LEAD PROGRAM
Advancing PSA-Activated Doxorubicin Prodrugs
Our initial program uses doxorubicin as a proof-of-concept payload to evaluate PSA-dependent activation, systemic stability, tumor selectivity, pharmacokinetics, tumor exposure, and preliminary tolerability.
What the Program Will Establish
PSA-Dependent Activation
Confirm efficient PSA-mediated drug release through preclinical biochemical and cell-based assays evaluating substrate cleavage efficiency and selectivity.
Systemic Stability
Assess resistance to off-target proteolysis and premature doxorubicin release in preclinical plasma and tissue stability models.
Tumor Exposure
Evaluate pharmacokinetics, tumor and plasma exposure, preliminary PK/PD relationships, and exploratory tolerability in preclinical models.
WHY DOXORUBICIN
Why Doxorubicin
Doxorubicin provides a well-characterized proof-of-concept payload for testing whether PSA-selective activation can improve tumor exposure while limiting premature systemic release. Success would establish design principles that may support future PSA-activated versions of other cytotoxic agents.
A well-characterized cytotoxin with decades of preclinical and clinical data – making it an ideal molecule to stress-test the PSA-activation hypothesis before advancing novel payloads.
Extensive PK/PD literature enables direct comparison of free versus prodrug exposure – giving the program a credible benchmark for interpreting early data.
Preclinical Development Framework
01
Prodrug Design and Synthesis
Design and synthesize doxorubicin prodrug candidates with PSA-cleavable linkers optimized for stability, selectivity, and synthetic tractability.
02
PSA Activation and Selectivity Testing
Evaluate PSA-mediated cleavage efficiency, substrate selectivity, and off-target protease resistance using biochemical and cell-based assays.
03
ADME, Stability, and Pharmacokinetics
Characterize prodrug absorption, distribution, metabolism, and excretion, alongside plasma and tissue stability profiles in preclinical systems.
04
Tumor Exposure, PK/PD, and Exploratory Tolerability
Assess tumor versus plasma exposure ratios, establish preliminary PK/PD relationships, and explore tolerability in preclinical in vivo models.
Candidate Advancement Criteria
Preserved PSA-Mediated Activation
Candidate prodrugs demonstrate consistent and efficient cleavage by PSA under relevant preclinical conditions, confirming the activation mechanism is intact after linker and payload integration.
Improved Stability in Biological Matrices
Prodrug candidates show meaningful resistance to non-PSA proteolysis and maintain structural integrity in plasma and relevant biological matrices under preclinical evaluation.
Limited Premature Doxorubicin Release
Free doxorubicin released in the absence of PSA remains low, supporting the premise that systemic exposure to active payload is substantially lower than for unconjugated doxorubicin.
Favorable Tumor Exposure and Tolerability
Preclinical in vivo data suggest a favorable tumor-versus-plasma exposure ratio with an exploratory tolerability profile that supports continued lead optimization.
Advancing Toward a Development Candidate
Initial preclinical work is designed to identify a PSA-activated doxorubicin prodrug suitable for further IND-enabling development and to establish design principles for future payloads.
