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Recently, the global cell and gene therapy (CGT) field has seen a series of advancements. Nanoscope Therapeutics announced itsMCO-010, an optogenetics-based gene therapy under research, inPhase 2b Clinical TrialSignificantly improved patient vision in China.The company plans to submit a Biologics License Application (BLA) to the U.S. FDA in the second half of this year. Adaptimmune Therapeutics announced the pivotal T-cell receptor (TCR)-T cell therapy afami-cel.Positive Phase 2 Clinical DataPublished in The Lancet. Afami-cel is under review by the U.S. FDA, and if approved, will becomeThe first TCR-T cell therapy for the treatment of solid tumors.This article will provide a brief introduction to some of the important advances, for readers' reference only.

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◇Nanoscope Therapeutics Announces MCO-010, Its Optogenetics-Based Gene Therapy in Development, Achieves Primary and Key Secondary Endpoints in the Phase 2b Clinical Trial RESTOREMCO-010 expresses a broad-spectrum, fast, and highly sensitive opsin through transgenic means, localized in bipolar cells via the mGluR6 promoter-enhancer.The company's proprietary adeno-associated virus 2 (AAV2) vector allows robust transduction of MCO-010 in bipolar cells following intravitreal injection.MCO-010 aims to treat permanent severe vision loss caused by advanced retinitis pigmentosa (RP) without considering the type of genetic mutation.

The test results showed that at week 52,Patients receiving high-dose MCO-010 treatment (improvement of 0.337 LogMAR; p=0.021) or low-dose MCO-010 treatment (improvement of 0.382 LogMAR; p=0.029) showed statistically significant improvement in best-corrected visual acuity (BCVA) compared to the placebo control group.

Based on these positive results, the company plans to submit a BLA to the U.S. FDA in the second half of this year. The press release also noted,This advancement represents a major breakthrough for optogenetics as a therapeutic modality.

Trial data showed that a total of 52 patients with synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8), confirmed by cytogenetics, were enrolled in cohort 1 and received afami-cel treatment. These patients had previously undergone a median of 3 lines of systemic therapy. The median follow-up time for the trial was 32.6 months. The overall response rate (ORR) for all patients was 37% (19/52; 95% CI: 24-51), with an ORR of 39% (17/44; 95% CI: 24-55) for synovial sarcoma patients and an ORR of 25% (2/8; 95% CI: 3-65) for myxoid round cell liposarcoma patients.

Afami-cel is an engineered TCR-T cell therapy targeting the MAGE A4 cancer antigen., designed as a one-time treatment for advanced synovial sarcoma.

◇REGENXBIO Announces Publication of Phase 1/2 Clinical Trial Results for ABBV-RGX-314, a Single-Dose Subretinal Gene Therapy for Wet Age-Related Macular Degeneration (Wet AMD), in The Lancet. ABBV-RGX-314 is a potential one-time gene therapy for the treatment of wet AMD.

The trial results published in The Lancet showed that a single administration of ABBV-RGX-314 was generally well-tolerated. Stable or improved vision and retinal thickness were observed in most patients over two years.Patients receiving the recommended therapeutic dose showed sustained expression of ABBV-RGX-314 protein, along with stable or improved vision and retinal anatomy. In most subjects, there was no or almost no need for additional anti-vascular endothelial growth factor (VEGF) drug injections over two years.

ABBV-RGX-314 is a gene therapy using an AAV8 vector, delivering a transgene that expresses an antibody fragment inhibiting VEGF.By inhibiting the VEGF signaling pathway, the formation of new blood vessels and retinal fluid accumulation can be prevented. It is jointly developed by REGENXBIO and AbbVie.

◇Opus Genetics Announces First Cohort Dosing Completed in Open-Label, Dose-Escalation Phase 1/2 Clinical Trial of Investigational Gene Therapy OPGx-LCA5OPGx-LCA5 uses the AAV8 vector to deliver functionalLCA5Transgene delivery to the outer retina for the treatment ofLCA5Caused by biallelic mutations in the geneLeberCongenital AmaurosisIn this cohort of patients, OPGx-LCA5 demonstrated good safety and tolerability, as well as biological activity. The company plans to initiate dosing in the next cohort and increase the dosage by mid-2024.

The combination of SYNCAR-001 and STK-009 is an inducible cell therapy treatment regimen built on Synthekine's proprietary orthoIL-2 technology. It consists of two components, including SYNCAR-001 (an autologous CD19-targeted chimeric antigen receptor T-cell).and STK-009 (an engineered pegylated IL-2 cytokine).SYNCAR-001Expresses an engineered IL-2 receptor capable of selectively receiving signals from STK-009.STK-009 has the potential to promote the engraftment and controlled proliferation of SYNCAR-001 cells without the need for prior depletion of the patient's existing lymphocytes.

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References:

[1] REGENXBIO Announces Lancet Publication of Phase I/IIa Study Evaluating ABBV-RGX-314 as a One-Time Gene Therapy for Wet AMD. Retrieved March 29, 2024, from https://www.prnewswire.com/news-releases/regenxbio-announces-lancet-publication-of-phase-iiia-study-evaluating-abbv-rgx-314-as-a-one-time-gene-therapy-for-wet-amd-302102175.html

[2] Opus Genetics Announces Completion of Dosing in First Cohort of Phase 1/2 Trial of Gene Therapy OPGx-LCA5 in Patients with Rare Inherited Retinal Disease LCA5. Retrieved March 29, 2024, from https://www.globenewswire.com/news-release/2024/03/26/2852307/0/en/Opus-Genetics-Announces-Completion-of-Dosing-in-First-Cohort-of-Phase-1-2-Trial-of-Gene-Therapy-OPGx-LCA5-in-Patients-with-Rare-Inherited-Retinal-Disease-LCA5.html

[3] Nanoscope Therapeutics Announces Positive Top-line Results from Randomized Controlled Trial of MCO-010 for Retinitis Pigmentosa. Retrieved March 29, 2024, from https://www.prnewswire.com/news-releases/nanoscope-therapeutics-announces-positive-top-line-results-from-randomized-controlled-trial-of-mco-010-for-retinitis-pigmentosa-302098510.html

[4] Synthekine Announces U.S. FDA Clearance of IND Application for CD19 CAR-T and Orthogonal IL-2 Combination Therapy, SYNCAR-001 + STK-009, for Treatment of Lupus Without Lymphodepletion. Retrieved March 29, 2024, from https://www.businesswire.com/news/home/20240326131869/en/

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