Aldeyra Therapeutics Profile
Aldeyra Therapeutics, Inc. operates as a biotechnology company.
The company engages in discovering innovative therapies designed to treat immune-mediated diseases. The company is developing a novel pharmaceutical platform targeting a class of pro-inflammatory mediators known as RASP (reactive aldehyde species) that exacerbate diseases characterized by inflammation. The company’s RASP modulator product pipeline includes ADX-629, a novel orally administered RASP modulator in clinical development for atopic dermatitis, idiopathic nephrotic syndrome, moderate alcohol-associated hepatitis, chronic cough, and Sjögren-Larsson Syndrome. The company’s preclinical RASP platform includes ADX-246, ADX-248, and other drug candidates in development for geographic atrophy and systemic inflammatory diseases. The validity of the RASP platform is supported by reproxalap, the company’s first-in-class product candidate under New Drug Application (NDA) review by the United States Food and Drug Administration (FDA) for the treatment of dry eye disease. Reproxalap has demonstrated broad-based, rapid-onset activity and consistent safety across a number of Phase 2 and Phase 3 clinical trials. The company has additional product candidates in development, including ADX-2191, which is under NDA review by the FDA for the treatment of a rare but fatal cancer known as primary vitreoretinal lymphoma. ADX-2191 is also in clinical development for the treatment of proliferative vitreoretinopathy and retinitis pigmentosa, two rare retinal diseases characterized by inflammation and vision loss. ADX-2191 has received Orphan Drug Designation for all three retinal diseases under development.
All of the company’s development plans and timelines are subject to adjustment depending on recruitment rate, regulatory review, preclinical and clinical results, funding, and other factors that could delay the initiation, completion, or reporting of clinical trials. In January 2019, the company acquired from Helio Vision, Inc. and thereby obtained rights to ADX-2191.
The company is developing ADX-629, ADX-246, ADX-248, and other novel RASP modulators for the treatment of immune-mediated disease. RASP modulators are novel small molecules designed specifically to bind, and thereby allow for the degradation of, RASP. The validity of the RASP platform is supported by reproxalap, the company’s first-in-class product candidate for the treatment of dry eye disease, which has demonstrated broad-based, rapid-onset activity and consistent safety across a number of Phase 2 and Phase 3 clinical trials and is under NDA review by the FDA. Reproxalap-RASP adducts appear to be rapidly degraded in cellular environments, after which neither reproxalap nor RASP are detectable.
In addition to the development of ADX-629, ADX-246, and ADX-248, the company intends to continue the discovery and development of other novel RASP modulators, and it intends to continue to develop intellectual property around the molecules derived from its RASP modulator platform.
ADX-2191 is a novel intravitreal formulation of methotrexate, a dihydrofolate reductase inhibitor that has been administered intravenously for decades to treat cancer and inflammatory diseases. Initially as an intravenous medication and subsequently as an intraocular injection, serial administration of methotrexate is the standard of care for the treatment of primary vitreoretinal lymphoma, also known as ocular lymphoma, a rare but often fatal cancer that originates in the eye.
ADX-629 is a novel, orally administered RASP modulator in Phase 2 clinical development for the treatment of systemic immune-mediated diseases. In a Phase 1 clinical trial of ADX-629, no treatment-related adverse events were observed at any dose tested, and target engagement was evidenced by statistically lower levels of the RASP malondialdehyde in drug-treated subjects relative to controls.
In 2022, the company announced results from Phase 2a clinical trials of ADX-629 in patients with psoriasis, atopic asthma, COVID-19, or alcohol intoxication, all of which suggested preliminary pharmacodynamic activity of ADX-629. The Phase 2a trials were performed as part of a systematic strategy to assess activity in different types of immunological diseases, including autoimmune disease, allergic inflammation, infectious disease, and toxin-induced inflammation. Across all Phase 2a clinical trials, in patients treated with ADX-629, no safety concerns were evident from adverse events and there were no treatment-related serious adverse events observed.
In 2021, the company announced that the randomized, double-masked, vehicle-controlled allergen chamber Phase 3 INVIGORATE Trial of topically administered reproxalap in patients with allergic conjunctivitis (Figure 5) achieved the primary endpoint (patient-reported ocular itching score after the second dose of test article) and all secondary endpoints (investigator-assessed ocular redness score and patient-reported ocular tearing score).
In 2022, the company initiated the randomized, double-masked, vehicle-controlled allergen chamber Phase 3 INVIGORATE-2 Trial of reproxalap in patients with allergic conjunctivitis.
In October 2022, the company announced results of Part 1 of the GUARD Trial, a two-part, multi-center Phase 3 clinical trial evaluating the efficacy of intravitreal injections of ADX-2191 versus standard-of-care for the prevention of proliferative vitreoretinopathy. The primary endpoint of GUARD Part 1, retinal detachment rate over six months following initiation of therapy relative to historical detachment rates, was achieved: relative to historical control, statistically significant reduction (P=0.024) in retinal detachment over six months was observed following serial intravitreal injection of ADX-2191. Although not statistically powered for secondary or exploratory endpoints, the results of the GUARD Trial demonstrated numerical superiority of ADX-2191 over routine surgical care in reducing the dichotomous endpoints of retinal detachment rate over six months, hypotony (low intraocular pressure), complete retinal attachment by six months, macular attachment by six months, and epiretinal membrane formation (overall P=0.047).
The company’s RASP modulator platform represents a potential novel therapeutic approach for a variety of common systemic immune-mediated conditions. In 2022, the company announced results from Phase 2a clinical trials of ADX-629, a first-in-class orally administered RASP modulator, in patients with COVID-19, atopic asthma, psoriasis, or alcohol intoxication, all of which suggested preliminary pharmacodynamic activity of ADX-629.
Intellectual Property and Proprietary Rights
Patent Portfolio
The company’s patent portfolio includes patents and patent applications covering the composition, formulation, and uses of reproxalap, ADX-629, ADX-246, ADX-248, and other novel compounds. As of December 31, 2022, the company owned twenty-five United States patents and twenty pending United States non-provisional patent applications, as well as numerous foreign counterparts to these patents and patent applications, relating to reproxalap and other RASP modulators. Additionally, the company retains an exclusive license to certain patents covering the formulation of ADX-2191 and uses thereof in preventing and treating retinal indications including proliferative vitreoretinal disease and primary vitreoretinal lymphoma. As of December 31, 2022, the company’s patent applications included one pending U.S. provisional application, four pending U.S. non-provisional patent applications, and approximately seven pending foreign counterparts to these patent applications, relating to ADX-2191.
The company expects the issued reproxalap composition of matter patent in the United States, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, to expire in 2028. It is possible that the term of the composition of matter patent in the United States may be extended up to five additional years under the provisions of the Hatch-Waxman Act. The company expects the foreign reproxalap composition of matter patents, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, to expire in 2026. The company expects other patent applications in the portfolio, if issued, and if the appropriate maintenance, renewal, annuity or other governmental fees are paid, to expire from 2026 to 2034. Reproxalap composition of matter patents have been issued in Australia, Canada, China, Europe (validated in approximately 14 member countries), Hong Kong, India, Japan, Mexico, Russia and South Korea. Reproxalap composition of matter patent claims are pending in Brazil.
Licenses and Agreements
MEEI Agreement
The company is developing ADX-2191 pursuant to an Exclusive License Agreement with Massachusetts Eye and Ear Infirmary (MEEI) originally entered into in July 2016 between MEEI and Helio Vision, Inc., as amended, (MEEI Agreement). The company assumed the MEEI Agreement in connection with its 2019 acquisition of Helio Vision.
Pursuant and subject to the MEEI Agreement, the company obtained an exclusive, worldwide license from MEEI to develop and commercialize ADX-2191 under certain patents and patent applications, and other licenses to intellectual property (MEEI Patent Rights).
Other Intellectual Property Rights
The company’s marks ALDEYRA THERAPEUTICS and its logo are registered with the United States Patent and Trademark Office.
Research and Development
For the year ended December 31, 2022, the company’s research and development expenses totaled $47.3 million.
Government Regulations
The company and its third-party manufacturers must comply with applicable the United States Food and Drug Administration (FDA) regulations relating to FDA’s current Good Manufacturing Practices (cGMP) regulations.
History
The company was founded in 2004. It was incorporated in the state of Delaware in 2004. The company was formerly known as Neuron Systems, Inc. and changed its name to Aldexa Therapeutics, Inc. in 2012. Further, the company changed its name to Aldeyra Therapeutics, Inc. in 2014.
