Aleta Biotherapeutics and Cancer Research UK Announce Promising Phase I/II Data from ALETA-001 Clinical Trial for Patients With Relapsed/Refractory B-Cell Malignancies Previously Treated with CD19 CAR T-Cell Therapy

• The ongoing phase I/II clinical trial is evaluating the safety, tolerability and early efficacy signals of Aleta’s first-in-class biologic CAR T-cell engager, ALETA-001
• Preliminary findings include a highly tolerable profile found at all ALETA-001 doses tested, with encouraging efficacy response in patients with refractory or relapsed disease four or more weeks post-CAR T-cell therapy

NATICK, Mass. & LONDON--(BUSINESS WIRE)--Aleta Biotherapeutics, a clinical stage immuno-oncology company developing CAR T-cell engager biologics that enable CAR T-cell cancer therapies to work more effectively, and Cancer Research UK’s Centre for Drug Development, today announced promising results from the phase I/II clinical trial of ALETA-001 in patients who have received anti-CD19 CAR T-cell therapy for the treatment of B-cell malignancies.

The multi-centre, open-label clinical trial (NCT06045910) is ongoing across the United Kingdom. The study examines patients with B-cell malignancies who have received standard-of-care anti-CD19 CAR T-cell therapy. It encompasses dose escalation from 0.4 mg/kg to 6.0 mg/kg of ALETA-001 following CD19-targeting CAR T-cell therapy. Two phase 1 cohorts have been enrolled having distinct dosing regimens, designed to determine safety and tolerability along with a recommended dose, timing and schedule of administration for a subsequent phase II expansion.

The late dosing cohort has enrolled patients who were at least four weeks post-CAR T-cell therapy and had not achieved a complete metabolic remission (CMR) on PET/CT scan or had achieved an initial CMR but subsequently relapsed with biopsy-proven disease within nine months. ALETA-001 demonstrated a highly tolerable safety profile at all doses, with no ALETA-001-related serious adverse events greater than Grade 1 observed. Robust CAR T-cell expansion was observed in four of six patients who received the lowest doses, demonstrating the ALETA-001 mechanism of action. In addition, a proportion of patients in the late dosing cohort showed encouraging clinical responses and achieved durable CMRs after ALETA-001 administration.

In the early dosing cohort, ALETA-001 is being administered to patients between 10 to 18 days post-CAR T-cell therapy. Patients in the early dosing cohort have shown no signs of toxicity and are being evaluated for signals of biomarker response and for durable efficacy.

Sridhar Chaganti, MD, PhD, Chief Investigator, University Hospitals Birmingham NHS Foundation Trust, Birmingham UK, said: “The majority of B-cell lymphoma patients relapse early after CD19-targeted CAR T-cell therapy. For these patients, time is critical and outcomes with further treatments are poor. ALETA-001 is a promising, off-the-shelf therapeutic that increases and maintains CD19 antigen density, thereby optimizing CD19-targeted CAR T-cell activity and offering the potential for a cure.”

Marco Ruella, MD, Associate Professor of Medicine at the University of Pennsylvania, Scientific Director of the Lymphoma Program, and advisor to Aleta Biotherapeutics, said, “Having agents that can enhance or even rescue CAR T-cell anti-tumor activity is highly desirable. These promising preliminary clinical results initially suggest that ALETA-001 can revitalize CAR T-cells that have struggled to clear the tumor.”

“The data presented by Dr. Chaganti and colleagues provide proof of mechanism for ALETA-001” said Paul Rennert, President and Chief Scientific Officer, Aleta Biotherapeutics. “This is an exciting milestone. ALETA-001 is now being provided to patients shortly after they receive a CD19 CAR T-cell therapy, giving these patients the opportunity for a robust and durable response.”

Cancer Research UK’s Centre for Drug Development is sponsoring and conducting the phase I/II clinical trial of ALETA-001, the lead agent in Aleta Biotherapeutics’ portfolio. Additional clinical trial sites are planned across the United Kingdom in 2026 to increase patient access.

About the CAR T-Cell Therapy Engager Protein, ALETA-001

ALETA-001 was designed specifically for the treatment of B-cell malignancies in patients who have received a CD19-directed CAR T-cell therapy and are at risk of treatment failure. ALETA-001 binds CD19 to the lymphoma antigen CD20 and thereby enables dual-antigen targeting by CD19 CAR T-cells. This mechanism of action improves the effectiveness of CD19-directed CAR T-cell therapies by increasing CD19 antigen density and restoring lost CD19 expression on the cancer cell. This allows CD19+/CD20+ cancer cells to be easily recognized and killed by CD19-directed CAR T-cells that were previously administered and are already circulating within a patient.

Aleta previously secured landmark clinical support and funding from Cancer Research UK for the ALETA-001 phase I/II clinical trials, and ALETA-001 has received a UK Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the UK Medicines and Healthcare products Regulatory Agency. ILAP designation is granted to medicines that address life-threatening or seriously debilitating conditions, and where there exists a significant patient or public health need.

About Aleta Biotherapeutics

Aleta Biotherapeutics is pioneering a transformation of cancer treatment by enabling CAR T-cell cancer therapies to work more effectively. The Company’s unique portfolio of multi-antigen CAR T engagers (CTEs) are simple, potent biologic therapies designed to transform the expression of cancer tumor cells to match CAR T-cell therapies circulating in patient blood. These CTEs produce deep and durable responses in patients receiving CAR T-cell therapies by increasing cancer target density and preventing resistance and escape from therapy, thus increasing the speed and effectiveness with which CAR T-cells can kill cancer cells.

Aleta’s lead clinical stage biologic, ALETA-001 was designed specifically for the treatment of B-cell malignancies in patients who have received a CD19-directed CAR T-cell therapy and are at risk of treatment failure. Aleta is further developing its CTE platform technology to address acute myeloid leukemia, multiple myeloma, and solid tumors, including breast cancer, gastric cancer, and pediatric brain cancers. Learn more: aletabio.com

About Cancer Research UK’s Centre for Drug Development

Cancer Research UK has an impressive record of developing novel treatments for cancer. The Cancer Research UK Centre for Drug Development has been pioneering the development of new cancer treatments for 30 years. It has completed over 170 clinical trials designed to explore potential new anti-cancer agents in patients. Six of these new agents have made it to market, including temozolomide for brain cancer, abiraterone for prostate cancer and rucaparib for ovarian cancer. Learn more: www.cruk.org.uk/cdd