoma; non-Hodgkin’s lymphoma; follicular lymphoma

US, EU, Japan, Canada, China Kite Pharma (Gilead)

Collategene beperminogene perplasmid 2019 Critical limb ischemia Japan AnGes

Zolgensma onasemnogene abeparvovec 2019 Spinal muscular atrophyUS, EU, Japan, Australia, Canada, Brazil, Israel, Taiwan, South Korea

Novartis

Zynteglo lentiviral beta-globin gene transfer 2019Transfusion-dependent beta thalassemia

EU bluebird bio

Tecartus brexucabtagene autoleucel 2020 Mantel cell lymphoma US, EU Kite Pharma (Gilead)

Libmeldy OTL-200 2020 Metachromatic Leukodystrophy EU Orchard Therapeutics

Breyanzi lisocabtagene maraleucel 2021 Diffuse large B-cell lymphoma US, Japan Celgene (Bristol Myers Squibb)

Abecma idecabtagene vicleucel 2021 Multiple myeloma US, Canada bluebird bio

Delytact teserpaturev 2021 Malignant Glioma Japan Daiichi Sankyo

Text highlighted in yellow represent new approvals during Q2 2021


8 / Q2 2021

Approved RNA therapies as of Q2 2021 (1/2)

Source: Pharmaprojects | Informa, July 2021 Text highlighted in yellow represent new approvals during Q2 2021


Disease(s) Locations approved* Originator company

Kynamro mipomersen sodium 2013 Homozygous familial hypercholesterolaemiaUS, Mexcio, Argentina, South Korea

Ionis Pharmaceuticals

Exondys 51 eteplirsen 2016 Dystrophy, Duchenne muscular US Sarepta Therapeutics

Spinraza nusinersen 2016 Muscular atrophy, spinal

US, EU, Canada, Japan, Brazil, Switzerland, Australia, South Korea, China, Argentina, Colombia, Taiwan,

Ionis Pharmaceuticals

Tegsedi inotersen 2018 Amyloidosis, transthyretin-related hereditary EU, Canada, US, Brazil Ionis Pharmaceuticals

Onpattro patisiran 2018 Amyloidosis, transthyretin-related hereditaryUS, EU, Japan, Canada, Switzerland, Brazil, Taiwan

Alnylam

Vyondys 53 golodirsen 2019 Dystrophy, Duchenne muscular US Sarepta Therapeutics

Waylivra volanesorsen 2019 Hypertriglyceridaemia; Lipoprotein lipase deficiency EU, UK Ionis Pharmaceuticals

Comirnaty tozinameran 2020 Infection, coronavirus, novel coronavirus prophylaxis

UK, Bahrain, Israel, Canada, US, Mexico, Kuwait, Singapore, Saudi Arabia, Chile, Switzerland, EU, Colombia, Philippines, Australia, Hong Kong, Peru, South Korea, New Zealand, Japan, Brazil, Sri Lanka, Vietnam, Thailand, Oman,

BioNTech

*For COVID-19 vaccines, this includes emergency use authorization and full approvals


9 / Q2 2021

Approved RNA therapies as of Q2 2021 (2/2)

Source: Pharmaprojects | Informa, July 2021 Text highlighted in yellow represent new approvals during Q2 2021


Disease(s) Locations approved* Originator company

Moderna COVID-19 vaccine

COVID-19 vaccine, Moderna 2020 Infection, coronavirus, novel coronavirus prophylaxis

US, Canada, Israel, EU, Switzerland, Singapore, Qatar, Vietnam, UK, Philippines, Thailand, Japan, South Korea, Brunei, Paraguay, Taiwan, Botswana, India, Indonesia, Saudi Arabia

Moderna Therapeutics

Givlaari givosiran 2020 Porphyria US, EU, Canada, Switzerland Alnylam

Oxlumo lumasiran 2020 Hyperoxaluria EU, US Alnylam

Ampligen rintatolimod 2020 Chronic fatigue syndrome Argentina AIM ImmunoTech

Viltepso viltolarsen 2020 Dystrophy, Duchenne muscular US, Japan NS Pharma

Leqvio inclisiran 2020Atherosclerosis; Heterozygous familial hypercholesterolaemia; Hypercholesterolaemia; Homozygous familial hypercholesterolaemia

EU, UK Alnylam

Amondys 45 casimersen 2021 Dystrophy, Duchenne muscular US Sarepta Therapeutics

*For COVID-19 vaccines, this includes emergency use authorization and full approvals


10 / Q2 2021

Key highlights in Q2 2021

Below are select noteworthy events that happened in Q2 2021

Source: Biomedtracker | Informa, July 2021

Brand Name Generic Drug Name Molecule type Disease Event Type Event Date

Zynteglo betibeglogene autotemcel Viral Gene Therapy Transfusion-dependent β-thalassemia Withdrawal from German Market Apr 20, 2021

Delytact teserpaturev Viral Malignant glioma Approval (Japan) Jun 11, 2021

Roctavian valoctocogene roxaparvovecViral Gene Therapy

Hemophilia A MAA Submission (Europe) Jun 28, 2021

N/A ciltacabtagene autoleucel Cellular* Multiple myeloma MAA Submission (Europe) Apr 30, 2021

Abecma idecabtagene vicleucel Cellular* Multiple myeloma CHMP (European Panel) Results (Positive) Jun 24, 2021

Skysona elivaldogene autotemcel Viral Gene Therapy Cerebral adrenoleukodystrophy CHMP (European Panel) Results (Positive) May 20, 2021

N/A ALLO-715 Cellular* Multiple myelomaRegenerative Medicine Advanced Therapy (RMAT) Designation

Apr 21, 2021

N/A AK-OTOF Viral Gene Therapy Hearing loss Rare Pediatric Disease (RPD) Designation Apr 13, 2021

N/A BBP-631 Viral Gene Therapy Congenital Adrenal Hyperplasia (CAH) Rare Pediatric Disease (RPD) Designation May 14, 2021

N/A LX-2006 Viral Gene Therapy Friedreich's Ataxia Rare Pediatric Disease (RPD) Designation Jun 30, 2021

*These are genetically modified cell therapies (CAR-T therapies)


Q2

20

21Gene therapy pipeline

Gene therapy and genetically modified cell therapies


12 / Q2 2021

Gene therapy pipeline

• In May 2021, there were 1,745 therapies in development from preclinical through preregistration.

• Preclinical therapies account for the majority of the pipeline with 1,223 therapies in preclinical studies. This accounts for 70% of therapies in clinical development.

Source: Pharmaprojects | Informa, May 2021

0

200

400

600

800

1000

1200

1400

1600

1800

2000

Number of Therapies by Year

Gene Therapy Pipeline updated to include 2021 data*

Preclinical Phase I Clinical Trial Phase II Clinical Trial Phase III Clinical Trial Pre-registration

*These snapshots are taken every May to allow for year-on-year comparisons


13 / Q2 2021

Global Status as of May

Number of Therapies

2020 2021

Preclinical 911 1,223

Phase I Clinical Trial 180 254

Phase II Clinical Trial 199 234

Phase III Clinical Trial 24 26

Pre-registration 7 8

Total number of therapies (preclinical to pre-registration) 1,321 1,745

Total number of therapies in the clinic 410 522

Gene therapy pipeline – 2020 vs 2021

• When comparing preclinical development between 2020 and 2021, there was a significant increase in the number of therapies in preclinical development with 911 in 2020 and 1,223 therapies in 2021

• There was a significant increase in Phase I clinical trials in 2021 (from 180 therapies in 2020 vs 254 therapies in 2021)


0

200

400

600

800

1000

1200

1400

Preclinical Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical Trials

Number of therapies in development as of May

2020 2021


14 / Q2 2021

Gene therapy pipeline – Q1 vs Q2 2021

• Over the course of the second quarter, the largest growth was a 9 percent increase in the number of therapies in preclinical development

• The number of Phase III therapies remained the same, and there is one less therapy in pre-registration with the approval of Delytact

• Therapies currently in preregistration:

• valoctocogene roxaparvovec (Biomarin)

• lenadogene nolparvovec (Genethon, GenSight Biologics)

• elivaldogene autotemcel (Bluebird Bio)

• nadofaragene firadenovec (Ferring, FKD Therapeutics, Trizell)

• relmacabtagene autoleucel (JW Therapeutics)

• ciltacabtagene autoleucel (Johnson & Johnson)

• eladocagene exuparvovec (PTC Therapeutics)


Global Status April 2021 July 2021

Preclinical 1,190 1,296

Phase I Clinical Trials 225 269

Phase II Clinical Trials 231 236

Phase III Clinical Trials 27 27

Pre-registration 8 7

Total 1,711 1,835


15 / Q2 2021

Gene therapy pipeline: Most commonly targeted therapeutic areas

• The top 2 therapeutic areas targeted by gene therapies from preclinical through pre-registration are oncology and rare diseases. Rare diseases includes oncology rare diseases

• The focus on oncology and rare diseases remains for therapies in clinical development


1048

869

202

139

135

76

71

53

52

49

39

29

26

7

4

1

Anticancer Products

Rare Diseases

Neurological Products

Alimentary/Metabolic Products

Sensory Products

Blood and Clotting Products

Musculoskeletal Products

Anti-infective Products

Immunological Products

NA/Unspecified

Cardiovascular Products

Respiratory Products

Dermatological Products

Genitourinary (including sex hormones)

Miscellaneous Products

Hormonal Products (excluding sex hormones)

Number of therapies

Number of therapies from preclinical through pre-registration

375

335

35

31

30

24

17

16

15

13

10

3

2

2

1

Anticancer Products

Rare Diseases


Sensory Products











NA/Unspecified

Number of therapies

Therapies in the clinic (excludes preclinical therapies)


16 / Q2 2021

275

157

118

107

83

82

70

69

57

55

54

52

44

43

42

38

36

35

35

33

Cancer, solid, unspecified

Cancer, unspecified

Cancer, myeloma

Cancer, leukaemia, acute lymphocytic

Cancer, lymphoma, non-Hodgkin's

Cancer, leukaemia, acute myelogenous

Cancer, haematological, unspecified

Cancer, lymphoma, B-cell

Cancer, pancreatic

Cancer, liver

Cancer, ovarian

Cancer, breast

Cancer, lung, non-small cell

Cancer, colorectal

Cancer, brain

Cancer, leukaemia, chronic lymphocytic

Cancer, melanoma

Cancer, gastrointestinal, stomach

Cancer, lung, unspecified

Cancer, leukaemia, unspecified

Number of therapies

Gene therapy pipeline: Most common oncology diseases targeted• From preclinical through pre-registration, 1,048 therapies are being developed for oncology• Multiple myeloma and acute lymphocytic leukemia (ALL) remain the top two specified oncology indications• Non-Hodgkin’s lymphoma is now the third most common indication (acute myelogenous leukemia in Q1)



17 / Q2 2021

27

21

19

19

18

16

16

15

12

11

11

11

10

9

8

8

7

7

6

6

Retinitis pigmentosa

Haemophilia A

Amyotrophic lateral sclerosis

Dystrophy, Duchenne's…

Anaemia, sickle cell

Cystic fibrosis

Haemophilia B

Thalassaemia

Batten's disease

Gaucher's disease

Leber's congenital amaurosis

Usher syndrome

Fabry's disease

Huntington's disease

Dementia, frontotemporal

Pompe's disease

Hyperphenylalaninaemia

Rett Syndrome

Angelman syndrome

Charcot–Marie–Tooth disease

Number of therapies

Non-oncology rare diseases

Gene therapy pipeline: Most common non-oncology rare diseases targeted

• There are 869 therapies in development for rare diseases from preclinical through pre-registration. This number includes oncology rare diseases. There are 435 therapies for non-oncology rare diseases in development

• Retinitis pigmentosa, Hemophilia A, amyotrophic lateral sclerosis (ALS), Duchenne’s muscular dystrophy (DMD), and sickle cell anemia make up the top 5 non-oncology rare diseases most targeted by gene therapies



18 / Q2 2021

Gene therapy pipeline: Most common additional diseases targeted

• From preclinical through pre-registration, there are 356 therapies that are in development for diseases outside of oncology or rare diseases

• Of diseases that are not oncology or rare diseases that are disclosed: neurological diseases, ocular disorders, Alzheimer’s disease, HIV/AIDs, and Parkinson’s Disease make up the 5 diseases most targeted by gene therapies


48

42

25

13

13

13

12

9

9

8

8

7

7

7

7

6

6

6

6

6

Undisclosed

Neurological disease, unspecified

Ocular disorder, unspecified

Alzheimer's disease

Infection, HIV/AIDS

Parkinson's disease

Hearing loss

Diabetes, Type 1

Macular degeneration, age-related, wet

Autoimmune disease, unspecified

Macular degeneration, age-related, dry

Arthritis, osteo

Cardiovascular disease, unspecified

Dermatological disease, unspecified

Musculoskeletal disease, unspecified

Hepatic dysfunction, alpha-1 antitrypsin…

Hepatic dysfunction, unspecified

Infection, coronavirus, novel coronavirus

Infection, hepatitis-B virus

Macular dystrophy, Stargardt's

Number of therapies

Non-oncology & non-rare diseases targeted by gene therapies


19 / Q2 2021

Gene therapy pipeline: Most common targets

Of the gene therapies in preclinical through pre-registration in which targets are disclosed:

• CD19 and B-cell maturation antigen (BCMA), also known as TNF receptor superfamily member 17, remain the most common targets for oncology indications

• Coagulation factor VIII is the most common target for non-oncology indications


14

9

8

8

7

6

6

6

5

5

5

5

5

5

4

4

4

4

coagulation factor VIII

glucosylceramidase beta

coagulation factor IX

vascular endothelial growth factor A

CF transmembrane conductance regulator

dystrophin

hemoglobin subunit beta

N-acetyl-alpha-glucosaminidase

ATP binding cassette subfamily A member 4

collagen type VII alpha 1 chain

galactosidase alpha

hemoglobin subunit gamma 1

N-sulfoglucosamine sulfohydrolase

serpin family A member 1

C-C motif chemokine receptor 5 (gene/pseudogene)

gap junction protein beta 2

hemoglobin subunit gamma 2

iduronidase alpha-L-

Number of therapies

Non-oncology targets

147

64

37

27

22

21

21

17

14

14

14

12

11

11

10

10

10

10

9

CD19 molecule

TNF receptor superfamily member 17

CD22 molecule

Not applicable

erb-b2 receptor tyrosine kinase 2

membrane spanning 4-domains A1

mesothelin

glypican 3

cancer/testis antigen 1B

interleukin 3 receptor subunit alpha

programmed cell death 1

CD33 molecule

CD7 molecule

killer cell lectin like receptor K1

claudin 18

epidermal growth factor receptor

mucin 1, cell surface associated

Not available on LocusLink/Entrez Gene

CD38 molecule

Number of therapies

Oncology targets


20 / Q2 2021

Gene therapy clinical trial activity in 2021

• A total of 75 clinical trials were initiated in 2021 so far

• The top 10 diseases for trial starts in 2021 were all for oncology with the top 3 being the blood cancers non-Hodgkin’s lymphoma (NHL), acute lymphocytic leukemia (ALL), and multiple myeloma

Source: Trialtrove | Informa, July 2021

0

5

10

15

20

25

30

35

I I/II II III Other

Number of trials by phase of study22

12

10

6

4

4

4

4

4

3

3

3

2

2

2

2

2

2

2

2

Oncology: Lymphoma, Non-Hodgkin's

Oncology: Leukemia, Acute Lymphocytic

Oncology: Multiple Myeloma

Oncology: Unspecified Solid Tumor

Oncology: Breast

Oncology: Cervical

Oncology: Head/Neck

Oncology: Leukemia, Acute Myelogenous

Oncology: Lymphoma, Hodgkin's

Oncology: Bladder

Oncology: Liver

Oncology: Lung, Non-Small Cell

Autoimmune/Inflammation: Epidermolysis Bullosa

Infectious Disease: HPV

Metabolic/Endocrinology: Sickle Cell Disease

Oncology: Colorectal

Oncology: Esophageal

Oncology: Gastric

Oncology: Leukemia, Chronic Lymphocytic

Oncology: Ovarian

Number of trials

Trials by Disease


21 / Q2 2021

Gene therapy pipeline: Most commonly used vectors

• 89% of gene therapies in development use viral vectors for delivery• Adeno-associated virus (AAV) and lentivirus remain most common viral vectors used in development • The largest quarterly growth: 33 percent increase in studies using a herpes simplex virus

Source: Cell and Gene Therapy dashboard | Informa, July 2021

405

288

123

73

3624 15

0

50

100

150

200

250

300

350

400

450

Adeno-associatedvirus (AAV)

Lentivirus Adenovirus Retrovirus Herpes simplex virus Poxivirus Other viruses

Viral vectors used in gene therapies


22 / Q2 2021

Gene therapy breakdown: CAR Ts dominate pipeline

▪ Of the gene therapies in development, 68% are genetically modified cell therapies

▪ Chimeric Antigen Receptor T cells (CAR Ts) represent 49% while T cell receptor T cells (TCR Ts) account for 12% of the genetically modified cell therapies in development

22

Gene therapy pipeline

Genetically modified cell therapies Gene therapy

Genetically modified cell therapy breakdown

CAR-T CAR-NK TCR-T Other

Source: Cell and Gene Therapy dashboard | Informa, July 2021


Q2

20

21Non-genetically modified cell

therapy pipeline


24 / Q2 2021

Non-genetically modified cell therapy pipeline

• In May 2021, there were 771 therapies in development (preclinical through pre-registration):

• 64% of candidates are in preclinical development

• There were 33 therapies in Phase III clinical studies

• There are 4 therapies in pre-registration (undergoing regulatory review):

• Gliovac (Epitopoietic Research)

• Astrostem (K-StemCell/Nature Cell)

• Donislecel (CellTrans)

• RVT-802 (Enzyvant Sciences/SinovantSciences)


0

100

200

300

400

500

600

700

800

900

Number of Therapies by Year

Non-genetically modified cell therapy pipeline*

Preclinical Phase I Clinical Trial Phase II Clinical Trial

Phase III Clinical Trial Pre-registration

*These are snapshots taken every May to allow for year-on-year comparisons


25 / Q2 2021

278

273

117

109

108

88

75

58

50

48

45

40

31

29

26

4

Anticancer Products

Rare Diseases









Sensory Products




NA/Unspecified


Number of therapies

Non-genetically modified cell therapy pipeline: Most common therapeutic areas targetedOf the cell therapies in development (preclinical through pre-registration):

• Similar to gene therapy, oncology and rare diseases are the most targeted therapeutic areas for non-genetically modified cell therapies (rare diseases includes oncology rare diseases).



26 / Q2 2021

Non-genetically modified cell therapy pipeline: Most common cancers targeted

Of the cell therapies in development (preclinical through pre-registration) for oncology:

• Of the diseases in which indications are specified, the top three indications are brain cancer, ovarian cancer and non-small cell lung cancer


9653

2925

2423

212121

1818

1713

1210

977

66

Cancer, solid, unspecifiedCancer, unspecified

Cancer, brainCancer, ovarian

Cancer, lung, non-small cellCancer, leukaemia, acute myelogenous

Cancer, haematological, unspecifiedCancer, liver

Cancer, melanomaCancer, head and neck

Cancer, pancreaticCancer, myeloma

Myelodysplastic syndromeCancer, breast

Cancer, colorectalCancer, prostate

Cancer, lymphoma, unspecifiedCancer, renal

Cancer, cervicalCancer, gastrointestinal, stomach

Number of therapies


27 / Q2 2021

Non-genetically modified cell therapy pipeline: Most common rare diseases targeted

Of the cell therapies in development (preclinical through pre-registration) for non-oncology rare diseases:

• Rare diseases: second most targeted therapeutic category for non-genetically modified cell therapies

• Of the non-oncology rare diseases being targeted, the top 3 are respiratory distress syndrome (ARDS), graft-versus-host disease (GVHD), and spinal cord injury


3825

2418

12888

66

5444

333333

Respiratory distress syndrome, acuteGraft-versus-host disease

Spinal cord injuryAmyotrophic lateral sclerosis

Cytokine release syndromeDystrophy, Duchenne's muscular

Huntington's diseaseRetinitis pigmentosaAnaemia, sickle cell

SclerodermaFibrosis, pulmonary, idiopathic

Buerger's syndromeEpidermolysis bullosa

Neuritis, opticAcute lung injury

Anaemia, aplastic, unspecifiedAnal fistula

Dementia, frontotemporalHaemophilia A

Hypoplastic left heart syndrome

Number of therapies


28 / Q2 2021

Non-genetically modified cell therapy trial activity in 2021


• A total of 40 clinical trials were initiated in 2021 so far

• The top four diseases for trial starts in 2021 were for COVID-19 infections, osteoarthritis, ovarian cancer, fallopian tube cancer and Parkinson’s disease

0

2

4

6

8

10

12

14

I II I/II III II/III Other

Number of trials by phase of study8

4

4

3

2

2

2

2

2

1

1

1

1

1

1

1

1

1

1

1

Novel coronavirus (2019-nCoV, COVID-19)

Osteoarthritis

Oncology: Ovarian

Oncology: Fallopian Tube

Parkinson's Disease

Cytomegalovirus Infection (CMV)

Respiratory Infections

Oncology: Multiple Myeloma

Oncology: Primary Peritoneal

Atopic Dermatitis

Cytokine Release Syndrome (CRS)

Epidermolysis Bullosa

Rheumatoid Arthritis

Transplantation/GVHD

Congestive Heart Failure

Alzheimer's Disease

Amyotrophic Lateral Sclerosis

Autism

Cerebral Palsy

Movement Disorders Number of trials

Trials by Disease


Q2

20

21

RNA therapy pipeline


30 / Q2 2021

RNA therapies pipeline

• In 2021:

• More than 600 therapies were in development (from preclinical to pre-registration stage), with 73% of therapies in preclinical development

• 20 therapies were in Phase III clinical studies

• 1 therapy in pre-registration (vutrisiran, Alnylam)


0

100

200

300

400

500

600

700

Nu

mb

er o

f th

erap

ies

RNA therapies pipeline*

Preclinical Phase I Clinical Trial Phase II Clinical Trial Phase III Clinical Trial Pre-registration

*These are snapshots are taken every May to allow for year-on-year comparisons


31 / Q2 2021

RNA therapy pipeline: Most common modalities

203

188

183

86

70

63

58

RNA interference

Antisense therapy

Messenger RNA

Anticancer, other

Prophylactic vaccine, anti-infective

Anticancer, immunological

Oligonucleotide, non-antisense, non-…

Number of therapies

April 2021


• Between Q1 and Q2 2021, messenger RNA therapeutics overtook RNA interference (RNAi) and antisense oligonucleotides to become the most common modality in development (preclinical through pre-registration

219

211

191

84

79

78

59

Messenger RNA

RNA interference

Antisense therapy

Anticancer, other

Prophylactic vaccine, anti-infective

Anticancer, immunological

Oligonucleotide, non-antisense,…

Number of therapies

July 2021


32 / Q2 2021

RNA therapies: Most common diseases targeted

Of the 692 RNA therapies currently in the pipeline (from preclinical through pre-registration):

• Oncology and rare diseases are the top 2 therapeutic areas being targeted. However, unlike gene therapies and non-genetically modified cell therapies, the top therapeutic area being targeted by RNA therapeutics is for rare diseases (please note that rare oncology diseases are included in the rare diseases therapeutic category)

241

173

142

96

94

59

47

44

42

37

25

19

17

16

7

3

2

Rare Diseases

Anticancer Products





Sensory Products



NA/Unspecified






Antiparasitic Products


Number of therapiesSource: Pharmaprojects | Informa, July 2021


33 / Q2 2021

RNA therapies: Most common diseases targetedOf the RNA therapies currently in the pipeline (from preclinical through pre-registration):

• Top oncology indications targeted are solid tumors with the top 5 (where specified) being melanoma, breast cancer, liver cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer

• For non-oncology rare diseases, Duchenne’s muscular dystrophy, cystic fibrosis, Huntington’s disease, amyotrophic lateral sclerosis (ALS), and retinitis pigmentosa are the top 5 targeted diseases


5452

2520202020

181515

1313

76

55555

4

Cancer, solid, unspecifiedCancer, unspecifiedCancer, melanoma

Cancer, breastCancer, liver

Cancer, lung, non-small cellCancer, pancreaticCancer, colorectal

Cancer, head and neckCancer, prostate

Cancer, brainCancer, ovarian

Cancer, renalCancer, bladder

Cancer, leukaemia, acute myelogenousCancer, lymphoma, unspecified

Cancer, mesotheliomaCancer, myeloma

Cancer, skin, unspecifiedCancer, lung, unspecified

Number of therapies

Oncology indications23

109

88

66

5555

444

333333

Dystrophy, Duchenne's muscularCystic fibrosis

Huntington's diseaseAmyotrophic lateral sclerosis

Retinitis pigmentosaDystrophy, myotonic muscular

Respiratory distress syndrome, acuteAngelman syndrome

COVID-19 complicationsFibrosis, pulmonary, idiopathic

Primary ciliary dyskinesiaAmyloidosis, transthyretin-related hereditary

HypertriglyceridaemiaLipoprotein lipase deficiency

Anaemia, sickle cellAngioedema, hereditary

Ataxia, spinocerebellarChronic obstructive pulmonary disease

Dystrophy, facioscapulohumeral muscularHyperphenylalaninaemia

Number of therapies

Non-oncology rare diseases


34 / Q2 2021

RNA therapy pipeline: Clinical trial activity

• 162 RNA therapy trials were initiated in the first 6 months of 2021

• Trials evaluating vaccines for COVID-19 infections predominate but there are also trials initiated for dyslipidemia and hepatitis B infections


0

10

20

30

40

50

60

II IV I III I/II II/III Other

Number of trials initiated by phase 102

9

7

4

3

3

3

3

2

2

2

2

2

1

1

1

1

1

1

Novel coronavirus (2019-nCoV, COVID-19)

Dyslipidemia

Infectious Disease: HBV

Oncology: Unspecified Solid Tumor

Hepatic Fibrosis

Hypertension

Amyotrophic Lateral Sclerosis

NAFLD

Muscular Dystrophy

Spinal Muscular Atrophies

Respiratory Infections

Oncology: Prostate

Vaccines (Infectious Disease): Other Viral Vaccines

Sjogren's Syndrome

Acute Coronary Syndromes

Congestive Heart Failure

Coronary Artery Disease

Peripheral Arterial Disease

Thrombotic Disorders

Number of trials

Trials by Disease


Q2

20

21

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


36 / Q2 2021

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

6 8

1712 10

49

40

72

5761

77

60

82

98

71

0

20

40

60

80

100

120

Q2 2020 Q3 2020 Q4 2020 Q1 2021 Q2 2021

Nu

mb

er o

f d

eals

Total number of deals by type, most recent five quarters

*Financing

Alliance

Acquisition

Source: Biomedtracker | Informa, July 2021 *Financings include public financings (IPOs and follow-ons) plus privately raised funding through venture rounds, debt offerings, or private investment in public equity

• The gene, cell, & RNA industry has seen a greater volume of alliances, plus a slight uptick in acquisitions in Q2 2021 vs one year ago

• Biggest decrease in Q2 2021 was seen in financings, with >20 fewer transactions done in Q2 than in Q1, and this was mainly attributable to fewer follow-on public offerings


37 / Q2 2021

Q2 2021 acquisitions in gene, cell, & RNA therapyDeal Date Deal Title Potential Deal Value (USD)

04/09/2021 Sanofi Acquires Tidal Therapeutics 470,000,000

04/20/2021 SparingVision Acquires GAMUT Therapeutics Undisclosed

05/04/2021Athenex Acquires Kuur Therapeutics to Expand Cell Therapy Development with Off-the-Shelf Engineered CAR-NKT Platform

185,000,000

05/17/2021 Charles River Laboratories to Acquire Vigene Biosciences to Enhance Gene Therapy Capabilities 350,000,000

06/01/2021 Auris Medical Acquires RNA Therapeutics Company Trasir, Changes Name and Strategic Focus Undisclosed

06/14/2021 Brooklyn ImmunoTherapeutics Executes Letter of Intent to Acquire Novellus Therapeutics 125,000,000

06/14/2021 Avalon GloboCare to Acquire SenlangBio in All Stock Transaction Undisclosed

06/22/2021uniQure to Acquire Corlieve Therapeutics and Advance its Gene Therapy Program to Treat Temporal Lobe Epilepsy

298,300,000

06/30/2021 Scopus BioPharma Expands Immunotherapy Pipeline with Acquisition of Olimmune Undisclosed

06/17/2021 Danaher Pays $9.6B for Aldevron, Manufacturer of High-Quality Plasmid DNA, mRNA, and Proteins 9,600,000,000



Q2

20

21

Start-up funding for gene, cell, & RNA therapy companies


39 / Q2 2021

Start-up financing for gene, cell, & RNA therapy companies

$1,043.7

$523.5

$744.8

$479.8

$1,445.3

11

1618

13

23

0

5

10

15

20

25

$-

$200.0

$400.0

$600.0

$800.0

$1,000.0

$1,200.0

$1,400.0

$1,600.0

Q2 2020 Q3 2020 Q4 2020 Q1 2021 Q2 2021

Nu

mb

er o

f fi

nan

cin

gs

Tota

l rai

sed

($

M)

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

Total raised ($M) Number of financingsSource: Biomedtracker | Informa, July 2021

• 23 companies raised seed or Series A financing in Q2 2021, reaching an aggregate $1.4 billion

• Nearly 75% (17/23) of biotechs are based in the US (mainly Massachusetts and California), the rest in Europe and Asia

• Top financing ($250M) was done by a new company created by Intellia, Cellex (and subsidiary GEMoaB), and Blackstone to develop allogeneic universal CAR-T therapies based on Intellia’s CRISPR/Cas9 platform and CEMoaB’s switchable, universal CAR T-cell platforms


40 / Q2 2021

Q2 2021 start-up financing for gene, cell, & RNA therapy companies (1/2)


Deal Date Deal Title Company Location Academic SourcePotential Deal

Value (USD)

04/07/2021Shoreline Biosciences Announces $43M Early Round To Advance Pipeline

United States, California, San Diego

University of California, San Diego 43,000,000

04/19/2021 Rejuvenate Bio Raises over $10M in Series A financing United States, California, San Diego

Harvard University: Harvard Medical School and Wyss Institute

10,000,000

04/20/2021 Code Biotherapeutics Launches with $10M in Seed FinancingUnited States, Pennsylvania, Hatfield

Undisclosed 10,000,000

04/29/2021 Capsida Biotherapeutics Debuts with $50M Series A RoundUnited States, California, Newbury Park

California Institute of Technology: Tianqiao and Chrissy Chen Institute for Neuroscience

50,000,000

04/30/2021 Treeline Biosciences Launches with $211M Series A RoundUnited States, Connecticut, Stamford

Undisclosed 211,669,568

05/05/2021 Isolere Bio Closes $7M in Seed FundingUnited States, North Carolina, Durham

Duke University 7,000,000

05/06/2021 Dyno Therapeutics Closes $100M Series A RoundUnited States, Massachusetts, Cambridge


100,000,000

05/10/2021Gennao Bio Closes $40M Series A Financing to Develop Pipeline of Targeted Nucleic Acid Therapeutics

United States, New York, New York

Yale University 40,000,000

05/11/2021 Appia Bio Launches With $52M Series A FinancingUnited States, California, Los Angeles

University of California, Los Angeles 52,000,000

05/18/2021G2 Bio Companies Launch with $200M to Develop Transformative Genetic-Based Therapies

United States, Pennsylvania, Philadelphia

University of Pennsylvania: Gene Therapy Program 200,000,000

05/18/2021Vedere Bio II Launches with $77M Series A Financing to Develop Ocular Gene Therapies

United StatesUniversity of California, Berkeley; University of Pennsylvania: School of Veterinary Medicine

77,000,000

05/20/2021HAYA Therapeutics Completes CHF 18M Seed Financing To Advance Anti-fibrotic Therapies Targeting Long Non-coding RNAs

Switzerland, Vaud Lausanne University Hospital 19,985,500

05/27/2021 miRecule Inc. Closes $5.7M Seed FundingUnited States, Maryland, Gaithersburg

National Institutes of Health: BioHealth Innovation 5,700,000


41 / Q2 2021

Q2 2021 start-up financing for gene, cell, & RNA therapy companies (2/2)


Deal Date Deal Title Company Location Academic SourcePotential Deal

Value (USD)

06/09/2021Alcyone Therapeutics Launches with $23M to Advance Gene Therapies for CNS Disorders

United States, Massachusetts, Lowell

Nationwide Children's Hospital: Abigail Wexner Research Institute

23,000,000

06/15/2021 VectorY Raises $37.58M in Seed Financing Netherlands, Amsterdam Undisclosed 37,582,695

06/16/2021Mnemo Therapeutics Announces $90M Series A to Accelerate Next Generation Integrated CAR-T and Epigenetic Targeting Platform

France, Paris Institut Curie; Memorial Sloan Kettering Cancer Center 90,000,000

06/16/2021 Ochre Bio Closes $9.6M Seed Financing United Kingdom, Oxford Working in collaboration with Oxford University 9,600,000

06/18/2021Nuevocor Closes $24M Series A Financing to Advance Novel Gene Therapies for Cardiomyopathies

Singapore Agency for Science, Technology and Research (A*STAR) 24,000,000

6/22/2021Unnamed autologous/allogeneic CAR-T company launched with $250M from Blackstone Life Sciences, Intellia Therapeutics, and Cellex Cell Professionals

United States, Massachusetts, Cambridge

n/a – founded around pooled resources from GEMoaBGmbH (Cellex’s parent company) and Intellia

250,000,000

06/23/2021 Abata Therapeutics Launches with $95M Series A FundingUnited States, Massachusetts, Cambridge

Co-founders are from Harvard Medical School, Massachusetts Institute of Technology, and University Hospital of Zurich

95,000,000

06/23/2021 Vita Therapeutics Raises $32M in Series A FinancingUnited States, Maryland, Baltimore

Johns Hopkins University; Kennedy Krieger Institute 32,000,000

06/23/2021Strand Therapeutics Raises $52M via Oversubscribed Series A Round

United States, Massachusetts, Cambridge

MIT Synthetic Biology Center 52,000,000

06/24/2021OliX' subsidiary mCureX Therapeutics Raises ₩6.5B in Pre-Series A Investment

Korea (South) n/a – subsidiary of OliX Pharmaceuticals 5,738,860


42 / Q2 2021

Notable Q2 2021 start-up gene, cell, & RNA therapy companies

Source: Biomedtracker | Informa, July 2021; company websites

Company details Academic sourceFinancing

type/amount raisedLead investor(s) Therapy areas of interest

T-cell engineering EnfiniTplatform technology, including identification of antigens with greater tumor specificity and development of next-generation CAR-T therapies

Institut Curie; Memorial Sloan Kettering Cancer Center

Series A; $90M

Casdin Capital, SofinnovaPartners, and an undisclosed investor

Oncology

CapsidMap platform, which designs AAV vectors using artificial intelligence


Series A/$100MAndreessen Horowitz

Liver, muscle, eye, central nervous system, lung, heart and kidney diseases

DiscoverHAYA platform to discover tissue and cell-specific long non-coding RNA drug candidates

Lausanne University Hospital

Seed/$20MBroadview Ventures

Fibrosis and conditions related to aging


Q2

20

21

Upcoming catalysts


44 / Q2 2021

Upcoming Catalysts

Therapy Generic Name Disease Catalyst Catalyst Date

Skysonaelivaldogene autotemcel, Lenti-D

Cerebral adrenoleukodystrophy

European Approval Decision

May 21 - Sep 30, 2021

Yescarta axicabtagene ciloleucel Marginal cell lymphoma FDA Approval Decision Jun 18 - Sep 30, 2021

Abecma idecabtagene vicleucel Multiple myelomaEuropean Approval Decision

Jun 24 - Aug 30, 2021

Below are noteworthy catalysts (forward looking events) that are expected in Q3 2021



Q2

20

21Appendix

Methodology, sources, & glossary of key terms


46 / Q2 2021

Methodology: Sources and scope of therapies

Pipeline and trial data• Data derived from Citeline (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: Gene

therapy, cell therapy; antisense, oligonucleotides

Sources for all data come from Informa Pharma Intelligence


47 / Q2 2021

Glossary of Key TermsTherapy Type Definitions

Gene therapy is the introduction, removal, or change in genetic material—specifically DNA or RNA—into the cells of a patient to treat a specific 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 of oligonucleotides without using vectors is covered separately in the antisense therapy class; RNA interference class; or oligonucleotide, non-antisense, non-RNAi class. Platform technologies for gene delivery are covered separately in the gene 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 cell surface 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

Therapies which have a replication-competent virus, that lyse pathogenic cells directly. These are normally genetically modified to render them harmless to normal tissues. Examples include oncolytic viruses which specifically attack cancer cells.


48 / Q2 2021

Glossary of Key TermsTherapy type definitions, cont.

Cell therapy includes the following therapeutic classes:

Cellular therapy, stem cellRegenerative therapy which promotes the repair response of injured tissue using stem cells (cells from which all other specialized cells would originate).

Cellular therapy, tumor infiltrating lymphocyteAdoptive 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, otherCellular therapies that do not fall under the categories of cellular therapy, stem cell; cellular therapy, CAR; cellular therapy, TIL; cellular therapy, TCR; or the specific cellular therapy are unspecified.


49 / Q2 2021

Glossary of Key TermsTherapy type definitions, cont.

RNA therapy includes the following therapeutic classes:

Messenger RNATherapies that carry the desired mRNA code to overcome genetic mutations. The mRNA sequence will replace the defective mRNA in a patient and starts 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. Sequences delivered 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 gene therapy (see “gene therapy" therapeutic class). In vivo, these sequences block the expression of a specific protein by forming 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, or antisense RNA may be expressed from a vector as a form of gene therapy. They may prevent the expression of a specific protein in vivo by binding to and inhibiting the action of mRNA, since they have a specific oligonucleotide sequence which is complementary to the DNA or RNA sequence which codes for the protein.


50 / Q2 2021

Glossary of Key TermsDevelopment status definitions

Pipeline Drugs that are in active development

Preclinical Not yet tested in humans

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

Phase II First efficacy trials in small numbers of patients

Phase III Large scale trials for registrational data

Pre-registration Filing for approval made to regulatory authorities

Approved Approval from relevant regulatory authorities for human use

Unspecified indications

Cancer, unspecified Indications for which the specific tumor type is not specified

Cancer, 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

Deal type categories

Alliances Co-marketing, co-promotion, disease management, joint venture, manufacturing or supply, marketing-licensing, product or technology swap, product purchase, R+D and marketing-licensing, reverse licensing, trial collaborations

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

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


51 / Q2 2021

Report Contributors

Ly Nguyen-Jatkoe, PhDExecutive Director, AmericasInforma Pharma Custom Intelligence

Amanda Micklus, MScSenior Pharma ConsultantInforma Pharma Custom Intelligence

David Barrett, JDCEOAmerican Society of Gene + Cell Therapy

Betsy Foss-Campbell, MADirector of Policy and AdvocacyAmerican Society of Gene + Cell Therapy

Alex Wendland, MSJDirector of CommunicationsAmerican Society of Gene + Cell Therapy

Doro Shin, MPHSenior Director, Content MarketingInforma Pharma Intelligence

Contact: David Barrett, JD at [email protected]

Contact:[email protected]

mailto:[email protected]

mailto:[email protected]?subject=ASGCT%20Quarterly%20Report

Cell, Gene, & RNA Therapy Landscape

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