|Posted by australiandryeye on December 4, 2017 at 10:15 PM||comments (0)|
Melbourne, October 11, 2017 – Azura Ophthalmics has received US$16 million in Series B funding to develop treatments for Meibomian Gland Dysfunction (MGD) – the number one cause of Dry Eye Disease.
The funding from Brandon Capital’s Medical Research Commercialisation Fund (MRCF), TPG Biotech, OrbiMed and Ganot Capital, will allow the Israeli-Australian company to move into its next clinical stage in the development of novel treatments for MGD – an eye condition where the Meibomian Glands becomes dysfunctional which results in rapid evaporation of the tear film.
Meibomian glands reside in the upper and lower eyelids and are responsible for producing the oily layer that forms the outer most layer of a person’s tear film. This oil (lipid) layer, in conjunction with the watery layer of the tear film work together to maintain clear vision and ocular health. An intact lipid layer ensures tears do not evaporate and keeps the eyes moisturised and nourished. If this layer is disturbed, it leads to tears evaporating too quickly, drying out the ocular surface and resulting in damage to the front of the eye, discomfort, and a significant reduction in both quality of life and productivity.
As Azura Ophthalmics Chief Executive Officer Marc Gleeson explained, “Meibomian gland dysfunction is responsible for at least 70 per cent of dry eye cases and affects about 300 million people worldwide, yet despite significant efforts there are no pharmaceutical treatments available for this condition. Using our novel therapy, Azura has generated promising results in a phase 1 study in MGD sufferers. We are therefore optimistic that Azura’s treatment could one day provide the first effective treatment for MGD sufferers.”
MGD sufferers represent one of the largest and most underserved patient segments in ophthalmology. If left untreated MGD will alter the tear ﬁlm, causing eye irritation, inﬂammation, and severe Dry Eye Disease (DED). Following initial clinical success with their lead compound, Azura Ophthalmics will undertake Phase 2a clinical testing of this new formulation in approximately 120 patients with MGD.
The Israeli-headquartered company was founded in Tel Aviv in 2014. All further research, clinical trials and the development of Azura’s Ophthalmics drug treatment will be undertaken in Australia.
MRCF Chief Executive Officer Dr Chris Nave noted, “Australia is an accepted world leader in medical research. However, historically a lack of investment funding in the life sciences sector has resulted in Australian medical discoveries leaving our shores to gain access to the capital required for further development. The government’s R&D tax incentive and the introduction of the $500 million-dollar Biomedical Translation Fund are addressing this problem and are attracting foreign life science companies like Azura Ophthalmics to Australia, stimulating the industry locally, creating jobs and keeping our talented clinicians and scientists, and their research, in Australia.”
Indeed, Sydney-based CEO, Marc Gleeson, is leveraging these incentives to bring innovation home. As Gleeson noted, “Australia has an attractive regulatory environment for early-stage clinical trials and the government’s R&D tax incentive, which sees eligible companies undertaking research and development in Australia, receive a refundable tax offset, helps preserve valuable capital. Azura Ophthalmics was established in Israel, which is highly-renowned for its innovation ecosystem. The Company is now looking to take advantage of Australia’s clinical research excellence and the incentives that support investment in Australian innovation”.
Through a combination of innovation from Azura Ophthalmics, the Australian government’s R&D tax incentive, and the Biomedical Translation Fund, Australia is now positioned to be at the forefront in developing innovative treatments for Meibomian Gland Dysfunction, the leading cause of dry eye disease, offering hope to hundreds of millions of people worldwide.
|Posted by australiandryeye on November 20, 2017 at 8:15 PM||comments (0)|
Cannabinoids could have potential in a novel topical drug delivery vehicle to treat neuropathic dry eye pain.
The disconnect between signs and symptoms in dry eye disease is an intriguing clinical problem. Although we know quite a lot about the etiology of dry eye, the ideal structure of the tear film and how to diagnose and treat dry eye disease, there are still some patients who do not respond to treatment or who present complaining of severe symptoms that seem to be poorly correlated with clinical signs. Complaints may include a burning or stabbing sensation or a feeling of pressure in the eyes.
Many clinicians find these patients—and the chair time they consume—frustrating. But before dismissing them as “crazy,” it may help to consider whether they could be suffering from a different form of dry eye that is difficult to detect by traditional methods.
In 2009, Perry Rosenthal and colleagues observed what they presumed to be corneal neuralgia, which they termed “pain without stain” because of the paucity of corneal staining or other clinical signs.1 They speculated that the pain symptoms could be related to a neuropathic disorder, rather than to qualitative or quantitative tear film factors.
Later work by Rosenthal further elucidated how the nociceptive system—critical to vision when functioning properly, because it monitors and restores the optical tear film—could become dysfunctional.2 When this happens, the corneal nerves, the central trigeminal sensory network, and/or the pain organising centres in the brain escalate the eye’s natural ‘alarm system’, sending pain signals that are out of proportion to the physical insult (if indeed there is any injury at all).
Neuropathic dry eye pain may be triggered or exacerbated by ocular surgery, systemic conditions or even psychological distress.
The dry eye community has been increasingly interested in neuropathic dry eye. In fact, the new DEWS II definition of dry eye explicitly includes “neurosensory abnormalities” in the list of etiological factors in dry eye.3
A DEWS II subcommittee report on pain and sensation notes that long-term inflammation can alter neuron excitability, connectivity and impulse firing and that disturbances in ocular sensory pathways may ultimately lead to neuropathic pain.4 However, as yet, there are no dry eye therapies that specifically target neuropathic pain.
The role of cannabis
Cannabinoids and, in particular, tetrahydrocannabinol (THC, the main active ingredient in recreational marijuana) is of great interest in the treatment of neuropathic pain. Cannabinoid receptors are known to modulate pain and inflammation and are located throughout the eye, including the corneal epithelium and the retina; they are present on immune cells and may be involved in wound healing, as well.5 So, from a theoretical perspective there are a number of reasons to pursue the use of cannabinoids to treat dry eye.
And the time may be right to conduct such research now. Regulatory restrictions around the use of cannabinoids are being loosened, with more than half of U.S. states and several European countries now permitting the use of THC for medical purposes.
In Germany, where I practice, a special permit is required and the drug must be used in a controlled research setting as part of a clinical trial, which seems to be a reasonable way to open the doors to research on cannabinoid compounds while still limiting the potential for abuse.
In my laboratory, we have been actively investigating what the best targets for treating neuropathic pain might be and how THC could be safely and effectively delivered to those targets.
There are a number of challenges in using THC therapeutically. Smoking marijuana or consuming THC in edible form is impractical for the treatment of ocular disease; these systemic applications deliver an unpredictable dose with unwanted systemic side effects.
Sublingual and dermal administration have similar effects and are probably not appropriate for ocular conditions. For these reasons, and due to a lack of evidence of predictable, long-lasting therapeutic effect, a number of professional organisations, including the Canadian Ophthalmological Society and the American Academy of Ophthalmology, have taken positions against the use of systemic THC treatment for ocular conditions.
Local application of THC is considerably more compelling. Cannabinoid eye drops have been investigated and are available for glaucoma from at least one small manufacturer. But noone yet has been particularly successful with this approach due to the challenges of formulating the drops appropriately.
THC and most other pain-relieving or anaesthetic compounds are quite lipophilic. Like oil with water, they do not mix well with the aqueous solutions in most eye drops, making it difficult to get THC into the target ocular tissues.
Enhanced topical drug delivery
Recently, we have been investigating the use of a novel semi-fluorinated alkane (SFA) drug delivery technology (EyeSol, Novaliq) as a vehicle to deliver cannabinoids to the ocular surface. This class of molecules has a number of advantages as an eye drop.
EyeSol-based drops contain no water, so they mix well with lipophilic substances, including cyclosporine and THC, and allow them to remain solubilised instead of separating out in the bottle. They have a very low surface tension so a drop on the eye rapidly forms a very thin layer, giving it spreading properties that are far superior to an aqueous eye drop (Figure 1).
These properties should help to distribute a drug across the uneven ocular surface without the drug being immediately drained or spilling out of the eye as excess aqueous. SFA molecules are metabolically inert and do not interact with the immune system. Finally, they have a refractive index similar to water, so they do not disturb vision the way oil emulsions of lipophilic ingredients can.
In several observational trials we conducted, q.i.d. treatment with an EyeSol delivery vehicle alone resulted in a highly significant reduction in corneal staining and a 20-point improvement in OSDI scores after just six weeks.6 We thought that if this vehicle could be combined with a compound like THC for pain and inflammation, it could be very beneficial in dry eye treatment.
We began to conduct experiments using an established mouse model for dry eye disease that relies on behavioural testing methods to determine pain levels, as well as other testing methods (Figure 2). We compared a group treated with EyeSol THC eye drops to a control group treated with topical cyclosporine.
One-year results of these preclinical studies suggest that the drop is at least as effective as cyclosporine and may have dual or even triple mechanisms of action, including lubrication, anti-inflammation and pain reduction. Although we continue to evaluate various parameters, the pharmacodynamics thus far are very promising.
We are fairly confident that topical application of THC dissolved in EyeSol will not result in any measurable systemic effects. The first human clinical trials in dry eye disorder are expected to begin in the second half of 2018.
Understanding neuropathic pain
Even as research into THC delivery to the ocular surface continues, we have also been seeking to gain a better understanding of neuropathic pain and the characteristics of patients who may suffer from this form of dry eye. To do this, we in the dry eye clinic have been working closely with experts from the University of Cologne’s pain clinic.
We retrospectively evaluated 52 patients seen in our dry eye clinic who fell into the ‘pain without stain’ category. These subjects had normal Schirmer’s, no corneal staining and no signs of blepharitis, but they had OSDI scores >40, in the ‘severe’ symptom range (median score 77).
In addition to a very thorough history and examination in our clinic, many of the patients also underwent a full pain inventory and Hospital Anxiety and Depression Score (HADS) questionnaire. Comorbidities included depression (n=9), chronic pain syndrome (9), anxiety disorders (4), and prior eye surgery (17).7 Other researchers have also recently shown that severe dry eye pain is correlated with antidepressant use but not with corneal staining.8
For ophthalmologists, these are exactly the sort of patients who are mystifying at best, and often get dismissed as people whose symptoms are “just” psychological. To the pain experts we consulted, however, it was very clear that these were typical pain patients, with the same types of concomitant psychosomatic conditions they often see among patients who suffer from chronic headache or back pain.
A typical patient in our study, for example, might have fibromyalgia and rheumatoid arthritis, with an OSDI score of 65 but no clinical signs of dry eye. Upon questioning, she might have first noticed the dry eye pain following LASIK or around the time of a particularly stressful life event, such as the death of a close family member.
In some cases, the patients had no response to topical anaesthesia or to systemic pain medications, which was quite interesting, since it indicates there is something very unusual going on with regards to their pain response. It seems that these individuals may be predisposed to systemic neuropathic pain, of which ocular pain is but one manifestation.
These insights have changed the way I practice in a number of ways. For example, I have started using the HADS questionnaire more frequently for patients with severe symptoms. I ask broader questions about fatigue, anxiety and depression as part of my history taking.
Recognising that ocular surgery can trigger an underlying pain syndrome, I am more thoughtful about evaluating postoperative patients with unexplained symptoms to determine whether they might be most appropriately managed as a pain patient. As medical doctors, it is our responsibility to see the whole patient and, when appropriate, help them to seek treatment for systemic autoimmune disorders, psychosomatic illnesses and other pain syndromes.
‘Pain without stain’ patients provide us with a model to understand the process of neuropathic dry eye. Because they do not have significant meibomian gland dysfunction or aqueous deficiency, we are able to isolate the neuropathic disease and hopefully identify new therapies to relieve their symptoms.
While these patients represent what is probably a very rare subtype of dry eye, it is likely that many more dry eye patients who do have clinical signs also have neuropathic pain as a component of their dry eye. In fact, I believe that most of the patients who fail, even partially, to respond to stepwise, appropriate dry eye therapy or for whom resolution of signs does not lead to significant improvement in symptoms, might also have an additional neuropathic disorder.
What we learn from treating the extreme form, therefore, has the potential to benefit a much broader range of patients whose pain is inadequately addressed with current therapy.
It has become clear to me that there is a strong unmet need for treatments that specifically address ocular surface pain. Although much research remains to be undertaken, I am optimistic about the potential for cannabinoid therapies, particularly if we are able to confirm that use of an SFA drug delivery technology is effective in reaching the target tissues without systemic side effects.
Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain: Is it real? Ocul Surf. 2009;7(1):28-40.
Rosenthal P, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016;100(1):128-134.
Nelson JD, Craig JP, Akpek EK, et al. TFOS DEWS II introduction. Ocul Surf. 2017;15:269-275.
Belmonte C, Nichols JJ, Cox SM, et al. TFOS DEWS II pain and sensation report. Ocul Surf. 2017;15(3):404-437.
Toguri JT, Caldwell M, Kelly MEM. Turning down the thermostat: modulating the endocannabinoid system in ocular inflammation and pain. Front Pharmacol. 2016;7:304.
Steven P, Scherer D, Krösser S, et al. Semifluorinated alkane eye drops for treatment of dry eye disease—a prospective, multicenter noninterventional study. J Ocul Pharmacol. Ther 2015;31(8):498-503.
Steven P, Schneider T, Ramesh I, et al. Pain in dry eye patients without corresponding clinical signs—a retrospective analysis. Association for Research in Vision and Ophthalmology. 2016, Abstract 2848-A0057.
Satitpitakul V, Kheirkhah A, Cmej A, et al. Determinants of ocular pain severity in patients with dry eye disease. Am J Ophthalmol. 2017;179:198-204.
Professor Philipp Steven, MD
Prof. Steven is principle investigator for the Ocular Surface Group in the Department of Ophthalmology at the University of Cologne, in Germany. He consults for and receives research funding from Novaliq and has a patent pending related to the work described within this article.
|Posted by australiandryeye on November 2, 2017 at 6:20 PM||comments (0)|
CHICAGO – Rich Mangan, OD, and Scott Hauswirth, OD, discussed a new area of ocular surface disease involving chronic, or neuropathic, pain.
Hauswirth said to consider this condition in dry eye patients who experience light sensitivity and those with symptoms that tend to never go away despite treatment.
https://www.healio.com/optometry/cornea-external-disease/news/online/%7B38eae214-7dac-483f-b33c-095b0c4f398d%7D/video-consider-neuropathic-pain-in-stubborn-dry-eye" target="_blank" rel="nofollow">Video Link
|Posted by australiandryeye on October 31, 2017 at 10:35 PM||comments (0)|
The possible causes are many and prescription treatments few, but new and potential dry-eye therapeutics keep coming.
The update reflects the most current understanding of dry-eye disease as a disruption in homeostasis and emphasizes the importance of hyperosmolarity in dry-eye tears and the role of inflammation in DED. Inflammatory mediators are frequent therapeutic targets. As things stand, Restasis and Xiidra (Allergan and Shire, respectively) are the only prescription eye drops approved by the Food and Drug Administration for the treatment of dry-eye disease. Both medications are thought to inhibit T cells by different mechanisms of action. The heterogeneous nature of dry-eye disease is one of the things confounding new drug development: Drug makers have multiple potential molecular and tissue targets to consider and DED is notorious for a lack of overlap between signs and symptoms.2 With an estimated global prevalence ranging from 5 to 50 percent3 and the potential for corneal surface damage and diminished quality of life absent good treatment, DED’s therapeutic pipeline is unlikely to run dry anytime soon.
Four dry-eye treatments at various stages follow: a freshly FDA-approved medical device; a drug in the middle of the investigational stage; a patented topical solution/gel formulation; and a protein-fragment-based drop beginning a human trial.
Approved by the Food and Drug Administration in the spring of 2017, Allergan’s TrueTear Intranasal Tear Neurostimulator device relies on an old idea—nerve stimulation—to address the problem of dry eye. Oculeve, the startup that invented the device before being purchased by Allergan, based TrueTear on technology used in TENS units and for the treatment of movement disorders. The TrueTear stimulates the trigeminal nerve and, in turn, the seventh cranial nerve with small electrical pulses that ultimately trigger the lacrimal gland to produce tears.
To reach the ophthalmic branch of the trigeminal nerve, this small handheld device has two prongs covered in disposable hydrogel tips that go up the patient’s nostrils. Patients can choose from five levels to control the intensity of electrical stimulation. According to patient information for the TrueTear,4 patients should
The TrueTear is an intranasal device that uses neurostimulation.
aim to use the device at least twice a day for no more than three minutes per session; the TrueTear automatically shuts off after 30 minutes of use in a 24-hour period. Allergan lists a tendency for nosebleeds, a history of clotting disorders, the use of pacemakers or wearable defibrillators, as well as the presence of metallic or electronic implants in the head or neck as contraindications to TrueTear use. The device is currently approved for patients 22 years of age and older.
Supportive data released by Allergan4 consist of two studies: OCUN-009, a look at one-day correct use of the device versus one-day sham control treatments, and OCUN-010, a six-month trial comparing tear production at six months to baseline. Forty-eight dry-eye patients at two sites underwent three applications of neurostimulation in OCUN-009: correctly applied intranasal stimulation treatment with an active TrueTear; intranasal application of an inactive TrueTear; or extranasal (incorrect) application of an active TrueTear. The average Schirmer’s score for the treatment group was 25 mm during treatment, versus 9 mm for both sham groups. OCUN-010 was an interventional open-label study looking at tear production in 97 dry-eye patients at treatment days one, seven, 30, 90 and 180. Patients were told to use the TrueTear anywhere from two to 10 times per day for a maximum of three minutes per session. At each follow-up visit, Schirmer’s testing without stimulation was compared to scores with stimulation; tear production was consistently significantly greater with active TrueTear stimulation than without. The effect appeared to decrease from the first-day results but then plateaued over time (still remaining higher than without stimulation). The average differences in Schirmer’s scores (with stimulation versus without) were 18 mm on day one, 13.1 mm at seven days, 8.1 mm at 30 days, 8.3 mm at 90 days and 9.4 mm at 180 days. In both studies, adverse events were minor and included nasal complaints such as irritation.
“Crazy,” is how John Berhdahl, MD, of Vance Thompson Vision in Sioux Falls, S.D., sums up his first impression of the TrueTear upon getting the chance to try it out a couple of years ago. “But I love outside-the-box ideas, and as I thought about it more deeply, it made sense,” he says. “We know that reflex tearing can occur when you stimulate nerves, and it’s not so different from other electrotherapies that we use to stimulate nerves in other parts of the body. I believed that it would be safe, so I thought, ‘Let’s try it. Let’s see if this crazy idea turns out to be legit,’” he recalls.
So far, Dr. Berdahl reports that patients are having “a very good response” to the TrueTear since it has become generally available. “I like that we’re using concepts outside of ophthalmology like electrostimulation and applying them to ophthalmology to see if we can control the pathophysiology of the eye: I think that’s great,” he says. He thinks that the high degree of control over treatment that the device affords patients is one factor in its success to date. “One of the things that’s really nice about it is that we allow them to try it in the office so that they can experience the increased tearing,” he notes. “Then they can try it for a month, and if it’s not working for them, it can be returned. Those two steps allow people to climb the learning curve in a noncommittal way.”
Dr. Berdahl also values the safety and flexibility of the TrueTear, since it fits well into comprehensive treatment plans that include other modalities. “I believe in treating severe dry eye by hitting it really, really hard to get it under control and then backing off the things that you no longer need, or that the patient likes the least,” he says. Using the TrueTear is part of that treatment philosophy for dozens of patients in his practice.
Surgeons say that the base price of the TrueTear is $750 and a month’s supply of disposable tips costs $250, although Allergan does offer some rebates to help defray costs.
In addition to stimulating the lacrimal gland in aqueous-deficient dry eye, Dr. Berdahl says that there is evidence that using TrueTear improves the tear film in dry eye as well. “They have done some work to show that it improves meibum secretion, so it would improve tear-film quality,” he says. A small study5 suggests that use of the neurostimulator can promote degranulation of conjunctival goblet cells in both dry and healthy control eyes.
Since its launch in 2003, Restasis (0.05% cyclosporine A emulsion), has been a dry-eye treatment mainstay, thought to inhibit the action of inflammatory T-cell mediators. Cyclosporine eye drops, however, present the same roadblocks to efficacy and compliance as other topical drops: Many patients have difficulty getting them into the eye without blinking as soon as they reach the cornea, which results in spillover and drainage into the lacrimal system before the drug can provide much therapeutic benefit.
Novaliq GmbH (Heidelberg, Germany) has combined cyclosporine A with its Eyesol drug-delivery platform, which is made up of semifluorinated alkanes, in a bid to create a more bioavailable and user-friendly alternative to aqueous drops.
Semifluorinated alkanes aren’t new to ophthalmology because they possess characteristics that make them suitable tamponades in vitreoretinal surgery, including good solubility in silicone oils, perfluorocarbon and hydrofluorocarbon liquids; a refractive index of 1.3; and a specific gravity of 1.35 g/mL.6 Those attributes also make semifluorinated alkanes good for mixing with cyclosporine A—a drug with poor water solubility—to make a slick, clear, preservative-free solution with low surface tension that spreads rapidly over the ocular surface.
One drop of a 0.05% aqueous emulsion has a volume of 40 to 50 μL: a drop of that size triggers reflexive blinking in many patients when it contacts the eye. To create a cyclosporine A drop that will more successfully reside on the cornea, Novaliq has developed CyclASol, a preservative-free cyclosporine A solution with Eyesol. Novaliq says that a drop of CyclASol is only about 10 μL in volume, so it doesn’t trigger a blink reflex and accompanying spillover in the eye, and its low surface tension allows the drop to spread over the cornea more quickly and evenly than aqueous eye drops. Alternate dry-eye treatments include gels and ointments, but these are often limited to nighttime use because they blur and distort vision, even though they reside on the cornea better than aqueous drops. The company claims that CyclASol’s refractive index is very close to that of the crystalline lens, so it will not blur or distort vision.
A Phase II study (Trial Identifier: NCT02617667) comparing two dose levels of CyclASol (0.05% and 0.1%) solution with cyclosporine A 0.05% emulsion and a placebo followed 207 randomized patients with moderate-to-severe dry-eye disease for four months. Novaliq released topline data from this study in early 2017.7 Although patients in all treatment arms showed reduced corneal fluorescein staining, patients enrolled in both CyclASol groups showed significantly more disease-sign improvement than patients in the vehicle (placebo) group. Novaliq says that its data also demonstrated that CyclASol patients began showing reduced corneal and conjuctival staining as early as 14 days into treatment. It reports that the drops were well tolerated with no serious adverse events. Novaliq added that improvement was most marked in the central area of the cornea and noted that area’s importance to good visual functioning.
Upon release of the topline data, a company press release7 quoted Claus Cursiefen, MD, PhD, FEBO, professor and chair of the ophthalmology department at University of Cologne, Germany, and member of Novaliq’s scientific advisory board, on the therapeutic benefits of CyclASol: “Consistent improvements in several measures of ocular inflammation of dry-eye disease, particularly the improvement in central corneal staining, is a very important feature of the formulation because it positively influences visual function. This, combined with the early onset of action and an excellent tolerability profile, represents a highly relevant improvement over currently available therapies.”
In the spring of 2017, Imprimis Pharmaceuticals (San Diego) announced that it had purchased the exclusive worldwide rights to Klarity, a patented topical ophthalmic solution created by Richard L. Lindstrom, MD, to protect and heal the ocular surface in moderate-to-severe DED. Klarity is also intended for dry eye and corneal irregularities arising from intraocular surgery or contact lens wear.
The preservative-free Klarity solution contains chondroitin sulfate, thought to have protective and healing effects on the corneal epithelium,8 and established as safe for intraocular use in viscosurgery. It also contains dextran and glycerol. Imprimis says that the solution can be formulated to vary in viscosity, making it suitable as a topical drop, a gel or even a dispersive OVD.
The company plans to make Klarity part of its emerging dry-eye program. According to the Imprimis website, another upcoming addition is the compounding of autologous serum tears at the company’s 503A PCAB-accredited pharmacies.
Lacripep (TearSolutions, Inc.) is a synthetic protein fragment incubated in the Laurie Cell Biology Laboratory at the University of Virginia in Charlottesville. Its inventor, Gordon W. Laurie, PhD, professor of cell biology, biomedical engineering and ophthalmology at UVA and co-founder and CSO of TearSolutions, and colleagues say that Lacripep is potentially the first therapeutic agent capable of improving dry-eye disease regardless of etiology.
“Lacripep is a synthetically generated 19-amino-acid fragment of lacritin,” Dr. Laurie explains. “Lacritin is a naturally occurring protein in tears, first identified in 2001 by the Laurie Cell Biology Lab out of an unbiased discovery screen for factors that regulate basal tearing.” He notes that Lacripep-like lacritin fragments occur naturally in tears secreted by healthy eyes—and that they are deficient (as is lacritin) in dry-eye tears. “Lacripep and lacritin have been studied in several dry-eye animal and human cellculture models, and have been found to restore ocular surface health by: promoting tear protein release and tearing, even under conditions of inflammation; transiently stimulating a cellular lysosomal pathway known as autophagy to rid cells of damaged proteins and organelles that accumulate under conditions of stress; and restoring mitochondrial oxidative phosphorylation. In unpublished data, both also appear to stimulate and benefit sensory nerves at the ocular surface that in dry eye are disrupted and diminished,” he says.
This neural stimulation may bring relief for both aqueous-deficient and evaporative dry-eye patients. “By apparently targeting corneal sensory nerves that in turn regulate all glandular and secretory elements of the ocular surface, Lacripep is expected to benefit both evaporative and aqueous-deficient dry eye,” Dr. Laurie explains.
With support from the National Eye Institute,
A molecular model of lacritin, a protein that is selectively deficient in dry-eye tears. Lacripep is a synthetic lacritin fragment.
Dr. Laurie and colleagues focused on the causes of dry eye rather than the effects of the disease. “With NEI R01 support, we were the first to explore the cell biological basis of dry eye using an unbiased biochemical screen. This differs from others who have largely employed a candidate approach, in most cases focused on downstream inflammation,” says Dr. Laurie. “It took years, but we succeeded in identifying a natural tear activity, encapsulated in Lacripep, that appears to be fundamental for the maintenance and restoration of ocular surface homeostasis. Yet, dry-eye tears are selectively deficient in lacritin and natural Lacripep-like fragments. This draws a parallel to type I diabetes and insulin, and offers a new way to think about dry eye with Lacripep as a replacement therapy, that based on the biology, could be a game changer.”
“A shout-out to the National Eye Institute for their many years of support, without which this discovery would not have been possible,” says Dr. Laurie. “We also wish to acknowledge the Lacritin Consortium of labs in the U.S. and outside, who have contributed fundamentally to our understanding of Lacritin,” he says.
Dr. Laurie, Marc G. Odrich, MD, associate professor of ophthalmology at University of Virginia and medical director of TearSolutions, Inc., and colleagues have recently begun an attempt to transition from the laboratory to the marketplace with a double-masked, randomized, placebo-controlled Phase II study of topical Lacripep in more than 200 patients with Sjögren’s-associated dry-eye disease at 27 U.S. sites (Trial Identifier: NCT03226444). Enrolled patients receive one of two concentrations of Lacripep eye drops or a placebo three times a day for four weeks. Improvement in fluorescein corneal staining is the primary endpoint.
Dr. Odrich says that they selected Sjögren’s patients for the first study because primary dry eye associated with the disorder “is the most homogenous form of dry-eye disease, with diagnosis aided by blood tests and salivary gland biopsy.” He adds, “Second, lacritin deficiency in Sjögren’s syndrome correlates with reduced corneal nerve fiber density and length, tear insufficiency, increased ocular staining and reduced corneal sensitivity. Third, in two different mouse models of Sjögren’s syndrome, lacritin promoted rapid resolution of corneal staining and/or tearing. Fourth, Sjögren’s syndrome patients are highly motivated.”
Dr. Odrich estimates that data will become available in the first half of 2018. Should Lacripep garner FDA approval in the future, he believes that patients could titrate the number of daily doses down from three once their condition stabilizes. “There appears to be a lasting effect with repeated dosing,” Dr. Odrich says of his team’s studies in rabbits that were dosed three times daily for two weeks. “Basal tearing steadily increased and remained elevated one week after washout.The molecular basis is under study. At least two different mechanisms are likely involved,” he says.
The dry-eye pipeline is tricky for a variety of reasons: the heterogeneity of the target disease; the lack of overlap between signs and symptoms; and the costly path to FDA approval, to name a few. As the most prevalent ocular surface disease globally, however, DED will never be without therapeutic contenders.
“Dry eye is a disease that has real unmet needs because we can’t get everybody better right now,” Dr. Berdahl observes. “So I’m excited about all of it, but it remains to be seen which things will be the most clinically useful.” REVIEW
Dr. Berdahl is a consultant to Allergan. As mentioned in the article, Drs. Laurie and Odrich are the CSO and medical director, respectively, of TearSolutions, Inc.
1. Craig JP, Nichols KK, Akpek EK, Caffery B, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf 2017;15;3:276-83.
2. Novack GD. Why aren’t there more pharmacotherapies for dry eye? Ocul Surf 2014;12;3:227-29.
3. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf 2017;15;3:334-65.
4. Allergan. Patient Guide to the TrueTear intranasal tear neurostimulator. https://allergan-web-cdn-prod.azureedge.net/actavis/actavis/media/allergan-pdf-documents/labeling/ifu_truetear_patient.pdf. Accessed August 28, 2017.
5. Gumus K, Schuetzle KL, Pflugfelder SC. Randomized controlled crossover trial comparing the impact of sham or intranasal tear neurostimulation on conjunctival goblet cell degranulation. Am J Ophthalmol 2017;177:159-68.
6. Alovisi C, Panico C, de Sanctis U, Eandi CM. Vitreous substitutes: Old and new materials in vitreoretinal surgery. J Ophthalmol 2017;2017:3172138. doi: 10.1155/2017/3172138. E-pub ahead of print.
7. Novaliq, “Novaliq announces positive topline results of Phase 2 clinical trial evaluating CyclASol in adults with moderate to severe dry eye disease,” (2017). Available at: http://bit.ly/CyclASol. Accessed August 28, 2017.
8. Sandri G, Bonferoni MC, Rossi S, Delfino A, Riva F, et al. Platelet lysate and chondroitin sulfate loaded contact lenses to heal corneal lesions. Int J Pharm 2016;25;509(1-2):188-96.
|Posted by australiandryeye on October 31, 2017 at 8:20 PM||comments (0)|
ROCKVILLE, Md., Oct. 31, 2017 /PRNewswire/ -- RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX) ("the Company" or "RegeneRx"), a clinical-stage drug development company focused on tissue protection, repair and regeneration, today announced the results of its phase 3 dry eye trial sponsored by its U.S. joint venture, ReGenTree, LLC. The ARISE-2 trial investigated the safety and efficacy of RGN-259 compared to placebo for the treatment of the signs and symptoms of dry eye syndrome in 601 patients.
The following two paragraphs are excerpted from the ReGenTree press announcement:
"The ARISE-2 study, which was conducted together with Ora, Inc., demonstrated a number of statistically significant improvements in both signs and symptoms of dry eye syndrome with 0.1% RGN-259 versus placebo, while showing excellent safety, comfort, and tolerability profiles. The ocular discomfort symptom showed a statistically significant reduction in the RGN-259-treated group at day 15 as compared to placebo (p=0.0149) in the change from baseline. For sign, RGN-259 also improved the dry eye patient's ability to withstand an exacerbated condition in a patient subgroup with both compromised corneal fluorescein staining and Schirmer's test at baseline. In this population, RGN-259 showed superiority over placebo in reducing corneal fluorescein staining in the change from baseline at days 15 and 29 (p=0.0207 and 0.0254, respectively). RGN-259 confirmed its global effects on dry eye syndrome and fast onset in multiple sign and symptom efficacies with no safety issues in the ARISE-1 and ARISE-2 studies as well as in the pooled data, although ARISE-2 was not successful in duplicating the results of ARISE-1 where the study population was limited and less diversified."
"Won S. Yang, President & CEO of ReGenTree, stated, 'We are very excited with the ARISE-2 results, which show RGN-259's important additional efficacies lacking in approved treatments, such as very fast onset and multiple global effects in both signs and symptoms of dry eye syndrome. I believe these two studies, ARISE-1 and ARISE-2 with efficacy of Tβ4 in both signs and symptoms, will continue building a strong foundation of its strengths when considered with the totality of the data set. ReGenTree plans to proceed with a development plan for the next step through a meeting with the FDA based on the results of ARISE-2 trial. We are optimistic that the results from ARISE-2 will accelerate discussions with potential investors interested in reaching a global deal for the development and marketing of RGN-259.'"
About RegeneRx Biopharmaceuticals, Inc. (www.regenerx.com)
RegeneRx is focused on the development of novel therapeutic peptides, including Thymosin beta 4 (Tβ4) and its constituent fragments, for tissue and organ protection, repair and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac and dermal indications, three active strategic licensing agreements in the U.S., China, and Pan Asia (Korea, Japan, and Australia, among others), and has patents and patent applications covering its products in many countries throughout the world.
RGN-259, the Company's Tβ4-based ophthalmic eye drops, is currently the subject of phase 3 clinical trials for patients suffering from dry eye syndrome as well and for patients having chronic neurotrophic keratopathy (NK), a non-healing corneal lesion designated an orphan indication in the U.S.
RGN-352, the Company's Tβ4-based injectable formulation, is a phase 2-ready drug candidate designed to be administered systemically to prevent and repair cardiac damage resulting from heart attacks and central nervous system tissue damage associated disorders such as peripheral neuropathy, multiple sclerosis and traumatic brain injuries such as stroke.
RGN-137, also designated an orphan drug in the U.S., is the Company's Tβ4-based dermal gel formulation that is being developed for epidermolysis bullosa, a rare skin condition by the Company's licensee, GtreeBNT.
For additional information about RegeneRx please visit www.regenerx.com.
Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. There can be no assurance that any current or future clinical trials will result in approved products or future value. Any forward-looking statements in this press release represent the Company's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information, as a result of future events or otherwise, except as required by applicable law.
SOURCE RegeneRx Biopharmaceuticals, Inc.
|Posted by australiandryeye on October 30, 2017 at 9:50 PM||comments (0)|
Approximately 16 million Americans have been told by their doctor that they have Dry Eye Disease – the itchy, uncomfortable and inconvenient condition that remains the number one reason people go see an ophthalmologist.
People with Dry Eye Disease either produce poor quality tears or do not produce a sufficient amount of tears to nourish and lubricate the front of the cornea, leading to eyes that feel chronically irritated, gritty, red, and scratchy.
But, despite its name, Dry Eye Disease is much more than just insufficient tears. The condition is multifactorial, and it’s characterized by underperforming tear production as well as inflammation and tissue degradation.
Treatments for the condition aim to replenish or maintain a normal amount of tears to minimize discomfort. But according to Robert Ritch MD, Professor of Ophthalmology at New York Medical College, the therapy options currently available to patients with Dry Eye Disease just don’t cut it.
Artificial tears, for example, provide short-term relief and have to be applied frequently – with many patients using these types of drops several times throughout the day. Dr. Ritch says that patients also often make the mistake of using artificial tears as needed, when their eyes feel dry, rather than using them prophylactically as they should be.
When it comes to prescription-strength options, there are just two eye drops that have been cleared by the FDA to treat dry eye. Patients can be prescribed either Allergan’s Restasis or Shire’s Xiidra, which was approved just last year. These two drops have a limited effect against Dry Eye Disease, however, because they act primarily as anti-inflammatory agents – and fail to address the tissue degeneration and tear production deficit that also characterize the condition.
Fortunately, patients suffering from the symptoms of Dry Eye Disease can start looking forward to a new treatment option that targets the condition from all three angles. Mitotech, a biotechnology developer based in Luxembourg, has been working on a novel compound that goes beyond the current treatment paradigm to approach the multifactorial nature of the disease.
Mitotech’s lead molecule, called SkQ1, has been clinically proven to relieve inflammation, tissue degeneration, and tear quality deficit in patients with Dry Eye Disease. Unlike the current standards of care, SkQ1 deals with the condition on a cellular level by protecting the eye from oxidative stress.
Cells produce a type of free radical called reactive oxygen species (ROS), which are important for cell signaling and general cellular function. Oxidative stress – a phenomenon widely evident in patients suffering from Dry Eye Disease – happens when the amount of ROS produced inside cells and tissues grows beyond normal levels. Naturally-occurring antioxidants typically keep ROS levels in check, but excess ROS react with nearby lipids, proteins or other cellular components – which hurts normal cell function.
This is where Mitotech’s SkQ1 comes in. One of the primary sources of ROS inside cells is an organelle called the mitochondria, but natural antioxidants aren’t able to penetrate mitochondria to neutralize excessive levels of free radicals. SkQ1 is part of a new class of molecules called mitochondria-targeted antioxidants – and it has already been proven to target and neutralize mitochondrial ROS to restore cellular function.
In Russia, Mitotech has already won regulatory approval for its eye drop formulation of SkQ1, called Visomitin – and about 1 million units of Visomitin have been sold in the Russian market since it was commercially launched. A recent clinical study completed in Russia showed a significant effect of SkQ1 on a range of dry eye signs and symptoms for a diverse patient population. On top of that, there were no safety issues observed.
“The study showed that the drug protected cornea from damage, improved quality of the tear and made patients feel better at the same time,” said Natalia Perekhvatova, Chief Executive Officer of Mitotech. “But most importantly, feedback we are getting from the market is very positive, both from physicians and patients.”
Here in the US, the company has advanced the drug candidate past a successful Phase 2 clinical evaluation, and is getting ready for Phase 3 with the aim to score an FDA approval by 2020.
Mitotech isn’t stopping there. Because SkQ1 is a mitochondrial stabilizer that improves cellular function, its potential reaches far beyond just Dry Eye Disease. According to Dr. Ritch, mitochondria lie at the basis of all neurologic diseases – including Glaucoma, Alzheimer’s Disease, Huntington’s Disease, Parkinson’s Disease, and many others.
“When the mitochondria die, the cell dies,” Dr. Ritch says, “If you preserve the mitochondria in those diseases where mitochondria die, you improve those diseases.”
Capitalizing on this wide-open potential for its mitochondria-targeted antioxidant, Mitotech is already looking forward to launching a clinical program for an oral formulation of SkQ1 in the US. They are targeting Multiple Sclerosis first, then moving on to develop a formulation for Alzheimer’s and Parkinson’s. According to the company’s CEO, their scientists have conducted multiple animal experiments in neurodegenerative disorders where SkQ1 showed remarkable efficacy.
|Posted by australiandryeye on October 26, 2017 at 2:20 AM||comments (0)|
The FDA notified Cambium Medical Technologies that its phase 1 study of topical fibrinogen-depleted human platelet lysate for treatment of dry eye disease can proceed, according to a company press release.
Cambium filed an Investigational New Drug Application in late August for this potential early phase efficacy trial.
Experts stage prescription therapies for dry eye
“We are delighted this study is about to start,” Terence Walts, president and CEO of Cambium, said in the release. “We continue to believe the potential for a standardized, commercialized, allogeneic (vs. autologous) and eventually FDA-approved growth-factor enriched biologic for dry eye remains significant. It is possible therapies with not one a.i. but numerous nutritive/regenerative components targeting not one but several dry eye etiologies will eventually help clinicians better address the often de-habilitating symptoms of dry eye and among a broader patient population.”
With support from AventaCell BioMedical Technology Corp., Cambium hopes to begin enrollment at up to five U.S. clinical sites later this year.
|Posted by australiandryeye on October 24, 2017 at 7:00 PM||comments (0)|
LUXEMBOURG (PRWEB) OCTOBER 24, 2017
Mitotech S.A, a Luxembourg based biotechnology company marketing its Dry Eye drug Visomitin in Russia, announced positive data from their recent study involving a novel Dry Eye model. Dry Eye Disease has been associated with several biological factors including inflammation, decrease in tear quality and corneal damage. Only two active treatments have been approved by the FDA for this disease, both acting as anti-inflammatory agents. Currently there is clear need for a drug that would address other aspects of Dry Eye Disease in its underlying mechanism of action. Throughout several experiments including clinical studies and post-marketing studies Mitotech’s lead molecule SkQ1 demonstrated multifactorial effect on signs and symptoms of Dry Eye. In the latest series of studies in rabbits SkQ1 – a small molecule engineered to reduce oxidative stress inside mitochondria – showed versatile effect of SkQ1: corneal staining, tear break-up time (TBUT) and corneal healing rate were significantly improved compared to placebo treatment.
“We have data from clinical studies that demonstrated effect of SkQ1 on a variety of signs and symptoms of Dry Eye Disease. We have very positive feedback from the market in Russia having sold roughly 1 million units to date.”, said Natalia Perekhvatova, CEO of Mitotech S.A. “But we always look for new ways to get a deeper insight into biological processes behind this complex disorder so that we could help patients better. Main challenge of this particular work was rooted in developing a new large species model with reliable and natural progression of major signs of Dry Eye Disease over a short time frame. We are glad that the team behind this project selected SkQ1 for their studies and that their work produced positive results. This research project gave us additional confidence in commercialization path we are pursuing in the U.S.”
The project was a collaborative effort between several research institutes in Russia including laboratories of the Moscow State University. In one of the studies rabbits were subjected to general anesthesia with a follow-up recovery period. Dry Eye and associated corneal abrasions are typical side effects of such medical procedure. In this experimental model animals developed typical signs of Dry Eye reflecting multifactorial nature of the disease and they were topically treated either with placebo (an artificial tear) or SkQ1 ophthalmic solution. Statistical analysis showed significant benefit of SkQ1 in how quickly animals recover in terms of both corneal staining and TBUT with difference from placebo treatment evident as quickly as hours after the procedure (p-values as low as 0.0005). In a separate series of experiments rabbits were subjected to UV light-induced corneal damage and SkQ1 again was superior to placebo judging by the healing rate of corneal tissue over a course of just one week. Initial results produced by the project were recently published in Oxidative Medicine and Cellular Longevity Journal.
“Developing a drug with innovative mechanism of action that affects a spectrum of pathways at cellular level can be challenging”, said Dr. Anton Petrov, COO of the company “We think such research work can be very important in terms of future market positioning as we progress towards pivotal clinical study in the U.S.”.
About Mitotech S.A
Mitotech S.A. is a Luxembourg-based biotechnology company developing novel drugs for the treatment of predominantly age-related disorders. The core technology behind Mitotech products is based on a novel class of small molecules – mitochondria targeting cardiolipin peroxidation inhibitors. Company’s lead compound SkQ1 is being developed in several drug formulations covering a variety of therapeutic areas with major focus on ophthalmology and neurodegenerative diseases. Mitotech successfully completed Phase 2 clinical study for Dry Eye indication in the U.S. with other indications also approaching clinical stage of development.
|Posted by australiandryeye on October 24, 2017 at 7:00 PM||comments (0)|
Huons said Tuesday it has received approval from the Ministry of Food and Drug Safety to go ahead with domestic phase 3 clinical trials for HU007, a nanocomposite eye drops used for treating dry eye syndrome.
Dry eye syndrome is a common eye condition in which the eye surface gets damaged due to insufficient tear production or excessive tear evaporation. The number of patients suffering from the disorder is on the rise because of the increase of computers, smart devices, air conditioners, and heaters.
Huons 휴온스 plans to start phase 3 clinical trials by the end of this year and plans to get sales approval from the ministry by 2019.
The treatment has proved its safety and efficacy on anti-tear film protection and anti-inflammatory effect for dry eye syndrome after completing phase 2 clinical trials in April of last year.
Currently, anti-inflammatory cyclosporine monotherapy and eye-protecting hyaluronic acid monotherapy are the typical treatments for dry eye syndrome. However, Huons’ nanocomposite eye drops decreases the use of cyclosporine compared to the existing therapies, while improving the convenience of the medication by giving superior tear film protection and anti-inflammatory effects.
“The company plans to complete the phase 3 clinical trials on its nanocomposite eye drops, which will become the new force that drives the dry eye syndrome market,” said Um Ki-han 엄기안, CEO of Huons.
The dry eye syndrome global market is expected to grow to about 5.2 trillion won ($4.6 billion) in 2024, recording an annual growth rate of 7.9 percent. In the domestic market, the number of patients has doubled in the past 10 years, according to a report published by Health Insurance Review & Assessment Service (HIRA).
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|Posted by australiandryeye on October 24, 2017 at 6:55 PM||comments (0)|
Imprimis Pharmaceuticals has created subsidiary focused on dry eye disease. The offshoot, Surface Pharmaceuticals, plans to develop three formulations in ophthalmology indications fought over by companies including Allergan and Shire.
San Diego, California-based Imprimis is a pharmacy that provides proprietary compounded formulations. This line of work has led Imprimis to identify compounded drugs it thinks have a shot at winning approval under the FDA’s 505(b)(2) pathway and going on to claim market share. Surface is the manifestation of this thinking.
The spinoff starts life with three candidates and aspirations to develop them in five indications. One of the candidates, SURF-100, uses the immunosuppressant mycophenolic acid as its active ingredient. Another, SURF-200 or SURF-201 depending on the indication targeted, is based on the steroid betamethasone.
These two candidates both combine their active ingredients with Klarity, a topical ophthalmic gel or solution technology Imprimis picked up the rights to in April. Surface thinks combining Klarity with mycophenolic acid will result in a formulation capable of challenging Allergan’s Restasis and Shire’s Xiidra for the chronic dry eye disease market.
The betamethasone formulations are aimed at patients with episodic dry eye disease and post-cataract-surgery pain and inflammation.
Surface’s third candidate consists of low-dose doxycycline—a tetracycline antibiotic—and omega-3. The combination is based on the belief that omega-3 supplements may prevent symptoms of dry eye disease and that adding the fatty acids to the antibiotic sometimes used as second-line treatments of the disease may therefore improve outcomes.
The scientific and business rationales behind the candidates remain uncertain and unproven. But Surface thinks it can start to address some of the uncertainties relatively quickly and cheaply. The startup thinks it can have phase 2 data in all of the indications by the first half of 2020, with most of the readouts coming in 2019.
At $3.4 million to $5.5 million, the development of SURF-100 is forecast to be the biggest line item. Surface’s ability to make that investment rests on its ongoing fundraising efforts. Imprimis wants Surface to be funded outside of its operation. At the last count, the compounding pharmacy had $4.2 million in cash.
The creation of Surface comes four months after Imprimis’ first spinoff, Eton Pharmaceuticals, put together a $20 million series A.
Imprimis’ business development activities have taken place against a backdrop of difficulties for its core business. The FDA hit Imprimis with a warning letter in August after inspectors found fibrous material thought to be wood in a product compounded by the pharmacy. Inspectors also blasted Imprimis for having inadequate cleaning procedures and cross-contamination controls.
The FDA issued a separate warning in August after a patient died following administration of a curcumin emulsion compounded by Imprimis.
Shares in the company are down almost 40% over the past year.
|Posted by australiandryeye on October 22, 2017 at 11:30 PM||comments (0)|
Australian and Israeli-based biotech startup Azura Ophthalmics has raised $US16 million ($20 million) to fund treatments for a disease many in the startup world may not be aware of, but which affects 300 million people worldwide: meibomian gland dysfunction, a leading cause of dry eye disease.
Meibomian gland dysfunction (MGD) is responsible for at least 70 percent of dry eye cases, according to Azura Opthalmics chief executive Marc Gleeson, who says there are currently no pharmaceutical treatments available for this uncomfortable condition.
The meibomian gland produces a lipid that protects the eyeball with a thin film, and plays an integral role in vision quality, according to Gleeson. In post-menopausal women and people with autoimmune deficiency, however, the eye’s surface can often deteriorate as individuals age, causing discomfort and damage to the eye.
“We believe we are the only company developing a pharmacological agent to treat this,” Gleeson tells StartupSmart.
“A lot of research to date has been associated with the inflammation associated with the end stage [of MGD], but we are targeting the upstream so we can prevent the downstream effects,” he explains.
The startup will use the $20 million raised to conduct clinical trials in Australia for a pharmacological product that will treat MGD by repairing dysfunctional meibomian glands. The trial will be conducted with 120 MGD patients in collaboration with the University of New South Wales and the University of Melbourne, as Azura looks to get the product approved by the US Food and Drug Administration (FDA).
The startup raised the funding from Brandon Capital’s Medical Research Commercialisation Fund (MRCF), TPG Biotech, OrbiMed and US family fund Ganot Capital, after previously raising $US1.2 million in a Series A round in 2014 from Ganot Capital and Israel’s Elron Industries, Gleeson says.
Investors keen to cash in on medtech
Gleeson says in Australia there is definitely “a lot more willingness to invest in biotech and medtech” with interest in the space from both the government and private sectors.
“There’s definitely willingness at a policy level as well as at a VC level to invest, and it’s an attractive environment,” he says.
“There’s been successes for investors [through exists] that continues to breed and energise the sector.”
As one of the largest capital raises for a biotech startup this year, Gleeson admits this deal didn’t happen overnight, but rather required patience in seeking out the right investors that fit well with the company’s future ambitions.
For startups similarly operating in the biotech or medtech sphere, where the problem you’re solving can’t be as easily described as ‘the Uber for’ something, Gleeson advises being clear and concise when pitching to investors.
“Make sure that the fundamental basis of the tech is clear, and try and limit the ambiguity around what you’re trying to do so everyone has a clear understanding of the steps to success and the incremental milestones along the way,” he says.
Laying out detailed, achieveable milestones is crucial to communicating your startup’s vision for the future, Gleeson says, adding that the process of innovation “only happens in incremental steps”
Australia’s attractive regulatory environment
While Azura was founded and headquarted in Israel, Gleeson, who is Sydney-based, says the startup decided to incorporate in Australia because it could leverage research incentives to support its clinical trials.
Gleeson says the company’s founder, Yair Alster, decided to conduct trials and develop the treatment in Australia because of its “attractive regulatory environment for early-stage clinical trials”.
Alster had previously undertaken clinical work in Australia for his previous startup, Forsight Vision5, and the experience opened his eyes to Australia’s “favourable regulatory environment”, Gleeson says.
Gleeson also points to the government’s R&D Tax Incentive, which sees eligible companies undertaking research and development in Australia receiving a refundable tax offset, as offering an attractive way for Azura to “preserve valuable capital”.
When paired with internationally-recognised universities, clinicians and research facilities, he says Australia was an attractive market for the startup to lay down roots.
“There are world-leading clinicians in this area, and when you couple that with the attractive regulatory environment, we can do it [develop our product] in a capital and time efficient manner in Australia,” Gleeson says.
|Posted by australiandryeye on August 5, 2017 at 4:30 AM||comments (0)|
After a long day of working at the computer, scratchy contact lenses are not only painful, over longer periods of time they can also damage ocular tissue. Relief may be in sight from a natural mucus component referred to as a mucin. A team from the Technical University of Munich (TUM) has now succeeded in demonstrating that contact lenses coated with purified porcine gastric mucin do not cause damage to the eye anymore.
Mucins are molecules capable of binding lots of water, thus they can act as a natural lubricant. Our tears contain such mucins, which also occur in the mucous layer protecting the stomach and intestines. The tear fluid of patients suffering from dry eyes usually does not contain enough of this molecular lubricant, the mucin MUC5AC.
Such a lack of MUC5AC can be problematic in particular for those of us who wear contact lenses: Without a protective lubricant film between the eye and the contact lens, the tissue of the cornea can be injured. Thus, a group of scientists led by Prof. Oliver Lieleg, professor for Biomechanics and head of the "Biopolymers and Bio-Interfaces" lab at the Munich School of BioEngineering, had the idea to apply the missing mucin directly to the contact lens.
Mucin coating prevents tissue damage
For their experiments, the researchers needed large quantities of the molecule, which eliminated human tears as a possible source. Therefore, the team optimized a method for isolating the necessary mucin MUC5AC from the stomachs of pigs. The chemical structure of this pig mucin is very similar to the human molecule. The purification procedure has to be conducted carefully to ensure that the purified molecule retains its characteristic property as a lubricant and does not suffer from chemical changes during the purification process. "Most of the commercially available mucins, which are already used e.g. for the treatment of oral dryness, have lost exactly this ability; we were able to demonstrate this in a series of experiments. These commercial mucins are therefore not suitable for treating dry eyes," Lieleg explains.
In experiments with porcine eyes they tested how their lab-isolated mucins affected the performance of contact lenses. Oliver Lieleg's team was able to prove that the lenses caused no tissue damage when they were coated with mucins. "We showed that the mucin passively adsorbs to the contact lens material and forms a lubricating layer between the contact lens and the cornea," explains Benjamin Winkeljann, first author of the study. Thus, in the opinion of the scientists, it should be sufficient to soak the contact lenses overnight in a mucin solution to obtain the protective effect.
Long-term protection without applying eye drops
The mucin coating offers several advantages: Conventional products for treating dry eyes are primarily based on hyaluronic acid. However, in contrast to mucin, this molecule does not occur naturally in the tear fluid. Also, hyaluronic acid has to be applied to the eye in the form of drops, requiring repeated applications throughout the day. Mucin, on the other hand, adheres directly to the contact lens, thus providing the eye with long-term protection. Before it is ready for application in humans, the pig stomach mucin will undergo further testing in the lab.
|Posted by australiandryeye on August 5, 2017 at 4:25 AM||comments (0)|
Putting carboxymethylcellulose sodium in one’s eyes two, three or more times a day may not sound like a great experience. But I can assure you that it can be. Drops of this chemical, called a topical lubricant, help to keep my eyes from burning, avoiding bright lights, becoming red and itchy, and generally feeling miserable.
Like tens of millions of Americans, especially women older than 50, I have dry eye disease, medically known as keratoconjunctivitis sicca. Fortunately, my problem is not severe, certainly not as bad as that of an elderly woman I know who has to use a nightly ointment of mineral oil and Vaseline, which minimizes the dryness but temporarily blurs her vision.
The drops I use, an over-the-counter preservative-free product called Refresh Plus (also sold as generic store brands) that I carry with me at all times, are a crucial measure I take to keep my eyes from becoming overly dry and chronically irritated — but not the only one.
To minimize the drying effect of wind when driving, cycling or sitting in a room cooled by a fan or air-conditioning, I wear wraparound glasses even when I don’t need them to see clearly. Watertight goggles are de rigueur when swimming, even in fresh water. And I refresh my eyes with drops when I watch a movie, work long hours at the computer, or do any activity that depresses the frequency of blinking, which moistens the eyes.
Dry eye is sometimes referred to as “a nuisance complaint — it’s not the sexiest of eye problems,” Dr. Rachel Bishop, chief consulting ophthalmologist at the National Eye Institute, told me. Nonetheless, she said, “Dry eye disease deserves serious professional — and personal — attention. It can be very debilitating and seriously diminish a person’s quality of life.”
Read more at:
|Posted by australiandryeye on July 13, 2017 at 6:25 AM||comments (0)|
University of Virginia Health System researchers have developed a potential therapeutic treatment for dry eye, with human testing to start in March. The drug differs from other treatments of dry eye in that it aims to treat the cause of dry eye instead of masking the symptoms.
The drug, trademarked as "Lacripep," is a topical eye drop that functions differently from conventional approaches. Rather than seeking to suppress inflammation – an approach with mixed results – Lacripep aims to eliminate inflammatory triggers by restoring the natural basal tearing mechanism and health of cells in contact with tears. This includes restoration of the nerves on the cornea of the eye, which signal the brain to produce more tears. It also stabilizes the tear film that in dry eye is very unstable.
Each dose of Lacripep remains in tears rather than being washed away, explained its developer, UVA dry eye research specialist Gordon Laurie of the UVA School of Medicine's Department of Cell Biology.
"Most ophthalmic drugs are washed away right away, but that's not the case here. Lacripep is still in the tears 24 hours later, because it goes into the lipid layer and apparently comes out of the lipid layer slowly to treat the eye," Laurie said.
Dry eye affects between 5 percent and 9 percent of the population, with that number increasing to around 35 percent in older women. The condition can occur due to hormonal imbalances, malfunctioning aqueous tear production or lipid production, and general inflammation of the eye. Current treatments aim to suppress the pain and damage caused by dry eye, including steroids to control inflammation, antibiotics and artificial tears.
But these are temporary fixes that do not treat what may be the root cause of the disease – a shortage of the tear protein lacritin – and often lead to frustration and pain for people with the condition. Lacripep is a short synthetic fragment of lacritin. If successful, Lacripep would be the first drug to treat that cause of dry eye.
"We think that dry-eye disease may be much simpler than people have thought in the past, sort of like insulin and type I diabetes," Laurie said. "With lacritin deficient in dry-eye tears, topical Lacripep is a replacement therapy, which will probably not cure the disease. You would still have to keep treating your eyes, but maybe just once a day."
The small-scale clinical trial, called a Phase I/II clinical trial, will begin in March at 25 clinical sites nationwide. More than 200 patients will be recruited. The patients will use two different dosages of Lacripep or placebo three times daily for four weeks. If safe and effective, testing will then expand to a much larger Phase III trial. Should that prove successful, the Food and Drug Administration could consider making the drug available as a treatment.
Laurie's Charlottesville company, TearSolutions Inc., has contracted with Lexitas Pharma Services in Durham, North Carolina, to run the clinical trial. The first trial will accept only patients with Sjögren's syndrome dry eye.
|Posted by australiandryeye on June 21, 2017 at 8:30 AM||comments (0)|
Register at: https://www.vantagestream.tv/nvlsop17/
|Posted by australiandryeye on June 9, 2017 at 4:05 AM||comments (0)|
The pharmaceutical Company Sylentis (PharmaMar Group) has announced the start of the first Phase III study, HELIX, with the investigational new drug, SYL1001 for the indication of dry eye syndrome. The Company has agreed with the U.S. Food and Drug Administration (FDA) on plans for the Phase III clinical program, which is designed to support the submission of a New Drug Application (NDA). The Company has received final, End-of-Phase II meeting minutes from the FDA.
SYL1001 is an advance in the development of innovative compounds in different therapeutic fields, through the novel technology of gene silencing, based on RNA interference (RNAi). In the HELIX study, more than 30 centers from 5 European countries (Spain, Germany, Estonia, Portugal and Italy) will participate with the objective of evaluating the effect of the ophthalmological solution SYL1001 for improvements in the signs and symptoms of dry eye syndrome in about 300 patients an area in which few therapeutic options exist today. SYL1001 is a compound based on RNAi being administered in the form of eye drops that block the synthesis of a receptor implicated in the pathology of dry eye syndrome.
Pharma Mar SA
Patients with dry-eye syndrome suffer the chronic loss of lubrication and hydration on the ocular surface. The risk of developing this disorder increases in 35% every decade thereafter. Around the world, 344 million people suffer from this syndrome.
Dry eye syndrome is characteristic in people that live in developed countries and is caused by pollution, air conditioning, the use of contact lenses, refractive eye surgery or the continued use of computers. The most common symptoms of this pathology are burning, a constant itching, eye fatigue, dryness, blurred vision, the sensation of having a foreign body or eye pain, are some of the symptoms
As explained by Dr Ana Isabel Jimenez, COO and Director of R&D at Sylentis, "the RNA interference on which we are working, could improve the signs and symptoms for patients that suffer from this syndrome, given that this compound could reduce the inflammatory parameters of the eye´s surface, could improve the quality of the tear and could reduce the ocular pain associated with dry eye syndrome. We consider that our molecule SYL1001 could be a very effective and important therapeutic alternative for these patients".
The Company is working on the investigation of new treatments for ophthalmological and inflammatory illnesses. "Up to today, the line of work in which we have more rapidly advanced in is in ophthalmology, for the treatment of illnesses such as dry eye syndrome, glaucoma, ocular allergies and illnesses of the retina", added Dr Jimenez.
What is RNA interference?
RNA interference is an innovative technology that looks for a reduction in the anomalous production of protein, silencing the RNA Messenger. The RNAi provides a step forward, as it provides a new mechanism of action to confront numerous pathologies. Nowadays there are two marketed products based on this technology and there are several drugs in different phases of clinical development.
Pathologies, such as dry eye syndrome, are produced by an alteration in certain proteins. Through this technology, the production of proteins that take part in various pathologies could be decreased or very specifically controlled.
HELIX, a clinical trial study
With the purpose of progressing in this field, Sylentis has begun the multicenter, random, controlled and double blind Phase III clinical trial in more than 30 hospitals in Spain, Germany, Estonia, Portugal and Italy. The trial, in which 300 patients are going to be enrolled will evaluate the efficacy of the product patented by Sylentis, SYL1001, in the treatment of the signs and symptoms of dry eye disease.
For more information about the clinical trial: https://clinicaltrials.gov/ct2/show/NCT03108664?term=SYL1001&rank=2
For more information (only available in Spanish)
Whats is RNA interference? https://youtu.be/T21N_dPM0_k
Dry eye syndrome: https://youtu.be/R-h_4_Yyq2g
1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf, 2007. 5(2): p. 75-92
2. Martínez T, Jimenez AI, Pañeda C. Short-interference RNAs: becoming medicines. EXCLI Journal, 2015;14:714-46
3. Pañeda C, González V, Martínez T, Ruz V, Vargas B and Jimenez AI. RNAi based therapies for ocular conditions. In Proceedings of the 11th ISOPT,2014, 25-30, Medimond, Bologna, Italy
4. Benitez-Del Castillo JM [https://www.ncbi.nlm.nih.gov/pubmed/?term=Benitez-Del-Castillo%20JM%5BAuthor%5D&cauthor=true&cauthor_uid=27893109 ], . Protocol No.: SYL1001_IV. EUDRACT No: 2016-003903-79. A double-masked study of SYL1001 in patients with moderate to severe dry eye disease (DED). HELIX Study (Phase III). Version 1.1: December 14th, 2016. Sylentis SAU-Pharma Mar Group
CONTACTS : Media Relations (+34-638-79-62-15) and Investor Relations (+34-914444500)
|Posted by australiandryeye on June 9, 2017 at 4:00 AM||comments (0)|
LEXINGTON, Mass., June 6, 2017 /PRNewswire/ -- Aldeyra Therapeutics, Inc. (NASDAQ: ALDX) (Aldeyra), a clinical-stage biotechnology company devoted to treating inflammation, inborn errors of metabolism, and other diseases related to aldehydes, today announced that it has enrolled the first patient into a Phase 2a clinical trial of topical ocular ADX-102 for the treatment of Dry Eye Disease (DED).
"Dry Eye Disease is a common ocular inflammatory condition with high unmet medical need, representing one of the largest ophthalmic markets worldwide," commented Todd C. Brady, M.D., Ph.D., President and CEO of Aldeyra. "Based on the success of ADX-102 in two ocular inflammation Phase 2 clinical trials announced last year, we are pleased to initiate clinical development in this disease, and we expect to report results in the third quarter of this year."
ADX-102 and other product candidates generated from Aldeyra's aldehyde trap platform sequester and facilitate the degradation of aldehydes, a class of endogenously generated pro-inflammatory mediators that are elevated in DED patients. The Phase 2a clinical trial will test three formulations of topical ocular ADX-102 over 28 days of dosing. Endpoints will include standard signs and symptoms characteristic of DED.
A clinical trial synopsis is available on clinicaltrials.gov (NCT03162783).
About Aldeyra Therapeutics
Aldeyra Therapeutics, Inc. is a biotechnology company devoted to improving lives by inventing, developing and commercializing products that treat diseases thought to be related to endogenous aldehydes, a naturally occurring class of pro-inflammatory and toxic molecules. Aldeyra's lead product candidate, ADX-102, is an aldehyde trap in development for ocular inflammation, as well as for Sjögren-Larsson Syndrome and Succinic Semi-Aldehyde Dehydrogenase Deficiency, two inborn errors of aldehyde metabolism. Aldeyra's product candidates have not been approved for sale in the U.S. or elsewhere.
About Dry Eye Disease
Dry Eye Disease is a common inflammatory disease characterized by insufficient moisture and lubrication in the anterior surface of the eye. Symptoms may include ocular irritation, burning or stinging, and, in severe cases, decreased vision. In patients with Dry Eye Disease, aldehydes may contribute to ocular inflammation as well as the impairment of lipids (fats) that lubricate the surface of the eye.
Lamellar Biomedical Recruits First Patients Into Clinical Study Assessing LAMELLEYE for Treatment of Dry Eye Disease
|Posted by australiandryeye on June 9, 2017 at 4:00 AM||comments (0)|
Lamellar Biomedical, a biotechnology company developing a range of patent-protected medical and pharmaceutical products, based on its LAMELLASOME™ technology, announces the recruitment of the first patients in a clinical study assessing LAMELLEYE for the treatment of moderate to severe Dry Eye Disease (DED). Moderate to severe DED is a significant clinical problem for which there are no effective treatments that tackle the underlying cause.
LAMELLEYE is designed to provide unique lubricating properties to patients with DED based on LAMELLASOME[TM] technology's ability to mimic the actions of serous lamellar bodies. The new study will assess the clinical utility of LAMELLEYE and compare its performance with Optive Plus, a leading over-the-counter eye-drop for patients with DED.
The single-blind, randomised, cross-over study will recruit 30 patients and the results are expected to be reported in the second half of 2017. The study aims to collect clinical follow-up data on the use of LAMELLEYE and to assess the relative effectiveness of LAMELLEYE compared with the Optive Plus comparator eye drop. Outcomes include: non-invasive tear breakup time, symptom scores, rate of tear film evaporation (evaporimetry) and effect on the structure and quality of the tear film (interferometry).
LAMELLEYE is a medical device, which received an EU CE mark in 2015.
Dr. Alec McLean, CEO of Lamellar Biomedical said, "We believe that LAMELLEYE has the potential to be an important advance in the treatment of DED given the unique lubricating properties of our LAMELLASOME[TM] technology. We anticipate that this new study will provide conclusive evidence of the clinical benefits that LAMELLEYE can deliver and demonstrate its superiority over an existing product for the relief of dry eye disease. We are looking forward to announcing the results of the study later this year, as they will be used to support the commercialization of this exciting new treatment in Europe in 2018, through a partner."
Lamellar Biomedical has recently concluded a £5.75 million fundraising, which was led by Invesco and supported by the Scottish Investment Bank.
About Dry Eye Disease (DED)
The major cause of Dry Eye Disease (DED) is when the outer lipid layer is deficient, allowing the eye to dry due to increased evaporation.
The consequences of DED are multiple, including symptoms of discomfort, burning and of grit in the eye. Visual disturbance is common with potential for damage to the cornea including long-term scarring and subsequent loss of vision. In severe cases Filamentary Keratitis can develop. This is a painful lesion where mucus filaments stick to the corneal surface and with each blink, the eyelids tug at the filaments, stimulating pain-sensitive corneal nerves.
The market for dry eye products is large and growing encompassing prescription and OTC products which in aggregate generate sales in excess of US$2 billion per annum and which are anticipated to grow significantly.
About Lamellar Biomedical
Lamellar Biomedical is the only company globally focused on LAMELLASOME[TM] technology (micron-scale lipid vesicles), which has multiple medical applications.
Lamellar Biomedical's development pipeline includes a number of patent-protected medical devices and pharmaceuticals targeting Dry Eye Disease, Dry Mouth in Head and Neck cancer, Cystic Fibrosis and Infection. These are all conditions that are poorly served by current medications and therefore represent areas of high value unmet medical need.
LAMELLASOME[TM] technology produces mimetics of human serous lamellar bodies. These regulate the internal interfaces between human tissues as well as the interfaces between tissues and the external environment as in the mouth and lungs. They act biophysically, are muco-restorative and have the potential to resolve a broad range of disease states that are associated with dry or sticky mucosal surfaces and topical infection.
Lamellar Biomedical is based near Glasgow, Scotland. It has been financed by a range of investors including Invesco, Scottish Enterprise, Barwell and TRI Capital. In March, the Company raised £5.75 million in a Series C fund raising.
For more information please visit: http://www.lamellar.com
For further information, please contact:
Dr. Alec McLean
Citigate Dewe Rogerson
David Dible / Shabnam Bashir
SOURCE Lamellar Biomedical
|Posted by australiandryeye on June 9, 2017 at 12:20 AM||comments (1)|
AustralianDryEye is currently in the process of developing new webstore to retail products specifically for the needs of dry eye patients.
Stayed tuned for updates.
|Posted by australiandryeye on May 14, 2017 at 6:50 AM||comments (0)|
ROCKVILLE, Md., May 9, 2017 /PRNewswire/ -- RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX) ("the Company" or "RegeneRx"), a clinical-stage drug development company focused on tissue protection, repair and regeneration, announced that its joint venture, ReGenTree LLC, presented the results of its ARISE-1 Phase 2b/3 dry eye clinical trial in a poster session to physicians, scientists, and analysts today at the 2017 ARVO meeting in Baltimore, Maryland.
As previously reported, the double-masked, placebo-controlled trial in 317 patients with dry eye syndrome demonstrated that after 28 days of treatment, RGN-259 was safe and significantly reduced ocular discomfort both during and after exposure to a controlled adverse environment (CAE®;). Ocular discomfort is a symptom of dry eye syndrome. ReGenTree also reported that after 28 days of treatment RGN-259 significantly reduced total and inferior corneal fluorescein staining in a subgroup of subjects with compromised baseline tear film break-up time, which is a sign of dry eye syndrome. Both symptom and sign improvements are typically required by FDA to obtain marketing approval of a pharmaceutical treatment for dry eye.
A second Phase 3 dry eye trial (ARISE-2) designed to reproduce the results seen in ARISE-1 is currently underway in the U.S. with over 500 patients. The trial is expected to be completed by the fall of 2017.
About RGN-259 for the Treatment of Dry Eye Syndrome
RGN-259 is a sterile, preservative-free topical eye drop for ophthalmic indications whose active ingredient is Thymosin beta 4 (Tβ4). Based on U.S. Phase 2 and Phase 2b/3 clinical trials in moderate and severe dry eye syndrome, RGN-259 is safe and found to show statistically significant improvements in several signs and symptoms of dry eye, as well as positive trends in other outcome measures. The data from these trials, as well as a previously completed clinical trial of RGN-259 in patients with NK, reflect RGN-259's mechanisms of action, support the "protective" effects of RGN-259, and provide FDA-approvable clinical endpoints to be targeted in these and any future clinical trials. Dry eye syndrome is a multifactorial disease and it is well known that Tβ4 can elicit a spectrum of therapeutic responses, including promotion of cell migration and proliferation, reduction of inflammation and acceleration of corneal epithelial growth and would represent a major step forward from current treatment options.
About RegeneRx Biopharmaceuticals, Inc. (www.regenerx.com)
RegeneRx is focused on the development of novel therapeutic peptides, including Thymosin beta 4 (Tβ4) and its constituent fragments, for tissue and organ protection, repair and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac and dermal indications, three active strategic licensing agreements in the U.S., China, and Pan Asia (Korea, Japan, and Australia, among others), and has patents and patent applications covering its products in many countries throughout the world. RGN-259, the Company's Tβ4-based ophthalmic drug candidate, has been designated an orphan drug in the U.S. for the treatment of neurotrophic keratopathy (NK). In March 2016, RegeneRx, through its U.S joint venture, ReGenTree LLC, completed a 317-patient Phase 2b/3 clinical trial in patients with dry eye syndrome. The dry eye trial results were announced in May 2016 and ReGenTree subsequently received permission from the U.S. FDA and has initiated a second Phase 3 trial in approximately 500 patients that is expected to be completed in the fourth quarter of 2017. ReGenTree is simultaneously conducting a 46-patient Phase 3 clinical trial in patients with NK. RGN-259 is also being developed in patients with dry eye syndrome in Asia through RegeneRx's two Asian partnerships. RGN-352, the Company's Tβ4-based injectable formulation, is a Phase 2-ready drug candidate designed to be administered systemically to prevent and repair cardiac damage resulting from heart attacks and central nervous system tissue damage associated disorders such as multiple sclerosis and traumatic injuries such as stroke. For additional information about RegeneRx please visit www.regenerx.com.
About ReGenTree LLC
ReGenTree is a U.S. joint venture company owned by GtreeBNT Co., Ltd, and RegeneRx Biopharmaceuticals, Inc. specifically to develop RGN-259 in the U.S. and Canada for ophthalmic indications. ReGenTree licensed the rights to RGN-259 from RegeneRx in 2015. While G-treeBNT is the majority owner of ReGenTree, RegeneRx retains a significant minority interest in the joint venture, in addition to a royalty on commercial sales, and is represented on the board of ReGenTree. Certain commercial and financial transactions require RegeneRx approval. G-treeBNT is responsible for operations of the venture and all funding required for clinical development of RGN-259 in the U.S. For additional information about ReGenTree, please visit www.regentreellc.com.
Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Forward-looking statements used in this press release relate to, among other things, the quality of clinical data, the activity of the active ingredient in our product candidates, and the expected timing of initiation and completion clinical trials in the United States and the potential benefits to RegeneRx of such trials. There can be no assurance that any proposed clinical trial will start within the estimated initiation timeframe or be completed within the estimated timeframe or that positive results from any clinical trials or research by the Company, its collaborators, or independent parties in the U.S. or any other country will result in subsequent clinical confirmation or future value. There can also be no assurance that any of the Company's drug candidates will result in any approved products in the U.S. or any other country. Please view these and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"), including those identified in the "Risk Factors" section of the annual report on Form 10-K for the year ended December 31, 2016, and subsequent quarterly reports filed on Form 10-Q, as well as other filings it makes with the SEC. Any forward-looking statements in this press release represent the Company's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information, as a result of future events or otherwise, except as required by applicable law.
SOURCE RegeneRx Biopharmaceuticals, Inc.