Opus Genetics has received FDA clearance for its investigational new drug (IND) application of the gene therapy OPGx-BEST1, indicated to treat bestrophine-1 (BEST1)-related inherited retinal disease (IRD).
Let’s start with a look at BEST1.
The BEST1 gene is responsible for providing instruction on making the bestrophin protein, which acts as a channel to manage charged (chlorine ion) atoms’ movement in and out of cells within the retina.
- Variants (mutations) in the BEST1 gene (as well as the PRHP2 gene) can result in the development of abnormally-shaped channels unable to control chloride flow.
- Also to keep in mind: BEST1 plays a key role in the retinal pigment epithelium (RPE), which is critical for vision.
As a result of these BEST1 mutations: BEST1-related IRDs (bestrophinopathies) can develop, impacting an estimated 9,000 patients across the United States.
A notable IRD included in this: Vitelliform macular dystrophy (VMD), a rare genetic eye disorder affecting the macula that can lead to worsening vision loss.
- Breaking this disease down, VMD can manifest into one of two forms: early-onset and adult-onset.
- The early-onset form is known as Best disease, which typically develops in childhood (though it can also appear later in life).
And how does OPGx-BEST1 target this macular degeneration?
The BEST1 gene therapy delivers a functional copy of the BEST1 gene to RPE cells to create a BEST1 protein and stabilize homeostasis between RPE cells and photoreceptors.
- How it accomplishes this: By leveraging an adeno-associated virus (AAV) vector via Opus Genetics’ proprietary AAV-based gene therapy platform.
The intent: To return RPE cells to their normal function and enable them to properly support photoreceptors—restoring vision.
Duly noted. Now, what does this IND mean?
A step forward in OPGx-BEST1’s clinical evaluation, to say the least.
In general: An IND is submitted to the FDA by a company or investigator in order to move from the preclinical stage of a proposed investigational drug on to human-based clinical trials.
- Included in this submission:
- Pharmacology and toxicology data from preclinical research
- Proposed clinical trial protocols
- Manufacturing and quality control info
Notably: The FDA will generally review a submission to ensure the safety and rights of research subjects as well as the quality of the scientific evaluation pertaining to the proposed drug.
And for OPGx-BEST1’s case?
With its IND clearance in place, Opus Genetics intends to initiate a phase 1/2 clinical trial.
Nice! Before we talk more about that, what did its preclinical performance look like?
Promising … and this is based on 2024 research presented at the Association for Research and Vision in Ophthalmology (ARVO) annual meeting.
The IND-enabling study: Evaluated a unilateral subretinal injection of OPGx-BEST1 (in three varying doses) administered (versus vehicle) in a group of canines diagnosed with bestrophinopathy (canine multifocal retinopathy).
The results: OPGx-BEST1 was well tolerated and resulted in no significant ophthalmic and systemic toxicity at two of its doses (low- and mid-doses)—with subtle clinical (funduscopic) signs of potential retinal toxicity noted among patients treated with a high-dose version.
- See here for more details.
Interesting … so what do we know about this upcoming study?
- The design: A multicenter, open-label trial
- The purpose: To evaluate the safety, tolerability, and preliminary efficacy of a single subretinal injection of OPGx-BEST1 in a to-be-determined number of patients
- The participants: Patients diagnosed with genetically-confirmed BEST1-related IRD
- The outcome measures: Exploring the biological activity via functional and anatomical endpoints—including changes in visual function and retinal structure
And the timeframe for its initiation?
Per the company: Before the end of 2025 (second half [H2]).
As for the big-picture significance: With no treatment currently approved for BEST1-related IRDs, OPG-BEST1 represents a potential groundbreaking opportunity for this patient base.