Peptide · PT00114

PT00114

Phase 1Protagenic Therapeutics, Inc. (PTIX)

First-in-class synthetic neuropeptide — a 41-residue synthetic form of teneurin C-terminal associated peptide-1 (TCAP-1), an endogenous brain signaling peptide that dampens overactive stress responses — developed by Protagenic Therapeutics under an exclusive worldwide license from the University of Toronto (laboratory of scientific founder Dr. David Lovejoy). Administered subcutaneously. Completed single-ascending-dose (30 subjects, five cohorts, up to 1,000 micrograms; zero clinically-relevant adverse events) and multiple-ascending-dose (well tolerated, no serious adverse events) Phase 1 studies in healthy volunteers conducted outside the United States, not under an IND. In August 2026 FDA Type B pre-IND written responses identified no clinical-hold issues and supported a new IND for a three-part Phase 1 program in generalized anxiety disorder; IND submission is guided for Q4 2026 with first patient dosing targeted 1H 2027. Preclinical activity reported in validated animal models of anxiety, depression, substance use and PTSD. Chemical identifiers (CAS/UNII/ChEMBL/PubChem) are not publicly disclosed.

Also known as: PT00114, PT-00114, PT 00114

Data current as of

Key facts

Modality
Peptide
Mechanism
Peptide
Highest phase
Phase 1
Lead indication
Generalized anxiety disorder
Developer
Protagenic Therapeutics, Inc. (PTIX)
Next catalyst
fourth quarter 2026 — Regulatory (Generalized anxiety disorder)

Mechanism of action#

PT00114 is a 41-residue synthetic form of teneurin C-terminal associated peptide-1 (TCAP-1), an endogenous brain peptide of ancient evolutionary origin discovered in Dr. David Lovejoy's laboratory (University of Toronto) during a genome-wide search for proteins related to corticotropin-releasing factor (CRF). Per the sponsor, TCAP-1 counterbalances excess stress signaling in the brain's stress-response cascade: it reverses the impact of stress on the hypothalamic-pituitary-adrenal (HPA) axis and counteracts endogenous or pharmacologically administered CRF via a non-CRF-receptor pathway, lowering circulating cortisol without the sedation or dependence liabilities of benzodiazepines. Pharmacological effects persist for weeks after a single subcutaneous dose despite plasma elimination within hours, consistent with lasting changes in gene expression and neuronal function. Independent academic work reports TCAP-1 attenuates restraint-stress-induced corticosterone rises and chronic-stress behaviors in rodents. No definitive receptor has been established for TCAP-1 (teneurin/TCAP biology intersects latrophilin adhesion-GPCRs and beta-dystroglycan in the literature), and no binding or potency values exist for PT00114 — so no canonical target is linked.

TargetActionAffinity

Formulations#

FormulationRouteRegimenPharmacokinetics
PT00114 subcutaneous injection
Subcutaneous injection; Phase 1 single-ascending-dose portion tested five cohorts up to 1,000 micrograms. Multiple-ascending-dose cohort doses were not disclosed. The clinical dosing cadence for Phase 2 has not been announced (preclinically, effects of a single subcutaneous dose persisted for weeks).
SubcutaneousOther—

Development timeline#

Jan 24Jul 24Jan 25Jul 25Jan 26Jul 26TodayPhase 131 Dec 2026 — upcoming — US IND submission for PT00114 in generalized anxiety disorder targeted before end of 2026, following FDA Type B pre-IND written responses that identified no clinical-hold issues; first patient dosing targeted 1H 2027.20 Aug 2026 — phase change — FDA Type B pre-IND written responses received for PT00114 in generalized anxiety disorder: no clinical-hold issues identified; no objection to the planned three-part Phase 1 program, dose-escalation approach or safety review governance; potency/comparability strategy and CMC + nonclinical packages deemed reasonable to support an IND. The new IND builds on the completed ex-US SAD/MAD studies (conducted outside the US, not under an IND). IND submission guided Q4 2026; first patient dosing targeted 1H 2027. Note: this is pre-IND feedback only — no IND has been filed or cleared.9 Dec 2025 — readout (met) — Phase 1 multiple-dose topline: PT00114 well tolerated across all dose ranges; no serious adverse events; all participants completed dosing; adverse events consistent with an injectable peptide (injection-site reactions).22 May 2024 — readout (met) — Phase 1 single-ascending-dose complete results: zero clinically-relevant adverse events in 30 subjects across five cohorts at subcutaneous doses up to 1,000 micrograms.26 Sept 2023 — phase change — First-in-human Phase I/IIa study of PT00114 commenced (ex-US, no public registry record): planned 56 subjects randomized to subcutaneous PT00114 or placebo — healthy volunteers first, with patient cohorts planned in treatment-resistant depression, PTSD and generalized anxiety disorder; cortisol biomarkers tracked. Designed and led by principal investigator Dr. Maurizio Fava (Massachusetts General Hospital); clinical program managed by CRO Axiom Real-Time Metrics.26 Sept 2023 — Trial started — First-in-human Phase I/IIa study of PT00114 commences (ex-US)
Phase change Readout Event UpcomingHover a marker for details.
Phase 1Sept 2023 – Dec 2026
  1. UpcomingUS IND submission for PT00114 in generalized anxiety disorder targeted before end of 2026, following FDA Type B pre-IND written responses that identified no clinical-hold issues; first patient dosing targeted 1H 2027.↗
  2. FDA Type B pre-IND written responses received for PT00114 in generalized anxiety disorder: no clinical-hold issues identified; no objection to the planned three-part Phase 1 program, dose-escalation approach or safety review governance; potency/comparability strategy and CMC + nonclinical packages deemed reasonable to support an IND. The new IND builds on the completed ex-US SAD/MAD studies (conducted outside the US, not under an IND). IND submission guided Q4 2026; first patient dosing targeted 1H 2027. Note: this is pre-IND feedback only — no IND has been filed or cleared.↗
  3. metPhase 1 multiple-dose topline: PT00114 well tolerated across all dose ranges; no serious adverse events; all participants completed dosing; adverse events consistent with an injectable peptide (injection-site reactions).↗
  4. metPhase 1 single-ascending-dose complete results: zero clinically-relevant adverse events in 30 subjects across five cohorts at subcutaneous doses up to 1,000 micrograms.↗
  5. First-in-human Phase I/IIa study of PT00114 commenced (ex-US, no public registry record): planned 56 subjects randomized to subcutaneous PT00114 or placebo — healthy volunteers first, with patient cohorts planned in treatment-resistant depression, PTSD and generalized anxiety disorder; cortisol biomarkers tracked. Designed and led by principal investigator Dr. Maurizio Fava (Massachusetts General Hospital); clinical program managed by CRO Axiom Real-Time Metrics.↗
  6. Trial startedFirst-in-human Phase I/IIa study of PT00114 commences (ex-US)↗

PT00114 for Generalized anxiety disorder#

Phase 1ActiveGeneralized anxiety disorder indication →

Generalized anxiety disorder is the indication Protagenic has committed PT00114's US regulatory path to. The ex-US Phase I/IIa study (commenced 2023-09-26; designed and led by Dr. Maurizio Fava of MGH; CRO Axiom Real-Time Metrics; planned 56 subjects, subcutaneous PT00114 vs placebo, cortisol biomarkers) completed its Phase 1 portions in healthy volunteers: single-ascending-dose complete results announced 2024-05-22 (30 subjects, five cohorts, doses up to 1,000 micrograms, zero clinically-relevant adverse events) and multiple-ascending-dose topline announced 2025-12-09 (well tolerated at all dose levels, no serious adverse events, injection-site reactions consistent with an injectable peptide). These studies were run outside the United States and not under an IND, and no registry record is public. The planned patient portion (Phase IIa) never started — guidance slipped from Q3 2025 to early 2026 — and is now gated on a US IND: on 2026-08-20 Protagenic announced FDA Type B pre-IND written responses identifying no clinical-hold issues and no objection to the planned three-part Phase 1 program in GAD, its dose-escalation approach, safety review governance, or CMC/nonclinical packages. IND submission is guided for Q4 2026, first patient dosing targeted 1H 2027; the FY2026 10-K anticipates Phase IIa initiation Q2 2027 with results Q3 2027. The company notes no new medicine has been FDA-approved specifically for GAD in nearly two decades. Funding risk is material: the FY2026 10-K carries going-concern doubt and the company operates a virtual model with two full-time employees.

Readouts

  • fourth quarter 2026AnticipatedRegulatory

    US IND submission for PT00114 in generalized anxiety disorder targeted before end of 2026, following FDA Type B pre-IND written responses that identified no clinical-hold issues; first patient dosing targeted 1H 2027. ↗

  • 2025-12-09ReportedTopline datamet

    Phase 1 multiple-dose topline: PT00114 well tolerated across all dose ranges; no serious adverse events; all participants completed dosing; adverse events consistent with an injectable peptide (injection-site reactions). ↗

  • 2024-05-22ReportedTopline datamet

    Phase 1 single-ascending-dose complete results: zero clinically-relevant adverse events in 30 subjects across five cohorts at subcutaneous doses up to 1,000 micrograms. ↗

Sources#

  1. Protagenic Therapeutics Initiates Phase I/IIa Clinical Trial for Groundbreaking Brain Peptide PT00114 (2023-09-26, ACCESSWIRE wire copy) — Protagenic Therapeutics, Inc. (via ACCESSWIRE/Nasdaq)
  2. Protagenic Therapeutics Receives FDA Pre-IND Feedback Supporting New IND for PT00114 in Generalized Anxiety Disorder (2026-08-20; 8-K Exhibit 99.1, accession 0001493152-26-039410) — Protagenic Therapeutics, Inc. via SEC EDGAR
  3. Protagenic Therapeutics, Inc. Annual Report on Form 10-K for the fiscal year ended 2026-03-31 (filed 2026-08-14; accession 0001493152-26-038255) — compound identity (41-residue synthetic TCAP-1), University of Toronto license, mechanism, formulation, clinical history and anticipated milestones — Protagenic Therapeutics, Inc. via SEC EDGAR
  4. Protagenic Therapeutics' Stress-Regulating Peptide Demonstrates Exceptional Safety in Single Dose Portion of Phase I Trial (2024-05-22; 8-K Exhibit 99.1, accession 0001493152-24-020973) — Protagenic Therapeutics, Inc. via SEC EDGAR
  5. Results from Phase 1 Multiple-Dose Study of PT00114 (2025-12-09, ACCESS Newswire wire copy) — Protagenic Therapeutics, Inc. (via ACCESS Newswire/BioSpace)