Targeted Protein Degradation
Cytosolic Delivery for
Targeted Protein Degradation
XELCIS XB is a cytosolic delivery platform designed for PROTACs, molecular glues, and emerging targeted protein degradation modalities. By improving delivery to proteins of interest, XELCIS XB supports functional degradation and helps address development barriers that limit TPD programs.
Platform Partner Value
Increase functional cytosolic delivery
Enhance target degradation and downstream biological activity
Enable or rescue TPD programs limited by intracellular delivery
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The Challenge
Delivery Failure Limits the Potential of Many TPD Programs
Many targeted protein degradation candidates show promising activity in vitro but fail to achieve adequate intracellular exposure in vivo. Their size and physicochemical properties constrain passive permeability and make them susceptible to efflux, so systemic exposure does not consistently translate into target degradation.
Limited Intracellular Exposure
Many degraders are large, beyond-Rule-of-5 molecules. Their high polar surface area, hydrogen-bond donor count, and efflux liability limit passive permeability, solubility, and biodistribution, so too little drug reaches the cytosol, where the target protein and E3 ligase reside.
Reduced Functional Activity
Limited cytosolic delivery can lead to weak or inconsistent target degradation despite adequate systemic exposure, a disconnect that complicates dose selection and program advancement.
Program Risk
Delivery constraints may require higher dosing, narrow the therapeutic window, and contribute to attrition, increasing cost and reducing the probability of success.
The XELCIS XB Solution
XELCIS XB Enables Cytosolic Delivery for Functional Activity
Designed to Bridge the Gap Between Exposure and Degradation Activity
XELCIS XB is designed to improve cytosolic delivery of degradation therapeutics, supporting the intracellular target engagement required for functional target depletion.
Enhanced Cellular Uptake
Designed to improve intracellular accumulation compared with free payload, increasing the amount of therapeutic available at the site of action.
Cytosolic Delivery
Carries degrader payloads into target cells independently of passive diffusion, then releases them into the cytosol, where they can engage the target protein and the degradation machinery.
Functional Degradation Activity
Designed to translate cytosolic delivery into measurable target degradation and downstream biological effects.
Platform Scope
An Enabling Platform Across TPD Modalities
XELCIS XB is being evaluated as a cytosolic delivery solution for multiple targeted protein degradation strategies.
PROTACs
Supports the intracellular exposure required for efficient ternary complex formation and catalytic degradation of target proteins.
Molecular Glues
Supports cytosolic delivery needed to facilitate productive E3–substrate interactions and functional molecular glue activity.
Next-Generation TPD
Applicable to emerging degrader modalities where intracellular delivery remains a limiting factor, including novel bifunctional and next-generation degrader chemistries.
Evidence & Validation
Partner-Focused Validation Strategy
XELCIS XB evaluation is designed around functional outcomes relevant to translational decision-making and technical diligence.
Cellular Uptake
Quantification of intracellular accumulation versus free payload under matched conditions.
Functional Activity
Target degradation or pathway inhibition assessed relative to matched controls and free payload.
Resistance Models
Assessment of activity in cell lines with reduced sensitivity to free payload, demonstrating the platform’s utility in challenging settings.
Translational Alignment
Correlation of intracellular exposure and cytosolic delivery with functional response, supporting confidence in translational decision-making.
Data packages are designed to support partnership evaluation and technical diligence.
Partner Opportunity
Partnership Opportunities
XELCIS XB may be deployed to enhance existing assets, enable new targets, or support platform-level collaboration in targeted protein degradation.
Target-Specific Licensing
Delivery rights structured for defined targets or programs, enabling partners to apply XELCIS XB to specific assets within their portfolio with clear licensing terms.
Platform Collaborations
Evaluation across multiple assets within a partner portfolio, allowing systematic assessment of XELCIS XB as a platform-level cytosolic delivery solution.
Co-Development
Joint development of XELCIS XB-enabled candidates, combining Xelcis Bio™’s delivery expertise with partner biology and therapeutic programs.