10 Gene and Cell Therapy Companies to Watch

The fields of cell and gene therapy have continued to experience exponential growth, with the emergence of mRNA vaccines for COVID-19 helping boost awareness and acceptance of these therapies with the general public all while regulatory agencies approve an increasing number of gene-editing and cellular therapies across multiple therapeutic areas. 

Since 2015, the global cell and gene therapy market has increased more than 25%, with gene therapies leading the way with an estimated 30% compound annual growth rate through 2025.¹ Although gene therapies targeted at rare and chronic diseases are fast-growing, oncology remains one of the top opportunities in the space, especially for cell therapies. 

With developments at the bench and the bedside occurring at unprecedented rates, GeneTherapyLive has compiled a list of 10 cell and gene therapy companies to watch as they advance their pipelines. (Listed in alphabetical order)

Abeona Therapeutics focuses on developing next generation adeno-associated virus (AAV) capsids with their AIM vector technology. Their lead program is EB-101 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), which is currently being evaluated in the phase 3 VITAL study (NCT04227106).² The therapy has received orphan drug designation (ODD), fast track designation (FTD), and regenerative medicine advanced therapy designation (RMATD) by the FDA. 

Other candidates the company is developing include ABO-102 for the treatment of mucopolysaccharidosis type 2 A (MPSIIA), which has received ODD, FTD, RMATD, and rare pediatric disease designation (RPDD), and ABO-101 for the treatment of MPS type 2 B, which has received ODD and RPDD from the FDA. Both programs are in phase 1 studies. Another candidate, ABO-201 for the treatment of juvenile Batten disease (CLN3), is in preclinical studies.

Atara Biotherapeutics uses their allogeneic Epstein Barr virus (EBV) platform to create cell therapies for a number of indications. Their lead program, tabelecleucel (Tab-cel), is being evaluated in the phase 3 ALLELE study (NCT03394365) for the treatment of EBV-associated post-transplant lymphoproliferative disease (EBV + PTLD) after failure of rituximab or rituximab and chemotherapy (RR EBV +PTLD).³ Their biologic license application (BLA) is expected in Q3 2021, with Tab-cel having the potential to be the first allogeneic T-cell immunotherapy on the market by 2022. 

Other candidates in development by Atara include ATA188 for the treatment of progressive multiple sclerosis (MS), which is in phase 2 studies, and ATA2271 for the treatment of mesothelioma and solid tumors, which is in phase 1 studies. Preclinical studies evaluating candidates for the treatment of B-cell malignancies and infectious diseases are also ongoing.

Bluebird Bio has faced some notable setbacks recently, with 4 studies halted over safety concerns in February 2021. Following a demonstration that their lentiviral vector BB305 was not associated with cancer, all studies resumed in June 2021. Despite these challenges, Bluebird has a promising pipeline of gene-modified cell therapies, with ide-cel approved for the treatment of relapsed/refractory multiple myeloma (R/R MM) in March 2021, and beti-cel approved in the European Union for the treatment of β-thalassemia. Beti-cel has received ODD and is in phase 3 studies in the US.

Additional candidates in phase 3 studies include eli-cel for the treatment of cerebral adrenoleukodystrophy (CALD) and lentiglobin for the treatment of sickle cell disease (SCD), which has received FTD, ODD, RMATD, and RPDD from the FDA.

Celularity is exploring the use of its placental-derived CAR T and modified natural killer (NK) cell therapies for hematologic and oncologic indications. Its candidates include CYNK-001, an off-the-shelf allogeneic unmodified NK cell therapy for the treatment of acute myeloid leukemia (AML) and glioblastoma multiforme (GBM), CYNK-101 for the treatment of HER2+ gastric cancer, CyCART-19 for the treatment of B-cell malignancies, and APPL-001 for the treatment of Crohn disease and degenerative diseases. 

Although most programs are currently in phase 1 or 2, the biotech company has a promising outlook with the recent expansion of its CYNK-001 study to include patients with relapsed/refractory AML. CYNK-001 has received FTD and ODD, and Celularity recently went public through a merger with GX Acquisition Corp in July 2021. 

CRISPR Therapeutics is developing autologous CRISPR/Cas9 gene-edited hematopoietic stem and progenitor cell (HPSC) therapies for multiple indications. Their candidates include CTX001, being developed in collaboration with Vertex Pharmaceuticals, for which a phase 1/2 study (NCT03745287) for β-thalassemia and SCD is currently enrolling. Other candidates in phase 1 studies include CTX110 for CD19+ malignancies, CTX120 for MM, and CTX130 for solid tumors and hematologic malignancies.

The company also recently announced a partnership with Capsida Biotherapeutics in June 2021 for the research and development of gene editing therapies for familial amyotrophic lateral sclerosis (ALS) and Freidreich ataxia.

Gamida Cell’s omidubicel, an AHSC transplant solution, met all primary and secondary end points in its phase 3 trial (NCT02730299) for high-risk hematologic malignancies and severe aplastic anemia.⁴ The treatment’s BLA submission is expected in Q4 2021 and it previously received breakthrough therapy designation (BTD) and ODD from the FDA.

The company’s next candidate in development is the NK cell immunotherapy GDA201 for the treatment of non-Hodgkin lymphoma and MM. GDA201 is currently being evaluated in phase 1 studies.

Intellia Therapeutics employs CRISPR gene editing technology in its iv vivo and ex vivo therapies. Their lead candidate, NTLA-2001, is an in vivo gene-editing therapy for the treatment of hereditary transthyretin (ATTR) amyloidosis. Interim data from its phase 1 study was recently reported in the New England Journal of Medicine, demonstrating preliminary safety and efficacy and support for in vivo CRISPR genome editing in humans. 

Another candidate, OTQ923/HIX76, is also being evaluated in phase 1 studies for the treatment of SCD, while NTLA-2002 and NTLA-5001 are being evaluated for the treatment of hereditary angioedema and AML, respectively, in preclinical studies.

Krystal Biotech is developing gene therapies using its Skin Targeted Delivery platform (STAR-D). Its lead program is investigating B-VEC for the treatment of RDEB currently in a phase 3 study (NCT04491604),⁵ with topline data expected in Q4 2021.

The company is also conducting phase 1/2 studies of KB105, which has received ODD from the FDA for the treatment of TGM-1-deficient autosomal recessive congenital ichthyosis and KB301 for the treatment of aesthetic skin conditions. Other candidates in preclinical studies include KB104 for the treatment of Netherton syndrome, KB303 and KB304 for aesthetic skin conditions, and KB407 for cystic fibrosis, which has received ODD from the FDA.

Passage Bio boasts a promising pipeline of gene therapy candidates in phase 1/2 studies, all of which have received FTD from the FDA. These include PBGM01 for the treatment of GM1 gangliodosis, PBKR03 for the treatment of Krabbe disease, and PBFT02 for the treatment of frontotemporal dementia-GRN. The company also has a preclinical study of PBML04 for the treatment of metachromatic leukodystrophy.

Sangamo Therapeutics has partnered with Pfizer to develop its lead program SB-525, a gene therapy being evaluated for the treatment of hemophilia A in the phase 3 AFFINE study (NCT04370054).⁶ The therapy has received FTD and RMATD from the FDA. Sangamo also partnered with Pfizer for the development of an ALS gene therapy which is currently in preclinical studies, among other candidates.

The company is also conducting phase 1/2 studies of TX200, a gene-edited cell therapy for preventing rejection of transplanted kidneys in patients with end-stage renal disease, ST-920 for Fabry disease, SAR445136 for SCD, and ST-400 for β-thalassemia.

REFERENCES

1. Gene therapy accounts for a major portion of the cell and gene therapy market and it is expected to have the most growth. News release. The Business Research Company. February 23, 2021. https://www.globenewswire.com/news-release/2021/02/23/2180767/0/en/Gene-Therapy-Accounts-For-A-Major-Portion-Of-The-Cell-And-Gene-Therapy-Market-And-It-Is-Expected-To-Have-The-Most-Growth.html

2. Phase 3, open-label clinical trial of EB-101 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). US National Library of Medicine. January 27, 2021. https://clinicaltrials.gov/ct2/show/NCT04227106
3. Tabelecleucel for solid organ or allogeneic hematopoietic cell transplant participants with epstein-barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) after failure of rituximab or rituximab and chemotherapy (ALLELE). US National Library of Medicine. June 18, 2021. https://clinicaltrials.gov/ct2/show/NCT03394365
4. Stem cell transplantation with NiCord® (Omidubicel) vs standard umbilical cord blood in patients with leukemia, lymphoma, and myelodysplastic syndrome (MDS). US National Library of Medicine. January 8, 2021. https://clinicaltrials.gov/ct2/show/NCT02730299
5. The objective of this study is to compare the efficacy and safety of beremagene geperpavec (B-VEC) topical gel with that of placebo for the treatment of dystrophic epidermolysis bullosa (DEB). US National Library of Medicine. April 29, 2021. https://clinicaltrials.gov/ct2/show/NCT04491604
6. Study to evaluate the efficacy and safety of PF-07055480 / giroctocogene fitelparvovec gene therapy in moderately severe to severe hemophilia A adults (AFFINE). US Naitonal Library of Medicine. July 16, 2021. https://clinicaltrials.gov/ct2/show/NCT04370054