Slide 1: Daily Low-Dose Psilocin Mucate and First-in-Human Pharmacokinetics
Daily Low-Dose Psilocin Mucate and First-in-Human Pharmacokinetics September 15, 2026 Dr. Frederick D. Sancilio, PhD — CEO & Chairman CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F
Slide 2: Disclaimer
Disclaimer • This presentation (“Presentation”) is an update of Lobe Sciences, Inc. (the “Company”) and is for information purposes only and should not be relied on for the purposes of making an investment decision. This Presentation does not, and it is not intended to, provide any financial, legal,
Slide 3: Lobe Operates Three Therapeutically focused Subsidiaries
Lobe Operates Three Therapeutically focused Subsidiaries This presentation will focus on Cynaptec’s L-130 (psilocin mucate) * *Alera is currently evaluating several new development opportunities CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 3
Slide 4: Psilocybin Development Landscape
Psilocybin Development Landscape Dosing across the class is episodic and medically monitored, with follow-up over weeks or months Treatment-session model Monitoring burden L-130 differentiation point One or two high-dose sessions, followed by Controlled clinical setting, trained facilitators and Des
Slide 5: Psilocybin is an Inactive Prodrug
Psilocybin is an Inactive Prodrug And must be Enzymatically Dephosphorylated to become Psilocin; the Active Metabolite Alkaline phosphatase Dephosphorylation 52% Activates serotonin (20–80%)* receptors Psilocybin bioavailability Psilocin 5-HT2A Serotonin *Hasler F, et al. Pharm Acta Helv. 1997;72(3)
Slide 6: Current Challenges Facing the Development of Psilocybin as a Therapeutic
Current Challenges Facing the Development of Psilocybin as a Therapeutic Psilocybin is a Prodrug which Psilocybin is poorly bioavailable To provide consistent therapeutic must be metabolized to Psilocin (50%) and inconsistent effect, dose levels must be higher to be active than needed causing severe
Slide 7: The Problem and the Solution: Psilocybin Psilocin
The Problem and the Solution: Psilocybin Psilocin Problem: Dosing psilocybin at • The hallucinations force the use of the therapeutic to be infrequent (weekly or levels that will be consistently less frequent dosing interval) efficacious requires doses that • Patients have to be observed for hours p
Slide 8: Psilocin (as the free base) is Unstable
Psilocin (as the free base) is Unstable Multiple Degradation Pathways Create a Stability Nightmare for Formulators PSILOCIN (Free Base) Oxygen / air Light Heat Moisture or pH Oxidants or metals Degradation Degradation Degradation Degradation Degradation products products products products products C
Slide 9: The Solution to Psilocybin's Challenges: L-130 (Psilocin Mucate)
The Solution to Psilocybin’s Challenges: L-130 (Psilocin Mucate) Delivers psilocin the active metabolite as a stable API Following 129 attempts to stabilize psilocin, the mucate (L-130) was synthesized CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 9
Slide 10: L-130 (Psilocin Mucate Salt)
L-130 (Psilocin Mucate Salt) Proposed Solid-State Stabilization Model Crystal packing may Ionic pairing at the reduce mobility and protonated amine exposure to oxygen or moisture Hydrogen-bond network around the phenolic 4-OH Conceptual hypothesis; exact proton positions and intermolecular contacts
Slide 11: Can Psilocin be given daily, at sub-hallucinogenic levels and still be effective?
Can Psilocin be given daily, at sub-hallucinogenic levels and still be effective? Four endpoints (n=12/group) were evaluated comparing daily versus weekly dosing. Animals were subjected to stress (CUMS*) then the impact of a human equivalent dose of ~2mg was measured as follows: • Cortisol Levels •
Slide 12: Cortisol Levels Following CUMS (n=12/group)
Cortisol Levels Following CUMS (n=12/group) Only Daily Dosing Results are Statistically Significant CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 12
Slide 13: Elevated Plus Maze
Elevated Plus Maze Only Daily Dosing Results were Statistically Significant CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 13
Slide 14: Open Field-Internal Zone
Open Field-Internal Zone Only Daily Dosing Resulted in Statistical Significance CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 14
Slide 15: Novel Object Recognition
Novel Object Recognition • Both Daily (G4) and Weekly(G5) achieved significant results • However, daily dosing results were nearly identical to those observed for the naïve group CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F 15
Slide 16: A Repeat Dose Study Assessing Potential Hallucinations at Dose Levels
A Repeat Dose Study Assessing Potential Hallucinations at 3 Dose Levels Head-twitch response (HTR) across repeat dosing, highlighting Day 1 and Day 7. Key observations (p-values appear in charts): • At doses test, 0.075, 0.15 and 0.3 mg/kg, HTR did not differ from control over 7 days. • At these dos
Slide 17: L-130 Psilocin Mucate's "First-In-Human" Study
L-130 Psilocin Mucate’s “First-In-Human” Study Published: Sancilio et al., 2024 Study Design • Single-dose Phase 1a safety study (4 mg psilocin mucate) Safety • No serious adverse events and no hallucinogenic effects at this dose Pharmacokinetics • Psilocin was rapidly absorbed after oral administra
Slide 18: Human Psilocin Exposure (Psilocybin vs Psilocin)
Human Psilocin Exposure (Psilocybin vs Psilocin) Psilocin derived from psilocybin shows broad variability; L-130 psilocin mucate shows a tighter exposure range. L-130 appears to deliver psilocin more efficiently and far more reproducibly than psilocybin, potentially enabling predictable therapeutic
Slide 19: L-130 Appears Active in Anxiolytic Models and Shows Similar Signs in Humans
L-130 Appears Active in Anxiolytic Models and Shows Similar Signs in Humans with no Hallucinations Any application utilizing psilocybin can be easily reformulated with psilocin (L-130) Psilocin (L-130) has demonstrated superior anxiolytic activity (preclinical) given daily compared to weekly dosing
Slide 20: Current Applications of L-130 (psilocin mucate)
Current Applications of L-130 (psilocin mucate) A Patented and New Chemical Entity and some Applications Cluster Headache (CH): Substance Use Disorder Generalized Anxiety (Addiction): Disorder (GAD): Targeting one of the most severe Preclinical data suggests L-130 may GAD impacts 2.7% of U.S. adults
Slide 21: L-130 (psilocin mucate): Development Progress and Next Steps
L-130 (psilocin mucate): Development Progress and Next Steps A patented, stabilized psilocin-based therapeutic platform advancing to address significant unmet needs Completed API Scale-Up Long-Term 28-Day Daily vs Pre-IND CTA Filed (ex- First-in-Human Patents Issued IND-Enabling for L-130 Completed
Slide 22: Thank You
Thank You Dr. Frederick D. Sancilio, PhD CEO & Chairman lobesciences.com CSE: LOBE • OTCQB: LOBEF • FSE: LOBE.F