Zylem Biosciences is on a mission to extend the healthy human lifespan, leveraging its world-renowned expertise in cellular oxidative damage and the central role that damage plays in disease and aging. Our core invention is a patented portfolio of Metabolic Redox Modulators (MRMs).
The technology platform was developed over fifteen years in the Thaxton Laboratory at Northwestern University and licensed to Zylem. Approximately $20M of non-dilutive funding from NIH, Department of Defense, Howard Hughes Medical Institute and others fueled the platform’s development. In addition, to-date Zylem has raised $6.8M of dilutive capital.
MRMs target the previously considered undruggable cell surface receptor SR-B1, which is critical in cancer, cardiovascular disease and aging. Known for its role in cholesterol transport, recent foundational science work, including by the Zylem team, has shown its critical role in tumor progression, atherosclerotic plaque formation and in skin barrier health and keratinocyte differentiation.
MRM formulations for oncology target the multifunctional receptor, SR-B1, to simultaneously engage three hallmark mechanisms of cancer to induce cell death. SR-B1 is a known cancer target that has been shown to be over-expressed in cancer cells vs. normal cells. High expression of SR-B1 is correlated with worse outcomes. Tumor cell survival is dependent on cholesterol uptake via SR-B1 by native HDLs.
MRMs bind SR-B1outcompeting native HDLs and effectively remove cholesterol from cancer cells leading to a metabolic cascade that ultimately ends in cell death. Healthy cells are not dependent on cholesterol uptake and therefore maintain healthy cholesterol balance, thus are unaffected by MRMs.
MRMs simultaneously target three hallmarks of cancer, resulting in Metabolic Checkmate:
These cancers are the targets of our clinical strategy. Phase I clinical trial recruitment begins in 2025.
MRM potently binds SR-B1 and effectively outcompetes native HDL. MRM reduces cancer cell cholesterol, increases membrane oxidation (while simultaneously decreasing cellular antioxidant capability by down-regulating GPX4), and inhibits survival signaling. This metabolic checkmate is highly effective at abolishing cancer cells, while sparing normal healthy cells.
MRMs exquisitely target SR-B1, attacking three hallmarks of cancer and inducing metabolic checkmate.
Atherosclerotic cardiovascular disease (ASCVD) is a disease of non-functional high-density lipoproteins (HDL). Native HDLs sequester and transport cholesterol, provide anti-inflammatory and anti-oxidative effects, and reduce the risk of cardiovascular disease.
Non-functional HDL results in cardiovascular disease. CVD patients lack sufficient amounts of functional HDL. MRM-CV1 is engineered to support each protective function of native HDL, and reverse and inhibit CVD.
MRM-CV1 replaces non-functional HDLs to inhibit and reverse CVD.
Heart disease remains the most common cause of death in the world. Current treatments for cardiovascular disease leave unaddressed residual disease. MRM-CV1 directly addresses the root causes of CVD as the first and only mature spherical mimic of native HDL. This breakthrough in engineering stems from building an HDL mimic using an organic scaffold, whereupon the targeting protein apolipoprotein A-I assembles with the scaffold and enables the self-assembly of HDL lipids. MRM-CV1 engages with the receptor SR-B1 to remove cholesterol and provide anti-inflammatory and antioxidant signaling. Due to the unique spherical nature, MRM-CV1 has shown profound reduction of plaque formation in the arterial wall in preclinical disease models.
Phase I clinical trial for MRM-CV1 begins recruitment in 2026.
Zylem is investigating MRM-type compounds to reduce oxidative damage and inflammation, replenish lipids and restore mitochondrial function.
HDL plays a critical role in maintaining corneal epithelial cell homeostasis and reduces inflammation. SR-B1, the HDL receptor, is expressed by corneal epithelial cells, limbal epithelia cells, stromal epithelial cells, and stromal keratocytes. In preclinical corneal wound models, including in diabetic models, topical application of MRM-OT1 significantly enhanced wound closure. Additional studies found MRM-OT1 to attenuate initial stages of inflammation resulting from chemical burns and other cell stressors. Overall, data suggest MRMs can be developed to treat acute and chronic inflammatory eye conditions, like dry eye, atopic keratoconjunctivitis, bacterial keratitis, eye injuries from chemical or thermal injury, long-term contact lens wear, and post-surgical treatment to enhance wound healing.
SR-B1 resides on the surface of epithelial and immune cells and has been implicated in viral entry and inflammation. Zylem has developed an MRM that binds SR-B1 and significantly impairs viral entry into epithelial cells and significantly reduces immune cell mediated inflammation. MRMs have been explored in preventing SARS-CoV-2 entry. MRM therapy is in early-stage preclinical development to treat early-stage viral infection.