OTI-2024 MMP therapeutics
OTI-2024 has the potential to reverse and stop glaucoma disease progression via TM rejuvenation.
OTI-2024 represents a new MMP (matrix metalloproteinase) based therapy for treating glaucomateous neural degeneration, effective in poor or non-responders in advanced stage glaucoma. Prior Phase 2/3 clinical trial demonstrated its superiority of clinical safety and MMP therapeutic effectivness (not recognized). It has the potential to fully stop the vision loss by removing the rate limiting root causes and restoring pressure sensing cell and sensor functionality, effective to all stages of glaucoma, in particular severe forms of glacuoma involving ECM pathological processes.
Rate Limiting Root Cause: Pressure Sensing Cell Loss
Pressure Sensor acts as chief IOP regulator
The pressure sensor is the chief regulator of IOP, composed of pressure sensing cells and the underlying basement membrane, similar in relation to RPE and its underlying Bruch’s membrane. Like RPE and cornea endothelium cells, the pressure sensing cells derive from the neural crest during embryonic development, lack of self-renew in adulthood. The pressure sensing cell loss reaches to a certain threshold (unknow, e.g. 60% loss), patients become poor or non-responders to current IOP lowering medication at which point an invasive surgery (e.g. tube shunt) becomes inevitable, however that fails at 50% in 3-5 years. Early intervention to protect the pressure sensing cell health is of strategic importance.
Figure adapted from Clin Exp Ophthalmol. 2022 at the courtesy by Prof. KE Keller and Prof. DM Peters.
The trabecular meshwork and glaucoma
Rate Limiting Root Cause of Glaucoma Vision Loss
Problem of glaucoma lies at the outflow engine broken underpinning the pressure sensor dysfunction along with pressure sensing cell loss. In clinics, it reflects the IOP irregularities (random spikes) which kills the neurons at the retina. To protect the pressure sensing cells is to protect the retinal ganglion cell health in patients with glaucoma.
Inventor; Tina Guanting Qiu. US Publication #US2024/00024348A1 and PCT 1 # PCT/18/356,875.
Figure adapted from Minimally Invasive Glaucoma Surgery, 2021 at the courtesy by Prof. Keith Barton.
OTI-2024 Dual Mode of Actions
OTI-2024 is a new MMP therapeutic agent
OTI-2024 is the best in class and first in class adenosine A1 receptor agonist (small molecule). OTI-2024 has unique dual MoAs (A1R+MMP Enhancer), offers both cytoprotecting to the pressure sensing cells and trabecular meshwork (TM) rejuvenation (via ECM remodeling by the MMP-14), as well as a fast mode IOP lowering (bell shape) via Muscarinic 2 activation. These attributes make OTI-2024 as the Best drug in MMP-based therapeutic domain.