Aptevo Therapeutics (NASDAQ:APVO) announced the presentation of new preclinical data for bispecific antibody candidates APVO436 and APVO437, at the American Association for Cancer Research 2017 annual meeting.
As quoted in the press release:
The new data highlight the potent in vitro and in vivo activity of APVO436 and APVO437 at inducing redirected T-cell cytotoxicity (RTCC) in preclinical models of acute myelogenous leukemia (AML), a form of blood and bone marrow cancer that is characterized by rapid disease progression. While treatments for AML are available, there remains a high unmet medical need for targeted therapies addressing patients with relapsed and refractory disease, and patients who cannot tolerate traditional chemotherapy.
“The latest pharmacokinetic data substantiate the improvements we have made to our next generation ADAPTIR™ candidates, which allow for enhanced stability, longer half-life, with reduced potential for immunogenicity, and antibody-drug-like characteristics that support straightforward and cost-effective manufacturing processes,” said Jane Gross, Senior Vice President and Chief Scientific Officer. “In contrast to other T-cell immune approaches, such as chimeric antigen receptor (CAR-T) therapies, bispecific antibodies are “off-the-shelf” medicines that may possess the same or similar immunotherapeutic potential, but with considerably improved convenience and cost-effectiveness.”
In a poster session on Sunday, April 2, 2017, Aptevo scientists presented comprehensive data from a series of preclinical studies of APVO436 and APVO437 demonstrating the molecules’ ability to potently and selectively induce tumor-specific immune responses and T-cell mediated cytotoxicity in vitro and in vivo through the dual targeting of CD123 (a cell surface receptor highly expressed in several hematological malignancies) and CD3 (a T-cell co-receptor that promotes cytotoxicity.)
The data presented by Aptevo show that APVO436 and APVO437:
- Have an antibody-like serum half-life in mice of up to 12.5 days – significantly longer than first generation ADAPTIR candidates and other bispecific candidates in development
- Induced potent, dose-dependent T-cell mediated lysis (killing) of CD123-expressing AML cell lines, accompanied by target-specific T-cell activation and proliferation
- Possess low (nM) binding affinity; bound with high affinity to human and cynomolgus CD123-expressing cells with EC50 values in the low nanomolar range
- Dose-dependently inhibited tumor growth and significantly prolonged survival compared to vehicle-treated animals in a Xenograft tumor model of AML
About APVO436 / APVO437 and the ADAPTIR Platform
APVO436 and APVO437 are optimized, next generation bispecific antibody candidates designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity. They were developed based on Aptevo’s proprietary ADAPTIR protein therapeutic platform. Initially focused on generating novel, targeted bispecific antibody-based immunotherapies for cancer, the ADAPTIR platform offers key advantages over other bispecific formats, derived in part from the flexible and modular nature of the ADAPTIR structure. These advantages include: (i) achieving potent biological activity and extended half-life, while retaining standard manufacturing characteristics; (ii) unique properties for redirecting T-cell cytotoxicity (RTCC) compared to other bispecific platforms, including a favorable cytokine release profile; (iii) ability to achieve target-dependent induction of RTCC at lower concentrations than other bispecific antibody formats. If these data are confirmed in clinical studies, it could suggest the potential for enhanced safety and tolerability compared to other immuno-oncology approaches.
Two ADAPTIR molecules are currently undergoing clinical trials, with several more bispecific immunotherapies in preclinical development. The advantages of the ADAPTIR platform provides an opportunity for diverse therapeutic applications in the future.
About Aptevo Therapeutics Inc.
Aptevo Therapeutics Inc. is a biotechnology company focused on developing novel oncology and hematology therapeutics to meaningfully improve patients’ lives. Our core technology is the ADAPTIR™ (modular protein technology) platform. Aptevo has four commercial products in the areas of hematology and infectious diseases, as well as various investigational stage product candidates in immuno-oncology.