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 researchProposed clinical trial protocolsManufacturing 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.

Interesting … so what do we know about this upcoming study?The design: A multicenter, open-label trialThe purpose: To evaluate the safety, tolerability, and preliminary efficacy of a single subretinal injection of OPGx-BEST1 in a to-be-determined number of patientsThe participants: Patients diagnosed with genetically-confirmed BEST1-related IRDThe outcome measures: Exploring the biological activity via functional and anatomical endpoints—including changes in visual function and retinal structureAnd 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.