Alpine Immune Sciences Announces Preclinical Data Demonstrating ALPN-202 Eliminates Tumors and Creates Persistent Tumor Resistance in a Murine Cancer Model
-- ALPN-202 is a potential novel immuno-oncology therapy providing dual PD-L1/CTLA-4 antagonism with CD28 costimulation --
-- Unique mechanism seeks to address lack of costimulatory activity of existing immuno-oncology therapies --
-- Data Presented at 2018
ALPN-202 is designed to antagonize PD-L1 and CTLA-4 while also providing CD28 costimulation. Recent literature suggests the lack of CD28 costimulatory signaling may be a principal reason why many tumors do not respond to PD-L1 or CTLA-4 blockade. ALPN-202’s ability to agonize the costimulatory receptor CD28 potentially improves the immune system’s response to cancer.
Alpine used its proprietary scientific platform to engineer Variant Ig Domains (vIgDs) based on CD80. Single vIgD proteins were created capable of binding PD-L1, CTLA-4, and CD28. These vIgDs were then fused to an Fc backbone and used in various in vitro and in vivo studies to characterize functional activity and assess anti-tumor activity in mice implanted with human PD-L1 transduced tumors. Results showed:
ALPN-202 eliminated tumors in most mice (73% or 8/11 tumor free)
compared to durvalumab, an
FDA-approved anti PD-L1 antibody (18% or 2/11 tumor free), and controls (0/11 tumor free).
- Importantly, those mice tumor free after receiving ALPN-202 were re-challenged with tumor and 100% of them were resistant to the newly-implanted cells without receiving additional doses of therapy, suggesting the potential for ALPN-202 to induce anti-tumor memory.
- ALPN-202 elicited CD28 costimulation only in the presence of PD-L1.
Scientific Support and Rationale for ALPN-202
PD-1/PD-L1 inhibitors likely are most effective only when sufficient T cell activating signals, such as via CD28 costimulation, are present. Indeed, recent research demonstrated CD28 costimulation appears to be required for PD-1 inhibition to rescue exhausted T cells in some settings (Science 355:1423, 2017), yet the CD28 ligands CD80 and/or CD86 are often poorly expressed in tumor microenvironments. Because it provides both checkpoint blockade and CD28 costimulation, the ALPN-202 program is therefore well positioned to potentially be a more potent and broadly applicable therapeutic.
“Previously published data suggest PD-1 blockade requires CD28
costimulation to work, at least in some cancers. The preclinical data we
are presenting at AACR indicate the ALPN-202 program proteins are
capable of delivering both with a single molecule,” said
“Our goal in oncology is to develop paradigm-shifting therapeutics that
meaningfully improve upon existing therapies like PD-1/PD-L1
This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact, and include statements regarding Alpine’s platform technology and potential therapies. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “plan,” “intend,” and other similar expressions among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause actual results, events or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: Alpine’s discovery-stage and pre-clinical programs may not advance into the clinic or result in approved products on a timely or cost-effective basis or at all; Alpine may not achieve additional milestone payments pursuant to its collaborations; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in Alpine’s filings with the
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