16 Mar Emerging Therapeutics for Dry Eye Syndrome seek to hit the bull’s eye
Dry Eye Syndrome is characterized by the inability to produce sufficient amount or quality of tears which leads to lack of lubrication and nourishment to the surface of the eye and manifests as chronic eye irritation, inflammation and damage to the surface. There are over 16 million diagnosed cases of dry eye syndrome in the U.S alone.
Dry eye leads to discomfort and pain and can greatly impact the quality of life by making it difficult to perform everyday functions such as reading, driving, using computers and performing daily activities. In the U.S, the financial implications of dry eye management was estimated to be US$11,302 per patient and US$55 billion overall according to a report.
There is no cure for dry eye disease currently and treatment options include topical medication, punctal plugs, practitioner visits, and nutritional supplements, these options are highly inadequate and hence the need for novel solutions. The prevalence of dry eye ranged from 5 to 30 % of individuals aged over 50 according to an estimate by The Epidemiology Subcommittee of the 2007 DEWS.
A report by Transparency Market Research projects that the industry will be worth $7,780 million by 2025 growing at a CAGR of 4.5%. A rising geriatric population, coupled with increased screen exposure, diabetes, environmental factors such as pollution and refractive surgeries are leading to a rise in the incidences of dry eyes, while the lack of adequate therapeutic options, expensive medication along with lack of patient adherence is a challenge for the growth of the market.
However, the market is poised for change with some novel technologies and drug candidates being developed for the treatment of this chronic disorder. We take a look at some promising therapeutics in the offing.
Aldeyra Therapeutics (NASDAQ: ALDX)
Market Cap: $204.18M; Current Share Price: 7.78 USD
Aldeyra’s lead product candidate is reproxalap, a small molecule RASP (Reactive Aldehyde Species) Inhibitor that can be used in the treatment of dry eye disease, allergic conjunctivitis, noninfectious Anterior uveitis, and Sjögren-Larsson Syndrome. It is also developing other drug candidates for cancer, autoimmune diseases, post-transplant lymphoproliferative disease and retinal inflammation. The company has six different compounds representing three unique mechanisms of action targeting ten potential clinical indications.
It seeks to leverage its understanding of Reactive Aldehyde Species (RASP) levels to tackle intracellular inflammatory factors including NF-kB, a prominent protein in the inflammatory response. Its reproxalap can bind to free aldehydes triggering a covalent reproxalap-aldehyde adducts that can degrade intracellularly within hours with significant lowering of aldehyde levels. The company plans to initiate part 1 of its Phase 3 clinical trials names RENEW in the first half of 2019 to test the efficacy of reproxalap ophthalmic solution (0.25%) in treatment of ocular dryness, and fluorescein nasal region staining.
In the pipeline are drug candidates ADX-1612 for Mesothelioma, PTLD and Ovarian cancer, ADX-
629 and ADX-1615 for autoimmune disorders that are undergoing clinical trials. The company has acquired Helio Vision for its Phase 3 ready ADX-2191, for proliferative vitreoretinopathy (PVR). ADX-2191 has received Orphan Drug Designation from the U.S. Food and Drug Administration for the prevention of PVR and the company intends to launch phase 3 clinical trials during second half of 2019.
It raised funds amounting to $67.6 million through its underwritten public offering in October 2018.
As of December 2018, its cash, cash equivalents, and marketable securities balance stood at $93.6 million including proceedings from the public issue.
Kala Pharmaceuticals (NASDAQ: KALA)
Market Cap: $287.26M; Current Share Price: 8.50 USD
The company is using its proprietary mucus-penetrating particle (MPP) technology to develop novel nano-particle based therapeutic solutions for eye diseases. The technology consists of selective-sized nanoparticles that have a proprietary coating that enhances the mobility of drug particles and overcomes the limitations of being eliminated by mucus, thereby improving efficiency of drug delivery to target areas.
The company has filed a New Drug Application (NDA) with the FDA for KPI-121 0.25% aimed at the treatment of dry eye disease, by creating nanosuspensions of loteprednol etabonate, or LE, a corticosteroid designed for ocular applications. It aims to be the first FDA-approved product approved for the short-term treatment of dry eye. In addition, the company has also launched INVELTYS, a first-in-class topical twice-a-day product candidate for patients with inflammation and pain as a result of cataract surgery. It is the only FDA approved ocular steroid with BID dosing.
Its novel MPP technology has shown favorable pharmacokinetics characteristics and the ability to penetrate underlying ocular tissues effectively, thereby overcoming the limitations of the traditional drug particles which are eliminated at the tear film level itself. The company has patented its technology and enjoys a strong intellectual property portfolio.
Kala has also patented its proprietary AMPPLIFY™ drug delivery technology and will enjoy patent protection through 2033. The company has hired a specialty sales organization to promote the sales of its product to eye care professionals (ECP’s) and payor customers. The company has projected peak net revenues for the U.S to be over $300 million.
As per its Q3, 2018 financial results, the company closed a $110 million credit facility from Athyrium Capital Management LP, a leading healthcare-focused investment firm. It also made a public offering of 8,625,000 shares of its common stock at $8.25 per share, resulting in total net proceeds of an estimated $66.4 million. Its cash and cash equivalents stood at $74.9 million as of 30 September 2018.
Aurinia Pharmaceuticals (NASDAQ: AUPH)
Market Cap: $592.81M; Current Share Price: 6.35 USD
It is developing an investigational drug voclosporin to be used as a topical ophthalmic solution for the treatment of dry eye disease. In addition, the company is also looking at using voclosporin for the treatment of lupus nephritis (LN) and focal segmental glomerularsclerosis (FSGS). Voclosporin’s unique binding action induces structural changes in calcineurin and increases immunosuppressive activity. It is a best-in-class calcineurin inhibitors (CNI) with a dual mechanism of action that can not only block IL-2 expression and T-cell mediated immune responses but also stabilizes the podocyte in the kidney.
Volcosporin has shown to be more effective than conventional calcineurin inhibitors (CNI) by demonstrating a more stable pharmacokinetic and pharmacodynamic interplay and improved metabolic profiles. It is currently recruiting patients for a phase II study of the ocular tolerability of VOS in dry eye syndrome patients.
The company has received a shot in the arm as the USPTO has granted a notice of allowance to the company for patenting voclosporin’s method of use and dosing protocol for Lupus Nephritis (LN) under U.S. patent application 15/835,219, entitled “PROTOCOL FOR TREATMENT OF LUPUS NEPHRITIS”. This could enable the company to stave off competition from generics at least until 2037.
As of September 30, 2018, its cash, cash equivalents and short-term investments were at $138.9 million. The company closed an At-the-Market (ATM) offering for the sale of 4,608,409 shares at $6.55 a share for gross proceeds of $30 million.
Wize Pharma (OTCQB: WIZP)
Market Cap: $7.0M; Current Share Price: 0.71 USD
A clinical stage biotechnology company, Wize Pharma, Inc, has developed a formula named LO2A, a drug candidate for the treatment of DES, and other ophthalmological illnesses, including conjunctivochalasis (“CCH”) and Sjögren’s Syndrome. The company is focused on creating solutions for ophthalmic disorders such as Dry Eye Syndrome and other inflammatory conditions.
L02A is an artificial tear preparation that can lubricate and safeguard ocular surface tissues. The formula has a robust safety profile with more than 10 years of sales in Europe with minimal side effects. The company holds exclusive marketing & distribution rights in US, ROW, Ukraine & Israel.
The company recently formed a joint venture (JV) with Cannabics Pharmaceuticals Inc., a company that offers customized cannabinoid medicine to undertake the research and development of cannabinoid based treatments for ophthalmic disorders.
In the words of Wize’s Chairman, Noam Danenberg, “We are very excited to announce the closing of this deal. As Wize Pharma continues to develop its own portfolio, focused on non-cannabinoid ophthalmic conditions, our joint venture with Cannabics will pursue therapeutic pathways with cannabinoids, supported by a growing body of research that indicates cannabinoid-based therapies have the potential to address significant unmet medical needs in the market.” He further opined that “Cannabics is a leader in the therapeutic development of cannabinoid products for oncology. Together, we have significant expertise to effectively identify and develop new potential therapeutics to support eye health.”
It also has an exclusive distribution agreement with HPGC Medical Co., Ltd. (HPGC), a division of Harbin Pharmaceutical Group Co. Ltd., one of China’s largest healthcare companies for the distribution of LO2A. According to the agreement, Wize will receive between $22.5 million and $40 million in sales in China over a five year term subject to receipt of regulatory approvals in China.
In October 2018, the company closed a private placement of 4,450,000 shares of common stock at $1.10 per share that resulted in gross proceeds of $4.45 million to the company.
RegeneRx Biopharmaceuticals (OTCQB: RGRX)
Market Cap: $20.73M; Current Share Price: 0.16 USD
The company’s lead candidate RGN-259, a Tβ4 Eye Drop, is being developed for the treatment of ophthalmic disorders such as dry eye syndrome, neurotrophic keratopathy (orphan), recurrent corneal erosions and corneal surgeries. In addition, it has drug candidates such as RGN-352, a Tβ4 injectable solution, for cardio vascular disorders and RGN-137, Tβ4 dermal gel, for dermatological conditions under development in collaboration with different partners.
It has received an Orphan Drug Designation for its RGN-259 Eye Drops for the treatment of neurotrophic keratopathy and dry eye syndrome, which is currently under late stage clinical trials in the U.S and China. It is a Tβ4-based sterile and preservative-free eye drop that combines the best of corneal repair and anti-inflammatory properties. Various studies have shown its efficacy in promoting cell migration, increasing cell-cell and cell-matrix contacts that it achieves through increase in laminin-5 production, which in turn results in apoptosis and inflammation in the cornea.
RGN-352, an injectable Tβ4 formulation is being developed for the treatment of cardiovascular, central nervous system and PNS disorders such as traumatic brain injury, stroke, peripheral neuropathy, spinal cord injuries and multiple sclerosis. Its RGN-137 is the first formulation of Tβ4 to be used in human clinical trials based on research generated at the National Institutes of Health and is indicated to affect multiple healing pathways such as apoptosis, angiogenesis, collagen deposition, and tissue inflammation.
RegeneRx has over 25 research colorations with universities, hospitals and medical research institutions worldwide covering multiple disease areas. It also received a $30 million research grant from the National Institutes of Health (NIH) for conducting pharmacokinetic studies for RGN-352.
It has numerous licensing agreement and collaborations for its product candidates such as a partnership with Defiante Farmaceutica L.d.a., for development and marketing of RGN-137 (a subsidiary of Sigma-Tau Group), a licensing agreement with Lee’s Pharmaceuticals, Inc., for development and marketing of Tβ4-related products in China, Macau, Hong Kong and Taiwan, an agreement with G-treeBNT, a Korea biotech company for development and marketing of RGN-259 in 28 Asian countries including Korea, Japan, and Australia and also to develop RGN-259 for dry eye syndrome and neurotrophic keratitis (an orphan indication) in the United States.
The company recently completed a $1.3 million convertible debt financing to fund its operations.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.