Days away from an FDA decision on a sickle cell gene therapy, CRISPR Therapeutics is ditching its “first-generation” allogeneic CAR-T candidates and expanding into autoimmune disease.

The pipeline update is the latest internal changes to come to the surface at the Vertex Pharmaceuticals-partnered biotech after a round of layoffs claimed 10% of staff.

CRISPR Tx is cutting two CAR-T candidates, dubbed CTX110 and CTX130, and shifting to its “next-generation candidates,” according to a Dec. 4 release shared after market close.

CTX110 was designed to target CD19+ B-cell malignancies, while CTX130 was being examined against both solid tumors and certain hematologic malignancies. The two programs gave CRISPR Tx “proof of concept that allogeneic CAR-T cells can produce durable remissions following a standard lymphodepletion regimen,” according to the release.

But CRISPR Tx thinks next-gen candidates CTX112 and CTX131 can do better. The decision is based on early data from ongoing clinical trials that suggest the newer assets could improve the efficacy observed with the earlier candidates.

According to the biotech, the gene edits made for CTX112 and CTX131 lead to higher CAR-T cell expansion and functional persistence in patients when compared to the earlier candidates. The next-gen candidates also have better manufacturing profiles, with a higher and more consistent number of CAR-T cells created per batch.

CRISPR Tx will transition patients treated with CTX110 and CTX130 to long-term follow-up programs where necessary.

In the spotlight now is CTX112, which targets CD19 and is being studied in a phase 1/2 trial for patients with B-cell malignancies. Meanwhile, CTX131 targets CD70 and is being tested in a phase 1/2 trial for solid tumors.

The two assets include a Regnase-1 edit that is supposed to remove a “brake” on T cell function, as well as an edit to TGFBR2 designed to delete a “brake” on T cell anti-tumor activity.

CRISPR Tx also plans to launch a clinical trial for CTX112 in systemic lupus erythematosus in the first half of next year, with the potential to expand into other autoimmune indications later on. The company cited early clinical studies showing CD19-directed autologous CAR-T therapies led to durable remissions in several autoimmune conditions.

All these changes come right before the FDA is set to decide on the Vertex-partnered exa-cel, which has been submitted for approval in sickle cell, on Dec. 8.

Despite an earlier approval from U.K. regulators and a fairly positive reception from FDA advisers during an Oct. 31 meeting, CRISPR Tx was still forced to make staff cuts this November. Three sources familiar with the decision told Fierce Biotech that the layoffs were communicated on Nov. 7, and two of the sources said about 50 employees were let go—making up about 10% of the company.

About PackGene

PackGene is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha 293 cell AAV high-yield platform and the π-Omega plasmid high-yield platform. PackGene's mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.

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