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In a presentation entitled, “From the Bench to the Clinic: Developing Next Generation ADAPTIR molecules,” Dr.
“Aptevo’s ADAPTIR therapeutic protein platform offers important advantages over other bispecific antibody formats,” remarked Dr. Bienvenue. “First, the flexible and modular nature of the ADAPTIR structure provides the ability to engineer protein therapeutics that can engage the immune system through diverse mechanisms of action, including redirected T-cell cytotoxicity, targeted cytokine delivery and receptor blockade, among others. Second, the unique homodimeric structure enables the easy assembly and screening of new drug candidates, while avoiding the pitfalls encountered with heterodimeric bispecific formats. Recent improvements to the ADAPTIR scaffold and screening processes have led to candidates with increased expression levels, stability, and improved serum half-life (up to 12.5 days in rodents), while retaining traditional antibody-like manufacturing characteristics. These enhanced features enable the design and development of custom-engineered protein therapeutics with novel mechanisms of action and highly favorable supply economics. We believe this optimally positions our ADAPTIR candidates vis-à-vis other immunotherapy strategies.”
Two first generation ADAPTIR molecules are currently in clinical development: MOR209/ES414, which is being investigated in a Phase 1, dose escalation, continuous infusion study to evaluate safety and tolerability in patients with metastatic castration resistant prostate cancer; and, otlertuzumab, a monospecific antibody targeting CD37 under investigation for the treatment of chronic lymphocytic leukemia. In addition, Aptevo has several ADAPTIR candidates in preclinical development, including: a next generation bispecific antibody candidate targeting ROR1-expressing tumor cells, under development for the treatment of hematological and solid tumors; and, APVO436 – an optimized, next generation bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity for the treatment of acute myelogenous leukemia (AML), a form of blood and bone marrow cancer.
Preclinical data presented by Dr. Bienvenue show that APVO436 can 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 member of the T-cell receptor complex that promotes T-cell activation and T-cell mediated cytotoxicity.) In these studies, APVO436 dose-dependently inhibited tumor growth and significantly prolonged survival compared to vehicle-treated animals in a Xenograft tumor model of AML.
“We’re excited about the enhancements to our next generation ADAPTIR platform and our ability to engineer novel bispecific antibody therapeutics against a broad range of disease targets,” said Dr. Bienvenue. “Aptevo is focusing its efforts initially in immuno-oncology as we’ve seen encouraging in vitro and in vivo data with our preclinical ADAPTIR candidates at low concentrations showing potent and selective T-cell engagement and tumor lysis (killing). We look forward to presenting additional data from these programs later this year.”
ADAPTIR Technology Platform – Key Differentiating Features
- Flexible, modular, adaptable structure promotes versatile functionality
- Adaptable for production of T-cell engagers, targeted cytokine delivery, targeted activation of immune cells, neutralization of soluble factors, receptor blockade
- Candidate screening in bispecific format to rapidly identify leads with the desired activity and stability
- A bispecific technology that retains monoclonal antibody-like characteristics
- Bivalent binding to targets, leveraging avidity for tight binding and potential for increased potency
- High expression levels using a single cell line production process
- Standardized process, analytical and formulation development that facilitate rapid advancement to the clinic
- Predictable and superior manufacturing attributes and highly favorable supply side economics
- Extended serum half-life of up to 12.5 days in rodents
- Optimized stability (with an emphasis on enhanced functional, conformational and colloidal properties)
- Fully human sequences with reduced potential for immunogenicity
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Aptevo Therapeutics Stacey JurchisonSenior Director, Investor Relations and Corporate Communications 206-859-6628 JurchisonS@apvo.com