Eyeworld

SUMMER 2025 | EYEWORLD | 53 C Relevant disclosures Farid: Kala Bio Sheppard: Bio-Tissue, Claris Bio, Dompe, Noveome Contact Farid: mfarid@hs.uci.edu Sheppard: jsheppard@cvphealth.com corneal healing, homeostasis to preserve corneal epithelium, and limbal stem cell function. The drug is currently recruiting patients with PCED for a Phase 2/3 clinical trial. BRIM Biotechnology: BRM424 is being developed to "[stimulate] the proliferation and differentiation of corneal limbal stem cells to effectively regenerate healthy limbus after extensive limbal layer removal and to speed up the cornea repair process," according to the company's website. BRM424 has an Orphan Drug Designation from the FDA for NK and is in a Phase 2 clinical trial. BRIM is also developing BRM423, a synthetic peptide derived from hu- man pigment epithelium-derived factor, target- ed to treat severe corneal damage. Claris Bio: CSB-001 ophthalmic solution 0.1% (oremepermin-α) was in Phase 1/2 clini- cal trials for patients with Stage 2 or 3 NK. This study began in 2021, and its published planned completion date was within 2024. Oremeper- min-α, according to the company, is a five amino acid-deleted variant of hepatocyte growth factor developed by Kringle Pharma with rights to ophthalmic indications licensed to Claris Bio. The mechanism of action augments NGF with potential anti-proptosis, anti-inflammatory, and anti-scarring effects, now under study for corne- al defects within 30 days of onset. Kala Bio: KPI-012, according to the com- pany, has a multifactorial mechanism of ac- tion based on human mesenchymal stem cell secretome therapy for the intended treatment of PCED. KPI-012 is in a Phase 2 clinical trial (topline results expected in the second quarter of 2025) and has a Fast-Track Designation from the FDA. Noveome: ST266 is listed on the company's website as in a Phase 2 clinical trial. ST266, ac- cording to the company, is based on secretome collected from immortalized amnion-derived epithelial cells. This aggregate of more than 500 potentially synergistic proteins may be effective for thermal burns and necrotizing enterocolitis and has been studied in dry eye disease. RegeneRx: RGN-259 is targeting NK as a thymosin ß4, preservative-free eye drop that promotes cell migration and wound healing and is anti-inflammatory. RGN-259 has an Orphan Drug Designation from the FDA. The company has completed one Phase 3 clinical trial, meet- ing its primary safety and efficacy endpoint, and is currently conducting two other Phase 3 clinical trials in the U.S. Dr. Farid thinks that many of the therapies in development will not be a blanket cure for all aspects of PCED or NK but that they each address different components of a disrupted mechanism of the ocular surface. "Down the road, I think we're going to be able to tease some of that out and figure out what works best and do more targeted medicine," she said. 'Epithelial reboot' procedure vs. pharmaceuticals Dr. Sheppard said many pipeline pharmaceuti- cals are intriguing, but he described an "epi- thelial reboot" procedure that he thinks can, in some cases, accomplish similar results to what some of the pharmaceuticals are aiming for, es- pecially in patients with hereditary or traumatic basement membrane dystrophies. He said that for these patients, you need to thoroughly remove all of the bad epithelium to give new cells a fresh start to migrate cen- tripetally, heal, and truly adhere to basement membrane. "I've had tremendous success, 99% plus, when you remove all the epithelium, pol- ish the basement membrane, and manage them for 3 months, first with an amniotic membrane (which somewhat competes pharmacokinetical- ly with these drugs we're talking about), then with the serial bandage contact lenses for up to 3 months. They heal, and I never see them for emergencies again." Dr. Sheppard said the non-neurotrophic patients can have problems with ring mounted cryopreserved amniotic membrane because they can feel them. However, he said manufacturers have come up with a way to secure the merits of cryopreserved amniotic membrane under a regular bandage contact lens. Similarly, a retrospective study published earlier this year looked at the use of a decellu- larized amniotic basement membrane (either single layer or three layer), combined with 24- hour use of an eyelid pressure patch in patients with PCED and reported 100% of cases in the single-layer group and 100% in the three-layer group experiencing corneal staining improve- ment, suggesting the technique is a "safe and effective approach for healing persistent corneal epithelial defects," according to the author. 1

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