Atorvastatin

Atorvastatin is multi-modal in its mechanism of action with  the potential to treat both evaporative and aqueous deficient forms of the disease. In a recent pilot study of 10 patients with blepharitis and dry eye, which often co-exist,  positive results with reduced corneal fluorescein staining and conjunctival redness, improved tear break-up times (TBUT) and normalised Schirmer’s wetting was recorded. There was improved blepharitis, as well as dry eye symptom scores. It is non-steroidal with no steroid-like related side effects. 

Watch video here.

Required: AUD$1M (Pitch Deck available). 

Preclinical data showed that, when Lacripep was added topically in animal models, it restored basal tearing without irritation and healed the corneal surface of the eye. TearSolutions has now completed a first-in-human Phase I/II trial in primary Sjögren’s Syndrome, who typically have a severe and often debilitating form of ocular surface disease and are known to be deficient in Lacritin.  The results showed a rapid improvement, as quickly as two weeks, in corneal health and a reduction in symptoms. 

Watch video here.

Required:  USD$10M

By inhibiting RASP, which are elevated in a variety of inflammatory diseases, reproxalap represents a novel mechanism for diminishing ocular inflammation in dry eye disease. In a number of clinical trials, reproxalap demonstrated consistent statistically significant and clinically relevant activity. Topical ocular reproxalap is an investigational new drug candidate that has been studied in more than 1,800 patients with no observed safety concerns; mild and transient instillation site discomfort is the most commonly reported adverse event in clinical trials. 

Watch video here.

FDA Approval expected 2025.

Lubricin™ functions like biologic Teflon®. It is naturally produced throughout the human body protecting tissues and other surfaces from friction-related damage and wear. Lubricin™ is the most lubricating and anti-adhesive molecule in the human body and has natural anti-inflammatory properties as well.  Originally identified in joints, lubricin™ is also found on the ocular surface and in numerous additional tissues throughout the human body. Supplementation with recombinant human lubricin™ is an innovative and exciting new approach to disease management.

Watch video here.

AZR-MD-001 harnesses the power of selenium sulfide in an easy-to-use ophthalmic ointment preparation applied directly to the meibomian glands in the lower eyelid. AZR-MD-001 is thought to have a multi-modal mechanism of action that treats the pathophysiology of MGD along with the resulting ocular surface symptoms. AZR-MD-001’s formulation targets the main pathophysiology of abnormal keratin production, keratin obstruction, poor meibum quality, and resulting ocular signs and symptoms through a variety of ways.

Watch video here.

Currently recruiting for clinical trials.

Branches of the trigeminal nerve innervating the cornea and lids selectively express cold-sensitive thermoreceptors, called transient receptor potential melastatin 8 (TRPM8) receptors. TRPM8 receptors are associated with the detection of ocular surface dryness and are activated by evaporative cooling and hyperosmolarity, leading to stimulation of tear production. In addition, agonists of TRPM8 promote a cooling sensation that may be beneficial for reducing ocular discomfort and pain. Thus, TRPM8 agonists such as TrypTyr™, may have a dual role in the potential treatment of DED by both stimulating tear production and reducing ocular discomfort.

Tivanisiran is a small interfering RNA (siRNA) that is administers as eye drops. It is currently in Phase III clinical research - it inhibits TRPV1. TRPV1 is directly involved in the pathophysiology of dry eye disease as it has a dual function on the ocular surface. It acts in the detection, transmission and regulation of pain in the eye, as well as in the mediation of innate inflammatory response mechanisms whose regulation is key for the treatment and prevention of dry eye disease. 

Watch video here.

This first-in-class prescription (Rx) eye drop aims to delivers Mycophenolate (MPA) in our proprietary vehicle to provide sustained immunosuppressive effects at the ocular surface. The active ingredient, mycophenolate, is a compound well characterized to selectively target and inhibit replication and proliferation of T-lymphocytes and antibody-producing B-lymphocytes involved in dry eye inflammation. This topical immunomodulatory effect is expected to both reduce immune-mediated damage to the lacrimal glands as well as stimulate tear film mucin production - addressing core inflammatory mechanisms underlying dry eye. With dual complementary effects suppressing inflammation while promoting mucin secretion, Mycosol has the potential to offer ECPs a novel anti-inflammatory option for addressing signs and symptoms.

IVW-1001 applied over the upper eyelid stimulates TRPM8 located in the eyelid margin and this signal is passed via the ophthalmic nerve (V1) towards the central nervous system. The perception of coolness reduces ocular discomfort and efferent signals for increased tear secretion may also be activated. IVW-1001 is well-differentiated from the only other TRPM8 asset in development by its superior physiochemical properties (water soluble molecule allowing rapid response) and route of administration (eyelid wipe application on the upper eyelid with persistent and longer duration of response).

PolyCol’s ability to rapidly repair the damaged collagen present in dry eye disease, coupled with the concurrent recovery of the corneal epithelium, corneal nerves and reduction of inflammation, make this the company’s initial focus through the drug candidate ST-100 (vezocolmitide). The development of ST-100 is supported by compelling animal testing results, with complete healing of damaged corneal tissues in 24 hours or less, and full recovery of damaged corneal and trigeminal nerve structures, including goblet cells and corneal epithelium.

Palatin is developing a truly novel class of drugs that selectively bind to melanocortin receptors (MCR), with both MCR1 and pan-agonists, to directly activate natural pathways that resolve disease inflammation in the eye. Melanocortin agonists provide potential advantages over current options to better meet the needs of patients and clinicians by directly addressing harmful inflammation, resulting in rapid, global improvement of affected tissues. PL9643 ophthalmic solution  is currently undergoing late-stage Phase 3 clinical development which demonstrated improvements in both the signs and symptoms of DED after just 2 weeks of treatment, with no safety signals and excellent tolerability.

Pro-ocular™’s mechanism of action is believed to involve targeting the underlying immunological processes that occur in oGvHD and other autoimmune diseases, such as Sjögren syndrome. It is designed to modulate the immune response in the eye, which is a key factor in the development and progression of these diseases. By targeting specific pathways, Pro-ocular™ aims to reduce inflammation and damage to the ocular surface, ultimately improving patient outcomes. Pro-ocular™ gel, when applied and massaged twice daily laterally to the forehead area, activates a neural pathway,  via the ophthalmic branch of the trigeminal nerve, that leads to the stimulation of lacrimal and meibomian gland functions.

In contrast to the three FDA approved DED drugs that affect T-cell function, SLG-100 is a biologic comprising pooled human immune globulins that have natural anti-cytokine antibodies and anti-idiotypic (anti-immunoglobulin) antibodies with specific actions against DED-specific cytokines and autoantibodies, and other anti-inflammatory actions on neutrophils, dendritic cells, T-regulatory cells and complement system. SLG-100 is a clinical stage product. We have performed a pilot clinical trial to determine the preliminary therapeutic potential and safety of SLG-100 eye drops in patients with DED. As compared to Vehicle treatment, SLG-100 eye drops twice a day for 8 weeks caused significant reduction in signs and symptoms of DED with no difference in tolerability or adverse events.

Topical administration of urcosimod was effective in suppressing  corneal pain in a ciliary nerve ligation mouse model of NCP similar to that of gabapentin, a commonly used oral drug for neuropathic pain, given by intraperitoneal injection. The pain-relieving potential  of urcosimod is very important because a considerable number of dry eye  patients with chronic inflammation also suffer from ocular pain. Urcosimod is a novel class of chemerin receptor agonist that produces an anti-inflammatory action and reduction in neuropathic pain. Inclusion of a lipid ‘anchor’ within the urcosimod drug molecule is designed to decrease washout due to tearing and blinking, and to enhance the ocular residence time of urcosimod. 

Protearin™ is based on the glycoprotein clusterin, a natural, protective component of fluid-tissue interfaces throughout the body. Protearin™ targets the final common end point for all forms of dry eye, i.e., damage at the ocular surface and disruption of the ocular surface barrier. Preclinical testing and results of Protearin™ make a strong case to use clusterin as a biological drug to prevent or treat not only dry eye but also other corneal disorders involving damage to the ocular surface barrier.  No drugs are currently on the market to address ocular surface barrier disruption.

NRO-1 is a topically delivered, nerve regenerative therapeutic that accelerates nerve regeneration and recovery of functional nerves. It is a GDNF releasing small molecule that ameliorates corneal epithelial layer and it is positioned to initiate P2a trial for neurotrophic keratitis patients.  

The compound, named OCS-02, is based on a proprietary single-chain antibody fragment technology specifically designed for topical delivery. Efficacy and safety were evaluated in three clinical trials including two controlled studies under IND. The studies demonstrated a promising profile for treating inflammatory conditions of the anterior segment of the eye including dry eye disease.

SYK is a protein kinase that relays immune receptor signaling within a cell. It transmits signals from a variety of cell surface receptors and sends signals throughout a cell in order to trigger an immune response if needed SYK is the critical starting point in the activation of the inflammatory/immune cascade. Inhibition of the SYK can cause a broad anti-inflammatory effect. Dual ENKephalinase Inhibitors (DENKIs), inhibit the two enkephalin-degrading enzymes in order to enhance the body’s natural pain management system. This means DENKI can provide an alternative, non-addictive, safe, and effective treatment option for pain management. Iolyx is developing broad-based immunomodulatory therapies with the hope to provide transformative treatments which are safer, more tolerable, and more convenient than the standard of care today. 

INV-102 is a small molecule that has been shown in vitro to activate 2 major pathways: The first being the protein p53, which is known as “the guardian of the genome”, and the second being Pax6 which is critical for cellular stability particularly in the eye. By activating these 2 pathways, INV-102 achieves accelerated DNA repair and enhanced cellular stabilization.