Amphiphile Technology platform

Our AMP platform
a differentiated approach to immunotherapy

We are addressing the challenge of direct lymph node engagement with next-generation immunotherapies based on our AMP platform. This platform allows us to develop numerous differentiated treatment modalities including therapeutic vaccines, adjuvants, and our proprietary cell therapy AMPlifiers. Our AMP platform is intended to deliver conventional immunomodulatory payloads including peptides, proteins and nucleic acids directly and preferentially to the lymph node, which can facilitate interaction with the various components of the adaptive immune system. In our preclinical studies, these interactions result in an enhanced therapeutic immune response. This lymph node-targeting technology may have the potential to be broadly applicable to address significant unmet medical needs.

An amphiphile is a chemical compound with both hydrophilic, or water soluble, and lipophilic, or lipid soluble, properties. This distinction is central to the development of our AMP platform. Of critical importance to our AMP platform is its use of endogenous albumin as the carrier molecule. Albumin is a large 66.5 kD molecule that has multiple roles that are important to maintaining healthy functioning, including stabilizing extracellular fluid volume and functioning as a carrier protein for a variety of compounds including drugs, thyroid hormones and fatty acids. In addition to being present in the serum in blood plasma, albumin is quite abundant in the interstitial fluid of the tissues, where it drains through the lymphatic capillaries and vessels of the body, passing through numerous lymph nodes prior to exiting through the subclavian vein and returning to the blood system.  As such, endogenous albumin and its ubiquitous presence in the tissues may make it an ideal carrier to transport immune therapies and vaccines to the lymph nodes.

Amphiphile infographic

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Our AMP platform capitalizes on the differences between the migration routes of large and small molecules through the lymphatic system to enhance the immunostimulatory capabilities of various agents by increasing their exposure in the lymph nodes. In addition, our AMP platform embraces modular conjugation, allowing for potential application to multiple therapeutic modalities, including peptides, proteins, nucleic acids and small molecules. Constructed from an albumin-binding lipid tail, a therapeutic payload, and an optional linker, our AMP configurations are designed to emulate the efficient lymphatic navigation of large macromolecules to preferentially accumulate in the lymph nodes, where they can activate immune cells to orchestrate key features of protective immune responses, including response magnitude and functional quality. When applied to immunostimulatory agents with poor inherent access to the lymph nodes, the AMP strategy can effectively reprogram their biodistribution to promote their lymph node uptake and enhanced action on key immune cells. By applying this fundamental mechanistic distinction throughout our portfolio of product candidates, we may develop immunotherapies that optimally engage the lymph nodes to overcome certain therapeutic limitations of currently approved immunotherapies and enable certain immunotherapy programs in research and development. Therapeutics developed using our AMP platform are made up of three core components:

Albumin-targeting binding vehicle: Binding to endogenous albumin at the injection site is enabled through the incorporation of a fatty acid chain. This moiety, which mimics endogenous fatty acids that bind naturally to albumin, is designed to provide for optimal binding characteristics which allow for efficient association with albumin and delivery of the desired payload to the lymph node. Through experimental refinement of this component’s structure, we have selected a two-chain, or diacyl, molecular configuration, with a specific chain length and saturation of the carbon-backbone, designed to enhance lymph node biodistribution.

Linker molecule: The second optional component of our AMP platform is a linker molecule made from PEG, which connects the lipophilic-binding functional domain with the therapeutic payload. Integration of the PEG-based linker into our AMP may offers multiple benefits. Specifically, that this may enhance our AMP’s hydrophilic properties, which enhances pharmaceutical properties such as solubility. The linker molecule is also intended to protect the therapeutic payload from enzymatic degradation as it travels through the lymphatic system and to permit us to control payload delivery characteristics.

Therapeutic payload: We have designed our AMPs for potential use with a broad array of therapeutic modalities, including small molecules, nucleic acids, peptides, and proteins. This range of available payloads, specifically designed for use with our AMP platform, which enables their direct lymph node engagement, holds promise to provide us significant flexibility related to modality selection for immune system activation and stimulation. Moreover, our use of well-characterized payloads with proven immunological activity may enable us to more quickly and reliably generate product candidates capable of eliciting a therapeutic response of clinical