At their previous company (1), the founders of Oculogics pioneered a new drug class called aldehyde traps that are designed to treat all diseases associated with chronic inflammation. These diseases cause lifetime disabilities and over 50% of global deaths (2). Aldehyde traps safely block chemical damage by toxins that surge during chronic inflammation. Depending on the type of inflammatory disease, these toxins cause cellular injuries in the affected organ, tissues or joints, or in the brain, spinal cord or retina. This chemical damage increases inflammation and advances the severity and progression of each such disease.
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Reproxalap (3), a first generation trap we developed at our previous company (4), has clinical proof of concept in a painful condition of ocular inflammation. It matched the potency of steroids without any of their safety risks (5). Our next generation traps at Oculogics are now over 500 times more potent with optimal oral availability and CNS exposure. This enables them to be more effective in a broader range of diseases and administered by safe oral dosing.
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This drug class pioneers a novel therapeutic strategy. The biology and chemistry of free aldehydes have been studied for years. Now it is possible to block their toxicities in the clinic and spare patients from the harmful effects of their chemical damage.
Introducing
next generation
aldehyde traps
(1) Neuron Systems at founding, changed to Aldeyra Therapeutics at IPO (ALDX); (2) Furman 2019, Nature Med 10.1038/s41591-019-0675-0; (3) aka NS2, ADX-102; (4) Jordan et al., US Patent 7,973,025; (5) Mandell (2020) J Ocul Pharm Ther 10.1089/jop.2020.0056
Clinical proof
of concept
Higher potency,
oral availability,
CNS exposure
Most drugs have protein targets. Aldehyde traps have a novel design paradigm: small molecule drugs with small molecule targets. Their targets are lipid and oxysterol aldehydes that form when cell membranes and cholesterol are oxidized during inflammation. These toxins cause chemical damage that injures cells and amplifies inflammation.
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Inflammation is a complex process that involves hundreds of interacting genes (1). Briefly, it is triggered by microglial cells that act as sentinels by monitoring neighboring cells for distress due to infection, injury or disease. When they detect distress, they release two types of protein signals: chemokines that recruit white blood cells from circulation, and cytokines that activate inflammatory responses in the recruited cells, in the distressed cells, and in glial cells that sustain and amplify this signaling. Depending on where the distressed cells are located, this initiates neuroinflammation in the nervous system, visceral inflammation in organs or somatic inflammation elsewhere in the body.
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Inflammation evolved as a protective response that helps cells recover from distress and then shuts down. In some cases, however, it advances to chronic inflammation that injures or kills the distressed cells it evolved to protect. Chronic inflammation drives a broad range of diseases that cause lifetime disabilities and over 50% of global deaths (2). These include type 2 diabetes and metabolic syndrome, cardiovascular disease, autoimmune diseases and chronic kidney disease (3), and multiple forms of neurodegenerative disease (4-7) including retinal degeneration that causes progressive blindness. Chronic inflammation is also associated with disabling neurological disorders including psychiatric conditions (8-9), brain fog complications of infection or immunotherapy (10-12), chronic pain, and spinal and peripheral neuropathy (13-15).
Inflammation is called a “canonical disease mechanism” because it contributes to so many different types of disease. Aldehyde traps are an “inflammation platform drug” because they are designed to treat this canonical disease mechanism in every such disease.
Novel design
paradigm
Inflammatory signaling
Inflammation
platform drug
(1) Zhao 2016 Molec Biosystems 10.1039/c6mb00240d; (2) Furman 2019, Nature Med 10.1038/s41591-019-0675-0; (3) Chen 2017 Oncotarget 10.18632/oncotarget.23208; (4) Shi & Yong 2025 Science 10.1126/science.adx0043; (6) Giri 2024 Intl J Molec Sci 10.3390/ijms25073995; (6) Zhang 2023 Signal Trans Targ Ther 10.1038/s41392-023-01486-5; (7) Cagle 2019 Curr Opin Toxicol 10.1016/j.cotox.2018.12.002; (8)Guo 2023 Transl Psychiatry 10.1038/s41398-022-02297-y; (9) Dunn 2020 Pharmacol Biochem Behav 10.1016/j.pbb.2020.172981; (10) Geraghty Cell 2025 10.1016/j.cell.2025.03.041; (11) Braga 2023 JAMA Psychiatry 10.1001/jamapsychiatry.2023.1321; (12) Monje & Iwasaki 2022 Neuron 10.1016/j.neuron.2022.10.006; (13) Albrecht 2018 Pain 10.1097/j.pain.0000000000001171; (14) Schomberg 2012 Annals Neurosci 10.5214/ans.0972.7531.190309; (15) Ellis & Bennett 2013 Br J Anaesth 10.1093/bja/aet128
Chronic
inflammation
The targets of aldehyde traps are free aldehydes that form as stressed mitochondria release superoxide, an oxygen radical that converts rapidly to hydrogen peroxide. Free aldehydes are chemically diverse and include lipid aldehydes, which form when hydrogen peroxide oxidizes membrane lipids such as DHA, an omega-3 fatty acid enriched in the CNS; and oxysterol aldehydes, which form when it oxidizes cholesterol. Free aldehydes attack proteins and nucleic acids, causing chemical damage that alters their structure and disrupts their function in all diseases associated with inflammation and aging. Free aldehydes surge a thousand-fold during inflammation, making this damage toxic and widespread. It disrupts cell functions, activates pattern recognition receptors that amplify inflammation, triggers destructive autoimmune responses, and impairs or overwhelms enzymes that normally protect us from aldehyde toxicities (1-12).
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Traps prevent this damage by deactivating free aldehydes with two chemical reactions. The first reaction binds the target weakly as the second reaction converts it potently to a small inert reaction product that is then safely cleared. In chemical terms, traps pull their targets into a thermodynamic sink as symbolized by the company logo, a Flamm paraboloid. Aldehyde traps have no dependencies on proteins, are not compromised by patient genetic variability, and remain active at full potency in cells and tissues that are chemically damaged and biologically dysregulated.
Free aldehydes cause
chemical damage
Aldehyde traps block that safely and potently
(1) Ellis & Bennett 2013 Br J Anaesth 10.1093/bja/aet128; (2) Sanotra 2022 Clin Biochem 10.1016/j.clinbiochem.2021.12.005; (3) Kulig 2016 Chem Phys Lipids 10.1016/j.chemphyslip.2016.03.001; (4) Dasuri 2013 Free Radical Res 10.3109/10715762.2012.733003; (5) Negre-Salvayre 2008 Br J Pharmacol 10.1038/sj.bjp.0707395; (6) Gladyshev 2021 Nature Aging 10.1038/s43587-021-00150-3; (7) Zhang 2021 Arch Biochem Biophys 10.1016/j.abb.2020.108749; (8) Zani 2015 Cells 10.3390/cells4020178; (9) Doorn 2006 Chem Res Toxicol 10.1021/tx0501839; (10) Gu 2003 J Biol Chem 10.1074/jbc.M305460200; (11) Salomon 2011 Chem Res Toxicol 10.1021/tx200206v; (12) Witztum 2015 Circ Res 10.1161/circresaha.115.306928
Drug safety has been a top priority throughout the invention and development of the aldehyde trap drug class. This goal has been achieved, based on the high drug safety found in all preclinical and clinical studies to date. Traps act only where they are needed at sites where toxic aldehyde levels are unsafe. Their drug structures are hardened to block the formation of toxic metabolites during clearance, and their chemical reaction mechanisms have been calibrated carefully to avoid toxic off-target reactions. They have none of the serious and sometimes fatal side effects of other drugs that target the complex gene and protein networks that mediate inflammation and advance disease.
Traps cannot deplete biologically essential aldehydes, such as the aldehyde forms of vitamins A (retinaldehyde) and B6 (pyridoxal), because unlike free aldehyde targets, they are sequestered inside proteins that block drug access by steric hindrance. As reviewed by the FDA (1), aldehyde traps have never caused any symptoms of vitamin A or B6 depletion in preclinical studies, even at maximum feasible dose (drug powder packed to full stomach capacity).
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Oculogics' next generation traps are over 500 times more potent than first generation traps in a validated neurocellular assay. This potency was achieved by using DFT computational methods of quantum mechanics to optimize drug structures for maximal drug-target reaction energies. TC11, a validated next gen lead, has exemplary preclinical safety pharmacology test results.
Traps act safely
only where needed...
and with high
drug potency
(1) Jordan 2009 FDA IND #104497