Platform Technology
XELCIS XB: A Platform for Cytosolic Delivery
A delivery platform designed to move therapeutic payloads beyond endosomal entrapment and into the cytosol, where intracellular targets can be engaged and biological activity can occur.
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The Delivery Challenge
Endosomal Entrapment Limits Therapeutic Activity
After cellular uptake, many therapeutics remain trapped in endosomal compartments, preventing access to intracellular targets and degradation machinery. As a result, systemic exposure does not reliably translate into biological effect.
Confined in Endosomes
Internalized payloads may enter cells but remain sequestered away from their site of action.
Exposure Without Activity
Systemic drug levels can be present without meaningful target engagement or functional response.
Designed for Functional Cytosolic Delivery
XELCIS XB is engineered around three defined features: Carbohydrate-based design & tumor-biology responsiveness, intracellular delivery, and surface functionality for modular cargo installation
Improved Cellular Uptake
Receptor-independent internalization drives higher intracellular accumulation than free payload. In a resistant tumor model, XELCIS XB showed 14 times greater uptake than Doxil.
Endosomal Escape
pH-responsive chemistry releases payload from the endosome into the cytosol. Measured escape is around 10%, versus roughly 1 to 2% for published RNA-delivery lipid nanoparticles.
Functional Target Engagement
Glutathione-triggered Z-Link cleavage releases the active payload at its intracellular site of action, translating delivery into measurable activity.
Mechanism of Action
How XELCIS XB Delivers Inside the Cell
XELCIS XB delivery follows a five-step cascade: extrahepatic biodistribution beyond first-pass hepatic clearance; prolonged circulation and extended exposure relative to free drug; tumor uptake, internalizing the conjugate into tumor cells; endosomal escape into the cytosol; and cytosolic release, in which glutathione-triggered cleavage of the Z-Link linker frees active payload at its intracellular site of action. The pre-cellular stages draw on the iron-oxide nanoparticle delivery lineage; the intracellular stages are the core XELCIS XB proposition.
Why It Matters
Translational Impact
By addressing the gap between exposure and activity, XELCIS XB is designed to improve the translational value of oncology programs across multiple modalities.
Increased Intracellular Exposure
More therapeutic reaches its intracellular site of action. In a multidrug-resistant model, this produced 9.5 times greater cytotoxic potency than Doxil.
Improved Target
Engagement
Greater cytosolic delivery supports stronger and more consistent biological activity.
Potential to Expand Therapeutic Window
More selective delivery may widen the margin between efficacy and toxicity.
Asset Rescue
Potential
Programs limited by delivery rather than biology may be enabled through improved cytosolic delivery.
Platform Flexibility
Broad Modality Compatibility
The same conjugation chemistry applies across therapeutic classes, because release depends on cytosolic glutathione rather than a specific receptor or lysosomal processing. XELCIS XB is being evaluated across targeted chemotherapy, nucleic-acid therapeutics, biologics and nanobodies, and, longer term, targeted protein degradation. Beyond carrying a single payload, XELCIS XB can co-conjugate two distinct payloads on one particle at defined stoichiometry.
To our knowledge, it is the only nanoparticle platform that co-conjugates a small-molecule drug and a nucleic-acid therapeutic on a single particle, with glutathione-triggered cytosolic release.
Targeted Chemotherapy
Our most advanced application. TDOX, XELCIS XB conjugated to doxorubicin, demonstrates the platform mechanism with preclinical data across uptake, escape, and cytotoxic activity in multidrug-resistant models, and anchors two dual-payload combination programs.
Nucleic Acid Therapeutics
siRNA and ASO programs require cytosolic access, where endosomal escape is the central barrier. The XELCIS XB pH-responsive mechanism addresses it, and supports our siBIRC5 and siPD-L1 combination programs.
Biologics (e.g., Nanobodies, Antibodies, ADCs/NDCs)
Nanobodies and antibodies depend on receptors for uptake and are often sequestered in endosomes or lysosomes. XELCIS XB enables receptor-independent cytosolic delivery, allowing ADC and NDC formats to reach the cytosol, overcome low receptor expression, and expand eligibility, supported by a completed protein-delivery proof of concept.
Protein Degraders
PROTACs, molecular glues, and next-generation degraders require productive intracellular access to engage their target proteins and the cellular degradation machinery. XELCIS XB could potentially extend to this class as a longer-horizon platform capability and partnering opportunity.
Platform Impact
One Platform. A Multiplier Effect.
Our vision is to make functional intracellular delivery a solved problem, enabling entire classes of oncology therapies to reach their full clinical potential.