KIO-101 / 4SC, Kiora Pharma - LARVOL DELTA

A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function. (PubMed, Acta Pharm Sin B) - "Using BRET-based biosensors, we show that PP-001, a pepducin derived from NTSR1's first intracellular loop, preferentially activates G protein over β-arrestin signaling while inhibiting NT binding, NT-induced β-arrestin recruitment, and NTSR1 internalization, thereby acting as biased allosteric agonist and negative allosteric modulator...Finally, thermodenaturation assays using purified NTSR1, combined with mutagenesis and molecular docking, provide evidence for the role of the receptor's H8 domain in direct pepducin interaction. Together, these findings highlight pepducins as versatile modulators of GPCR function and as valuable pharmacological tools for GPCR-targeted drug development."

Journal

Immunology of Uveitis - From Bench to Bedside. (PubMed, Klin Monbl Augenheilkd) - "The discovery of the tolerance-inducing but non-pathogenic mimicry epitope B27PD made it possible to treat therapy-refractory uveitis patients by inducing oral tolerance. These new animal models also enabled the development of a small molecule dihydroorotate dehydrogenase (DHODH) inhibitor PP-001/KIO-100 for the treatment of uveitis, which inhibits lymphocytes but has no toxic effects on intraocular cells (in vivo: rat) and human retinal pigment epithelial cells (RPE, in vitro). This was followed by a successful phase I trial for patients with non-infectious posterior uveitis, by intraocular application of PP-001/KIO-100 - without side effects, but with improvement of visual acuity and reduction in inflammation and CME."

Journal • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Uveitis

A Safety Study of Intravitreal PP-001 in Patients With Chronic, Non-Infectious Uveitis (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: Panoptes Pharma GmbH | Unknown status ➔ Completed | N=18 ➔ 12

Enrollment change • Trial completion • Inflammation • Ocular Inflammation • Ophthalmology • Uveitis

Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study. (PubMed, Pharmaceutics) - "A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia."

Journal • P1 data • Ocular Inflammation • Ophthalmology

A Phase I Study of PP-001 Eye Drops in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Panoptes Pharma GmbH | Unknown status ➔ Completed | N=24 ➔ 45

Enrollment change • Trial completion • Conjunctivitis • Dry Eye Disease • Ocular Infections • Ocular Inflammation • Ophthalmology

A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: Kiora Pharmaceuticals, Inc. | N=132 ➔ 4 | Trial completion date: Nov 2024 ➔ Jan 2024 | Suspended ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Jan 2024; Study halted prematurely but potentially will resume

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Dry Eye Disease • Immunology • Ophthalmology • Psoriatic Arthritis

A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - P2 | N=132 | Suspended | Sponsor: Kiora Pharmaceuticals, Inc. | Trial completion date: Nov 2023 ➔ Nov 2024 | Trial primary completion date: Nov 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Dry Eye Disease • Immunology • Ophthalmology • Psoriatic Arthritis

A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - P2 | N=132 | Suspended | Sponsor: Kiora Pharmaceuticals, Inc. | Not yet recruiting ➔ Suspended

Trial suspension • Dry Eye Disease • Immunology • Ophthalmology • Psoriatic Arthritis

A phase 1 trial treating autoimmune uveitis with a novel intraocular small molecule - further data analysis (ARVO 2023) - "Purpose After extensive and successful preclinical investigations of effects and side effects of the small molecule inhibitor of pyrimidine synthesis that targets DHODH (KIO-100/PP-001) and thus efficiently suppressed T and B cells and uveitis in rats we have performed a clinical phase 1 trial for patients suffering from posterior uveitis...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

P1 data • Ocular Inflammation • Ophthalmology • Uveitis

A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Kiora Pharmaceuticals, Inc.

New P2 trial • Dry Eye Disease • Immunology • Ophthalmology • Psoriatic Arthritis

A new small molecule DHODH-inhibitor [KIO-100 (PP-001)] targeting activated T cells for intraocular treatment of uveitis - A phase I clinical trial. (PubMed, Front Med (Lausanne)) - P1/2 | "Macular edema, a sight-threatening complication in uveitis, showed regression 2 weeks after intraocular KIO-100 (PP-001) injection in some patients, indicating that this novel small molecule has a high potential as a new intraocular therapy for uveitis. [https://www.clinicaltrials.gov/ct2/show/NCT03634475], identifier [NCT03634475]."

Journal • P1 data • Immune Modulation • Immunology • Inflammation • Macular Edema • Ocular Inflammation • Ophthalmology • Uveitis

A Phase I Study of PP-001 Eye Drops in Healthy Adult Volunteers (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Panoptes Pharma GmbH; Trial completion date: Dec 2019 ➔ Jan 2021; Trial primary completion date: Nov 2019 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date

Cell-penetrating pepducins targeting the neurotensin receptor type 1 relieve pain. (PubMed, Pharmacol Res) - "Finally, we designed a TAMRA-tagged version of PP-001 and found by confocal microscopy that the pepducin reached the rat dorsal root ganglia post i.t. injection, thus potentially modulating the activity of NTS1 at this location to produce its analgesic effect. Altogether, these results suggest that NTS1-derived pepducins may represent a promising strategy in pain-relief."

Journal

A Safety Study of Intravitreal PP-001 in Patients With Chronic, Non-Infectious Uveitis (clinicaltrials.gov) - P1/2; N=18; Active, not recruiting; Sponsor: Panoptes Pharma GmbH; Trial completion date: Dec 2019 ➔ Dec 2020; Trial primary completion date: Nov 2019 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date

A Phase I Study of PP-001 Eye Drops in Healthy Adult Volunteers (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Panoptes Pharma GmbH; Recruiting ➔ Active, not recruiting; Trial completion date: May 2019 ➔ Dec 2019; Trial primary completion date: Apr 2019 ➔ Nov 2019

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

A Safety Study of Intravitreal PP-001 in Patients With Chronic, Non-Infectious Uveitis (clinicaltrials.gov) - P1/2; N=18; Active, not recruiting; Sponsor: Panoptes Pharma GmbH; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2019 ➔ Dec 2019; Trial primary completion date: Jul 2019 ➔ Nov 2019

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

A Safety Study of Intravitreal PP-001 in Patients With Chronic, Non-Infectious Uveitis (clinicaltrials.gov) - P1/2; N=18; Recruiting; Sponsor: Panoptes Pharma GmbH; Trial completion date: Oct 2018 ➔ Aug 2019; Trial primary completion date: Sep 2018 ➔ Jul 2019

Clinical • Trial completion date • Trial primary completion date