Editing Therapy Trial for Severe Sickle Cell Enrollment in US | Ongoing recruitment of 15 patients for the phase 1/2 BEAM-101 trial

Editing Therapy Trial for Severe Sickle Cell Enrollment in US |  Ongoing recruitment of 15 patients for the phase 1/2 BEAM-101 trial

Recruitment is now underway in BEACON, a US Phase 1/2 trial testing BEAM-101, a transplant-based gene-editing cell therapy for Sickle-cell anaemia (SCD).

The intervention study, in which all participants will receive a single dose of the experimental treatment, is expected to enroll up to 15 adults with SCD, ages 18 to 35. All patients eligible for the gene editing trial will have severe sickle cell disease.

Hosted by beam therapydeveloper of the therapy, the trial will take place at Boston Children’s Hospital in Massachusetts. Interested patients can contact Stephen Huang, MD, at 603-401-2798, or by email at [email protected].

“Bringing a new transplant-based drug into clinical development in the US has been a huge effort, and we are laser-focused on screening and site activation efforts to enroll our first sickle cell patient by the end of the year. ”, John Evans, CEO of Beam. said in a Press release.

“Our top priority is running the BEACON test for BEAM-101,” Evans added.

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This is an illustration of a DNA chain.

Testing gene editing in sickle cell patients

BEAM-101 is part of the company’s Wave 1 strategy to rapidly advance a disease-modifying therapy for people with SCD. The genetic blood disorder is caused by mutations that lead to the production of an abnormal form of hemoglobin, the protein in red blood cells that carries oxygen.

The therapy is designed to allow the production of fetal hemoglobin (HbF) to compensate for the lack of functional adult hemoglobin.

In general, most people stop making HbF and start making the adult form of the protein within the first few months after birth. By activating HbF, a form of hemoglobin that is more efficient at transporting oxygen than its adult counterpart, BEAM-101 can decrease symptoms of SCD and other inherited blood diseases caused by hemoglobin defects. This includes beta-thalassemia.

To be eligible for BEACON, patients must have severe SCD, defined by the occurrence of at least four severe and typically painful symptoms. vaso-occlusive crises (VOC) in the two years prior to study selection. Such crises will have occurred despite patients receiving hydroxyurea or other supportive therapies. In a VOC, sickle-shaped red blood cells block blood flow so severely that tissues are deprived of oxygen.

According to the BEACON Trial (NCT05456880) protocol, once the first patient is enrolled, the individual will undergo a procedure to retrieve blood cell precursors, called hematopoietic stem cells (HSCs), from the bone marrow.

These cells are then genetically edited to activate HbF, creating a BEAM-101 product that is specific to the patient.

After that first procedure, the patient will receive pre-transplant conditioning using a standard chemotherapy regimen to eliminate HSCs currently living in the bone marrow. This procedure ensures that only newly engineered cells can repopulate the bone marrow and produce HbF.

After a manufacturing process to increase the number of cells, the edited cells are returned to the same patient by intravenous injection (into the vein), in the form of stem cell transplant.

With the successful engraftment of the first patient, you can continue the treatment of a second participant.

One of the main objectives of BEACON is to assess changes in the annual number of serious VOCs, which will be assessed six months after treatment. In addition to safety and tolerability, other outcomes include time to engraftment of various blood cell types over two years and transplant-related mortality within 100 days (3.2 months) after treatment.

Due to current regulations covering SCD trials, Beam is working to amend the BEACON protocol to allow for trial modifications that streamline and expedite patient enrollment and ultimately seek regulatory approval of data generated from the study.

The company also plans to complete the manufacturing process for BEAM-101 by making the necessary investments.

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Reduce security risks in gene editing

Beam’s Wave 2 strategy, which includes paired engineered stem cell antibody evasion (ESCAPE), aims to improve the conditioning regimen for patients undergoing HSC transplants.

Because current conditioning regimens use toxic chemotherapeutic agents, these approaches have safety risks. ESCAPE is an antibody-based method designed to eliminate HSCs from the bone marrow, while allowing the engineered cells to “escape” and establish themselves with reduced toxicity.

The company has announced its plans to present new data on ESCAPE at the upcoming American Society of Hematology (ASH) annual conference. The 64th Annual ASH Meeting & Expo will be held December 10-13, virtually and in person, in New Orleans, Louisiana.

Meanwhile, Beam’s Wave 3 strategy focuses on delivering gene editors directly to HSCs using lipid nanoparticles, tiny particles made up of fatty molecules.

As a result of all these efforts, the company has decided to postpone clinical testing of BEAM-102. That investigational gene-editing therapy directly alters a mutation that causes SCD; such an approach would create the natural version of normal adult hemoglobin, called HbG-Makassar.

Overall, the company says it has changed its strategy and will first optimize its Makassar approach, as well as its HbF strategy, rather than seek permission from regulators to begin testing BEAM-102 in human trials.

“We are also accelerating our overall BEAM-101 development program, where we see an opportunity to potentially seek regulatory approval of data generated from the BEACON assay,” Evans said.

Therefore, the company will not file an investigational new drug (IND) application in 2022 for BEAM-102.

“Instead, we will take the opportunity to optimize the BEACON assay as we focus the next phase of our investment in sickle cell disease on our Wave 2 programs for non-genotoxic conditioning, as well as our Wave 3 strategy for live supply of lipid nanoparticles from grassroots publishers, who continue to take advantage of HbF and Makassar editing strategies,” said Evans.

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