Kiora Pharmaceuticals, Inc. has secured a U.S. patent for KIO-104, an investigational small molecule, for the treatment of an expanded range of ocular diseases.
First up, Kiora.
Since its 2023 announcement of a shift in operations to focus on developing rare retinal disease candidates, the clinical-stage specialty pharmaceutical company has pursued two investigational assets:
- KIO-104 (our topic of interest)
- KIO-301 for the treatment of retinitis pigmentosa, choroideremia, and Stargardt disease
To note: Both intravitreal (IVT) injection-administered assets are small molecules formulated to slow, stop, or restore vision loss.
Talk more about KIO-104.
KIO-104 is referred to as a next-generation, non-steroidal, immuno-modulatory, and small-molecular inhibitor of dihydroorotate dehydrogenase (DHODH) under development as an alternative treatment to steroids or systemic anti-inflammatory drugs.
- Quick note: DHODH is an enzyme encoded by the DHODH gene and located in the mitochondria of cells; it’s considered crucial for cellular processes such as cell proliferation and immune function.
And its mechanism of action?
The small molecule suppresses certain T-cells and cytokines within the eye that cause inflammation
How: By blocking DHODH, which is known to have a key role in combining the building blocks of DNA and RNA. Without these building blocks—which are needed for T-cell function—T-cell replication is significantly reduced.
- See here for a visual of the DHODH inhibition process.
Why this is important: A smaller number of those building blocks also lowers the ability of T-cells to cause inflammation—and, as a result, potentially helps to restore vision loss in such retinal diseases.
Noted. So which retinal disease is KIO-104 targeting?
Per Kiora, the candidate is under clinical development for the treatment of:
- Retinal inflammation (currently in phase 2)
- Proliferative vitreoretinopathy (currently in preclinical stage)
And with this new U.S. patent secured?
The patent (US Patent No. 12,364,680) now covers KIO-104 in potentially treating a wider range of ocular diseases, including (but, notably, not limited to):
- Ocular inflammation
- Uveitis
- Age-related macular degeneration (AMD)
- Complications from refractive surgery
Specifically: In regard to those conditions, the patent covers varying dosing schedules, any necessary excipients, and other “novel methods for optimizing treatment of ocular inflammatory diseases," according to the company.
- Take note: This isn’t the first patent Kiora has received for the candidate.
Now let’s talk significance.
Kiora President and CEO Brian M. Strem, PhD, noted that this patent significantly “builds on our IP strategy to protect KIO-104 around its proprietary structure, delivery methods, formulation, and therapeutic applications.”
Speaking of protections … how long will it last?
The patent is expected to provide KIO-104 protection—and extend its market exclusivity—through 2043.
Keep in mind:
- Patent protections are typically sought and granted to protect the intellectual property (IP) of a pharmaceutical drug (or invention)
- In terms of regulatory exclusivity, this would only apply to KIO-104 if/when it receives FDA approval
- With this exclusivity, Kiora could potentially charge higher-than-competitive prices for the drug
Definitely some advantages here. So, how has KIO-104 performed in trials thus far?
The asset was last studied in a phase 1 trial (NCT03634475) evaluating its ability (in three varying doses via single IVT injection) to suppress T- and B-cells in patients with non-infectious posterior segment uveitis.
The findings:
- No toxic side effects on intraocular tissues (or other adverse events [AEs]) were observed
- Intraocular inflammation decreased
- Visual acuity significantly improved
- Macular edema regressed two weeks after injection in some patients—“indicating … high potential as a new intraocular therapy for uveitis”
Nice! And what’s next?
Next up is the phase 2 KLARITY trial (NCT06825702), which is currently screening participants for enrollment. A few details about this:
- The design: Multicenter, open-label, multi-dose, interventional study
- The participants: Up to 28 patients (aged 18 to 85) diagnosed with macular edema (ME) in the study eye secondary to non-infectious uveitis, retinal vein occlusion, diabetic retinopathy, or cataract surgery
- See here for full inclusion and exclusion criteria
- The setup: Two-part study, with:
- Part A: Evaluating safety, tolerability, and efficacy of up to three doses of KIO-104, administered every 2 weeks, investigated into two potential dose cohorts:
- Cohort 1: Low-dose KIO-104
- Cohort 2: High-dose KIO-104
- Part B: Investigating the safety and efficacy of up to three KIO-104 doses with two differing dosing regimens (administered either every 2 or 4 weeks), in ME patients at a dose selected from Part A
- Part A: Evaluating safety, tolerability, and efficacy of up to three doses of KIO-104, administered every 2 weeks, investigated into two potential dose cohorts:
What will be measured?
One primary outcome: The safety and tolerability of KIO-104, as determined via the development of AEs within each of the dose cohorts.
- This will be measured at 23 months
Last question: When can we anticipate a data readout from this?
Per Clinical Trials, the study kicked off in May 2025—and isn’t expected to conclude until December 2026 (with a primary completion in November of that year).
In the meantime, stay tuned for interim results!