AB-110-001 Phase 1b Trial and Related Activities to Support Clinical Development of AB-110

Angiocrine Bioscience Inc., a clinical-stage biopharmaceutical company, completed enrollment of clinical study AB-110-001, a first-in human Phase 1b open-label, multi-center, prospective study of AB-110 in adult subjects with the diagnosis of high-risk hematologic malignancies and who are candidates for allogeneic cord-blood hematopoietic cell transplantation (CB HCT).

AB-110 consists of E-CEL UVEC^® cells, which are engineered human endothelial cells obtained from umbilical cord tissue. Angiocrine’s proprietary technologies enable these cells, which are normally difficult to grow, to be produced at clinical and commercial scales. The E-CEL UVEC cells can multiply blood stem cells outside the body. That is because E-CEL UVEC cells mimic a natural process in the body called the ‘stem cell vascular niche’ where endothelial cells nurture, grow and instruct stem cells. For AB-110, Angiocrine cultures E-CEL UVEC cells with cord blood stem cells outside the body and expands the cells in bioreactors. Because cord blood stem cells come in very small amounts, multiplying these stem cells with E-CEL UVEC cells provided a larger dose, and that may lead to a more effective and safer stem cell therapy. With many ‘expansion’ technologies, growing stem cells causes them to lose their quality. However, since E-CEL UVEC cells mimic the natural process found in the human stem cell vascular niche of bone marrow, E-CEL UVEC cells can multiply blood stem cells without loss of quality. AB-110-001 clinical trial studied patients who have life-threatening blood and bone marrow cancers. AB-110 is designed to rebuild a new blood and immune system for the treated patient. The new blood and immune system not only could help the patient recover and live a normal life again but could also fight against recurrence of the cancer. Hence, AB-110 is potentially curative.

The enrollment of AB-110-001 study has been closed with 10 subjects treated in 3 Cohorts. The subjects were all adults eligible for cord-blood transplantation, undergoing chemotherapy and radiation therapy, with the with the intent to cure their acute leukemia or other blood cancer. Cohort 1 subjects (n=3) received one unit of AB-110 Bag 1 (cord-blood stem cells expanded with E-CEL UVEC^® cells) and one other unit of cord blood stem cells. Cohort 2 subjects (n=5) received one unit of AB-110 Bag 1, one unit of AB-110 Bag 2 (T-cells from the cord blood stem cells used to manufacture AB-110 Bag 1), and one additional unit of cord blood cells. Cohort 3 subjects (n=2) received one unit of AB-110 E-CEL UVEC cells and two units of cord blood stem cells.

As of December 13, 2021, 90% of the subjects are alive and no relapse has occurred. In addition, 70% of the subjects have reached the 2-year post-transplant milestone. No clinically meaningful serious adverse event attributable to AB-110 was observed. All subjects successfully engrafted.

Beyond accelerated hematologic reconstitution, AB-110 may have other clinical benefits such as reducing toxicities and complications related to myeloablative chemotherapy followed by allogeneic hematopoietic transplant.

In conclusion, in this first-in-human study, AB-110 E-CEL UVEC cells appear safe for systemic injection in subjects with hematologic malignancies undergoing allogeneic hematopoietic transplantation following myeloablative conditioning. The primary endpoint was met with no infusional toxicities or engraftment failure observed.

Angiocrine was awarded a $5 million grant from CIRM in 2017 for the clinical development of AB-110.

Grant Application Details

Application Title:

AB-110-001 Phase 1b Trial and Related Activities to Support Clinical Development of AB-110

Public Abstract:

Therapeutic Candidate or Device

AB-110 consists of cord blood derived hematopoietic stem and progenitor cells co-cultured and expanded with E-CEL UVEC cells

Indication

Hematologic and immune reconstitution in patients who have received myeloablation conditioning

Therapeutic Mechanism

Stem and progenitor cells (active ingredient) of AB-110 engraft into the bone marrow of patients, rebuilding a new blood and immune system after appropriate preparation called myeloablation. The E-CEL UVEC cells are thought to aid the engraftment of the stem and progenitor cells into the bone marrow via secretion of angiocrine factors. The remainder of the cord blood cells in AB-110 also aid in the engraftment as well as provide anti-viral and anti-bacterial effects after transplantation.

Unmet Medical Need

Unmet medical need is for a safer, more tolerable and effective stem cell transplantation. AB-110 aims to fullfil this need and provide patients greater access to this potentially curative treatment.

Project Objective

The objective is to complete the Phase 1b trial.

Major Proposed Activities

Initiation of patient recruitment and submission of Interim Analyses Report of initial cohort to the FDA
Submission of 180 Day Subject Data to FDA
Completion of Phase 1b trial and submission of Final Study Report to FDA

Statement of Benefit to California:

Hematologic malignancies in CA affect 19,000 patients/year with an annual mortality of 7,000 and carries a disease burden of ~$2.1 billion. Meeting the target profile of AB-110 would allow patients to experience: 1) much lower risk for mortality and morbidity; 2) decreased risk for serious, opportunistic infections and severe bleeding; 3) reduction in intensive care unit and in-hospital stay; 4) increased long-term survival rate, and 5) a sustained reduction in long-term relapse rate.