Kiora Pharmaceuticals Stock

Kiora Pharmaceuticals, Inc., a clinical-stage specialty pharmaceutical company, engages in developing and commercializing therapies for the treatment of ophthalmic diseases.

The company's lead product is KIO-301, with an initial focus on patients with later stages of vision loss due to retinitis pigmentosa (RP, any and all sub-forms). KIO-301 is a potential vision-restoring small molecule that acts as a 'photoswitch' specifically designed to restore vision in patients with inherited and age-related degenerative retinal diseases, including RP. The molecule is designed to restore the eyes' ability to perceive and interpret light in visually impaired patients through selectively entering viable downstream retinal ganglion cells (no longer receiving electrical input due to degenerated rods and cones) and turning them into light sensing cells, capable of signaling the brain as to the presence or absence of light. The company initiated a Phase 1b clinical trial in the third quarter of 2022 and dosed the first patient in November 2022. On March 17, 2022, the company was granted orphan drug designation (ODD) by the United States Food and Drug Administration (FDA) for the active pharmaceutical ingredient (API) in KIO-301. KIO-301 (formerly known as B-203) was acquired through the Bayon Therapeutics, Inc. (Bayon) transaction which closed October 21, 2021.

KIO-101 focuses on treating the ocular manifestation of patients with autoimmune diseases, including rheumatoid arthritis and, as such, is termed the Ocular Presentation of Rheumatoid Arthritis and Other Autoimmune Diseases (OPRA+). KIO-101 is a next-generation, non-steroidal, immuno-modulatory, small-molecule inhibitor of dihydroorotate dehydrogenase (DHODH). KIO-101 to be best-in-class with picomolar potency and a validated immune modulating mechanism designed to overcome the off-target side effects and safety issues associated with commercially available DHODH inhibitors. In a 14-day good laboratory practice (GLP) intravenous (IV) repeated dose toxicity study in rats, no adverse or test item related effects were observed in any of the tested parameters (mortality, clinical observations, ophthalmoscopy, body weight and food consumption, hematology and coagulation, clinical biochemistry, organ weight, pathology, and histopathology) at the highest doses tested (1.0 mg/kg). In the fourth quarter of 2021, the company reported top-line safety and tolerability data from a Phase 1b proof-of-concept (POC) study evaluating KIO-101 in patients with ocular surface inflammation. As a further sign of safety, there were zero clinically significant laboratory (including liver enzymes) findings observed in both healthy patients and those with ocular surface inflammation. The company expects to initiate a Phase 2 clinical trial in the first quarter of 2023. KIO-101 (formerly known as PP-001) was acquired through the acquisition of Panoptes Pharma GmbH (Panoptes) in the fourth quarter of 2020.

The company is developing KIO-201 for patients with persistent corneal epithelial defects (PCED). PCED is an orphan disease and as such, the company is seeking orphan drug designation (ODD). KIO-201 is also being evaluated for patients recovering from surgical wounds, such as those undergoing the laser vision correction procedure, photorefractive keratectomy (PRK). KIO-201 is a modified form of the natural polymer hyaluronic acid, designed to protect the ocular surface to permit re-epithelialization of the cornea and improve and maintain ocular surface integrity. KIO-201 has unique properties that help hydrate and protect the ocular surface. The company is evaluating KIO-201 in a Phase 2 clinical trial in patients with PCEDs and released top-line data in Q1 2023. The company expects to release full data in Q2 2023. The company is in planning stages of a Phase 3b trial for patients recovering from PRK and plan to initiate the study before the end of 2023.

Strategy

The key elements of the company's strategy are to:

Develop Core Assets

Continue clinical development of KIO-301 in a Phase 1b clinical study in patients with mid to late stage retinitis pigmentosa.

Continue clinical development of KIO-101 in a Phase 2 clinical study for the treatment of the ocular manifestations of autoimmune diseases (e.g., rheumatoid arthritis). In the first quarter of 2023, the company received approval to initiate a Phase 2 study, slated to start enrollment in the second quarter of 2023.

Continue clinical development of KIO-201 in patients with PCEDs and advance the company's late stage program for patients undergoing surgical vision correction, including PRK and certain types of keratoconus surgical procedures. These programs will benefit from discussions with the FDA regarding clinical trial designs and approvable endpoints.

Expand Portfolio through Collaborations

Pursue strategic collaborations to further the company's existing assets with respect to new indication potential and more detailed mechanism of action, which can result in new intellectual property.

Development Pipeline

Clinical Development

KIO-101: Ocular Presentation of Rheumatoid Arthritis and Other Autoimmune Diseases (OPRA+)

Mechanism of Action

KIO-101 is a promising novel third generation DHODH inhibitor, with a half-maximal inhibitory concentration IC50-value of 0.3 nM. Based on internal work completed, this means that 1,000-fold more potent than teriflunomide (IC50 DHODH 415 nM). Furthermore, KIO-101 suppresses the expression of key pro-inflammatory cytokines such as IL-17, IFN-g, VEGF and others, potentially as a consequence of inhibiting DHODH. IL-17 and IFN-g are the hallmark cytokines expressed by Th1 and Th17 T-cells, respectively, and play a crucial role in initiating the inflammatory processes in several ocular diseases, including dry eye disease (including the association with autoimmune conditions, such as rheumatoid arthritis) and non-noninfectious uveitis. KIO-101 is structurally and mechanistically different from Arava, a drug approved by the FDA for the treatment of rheumatoid arthritis. The IC50 of KIO-101 on selected tyrosine kinases, such as PI3K, AKT and JAK, is more than 10,000-fold above the IC50 of KIO-101 for DHODH. In general, side effects are not expected and have not been observed to date in animal and human studies after KIO-101 administration.

Phase 1b Study: The results of a Phase 1b study of KIO-101 eye drops in adults with and without ocular surface inflammation were reported in Q4 2021.

Clinical Development Plan

The company received conditional approval to initiate a Phase 2 clinical trial with KIO-101 eye drops in Q4 2022. In February 2023, the company received investigational new drug application approval for a Phase 2 study of KIO-101 for the treatment of OPRA+ and expect to initiate enrollment in Q2 2023. The study will enroll approximately 120 patients in a multi-center, controlled, randomized, double-masked trial assessing the safety and efficacy of KIO-101 eye drops in patients living with autoimmune disease who have signs and symptoms of ocular surface disease.

KIO-101: Non-Infectious Posterior Uveitis

Phase 1a/2b Safety Study: A first, in human clinical study to evaluate the safety of intravitreally applied KIO-101 in patients with chronic, non-infectious uveitis was conducted and the final study report was completed in 2021.

KIO-201: PRK Surgical Recovery Pivotal Study

Pivotal Study: In Q4 2019, the company reported positive topline results from the company's corneal wound repair pivotal clinical trial of KIO-201 for the corneal re-epithelialization in patients having undergone PRK surgery.

Clinical Development Plan

The company is assessing the requirements on a registration clinical trial, as well as evaluating the market opportunity. The company expects to begin further clinical work in 2023.

KIO-201: Persistent Corneal Epithelial Defects

Phase 2 Study: In Q1 2022, the company initiated a clinical trial of KIO-201 evaluating the potential to help patients with PCEDs. The company expects results from this study in early-mid 2023.

Clinical Development Plan

PCED qualifies as a rare disease, and therefore the company applied for orphan drug designation as part of the company's clinical development plan for KIO-201 in Q4 2022. The company expects to receive ODD in 2023 and with the results from the aforementioned clinical trial, the company plans to meet with the FDA to discuss next steps.

KIO-301: Retinitis Pigmentosa

Phase 1b Study: In Q4 2022, the company initiated a clinical trial of KIO-301 in patients with later stage Retinitis Pigmentosa. The company expects results from this study in late 2023.

Clinical Development Plan

In Q1 2022, the company received ODD from the FDA. The company will assess the results from the Phase 1b clinical trial and determine next steps in the development of KIO-301 in late 2023.

Intellectual Property and Proprietary Rights

Patent Portfolio

The company's patent portfolio includes patents covering KIO-101 including composition-of-matter, formulations thereof and its therapeutic uses in the treatment of ocular disorders and diseases and more. In addition, the company holds a patent portfolio covering KIO-301 consisting of composition-of-matter, methods of use, and formulations thereof patents. The company's KIO-201 portfolio of patents covers composition-of-matter and methods of use claims. These issued patents will expire between 2023 and 2036.

Globally, the company holds 26 active and valid patents.

License Agreements

The company is a party to seven license agreements as described below. These license agreements require the company to pay or receive royalties or fees to or from the licensor based on revenue or milestones related to the licensed technology.

On July 2, 2013, the company (through its subsidiary, Kiora Pharmaceuticals, GmbH) entered into a patent and know-how assignment agreement with 4SC Discovery GmbH (4SC) transferring to the company all patent rights and know-how to the compound KIO-101.

On July 2, 2013, the company (through its subsidiary, Kiora Pharmaceuticals, GmbH) entered into an out-license agreement with 4SC granting 4SC the exclusive worldwide right to commercialize the compound KIO-101 for rheumatoid arthritis and inflammatory bowel disease, including Crohn's disease and ulcerative colitis.

On September 12, 2013, the company (through its subsidiary, Jade Therapeutics, Inc.) entered into an agreement with Lineage Cell Therapeutics, Inc. (Lineage), formerly known as BioTime, Inc., granting to the company the exclusive worldwide right to commercialize cross-linked thiolated carboxymethyl hyaluronic acid (modified HA) for ophthalmic treatments in humans. The agreement expires when patent protection for the modified HA technology lapses in August 2027.

On November 17, 2014, the company (through the company's subsidiary Kiora Pharmaceuticals GmbH) entered into an intellectual property and know-how licensing agreement with Laboratoires Leurquin Mediolanum S.A.S. (Mediolanum) for the commercialization of KIO-101 (the 'Mediolanum Agreement') in specific territories. Under the Mediolanum agreement, the company out-licensed rights to commercialize KIO-101 for uveitis, dry eye, and viral conjunctivitis in Italy and France. This agreement was amended on December 10, 2015, to also include Belgium and the Netherlands.

On September 26, 2018, the company entered into an intellectual property licensing agreement (the 'SentrX Agreement') with SentrX, a veterinary medical device company that develops and manufactures veterinary wound care products. Under the SentrX Agreement, the company in-licensed the rights to trade secrets and know-how related to the manufacturing of KIO-201. The SentrX Agreement enables the company to pursue a different vendor with a larger capacity for manufacturing and an FDA-inspected facility for commercialization of a product for human use.

On May 1, 2020, the company (through its subsidiary, Bayon Therapeutics, Inc.) entered into an agreement with the University of California (UC) granting to the company the exclusive rights to its pipeline of photoswitch molecules. The agreement expires on the date of the last-to-expire patent included in the licensed patent portfolio which is January 2030.

On May 1, 2020, the company (through its subsidiary, Bayon Therapeutics, Inc) entered into an agreement with Photoswitch Therapeutics, Inc. (Photoswitch) granting to the company access to certain patent applications and IP rights with last-to-expire patent terms of January 2030.

Government Regulation

The company and its third-party manufacturers must comply with applicable FDA (the United States Food and Drug Administration) regulations relating to FDA CGMP (current Good Manufacturing Practice) regulations.

History

The company was incorporated in 1998. It was formerly known as EyeGate Pharmaceuticals, Inc. and changed its name to Kiora Pharmaceuticals, Inc. in 2021.