Clinical-stage. GMP manufactured. Human safety data in hand. ODD, RPDD, and Priority Review Voucher are the planned regulatory levers — none filed or granted yet. Licensed from Sapu Biosciences into PDAOAI — neurology and longevity fields only. Sapu retains worldwide oncology.
PDAOAI's SAPU003 franchise covers two fields only: rare pediatric neurology (mTORopathies) and healthy aging / longevity. Oncology remains with Sapu Biosciences worldwide. Prevalence across these indications: ~72,000 US, roughly 140,000 across US + EU5 — prevalence, not the treated or reimbursed population, and not additive across rows.
| Indication | Tier | Incidence / Prevalence | Patients (US) |
|---|---|---|---|
| Tuberous Sclerosis Complex (TSC) | Tier 1 | ~1:6,000–1:10,000 live births | ~50,000 |
| Focal Cortical Dysplasia (FCD) | Tier 1 | ~1:25,000 prevalence | ~14,000 |
| GATOR1-related epilepsy (DEPDC5, NPRL2, NPRL3) | Tier 2 | ~1:35,000–1:50,000 live births | ~5,000–9,000 (est.) |
| MTOR gain-of-function syndromes (germline; Smith-Kingsmore) | Tier 2 | ~1:32,000,000 | <100 diagnosed |
Population incidence or prevalence — not treated or reimbursed patients. Rows overlap biologically (somatic MTOR and DEPDC5 variants drive much of FCD type II) and are not additive. Sources: GeneReviews 2024 and TSC Alliance (TSC); López-Rivera et al. 2022 (FCD; surgically treatable lesions); Symonds et al. 2019 (GATOR1; US count derived); Raski & Prada 2026 (Smith-Kingsmore).
The biology holds together at three levels: mTOR as the root, KCC2 as the downstream chloride cotransporter, and GABAergic signaling as the clinical readout.
mTOR pathway dysregulation drives multiple pediatric epilepsy syndromes across the mTORopathy spectrum. Both mTORC1 and mTORC2 signaling implicated.
mTOR hyperactivation impairs KCC2, the neuronal chloride cotransporter. Chloride accumulates inside neurons. GABA — the brain's main inhibitory signal — flips from calming to excitatory. Neurons fire uncontrolled. Seizures.
SAPU003 is designed to act on this chain: inhibit mTOR → restore KCC2 function → normalize chloride homeostasis → GABA regains its inhibitory role → seizures suppressed. The chain has been demonstrated with rapamycin in a preclinical model, not yet with SAPU003 — confirming it for SAPU003 is Workstream III. Reference: Bakouh N, et al. Brain 2025;148(2):549–563.
Oral everolimus is FDA-approved and works — for the indications where oral delivery is sufficient. SAPU003 is the intravenous nanoparticle reformulation that changes the pharmacokinetics.
| Feature | SAPU003 (IV nanoparticle) | Oral rapalogs (Afinitor) |
|---|---|---|
| Route | Intravenous | Oral |
| GI absorption | Bypassed | Variable |
| First-pass metabolism | Bypassed | Significant |
| Food effect | None | Yes |
| Onset / exposure | Rapid | Slower / variable |
| Drug interactions | Reduced | High (CYP3A / P-gp) |
| Dosing paradigm | Intermittent | Continuous daily |
| Chronic GI exposure | Minimized | Persistent |
| Microbiome impact | Lower risk | Higher risk |
The formulation and the delivery class behind SAPU003, in the peer-reviewed record.
Min SH, Forero K, Putnam W, Anderson J, Hoff R, Lopp J, Trieu V, Ho K, Lee C.
Int J Mol Sci. 2026;27(13):5775
Formulation discovery, cGMP manufacturing and physicochemical characterisation of SAPU003.
De T, Trieu V, Myers S, Qazi S, Saund S, Lee C.
Int J Mol Sci. 2025;26:10842
The sub-15 nm delivery class SAPU003 sits in.
None of these designations have been filed or granted yet. This is the pathway the IND-enabling program is targeting — the three regulatory levers that make a small-population pediatric neurology asset economically meaningful.
Target: file ODD applications for Tier 1 mTORopathies (TSC, FCD) once IND-enabling data supports it. If granted, ODD carries 7-year U.S. market exclusivity, tax credits, and development incentives for the qualifying rare indication.
Target: file Rare Pediatric Disease Designation to qualify for a Priority Review Voucher on approval. Recent Priority Review Vouchers have sold at $150–200M (Jazz Pharmaceuticals: $200M, Jan 2026). Program reauthorized through September 2029. Optionality only — not booked value.
Pediatric exclusivity extension (6 months) and Breakthrough / Accelerated Approval pathways are available for high-unmet-need pediatric neurology. Eligibility to be established on the biomarker package generated in the IND-enabling program.
The IND-enabling program is organized to accelerate biomarker data on existing clinical patients while running parallel translational and regulatory work.
Timeline: Immediate. Collection and analysis on existing clinical SAPU003 patients — PBMCs, plasma, exosomes, cfDNA, cytokine panels. Every patient generates biomarker data that would otherwise take years and millions in a separate program.
Timeline: 6–12 months. ODD and RPDD applications for Tier 1 mTORopathies (TSC, FCD). Natural history review. Regulatory briefing package. Development roadmap.
Timeline: 6–18 months. Focused preclinical studies on three questions: does SAPU003 restore KCC2 function; does it normalize chloride homeostasis; can KCC2 serve as a predictive biomarker for patient selection.
Timeline: 6–12 months. PK modeling, CNS penetration studies, exposure-response modeling. Establishes SAPU003's primary differentiation vs. oral rapalogs quantitatively.
Compound IP, the Deciparticle™ nanoparticle platform, and worldwide oncology rights.
Exclusive worldwide development and commercial rights across the neurology and longevity fields. Structured on standard field-license economics.
PDAOAI holds right of reference to Sapu's clinical safety and pharmacokinetic data for SAPU003. The formulation has been dosed in humans and that record is available to the neurology program — so the IND package starts from real human exposure to this nanoparticle, not from the oral active alone.