CGTLive's 2023 Pillars of Progress: Most-Read Conference Coverage Stories

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

One of the key places to find the latest updates on these treatments is during major medical society meetings. In 2023, our team covered updates from more than 30 meetings of organizations across the breadth of medical specialties in search of the biggest news in cell and gene therapy.

Here, we'll highlight some of the most-read content from CGTLive's conference coverage this year. Click the buttons to read further into these stories.

AHA — Patients With Congestive Heart Failure Show Clinically Meaningful Improvements After Gene Therapy

• AB-1002 gene therapy demonstrated clinically meaningful improvements in multiple functional outcomes in a phase 1/2 clinical trial.
• The therapy aims to increase the production of a therapeutic protein inhibitor 1 and block protein phosphatase 1 linked to CHF.
• The therapy is delivered using the AAV2i8 vector capsid through intracoronary injection at relatively low doses.

Data from a phase 1/2 clinical trial (NCT04179643) of AB-1002 (AskBio; NAN-101) gene therapy were presented at the American Heart Association’s (AHA) Scientific Sessions 2023. Investigators found that 3 of 6 patients in cohort 1, those that completed 12-month follow-up, showed clinically meaningful improvements in left ventricular ejection fraction, NYHA Functional Class, Minnesota Living with Heart Failure Questionnaire, cardiopulmonary exercise test, and 6-minute walk test compared to baseline. The remaining 3 patients were still within 3 months of treatment and were not yet evaluable.

"We believe these encouraging early results in patients with advanced heart failure are important for the congestive heart failure community, as they bring hope to a sub-population where treatment options are needed."
— Litsa G. Kranias, PhD, of University of Cincinnati

ASCO — Evidence of Disease Reduction Observed Among Patients Treated With Ovarian Cancer CAR-T PRGN-3005

• PRGN-3005, an investigational MUC16-directed CAR-T therapy, was designed to target the MUC16 antigen expressed on ovarian tumors and enhance T-cell persistence by expressing a cytokine.
• The CAR-T therapy demonstrated favorable safety, with mild cytokine release syndrome, and T-cells persisted for an extended period after infusion.
• The next phase involves a larger phase 2 clinical trial, already underway, to expand patient enrollment and further assess the clinical activity of PRGN-3005.

PRGN-3005, an investigational MUC16-directed CAR-T therapy intended for the treatment of patients with platinum-resistant ovarian cancer, is currently being assessed in a phase 1/1b clinical trial (NCT03907527). The CAR-T was designed with a feature expected to improve persistence and overcome limitations that have held back the success of trials for other CAR-T therapies directed at ovarian cancer. Interim results from the study evaluating PRGN-3005 were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting.

"This CAR T-cell was engineered not only to express the antigen, but also to express a cytokine that would keep the T-cells alive for a long period of time. We think this overcomes 1 of the main reasons why CAR T-cells may not work in solid tumors."

– Mary 'Nora' Disis, MD, of University of Washington

ESGCT — CRISPR Therapy Well Tolerated, Detectable in First 3 Participants With HIV

• EBT-101, an investigational gene therapy targeting latent HIV-1 using CRISPR-Cas9 technology, has been well-tolerated with mild adverse events in participants with HIV-1.
• EBT-101 gene therapy has demonstrated biodistribution with peripheral exposure in the first cohort of patients and is planned to advance to the next dosing cohort.
• The EBT-101-001 trial aims to evaluate the safety, efficacy, and long-term outcomes of EBT-101 therapy.

EBT-101 (Excision Biotherapeutics) was well-tolerated and detectable in all participants with human immunodeficiency virus type 1 (HIV-1) treated so far in a phase 1/2 trial (NCT05144386). Updated data from the first-in-human trial were presented at the 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), in which the therapy was shown to remove large sections of HIV proviral DNA in preclinical studies and was granted Fast Track designation by the FDA in 2023.

"We believe that sharing this initial safety and biodistribution data is important for the HIV/AIDS community, the larger infectious disease community, and for gene therapies in development for other indications."
— Daniel Dornbusch, of Excision

AACR — Metastatic Colorectal Cancer Therapy CAR-T GCC19CART Improves Upon Third-Line SOC Therapies

• GCC19CART exhibited superior efficacy in comparison to standard of care third-line therapies.
• Median overall survival for the DL2 group was not reached, showcasing prolonged survival, while DL1 had a median OS of 13.32 months. The overall median OS was also not reached.
• In addition to the ongoing clinical trial in China, a phase 1 clinical trial (NCT05319314; CARAPIA-1) has been initiated in the United States.

GCC19CART (Innovative Cellular Therapeutics), an investigational autologous CAR-T therapy being evaluated in an investigator-initiated clinical trial (ChiCTR2000040645) in China for the treatment of relapsed/refractory metastatic colorectal cancer (r/r mCRC), and demonstrated efficacy improvements over standard of care (SOC) third-line therapies, according to data presented at the American Association for Cancer Research (AACR) Annual Meeting 2023.

"The new AE specific to this product is diarrhea because the target is GCC, which plays a role in intestinal homeostasis... So, that's expected, theoretically. Most patients treated with this product experienced diarrhea, but it can be controlled and because of the diarrhea management most of the patients actually recovered very quickly."

– Victor Lu, MD, PhD, of Innovative Cellular Therapeutics

WORLDSymposium — UX111 Shows Continued Dose-Dependent Efficacy as an MPS IIIA Treatment

• The self-complementary AAV9-based gene therapy vector encoding hSGSH demonstrated promising results in treating patients with mucopolysaccharidosis IIIA, also known as Sanfilippo syndrome type A.
• Importantly, there were no deaths, drug-related serious adverse events, or severe adverse events reported to date in the Transpher A trial.
• Reduction in CSF HS levels was dose-dependent, with varying doses administered in different cohorts.

The administration of the investigational treatment UX111, an intravenously administered self-complementary AAV9-based gene therapy vector encoding hSGSH in development by Ultragenyx to treat patients with mucopolysaccharidosis IIIA (MPS IIIA)—also known as Sanfilippo syndrome type A—is associated with rapid and sustained reductions of relevant cerebrospinal fluid (CSF) biomarker levels in those treated prior to advanced neurodegeneration. The data were presented at the annual WORLDSymposium 2023.

"[MPS IIIA] is caused by a deficiency in the lysosomal enzyme N-sulfoglucosamine sulfohydrolase, resulting in toxic accumulation of lysosomal HS in the brain and other tissues. Neurodegeneration occurs in children with MPS IIIA, and that preclinical data have thus suggested that administration of UX111 results in expression of SGSH in the brain in MPS IIIA animal models.”

– Kevin M. Flanagan, MD, of Nationwide Children's

ASGCT — High Dose Fordadistrogene Movaparvovec Improves NSAA, Muscle Volume in Patients With DMD

• The high dose of 2E14 vg/kg intravenous fordadistrogene movaparvovec showed a significant difference in motor function in ambulatory participants with DMD two years after dosing.
• Patients aged 6-7 years showed a 2.5-point difference on the NSAA scores, while patients aged 8-12 years showed a 2.3-point difference after 2 years.
• The safety profile was consistent with other DMD gene therapies, with three serious adverse events considered related to treatment, all of which resolved within 15 days.

Fordadistrogene movaparvovec (Pfizer; PF-06939926) was associated with clinically meaningful preservation of motor function in participants with Duchenne muscular dystrophy compared with external controls in a phase 1b clinical trial (NCT03362502). Data from the trial were presented in a late-breaking session at the the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting.

“Two years after dosing, high dose fordadistrogene movaparvovec in this phase 1 study supports a clinically meaningful difference in motor function in ambulatory participants with DMD versus external controls with similar pretreatment characteristics. The change 2 years after dosing varied by age and was largest in those aged 6-7 years.”

– Perry B. Sheih, MD, PhD, of UCLA