TCR-T Cell Therapy Cleared for Phase 1/2 Study in Acute Myeloid Leukemia


Intellia Therapeutics is also initiating a phase 1/2 study of a CRISPR therapy for hereditary angioedema in New Zealand.

The FDA has accepted Intellia Therapeutics’ investigational new drug application for NTLA-5001, an investigational CRISPR/Cas9 T cell receptor (TCR)-T cell therapy for the potential treatment of acute myeloid leukemia (AML).1

“Engineered T Cell therapies hold significant promise in the treatment of many hematological malignancies, including AML. NTLA-5001 has been specifically engineered using Intellia’s differentiated and proprietary CRISPR/Cas9 genome editing technology to create a homogeneous T cell product with optimized cell health and function, which we hope will lead to better outcomes for patients as compared to current therapies,” John Leonard, MD, president and chief executive officer, told GeneTherapyLive.

NTLA-5001 is an autologous, engineered, ex-vivo T-cell therapy designed to target Wilms’ Tumor 1 (WT1), an antigen overexpressed in both hematologic malignancies and solid tumors. Preclinical data have previously demonstrated the investigative therapy’s safety and efficacy. Intellia has also submitted a regulatory application for NTLA-5001 in the UK.

“Based on clinical data with other TCRs, we expect NTLA-5001 to have an improved safety profile over other AML T cell therapies, as there is minimal expression of our WT1 target in the bone marrow... Additionally, WT1, the target of NTLA-5001, is an intracellular antigen which would be inaccessible by current CAR-T approaches, further differentiating NTLA-5001 from other treatment options in development,” Leonard added.

READ MORE: Celularity Cements Focus on Placenta-Derived Cell Therapies

Intellia is planning to initiate patient screening in a phase 1/2a trial in patients with persistent or recurrent AML that have received standard first-line therapy by the end of 2021. The study will evaluate a single dose of NTLA-5001's safety, tolerability, cell kinetics, and anti-tumor activity with dose escalation and expansion phases. The study is planning to enroll up to 54 participants.

“Our study is an important first step toward improving treatment for people living with this aggressive form of cancer. AML is the most common type of acute leukemia in adults, that, despite currently available treatments, has a five-year survival rate of less than 30 percent,” Leonard said in a statement.1

The study will evaluate patients with both lower disease burden (less than 5% AML blasts in bone marrow) and patients with higher disease burden (greater than or equal to 5% AML blasts in bone marrow) in 2 different arms. Once doses are identified, expansion cohorts will be created for each arm.

“Despite recent therapeutic advances in subsets of AML, long-term outcomes continue to be poor with overall 5-year survival below 30%. Based on this high level of unmet need, we identified AML as an important disease to target with our CRISPR/Cas9 genome editing technology. Importantly, NTLA-5001 is engineered to target the Wilms’ Tumor (WT1) antigen which is overexpressed in an estimated 90% of AML patients regardless of genetic subtype. In addition, WT1 is highly expressed across many liquid and solid tumor types, providing significant potential to subsequently target a number of additional cancers,” Leonard told GeneTherapyLive.

Intellia also received the go-ahead from the New Zealand Medicines and Medical Devices Safety Authority to initiate a phase 1/2 study of NTLA-2002, an engineered in-vivo CRISPR genome editing therapy, for the potential treatment of hereditary angioedema (HAE), in October 2021.2 The candidate is designed to inactivate the Kallikrein B1 (KLKB1) gene to prevent HAE attacks by reducing plasma kallikrein activity. The company is also pursuing regulatory applications in other countries.

The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type 1 or Type 2 HAE. The phase 1 part of the study will identify up to 2 dose levels of the therapy to be further assessed in the placebo-controlled phase 2 part of the study.

Intellia Therapeutics announces U.S. FDA acceptance of investigational new drug application for NTLA-5001, its CRISPR/Cas9-engineered TCR-T cell candidate for acute myeloid leukemia. News release. Intellia Therapeutics. September 16, 2021.
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