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In a presentation entitled, “ADAPTIR™ Platform:
In his overview, Dr. Pavlik describes the expansion of Aptevo’s ADAPTIR platform into several different mechanisms of action, including, T-cell engagers targeting CD3; a bispecific targeting the costimulatory receptor 41BB and a solid tumor antigen; and a bispecific that targets a cytokine to specific cells via an ADAPTIR platform. This evolution highlights the flexible and versatile nature of the ADAPTIR platform and its utility in generating multiple bispecific candidates.
These attributes have been demonstrated with Aptevo’s next generation lead bispecific T-cell engager, APVO436, which simultaneously targets CD123 (a cell surface receptor highly expressed in several hematological malignancies) and CD3 (a T-cell co-receptor that promotes cytotoxicity.) Data from preclinical studies of APVO436 show that it:
- Potently and selectively induces tumor-specific immune responses and T-cell mediated cytotoxicity in vitro and in vivo
- Has 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
- Induces potent, dose-dependent T-cell mediated lysis (killing) of CD123-expressing acute myelogenous leukemia (AML) cell lines, accompanied by target-specific T-cell activation and proliferation
- Possess low (nM) binding affinity; binds with high affinity to human and cynomolgus CD123-expressing cells with EC50 values in the low nanomolar range
- Dose-dependently inhibits tumor growth and significantly prolongs survival compared to vehicle-treated animals in a Xenograft tumor model of AML
“Our data on APVO436 confirm the important advances we have made with our next generation ADAPTIR candidates, specifically improved stability, half-life, activity and manufacturability – all critical attributes for commercialization,” said
ADAPTIR Bispecific Antibody Platform: Differentiating Characteristics
- Unique Homodimer Structure - simplifies candidate generation; facilitates rapid substitution of target binding domains to evaluate numerous candidates simultaneously
- Bivalent for Both Binding Domains - increases the avidity and potency of ADAPTIR candidates
- Unique IgG Fc ‘Backbone’ - extends the half-life of ADAPTIR molecules (up to ~12.5 days in rodents)
- Antibody-like Production Processes – demonstrated capability to produce up to 2.0g/L comparable to traditional antibody manufacturing processes
- Improved Yield and Cost of Goods - use of a single gene and ease of CHO cell line production enhances ADAPTIR bispecific manufacturing productivity
ADAPTIR Clinical and Preclinical Portfolio:
- APVO414 – a bispecific ADAPTIR candidate, currently in Phase 1 development, targeting prostate specific membrane antigen (PSMA), an enzyme that is expressed on the surface of prostate cancer cells, and, CD3, a component of the T cell receptor complex expressed on all T cells. APVO414 redirects T cells to specifically kill PSMA expressing tumors and is being developed for metastatic castration-resistant prostate cancer, which is advanced prostate cancer that has spread to other organs and no longer responds to hormone blocking therapies.
- Otlertuzumab – a monospecific ADAPTIR candidate currently in Phase 2 development for the treatment of chronic lymphocytic leukemia (CLL). Data from a Phase 2 clinical trial evaluating otlertuzumab in combination with bendamustine, compared to bendamustine alone, demonstrated a significant increase in median progression free survival for the combination, from approximately 10 to 16 months.
- APVO436 – a bispecific ADAPTIR candidate currently in preclinical development targeting CD123, a cell surface receptor highly expressed on several hematological malignancies and CD3, a component of the T-cell receptor. APVO436 engages T cells to kill tumor cells.
- ALG.APV-527 – a bispecific antibody candidate, partnered with
Alligator Bioscience, featuring a novel mechanism of action designed to simultaneously target 4-1BB (CD137) and an undisclosed tumor antigen. 4-1BB, a costimulatory receptor on T cells, is known to enhance the immune response to cancer through activation of tumor-specific T cells and is believed to be a promising target for new immunotherapeutic approaches. ALG.APV-527 could potentially have utility in the treatment of a broad spectrum of cancers over-expressing the tumor antigen, including breast, cervical, non-small-cell-lung, prostate, renal, gastric, colorectal and bladder cancers.
- APVO210 – a bispecific ADAPTIR preclinical candidate with a novel mechanism of action based on targeted cytokine delivery. APVO210 is composed of a humanized anti-CD86 antibody fused with a modified form of IL-10 that specifically induces IL-10 signaling on antigen presenting cells, but not on lymphoid populations. APVO210 functions by suppressing immune responses and inducing certain tolerogenic responses and therefore may have potential benefit for the treatment of autoimmune and inflammatory diseases.
- ROR1 Bispecific – a proof-of-concept bispecific candidate targeting ROR1, an antigen found on several solid tumors and hematologic, or blood-related malignancies. Initial preclinical data demonstrate redirected T cell killing of tumors expressing ROR1 in vitro and in vivo in animal models.
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