Development
Roadmap
A rigorous, milestone-driven path from discovery to clinical entry, structured in investable tranches.
Strategic Execution Timeline (2026–2031)
Five investable phases with clear technical milestones and go/no-go decision points.
In Silico Validation & Hit Generation
Months 0–9 | Milestone: Computationally Validated Hit List
Identify chemical matter (binders) for the ASPSCR1-TFE3 fusion using structural biology and computational design.
1.1 Target Modeling
Generate conformational ensembles of ASPSCR1-TFE3 using AlphaFold 3 + MD. Map interface hotspots.
1.2 Virtual Screening
DiffDock campaigns against hotspots using fragment binders and E3 ligase ligands.
1.3 Ternary Design
Design PROTACs linking hits to VHL/CRBN E3 ligases using DeepTernary.
Deliverable: Prioritized list of 50–100 PROTAC designs ready for synthesis.
Biological Proof of Concept
Months 10–18 | Milestone: Lead Declaration (Series A Trigger)
Demonstrate selective degradation of ASPSCR1-TFE3 in ASPS cells and validate cellular phenotype.
2.1 Synthesis
Contract synthesis of top 50 designs (~$3k–$5k per compound).
2.2 Cloud Lab Screening
HiBiT degradation assays in ASPS-1 cells. Establish DC₅₀ and Dmax metrics.
2.3 Selectivity
Counter-screen vs. wild-type TFE3 and VCP to ensure fusion-specific degradation.
2.4 Phenotypic Screen
Confirm cell death (CellTiter-Glo) and target engagement via qPCR/Western Blot.
Deliverable: 1–2 Lead Series with DC₅₀ < 100 nM and >70% degradation depth.
Lead Optimization & In Vivo Efficacy
Months 19–30 | Milestone: Preclinical Candidate Nomination
Develop drug-like properties and validate efficacy in in vivo tumor models.
3.1 MedChem
Optimize linkers for solubility, permeability, and metabolic stability (ADME profiling).
3.2 PK/PD
Pharmacokinetic studies in mice to determine half-life and systemic exposure.
3.3 In Vivo Efficacy
Test in ASPS patient-derived xenograft (PDX) models. Demonstrate tumor regression.
Deliverable: Preclinical Candidate (PCC) with validated in vivo efficacy and acceptable safety profile.
IND-Enabling Studies
Months 31–42 | Milestone: Clinical Entry (FDA Safe to Proceed)
Regulatory clearance package for human trials.
4.1 GLP Toxicology
Pivotal tox studies in rodent + non-rodent species. Establish NOAEL (No Observed Adverse Effect Level).
4.2 CMC
Process development for GMP manufacturing of drug substance and product.
4.3 Regulatory
Pre-IND meeting with FDA. Submit Investigational New Drug (IND) application.
Deliverable: FDA "Safe to Proceed" letter; regulatory clearance for Phase 1 initiation.
Clinical Proof of Concept & Exit
Year 4+ | Milestone: Phase 1 Data Readout & M&A/IPO
Initiate clinical trials and prepare for strategic exit.
Phase 1/2 Basket Trial
Enroll patients with TFE3-rearranged malignancies (ASPS + tRCC). Establish safety, tolerability, and preliminary efficacy signals in humans.
Exit Strategy: Phase 1 safety + efficacy data typically triggers interest from large pharma partners for acquisition or co-development, or positions company for IPO.
Regulatory & Competitive Strategy
Orphan Drug Designation (ODD)
Early filing for ODD for Alveolar Soft Part Sarcoma provides 7 years of market exclusivity, tax credits, and FDA fee waivers—reducing commercial risk.
Basket Trial Design
Clinical trials targeting all TFE3-rearranged malignancies (ASPS + translocation-associated RCC) expands addressable market and accelerates enrollment.
IP Fortress
Parallel patent filings throughout development ensure composition of matter, methods of use, and formulation claims covering the therapeutic and manufacturing innovations.