For the first time in complete remission, Aptevo shows new positive clinical data for targeting CD123xCD3 double antibodies, Yi Mai Meng broke the news

Recent popular reports from Yimicke ★ Invitation Letter2021 CSGCT Gene and Cell Therapy Medical Summit will be held in Shanghai ★ Online Sharing｜Sino-US dual reporting strategy and upstream process development strategy for gene therapy products November 26, 2021 / Yimai Ke News eMedClub News/--Recently, a clinical-stage biotechnology company Aptevo Therapeutics announced that its innovative immuno-oncology therapy APVO436 has observed positive preliminary data in its phase 1b extended trial.
APVO436 is a bispecific antibody targeting CD123 and CD3 The candidate product is currently being evaluated for efficacy and safety in the treatment of acute myeloid leukemia (AML)
.

Efficacy and safety are currently being evaluated in a Phase 1/1b open-label clinical trial in patients with acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS)
.

Acute myeloid leukemia is a cancer of the blood cells of the bone marrow.
Its main feature is the rapid growth of abnormal white blood cells
.
These abnormal white blood cells accumulate in the bone marrow and interfere with the production of normal blood cells .

Due to the high expression of CD123 in AML, CD123 is an attractive target for T cell adoptive immunotherapy
.

APVO436 is an optimized ADAPTIR bispecific antibody candidate designed to dually target CD3 (a T cell co-receptor that promotes cytotoxicity) and CD123 (a highly expressed tumor in a variety of hematological malignancies).
Cell surface receptors) to redirect the cytotoxicity of T cells
.

▲ APVO436 (anti-CD123 x anti-CD3) target (picture source: Aptevo Therapeutics) The primary goal of the phase 1b extension study is to determine whether APVO436 treatment can increase high-risk AML by reducing the burden of residual chemotherapy resistance and measurable residual disease (MRD) The patient’s quality of life
.

The degree of remission will be quantitatively assessed in the central laboratory using the most advanced multi-parameter flow cytometry method
.

MRD, formerly known as minimal residual disease in AML, refers to leukemia cells that exist in very low numbers but can be detected using highly sensitive flow cytometry or genomic methods
.

A recent systematic review of the clinical significance of MRD in more than 10,000 AML patients showed that achieving MRD negative is associated with excellent leukemia-free survival and overall survival
.

Therefore, MRD status has become an attractive and clinically significant endpoint that can accelerate the evaluation of new therapies for AML
.

Aptevo scientists presented new preclinical data, demonstrating that a patient in cohort 6 has achieved complete remission: the patient’s bone marrow blasts dropped from 29% at the time of screening to 6% after the first treatment cycle, and in the first treatment cycle.
After two treatment cycles, it dropped to 0%; the patient's platelet count and absolute neutrophil count (ANC) met the criteria for complete remission (CR)
.

Aptevo believes that, due to its structure and the reduction of cytokine release observed in preclinical studies, APVO436 can produce therapeutic effects and may alleviate the release of inflammatory cytokines.
These inflammatory cytokines and some clinical studies conducted by other companies The harmful side effects found are related
.

The preclinical data of APVO436 presented on AACR supports this hypothesis, indicating that APVO436 induces the activation and proliferation of primitive CD4 and CD8 T cells in the presence of targeted CD123-positive tumor cells, but is compatible with the version of anti-CD123x anti-CD3 bispecific molecules In contrast, the level of cytokine activation is reduced
.

Detailed description of CD123 targets.
Researchers have found that CD123 is widely expressed in various hematological malignancies, such as acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin’s lymphoma and plasmoplasm Like dendritic tumor (BPDCN)
.

At the same time, CD123 is low expressed in normal cells, which makes CD123 a very attractive target protein
.

On July 24, 2019, Mustang Bio announced that the U.
S.
Food and Drug Administration (FDA) has approved MB-102 (CD123 CAR-T) for the treatment of acute myeloid leukemia (AML) orphan drug designation
.

The FDA also previously awarded MB-102 (CD123 CAR-T) the title of orphan drug for the treatment of cytoplasmic dendritic cell tumor (BPDCN)
.

Recommended reading: Mustang Bio-targeted CD123 CAR-T candidate therapy was approved by the FDA as an orphan drug for the treatment of acute myeloid leukemia Yimai Meng broke the news on January 21, 2021, the European Commission (EC) approved the CD123 targeted therapy ELZONRIS (tagraxofusp) ) Was launched as a monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell tumor (BPDCN)
.

According to incomplete statistics, for the development of CD123 targets, there are currently 27 drugs in the research phase, including 1 listed drug, 2 phase III drugs, 5 phase II drugs, 17 phase I drugs, and preclinical drugs 2 pcs
.

Domestic companies that are deeply engaged in CD123 include Precision Biology, GenScript Biology, Hebei Senlang Biology, Nanjing Legend Biology, Jikai Gene, Ucardi Biology, etc.
, all focus on CAR-T cell therapy.
This may be the same as in recent years.
The outstanding performance of CAR-T cell therapy in the field of hematoma is related
.

Reference materials: 1.
https:// -cohort-expansion-trial-in-the-treatment-of-acute-myeloid-leukemia/