CRISPR Therapeutics Eyes Historic First in Gene Therapy

The DNA molecule crispr cas 9

CRISPR Therapeutics (CRISPR) could be on the cusp of achieving a first in gene therapy, the first company to achieve regulatory approval for a CRISPR-Cas9 program. The company is anticipating the filing of a Biologics License Application for CTX001, a potential cure for transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).

On Tuesday, the Cambridge, MA-based gene editing company hosted an Innovation Day presentation that highlighted its pipeline and the promise that its multiple approaches have in mitigating or even curing different diseases. Chief Executive Officer Samarth Kulkarni said it has been less than 10 years since Jennifer Doudna and Emmanuelle Charpentier first published an article in the journal Science about gene editing technology and less than eight years since CRISPR Therapeutics was founded on that technological promise. Now, the company is on the cusp of vying for potential approval of its CRISPR therapy, he said.

CTX001, also known as exa-cel, is a CRISPR-Cas9-based gene editing therapy for both TDT and SCD. Earlier this month, CRISPR and its partner Vertex Pharmaceuticals released positive data for exa-cel in TDT and SCD. In the first space, data showed that 42 of 44 patients with TDT who received exa-cel remained transfusion free for up to 37.2 months. The two patients who were not transfusion free had 75% and 89% reductions in transfusion volume, respectively, the companies said. In SCD, all 31 patients with disease characterized by recurrent vaso-occlusive crises (VOCs) were free of the issues following treatment with the gene therapy. Data showed the patients had a duration of up to 32.3 months, CRISPR and Vertex reported. The two companies expanded their partnership in this space last year.

“We are extremely excited about exa-cel,” Kulkarni said.

Phuong Khanh (P.K.) Morrow, CRISPR’s new chief medical officer, echoed Kulkarni, saying that she believes exa-cel will be the first CRISPR-Cas9 product approved for both TDT and sickle cell disease. Her prediction comes about a week after an advisory committee with the U.S. Food and Drug Administration recommended approval of a different gene therapy approach for these diseases that were developed by bluebird bio.

In immuno-oncology, CRISPR is also blazing a trail with its approach, particularly with CTX130, a donor-derived gene-edited allogeneic CAR T therapy that targets CD70, which is expressed on various solid tumors and hematologic malignancies. The company is developing the asset for solid tumors, such as renal cell carcinoma, as well as T cell and B cell hematologic cancers. Morrow suggested the positive data the company has seen with CRX130 in both solid and hematologic tumors is “something of the Holy Grail that researchers have been searching for." 

In May, CRISPR presented exciting CTX130 data from two Phase I studies for relapsed or refractory renal cell carcinoma and various subtypes of lymphoma. The company reported positive early signs, including an overall response rate of 71% from patients with T-cell lymphoma. Of those, 29% experienced a complete response, CRISPR said.

In renal cell carcinoma, cancer that expresses high levels of CD70, CTX130 is also showing significant promise, even leading to a complete response in one patient. Renal cell carcinoma represents a high unmet need, with less than 20% of patients surviving beyond five years. About 40% of RCC patients have shown poor response rates to current therapies.

“There is a high potential opportunity with CTX130 because of the CD70 expression in RCC,” Morrow said.

Beyond those two assets, CRISPR is also advancing other therapeutics. The company is also developing VCTX210, a potential treatment for type 1 diabetes that is being co-developed with ViaCyte. VCTX210 is an allogeneic, gene-edited, stem cell-derived therapy designed to generate pancreatic cells that can evade recognition by the immune system, which would otherwise destroy them. Earlier this year, the companies dosed the first patient in a Phase I study. As BioSpace previously reported, the goal is for the cell line to be differentiated into pancreatic endoderm cells, generating glucose-responsive insulin-secreting cells in the patient. It is expected that about 10 patients will be included in the study. Data is anticipated by the end of the year.

While those programs for CRISPR Therapeutics stand out, Kulkarni said the company sees significant potential with its total pipeline, with a chance to delve into multiple disease indications and potentially bring new treatment options to patients.

“We’re very excited about the potential,” he said.

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