Our Mission
Precision Delivery of
Proven Chemotherapy
Conventional chemotherapy reaches healthy and cancerous cells alike, driving many of its side effects, and in drug-resistant tumors, efflux pumps push it back out before it can act. Liposomal formulations such as Doxil® improve circulation but rely on passive release, with no defined mechanism for delivering drug into the cytosol. XELCIS XB is a cytosolic delivery platform designed to concentrate chemotherapy in tumors and release it inside cancer cells faster than efflux pumps can remove it. Our lead program, TDOX, applies this to doxorubicin, designed to overcome multidrug resistance and reduce cardiac exposure.
A Proven Payload, Redefined
Doxorubicin remains one of oncology's most potent cytotoxics, but cardiotoxicity and efflux pumps limit its use. TDOX keeps this established payload and changes how it reaches the tumor, designed to release it inside tumor cells rather than exposing healthy tissue.
Built for Resistant Tumors
In multidrug-resistant 3D spheroid models, TDOX showed 9.5-fold greater potency and 14-fold greater uptake than Doxil® in vitro, with significantly lower toxicity to cardiomyocytes than free doxorubicin.
Designed for Manufacturing
XELCIS XB uses a streamlined conjugation process and standard purification methods, designed for reproducible manufacturing and efficient scale-up. Process development for cGMP production is planned with our manufacturing partner.
WHY TDOX
A Proven Drug, Limited by Delivery
Doxorubicin is effective across many solid and hematologic cancers, but two known limits constrain it: efflux pumps clear the drug from resistant tumor cells, and cardiotoxicity caps the lifetime dose. Our approach is not a new drug, but better delivery of a proven one.
Multi-Drug Resistance
Efflux transporters, including MRP1 (ABCC1), pump doxorubicin out of tumor cells and keep intracellular levels below the cytotoxic threshold. Resistance is often enriched after prior chemotherapy, exactly where new options are most needed.
Cardiac and Systemic Toxicity
Doxorubicin's cardiac damage is cumulative and limits the lifetime dose. Delivered throughout the body, it also harms healthy tissue. More selective delivery into tumor cells is designed to improve that trade-off.
Current Limitations
Liposomal doxorubicin such as Doxil® changes biodistribution and reduces some toxicities, but it relies on passive accumulation and does not address efflux-mediated resistance or provide a defined trigger for cytosolic release. TDOX is designed to do both.
Our Programs
Three Programs Advancing Toward the Clinic
Each program targets a clear unmet need and uses what XELCIS XB uniquely enables. TDOX is advancing into in vivo studies toward IND-enabling work. The two dual-payload programs follow, with combination studies gated on single-agent results.
TDOX (Targeted Doxorubicin)
Our lead program: doxorubicin conjugated to XELCIS XB through Z-Link™ chemistry, designed to overcome multidrug resistance and reduce cardiac exposure. In vitro, TDOX showed 9.5-fold greater potency and 14-fold greater uptake than Doxil® in a resistant tumor model. Lead indication: small cell lung cancer, with platinum-resistant ovarian cancer as an expansion indication.
XB-siBIRC5-DOX
A dual-payload program pairing doxorubicin with an siRNA that silences survivin, an apoptosis brake that many tumors use to resist chemotherapy. Both payloads reach the same tumor cell. Lead indication: advanced undifferentiated pleomorphic sarcoma.
XB-siPD-L1-DOX
A dual-payload chemo-immunotherapy program pairing immunogenic doxorubicin with an siRNA that lowers PD-L1, a checkpoint that tumors use to evade the immune system. Lead indication: PD-L1-expressing triple-negative breast cancer.
THE CHALLENGE
Cytosolic Access Limits Many Cancer Therapeutics
Many promising cancer therapeutics underperform not because of weak biology, but because too little of the drug reaches its intracellular site of action. The same delivery gap that limits doxorubicin in resistant tumors also limits other modalities.
The barrier differs by modality: RNA therapeutics and intracellular biologics are largely trapped in endosomes after uptake, chemotherapy is pumped out of resistant tumor cells by efflux transporters, and protein degraders are limited by poor membrane permeability. Each needs a better route to the cytosol.
The Endosomal Trap
Most endocytosed macromolecules, including siRNA, antisense oligonucleotides, and proteins, are recycled or degraded before they can escape into the cytosol. For these payloads, endosomal escape is the primary efficiency barrier.
Dose Compression
Inefficient intracellular delivery forces higher systemic doses, narrowing therapeutic windows and driving off-target toxicity.
One Destination, Different Barriers
Chemotherapy, siRNA, nanobodies, and protein degraders all need to reach the cytosol, but each faces a different obstacle. A platform that provides an active route into the cell creates value across all of them.
The XELCIS XB Platform
Engineered for Cytosolic Delivery Across Modalities
XELCIS XB is a pH-responsive, biocompatible nanoparticle platform. It combines receptor-independent cellular uptake, endosomal escape, and glutathione-triggered payload release through Z-Link™ surface chemistry, so the payload is released inside the cell, where it acts. Because release depends on cytosolic glutathione rather than a specific receptor or lysosomal processing, the same chemistry can carry very different payloads.
Enhanced Cellular Uptake
Receptor-independent uptake improves intracellular accumulation relative to the free payload, increasing the amount of therapeutic available at the site of action.
Endosomal Escape
pH-responsive chemistry enables release from endosomal compartments, allowing payloads to access the cytosol before degradation.
Cytosolic Release
Z-Link™ disulfide chemistry is designed to trigger payload release in response to cytosolic glutathione, so release occurs where intracellular activity is needed.
BEYOND CHEMOTHERAPY
One Platform. Multiple Therapeutic Classes.
Targeted chemotherapy is our focus. The same delivery engine extends to other payload classes, which we pursue through our combination programs and with partners.
Targeted Chemotherapy
Our lead focus. TDOX is the first XELCIS XB chemotherapy. Targeted gemcitabine is planned next, using the same linker chemistry, and the approach is designed to extend to other established cytotoxics.
RNA Therapeutics
Endosomal entrapment remains a major barrier to siRNA, ASO, and mRNA delivery. XELCIS XB is designed to deliver nucleic acid payloads to the cytosol and is the basis of our XB-siBIRC5-DOX and XB-siPD-L1-DOX programs.
Nanobodies and Biologics
Biologics with intracellular targets need cytosolic access to act. XELCIS XB has delivered a model protein payload in feasibility studies, and we see this class as a partnering opportunity.
Protein Degraders
PROTACs and molecular glues must reach the cytosol to engage E3 ligases, but their large, beyond-Rule-of-5 structures limit passive permeability and invite efflux. XELCIS XB offers an alternative route into the cell and extends to this class as a longer-horizon platform capability and partnering opportunity.
Partnership
Partnering on Delivery-Limited Assets
Alongside our own programs, we work with pharmaceutical and biotech partners to evaluate XELCIS XB for assets where intracellular delivery is the barrier to progress.
8-Week Payload Demonstration Program
Generate early proof-of-concept data with your payload on XELCIS XB through a time-defined engagement designed to reduce partner risk.
If your pipeline includes assets limited by intracellular delivery, we welcome a discussion.
Leadership
Led by a Team That Has Done This Before
Xelcis Bio™ was founded by R. Michael Dudley (CEO) and Dr. Peter Liu (CSO), who previously co-developed and advanced an antisense RNA therapeutic into clinical-stage development at TransCode Therapeutics (NASDAQ: RNAZ). The leadership and advisory team bring expertise in oncology drug delivery, clinical development, regulatory strategy, and biotech financing.
R. Michael Dudley
CEO & Co-Founder
Former Co-Founder and CEO of TransCode Therapeutics (NASDAQ: RNAZ). Raised $60M+ in public and private capital.
Rick Clemon, CPA, CGMA
Chief Financial Advisor
Financial strategy and capital markets for biotech and life sciences.
Dr. Peter Liu
CSO & Co-Founder
Lead scientist on the predecessor platform and architect of the XELCIS XB delivery platform.
Dr. Allan Green & Dr. Lee Simon
Regulatory Consultants: SDG LLC
FDA regulatory strategy and IND advisory for novel drug delivery systems.
Dr. Candida Fratazzi
Chief Medical Advisor
Oncology clinical development, IND strategy, and trial design.
Our Track Record
A Platform Built on Clinical Lineage
XELCIS XB grew out of a decade of clinical and translational work with iron-oxide nanoparticle delivery in oncology. The founding team took a predecessor company public on NASDAQ, raised more than $60 million, and advanced an antisense RNA candidate through Phase 1 in oncology patients. XELCIS XB is a new platform, built with defined, CMC-aligned conjugation chemistry, and Xelcis owns its own intellectual property.
XELCIS XB Preclinical Data
9.5x
Greater cytotoxic activity vs. Doxil®
(3D spheroid MDR model)
~5x
Wider cardiac safety margin. Lower ROS generation vs free doxorubicin
( IC₅₀ ≥10µM vs DOX 1.8–2.0µM)
14x
Greater cellular uptake vs. Doxil®
(MDR resistant cells)
~10%
Endosomal escape to the cytosol, versus about 1 to 2% for published RNA-delivery lipid nanoparticles
(Where most fail)
Xelcis Bio conducted the in vitro studies utilizing the XELCIS XB platform. The company generated data through in vitro experiments employing 3D spheroid multidrug-resistant cancer cell models. These results are at the preclinical stage and may not necessarily forecast clinical outcomes.