We are a late clinical stage biopharmaceutical company, focused on the development and commercialization of novel pharmaceutical therapies to address unmet need in blinding diseases of the eye with underlying inflammatory pathologies. Our dazdotuftide platform technology is a bio-inspired immunomodulator, designed to treat blinding inflammatory ocular diseases, and is currently being developed as both eye drops (TRS01) and intravitreal injections (TRS02). For the last seven decades, the standard of care for active non-infectious anterior uveitis (“NIAU”) has remained unchanged: topical steroids. While steroids effectively resolve inflammation, they are directly associated with a critical, sight-threatening side effect known as elevated intraocular pressure (“IOP”). This steroid-induced IOP elevation may promptly progress to glaucoma. Uveitis with co-morbid glaucoma — uveitic glaucoma (“UG”) — is a condition considered the end-stage of the disease. The clinical reality is severe. Vision loss in patients with uveitic glaucoma is nearly three-fold higher than in uveitis patients without glaucoma. Clinicians are forced to treat the inflammation that causes blindness with a drug that increases the risk for blindness via glaucoma. In the United States alone, there are approximately 160,000 patients with uveitic glaucoma who are trapped in this treatment cycle. --- Based on the literature covering epidemiology data and disease course combined with a third-party payer survey that we commissioned, and subject to such epidemiology data’s and survey’s analysis and assumptions, the potential U.S. market for the treatment of non-infectious anterior uveitis in patients with uveitic glaucoma is estimated to be over $5 billion per year. The U.S. uveitis specialist community, comprising approximately 450 physicians who treat this patient population, represents a concentrated target prescriber base for TRS01 and also TRS02. This concentration we believe provides an opportunity to execute an efficient go-to-market strategy and capture significant commercial opportunities in a multi-billion-dollar market. --- Despite the known risks of steroid-induced glaucoma, there is currently no FDA-approved non-steroid alternative for treating active NIAU. Patients and physicians face an impossible choice: leave the inflammation untreated and risk vision loss, or use steroids and risk vision loss due to glaucoma. Current steroid-sparing agents, such as systemic immunosuppressants, are slow-acting, often taking two to twelve weeks to work, and are used for maintenance rather than for treating active flares. Consequently, for acute flares, which are ophthalmic emergencies, steroids remain the only option, perpetuating the cycle of ocular damage. Awareness of the consequences of current standard of care for NIAU patients is increasing, which may lead to a shift in prescriber treatment practices once a safer drug will be available. A panel of ophthalmologists specializing in uveitis and glaucoma, the Uveitic Glaucoma Interest Group, recently presented recommendations to lower the IOP threshold in uveitis to a more stringent threshold, to safeguard vision. This stringent threshold presents a clinical challenge when using steroids given their associated IOP elevation side effect. Hence, we anticipate a potential decline in the use of steroids and a potential increase in demand for safer, yet effective treatments, once available. Our lead product candidate, TRS01, is designed to break the cycle of ocular damage due to inflammation and steroid use. It is a steroid-free eye drop formulation of dazdotuftide, a new chemical entity. TRS01 is developed to be the first safer, effective alternative to steroids for active NIAU including patients with uveitic glaucoma. Our completed Phase 3 trial, the TRS4Vision trial, was a head to head trial with steroids, and while the primary endpoint (Anterior Chamber Cell (“ACC”); ACC=0) was not met, a majority of TRS01-treated patients (64%) reached clinically meaningful improvement, of zero or trace ACC (i.e., ≤5 cells) on Day 28 with a median time of 9 days. Ocular pain, changed from baseline, was found equivalent in TRS01 and steroid treatment arms. Importantly, TRS01-treated patients experienced meaningfully fewer IOP spikes compared to steroid-treated patients (with a p-value (as described below) of less than 0.05; post hoc). These observations are based on post hoc analyses and are exploratory in nature. We have secured a Special Protocol Assessment agreement with the FDA for our upcoming pivotal Phase 3 trial, Tarsier-04, which we refer to as the SPA Agreement (the “SPA Agreement”). The FDA has agreed to a primary endpoint of IOP safety (superiority to steroids) with inflammation resolution as a secondary endpoint, acknowledging that a safer drug constitutes a major clinical benefit. TRS01 does not rely on broad immunosuppression like steroids. Instead, it utilizes dazdotuftide, a bio-inspired immunomodulator that promotes immune tolerance. Dazdotuftide is a conjugate of two molecules, tuftsin and phosphorylcholine, and is designed to modulate the immune system rather than suppressing it. Specifically, it shifts macrophages from an inflammatory state (“M1”) to an anti-inflammatory, healing state, or M2. Crucially, dazdotuftide is designed to act without binding to glucocorticoid receptors in the eye, a mechanism that could reduce the risk of trabecular meshwork obstruction and associated IOP increases observed with corticosteroids. In addition to our lead product candidate, TRS01, we are developing our second product candidate, TRS02, which is a slow-release intravitreal injection formulation of dazdotuftide for the treatment of back-of-the-eye ocular diseases. Our principal executive offices are located in Zichron Yaacov, Israel.
