Our Mission
Solving the Cytosolic Delivery Challenge
Xelcis Bio™ is a Boston-based preclinical stage oncology company built on a single conviction: cytosolic delivery is a defining bottleneck that limits many of today's most promising cancer therapeutics.
We are advancing XELCIS XB, a biocompatible nanoparticle platform engineered to deliver payloads to the cytosol across targeted chemotherapy, RNA therapeutics, nanobodies and biologics, and targeted protein degraders. We are applying it first to our own programs, led by TDOX, our targeted doxorubicin conjugate, alongside two dual-payload combination programs. The approach builds on a decade of clinical and translational experience with the iron-oxide nanoparticle delivery class, including Phase 1 experience with the predecessor platform in oncology patients.
Proven Platform Lineage
Built on a predecessor iron oxide nanoparticle platform with Phase 1 clinical experience and no dose-limiting toxicities were observed.
Preclinical Evidence
TDOX (XELCIS XB-Doxorubicin) has shown strong in vitro activity in 3D spheroid multidrug-resistant models. In parallel, feasibility work with model protein cargoes and dual-payload conjugation has shown that XELCIS XB can co-deliver two distinct payloads on a single nanoparticle, the basis of our combination programs.
Multi-Modality Platform
Modular surface chemistry enables application across diverse therapeutic classes without redesign of the core platform.
The Challenge
Cytosolic Access Is the Last-Mile Problem in Oncology Drug Delivery
Many promising cancer therapeutics underperform not because of weak biology, but because they cannot efficiently reach their intracellular site of action. After systemic administration and cellular uptake, payloads are routinely sequestered in endosomes and never reach the cytosol, where targets reside.
This is not a niche problem. It limits the potential of RNA therapeutics, intracellular biologics, and chemotherapy, as well as PROTACs and molecular glues, in multidrug-resistant tumors. Solving cytosolic delivery can expand the value of each of these modalities.
The Endosomal Trap
Most endocytosed payloads are recycled or degraded before they can escape into the cytosol. This represents the primary efficiency barrier for all modalities that necessitate intracellular access.
Dose Compression
Inefficient cytosolic delivery requires higher systemic dosing, narrowing therapeutic windows and driving off-target toxicity across programs.
A Universal Limitation
PROTACs, siRNA, nanobodies, and chemotherapy all face the same last-mile barrier. Solving it once creates value across all modalities.
WHY TDOX
A Proven Cytotoxic, Limited by Delivery, Not Biology
Doxorubicin is one of the most effective and widely used cytotoxic agents in oncology, active across many solid and hematologic cancers. Its benefit is constrained by two well-characterized problems: multidrug resistance, where efflux pumps limit how much drug accumulates inside tumor cells, and cumulative cardiotoxicity, which caps the total dose a patient can receive over a lifetime. The opportunity is not a new anthracycline, but a better way to deliver the one that already works: a mechanism that drives doxorubicin into resistant cells and releases it in the cytosol, while decoupling efficacy from the oxidative and mitochondrial damage that drives cardiotoxicity.
Doxorubicin Challenges Today
Multi-Drug Resistance
ATP-dependent efflux transporters, including MRP1 (ABCC1), pump doxorubicin out of tumor cells, lowering intracellular concentration below the cytotoxic threshold. This resistance is often enriched after prior chemotherapy, exactly the relapsed and refractory setting where new options are most needed.
Systemic Toxicity
Doxorubicin's cardiac damage is cumulative and caps the lifetime dose. As a chemotherapy drug delivered throughout the body, it also causes broader side effects when it reaches healthy tissue. More selective delivery into tumor cells is designed to improve that trade-off.
Current Limitations
Existing reformulations address only a portion of the issue. Liposomal doxorubicin, such as Doxil, modifies biodistribution and reduces certain toxicities; however, it relies solely on passive accumulation and does not directly address efflux-mediated resistance,nor does it provide a specific mechanism for cytosolic drug release that ensures deep cytosolic delivery. The persistent unmet need is an active mechanism that facilitates intracellular uptake, internalization into resistant cells, and release of the therapeutic payload within the cytosol through a precisely defined intracellular trigger.
The XELCIS XB Platform
Engineered for Cytosolic Delivery Across Modalities
XELCIS XB is a pH-responsive biocompatible nanoparticle platform designed to enable cytosolic delivery. By combining cellular uptake, endosomal escape, and glutathione-triggered payload release through Z-Link™ surface chemistry, XELCIS XB addresses the key steps required for cytosolic delivery. Unlike approaches that depend on receptor expression or lysosomal processing, XELCIS XB is designed for broader applicability across payload classes. Payload release is designed to occur in response to cytosolic glutathione.
Enhanced Cellular Uptake
Receptor-independent uptake improves intracellular accumulation versus 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, helping release occur where intracellular activity is needed.
Modality Coverage
One Platform. Multiple Therapeutic Classes.
The same delivery engine applies across therapeutic classes. Because release depends on cytosolic glutathione rather than a specific receptor or lysosomal processing, XELCIS XB can carry very different payloads with the same core chemistry, letting each program build on the last.
Targeted Chemotherapy
TDOX, our lead program, conjugates doxorubicin to XELCIS XB to overcome multidrug resistance, raising drug levels inside resistant tumor cells while sparing healthy tissue and the heart. Two dual-payload combination programs build on it.
Nanobodies and Biologics
Biologics with intracellular targets require cytosolic access for functional activity. XELCIS XB is designed to improve intracellular delivery of these payloads beyond endosomal confinement.
RNA Therapeutics
Endosomal entrapment remains a major barrier to siRNA, ASO, and mRNA delivery. XELCIS XB delivers nucleic acid payloads to the cytosol, informed by the team's prior experience advancing iron-oxide nanoparticle RNA delivery in oncology, and is the basis of our XB-siBIRC5 and XB-siPD-L1 combination programs.
Protein Degraders
PROTACs and molecular glues require cytosolic access to engage E3 ligases and drive target degradation. XELCIS XB extends to this class as a longer-horizon platform capability and partnering opportunity.
Our Lead Programs
Three Programs Advancing Toward the Clinic
Each program was chosen for a clear unmet need and matched to what XELCIS XB uniquely enables. All three are moving into in vivo studies, with TDOX leading toward IND-enabling work.
TDOX (Targeted Doxorubicin)
Our lead program: doxorubicin conjugated to XELCIS XB via Z-Link, 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 expansion indication: platinum-resistant, recurrent ovarian cancer.
XB-siPD-L1-DOX
A dual-payload chemo-immunotherapy program pairing immunogenic doxorubicin with an siRNA that lowers PD-L1, a checkpoint tumors use to evade the immune system. Lead indication: PD-L1-expressing triple-negative breast cancer.
XB-siBIRC5-DOX
A dual-payload program pairing doxorubicin with an siRNA that silences survivin, an apoptosis brake many tumors use to resist chemotherapy. Both payloads are delivered to the same tumor cell. Lead indication: advanced undifferentiated pleomorphic sarcoma.
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 $60M, and advanced an antisense RNA candidate through Phase 1 in oncology patients, with FDA acceptance of a Phase 2a, which commenced in 2026. XELCIS XB builds on that foundation with defined, CMC-aligned conjugation chemistry, purpose-built for next-generation oncology modalities.
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.