Around the Helix: Cell and Gene Therapy Company Updates – September 28, 2022

The cell and gene therapy sectors are growing exponentially, with new players emerging daily and much progress being made both in and out of the lab. CGTLive’s Around the Helix is your chance to catch up with the latest news in cell and gene therapies, including partnerships, pipeline updates, and more.

Zevorcabtagene autoleucel (zevor-cel; CARsgen; CT053) yielded a 100% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (R/R MM) enrolled in the phase 1b/2 LUMMICAR-2 study (NCT03915184).

Calibr’s CLBR001 + SWI019, an investigational combination immunotherapy, has demonstrated promising safety and efficacy in preliminary data from a phase 1 clinical trial (NCT04450069) in patients with relapsed/refractory (r/r) B-cell malignancies presented at the 7th Annual CAR-TCR Summit, in Boston, Massachusetts, on September 20-22.

Decibel Therapeutics has submitted an investigational new drug application (IND) to the FDA for its gene therapy candidate DB-OTO for the intended treatment of profound congenital hearing loss due to an otoferlin deficiency in pediatric patients.

Pfizer and Sangamo Therapeutics have reopened enrollment in the phase 3 AFFINE study (NCT04370054) of giroctocogene fitelparvovec for the potential treatment of moderately severe to severe hemophilia A.

The first patient has been dosed in a phase 1/2 clinical trial (NCT05144386) of Excision BioTherapeutics’ EBT-101, an in vivo CRISPR-based gene editing approach intended for the treatment of human immunodeficiency virus type 1 (HIV-1).

Deleting the 3′-untranslated region (3′-UTR) miR-17 microRNA binding site on PKD1 mRNA via CRISPR/Cas9 editing in cellular, ex vivo, and mouse models of autosomal dominant polycystic kidney disease (ADPKD) alleviated cyst growth and increased levels of Polycystin-1 (PC1), the disease-targeted protein, shedding light on a potential gene therapy approach for treating the disease, according to research recently published in Nature Communications.

The FDA has cleared the investigational new drug application (IND) for SynKIR-110, Verismo Therapeutics’ killer immunoglobulin-like receptor - chimeric antigen receptor (KIR-CAR) T-cell therapy for the intended treatment of mesothelin expressing ovarian cancer, cholangiocarcinoma and mesothelioma.

The first patient with FRKP-related limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) has been treated with Atamyo Therapetuics’ ATA-100 (GNT0006), an investigational gene therapy, in a phase 1/2 clinical trial (EudraCT 2021-004276-33, NCT05224505).

The National Institute on Deafness and Other Communication Disorders (NIDCD), of the National Institutes of Health, has granted $3.5 million to Xue Zhong Liu, MD, PhD, from University of Miami Miller School of Medicine to develop a gene therapy to treat hearing loss-related Usher syndrome.

Dystrogen Therapeutics’ DT-DEC01, an investigational chimeric cell therapy intended for the treatment of Duchenne muscular dystrophy (DMD), has demonstrated promising safety and efficacy in 6-month data from 3 patients treated in an on-going clinical trial in Poland.

High-dose, repeated injections of Engensis, an intramuscularly delivered gene therapy developed by Helixmith, were found to be safe and well-tolerated in participants with amyotrophic lateral sclerosis (ALS) enrolled in a phase 2a trial (NCT04632225).

Vertex Pharmaceuticals and CRISPR Therapeutics have announced that they will be submitting biologics license applications (BLA) for exagamglogene autotemcel (exa-cel) for rolling review for the treatments of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) beginning in November 2022.

The first patient has been treated in a phase 1/2/3 clinical trial (GOLD; NCT04912843) of Neurophth’s NR082, an investigational gene therapy intended for the treatment of Leber hereditary optic neuropathy (LHON) associated with mtND4 mutations.

The data was published in PLOS ONE and showed that MMUT-deficient mice treated with an AAV vector (mLB-001) carrying the mouse MMUT gene experienced less body-weight loss and had improved mortality while on a high protein diet.

Allogene Therapeutics will now have a right to elect a license to UCART19, ALLO501, and ALLO-501A16 outide the United State.

The method seeks to avoid toxicity associated with traditionl approaches and utilizes GenExact ssDNA designed with Cas9-targeted sequences to achieve up to 40% knock-in editing efficiency.

The cell analysis solution allows for multiple critical quality attributes to be assessed in 1 automated workflow, and PerkinElmer exptects that it will be of particular interest for CAR-T therapy research.

The Chimeric Antigen Receptor Macrophages (CAR-iMAC) are derived from induced pluripotent stem cells (iPSC) and are intended to be an off-the-shelf approach to cancer immunotherapy.

TILT-123, an oncolytic adenovirus, is intended to boost anti-tumor T-cell immune responses with 2 human cytokines. It will be evaluated in combination with MSD's KEYTRUDA, an anti-PD-1 therapy, in a phase 1 clinical trial for patients with immune checkpoint inhibitor refractory non-small cell lung cancer.

LAVA-1223 is intended to target and activate gamma delta T-cells in order to treat solid tumors that express epidermal growth factor receptor (EGFR). It is currently in the preclinical stage.

The phase 1/2 clinical trial evaluating an investigational gene therapy for Huntington disease will use the synthetic DNA material as a component in the therapy.

The collaboration aims to utilize machine learning and artificial intelligence in the pursuit of identifying features that could help T-cell therapies succeed in solid tumors.

Research and early-clinical grades are available, with late-clinical/commercial grades planned to be offered next year. The services will be available only to clients doing AAV manufacturing via Forge Biologics.

The rights to the platform are non-exclusive, and Sanofi will use them to advance development of ex vivo NK cell therapies for cancer indications.

The AAV5 DetectCDx Kit will be ARUP's first test kit to be used in Europe.

As part of the strategic platform license, Vertex Pharmaceutircals will have non-exclusive rights to utilize the Flow Electroporation technology and ExPERT™ platform for its CRISPR/Cas9-based therapy.