Pipeline + Disease Areas

Deep & Innovative Pipeline Focused on Immune-Mediated Diseases


Ocular Inflammation

Inflammation is a component of most ocular diseases. Aside from trauma, inflammatory ocular diseases, in aggregate, are the leading cause of blindness worldwide. Aldeyra is currently developing therapies for the treatment of three ocular inflammatory diseases:

Dry Eye Disease

Dry eye disease is a sub-optimally treated chronic condition that affects 20 million patients in the United States.

Allergic Conjunctivitis

Allergic conjunctivitis is a persistently disturbing disease, characterized by ocular itching, that is not effectively treated in up to 30 million patients in the United States.

Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy is a rare blinding disease, for which no therapy is available, that occurs following retinal detachment.

In addition, Aldeyra is developing product candidates for the treatment of other forms of retinal inflammation, potentially including dry age-related macular degeneration, Stargardt disease, geographic atrophy, diabetic macular edema, diabetic retinopathy, posterior uveitis, and retinal vein occlusion.

RASP: A Novel Target for the Treatment of Ocular Inflammation

Reactive aldehyde species (RASP) are important immunological mediators that are pro-inflammatory. Aldeyra’s RASP inhibitors represent a novel approach for the treatment of ocular inflammation. RASP inhibitors, which appear to be broadly active in clinical trials across several ocular inflammatory diseases, have the potential to dramatically improve the ocular therapy paradigm: there is currently no available therapy that can be used broadly for the treatment of ocular inflammation, aside from corticosteroids, which can lead to glaucoma, cataracts, and other ocular toxicities.

ADX-2191: a Potential Therapy for Proliferative Vitreoretinopathy

There is currently no therapy for proliferative vitreoretinopathy, an ocular inflammatory disease that leads to blindness following retinal detachment. ADX-2191 has shown to inhibit scarring, an inflammatory process that can lead to further retinal detachments and loss of vision.

Systemic Diseases

Aldeyra’s broad product candidate pipeline applies to many diseases that may affect diverse aspects of the body. We are developing product candidates that can be administered orally or by injection to treat disease systemically.

Immune-Mediated Systemic Diseases

Immune-mediated systemic diseases, such as autoimmune disease, are generally chronic conditions characterized by excessive and misdirected inflammatory responses. In aggregate, autoimmune diseases and related systemic inflammatory disorders represent tens of millions of patients in the United States, with aggregate drug sales expected to exceed $74 billion by 2022. In 2018, three of the top five highest-selling drugs, totaling more than $32 billion globally and $22 billion in United States sales, were prescribed for a variety of immune-mediated disorders, including Crohn’s disease, rheumatoid arthritis, psoriasis, ulcerative colitis, and ankylosing spondylitis.

The potential market for immune-modulating therapies could continue to expand as a result of growing evidence that excessive inflammation may be critical to the development and progression of cardiovascular disease, diabetes, Alzheimer’s disease, and many other common conditions that are not typically characterized  as inflammatory or autoimmune diseases.

Given the complex pathophysiology of systemic immune-mediated disorders, many of which are caused by a variety of pro-inflammatory mediators, therapy often requires combinations of drugs with distinct mechanisms of action. As such, we believe novel product candidates for immune-mediated diseases are in high demand.

Aldeyra’s RASP, dihydrofolate reductase, and chaperome inhibitors are being developed to down-regulate the immune system across a number of inflammatory diseases.

Sjögren-Larsson Syndrome

Sjögren-Larsson Syndrome (SLS) is a rare systemic disease and inborn error of metabolism caused by mutations in an enzyme that metabolizes fatty (long-chain carbon) RASP, resulting in severe skin, neurological, and retinal disorders. Genetic mutation analysis suggests that there are approximately 1,300 SLS patients in the United States, and a greater number of SLS patients in Europe.

Reproxalap, Aldeyra’s lead RASP inhibitor, is being developed in SLS for the treatment of ichthyosis, a serious skin disorder characterized by excessive dryness, leading to comprise of dermal integrity, infection, and bleeding. Other RASP inhibitors in Aldeyra’s pipeline may be tested in SLS retinal or neurological diseases.

Post-Transplant Lymphoproliferative Disorder

Many immune-mediated diseases are at least in part the result of hyper-proliferation of immune cells, a phenomenon known as lymphoproliferation. Lymphoproliferative diseases include systemic lupus erythematosus (lupus), autoimmune lymphoproliferative syndrome, Waldenstrom’s macroglobulinemia, Wiskott-Aldrich syndrome, myelodysplastic syndromes, and post-transplant lymphoproliferative disorder (PTLD).

PTLD is a serious cancer-like condition characterized by increased immune cell replication following solid organ transplant. The disease can be fatal, and is often poorly responsive to currently available therapy.

PTLD and other lymphoproliferative disorders are caused in part by excessive activity of the chaperome, which leads to aberrant stimulation of immune cellular replication. Aldeyra’s chaperome inhibitor product candidates are being developed for the treatment of PTLD and related diseases. We are not aware of any other company that is developing an chaperome inhibitor for systemic immune-mediated disease, including PTLD.


Malignant pleural mesothelioma is a rare, aggressive cancer that develops in the pleura, a thin layer of tissue surrounding the lungs. Approximately 3,000 people are diagnosed each year in the United States. Response rates to chemotherapy are generally less than 40%, and five-year survival rates are less than 20%.

Aldeyra’s chaperome inhibitors, in combination with DNA-damaging agents, may have utility in the treatment of certain cancers. The chaperome inhibitor system is required for DNA repair, and chaperome inhibition in the setting of DNA damage could lead to cancer cell death.

Clinical Results in Mesothelioma

In an Investigator-Sponsored Trial in mesothelioma patients, the overall response rate to Aldeyra’s lead chaperome inhibitor ADX-1612 was 61%, relative to historical standard of care response rates of 20% to 40%*. In seven patients, reduction of tumor burden was greater than 50%. One patient remained progression-free after 37 months.

Data presented at the International Association for the Study of Lung Cancer (ASLC) 19th World Conference on Lung Cancer (2018).

*Vogelzang NJ et al.; J Clin Oncol. 2003 Jul 15;21(14):2636-44.

Ovarian Cancer

Ovarian cancer is often fatal but is generally diagnosed only after significant tumor progression. Five-year survival is less than 50%. In the United States, over 225,000 women have ovarian cancer.

Aldeyra’s chaperome inhibitors, in combination with DNA-damaging agents, may have utility in the treatment of certain cancers. The chaperome inhibitor system is required for DNA repair, and chaperome inhibition in the setting of DNA damage could lead to cancer cell death. In ovarian cancer cell lines, preclinical studies have demonstrated the anti-proliferative synergy of ADX-1612 in combination with platinum-containing DNA damaging agents.*

*Kramer, Daniela et al. “Strong antitumor synergy between DNA crosslinking and HSP90 inhibition causes massive premitotic DNA fragmentation in ovarian cancer cells.” Cell death and differentiation vol. 24,2 (2017): 300-316. doi:10.1038/cdd.2016.124