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Azura Ophthalmics Raises US$20 Million for Registration Studies for Treatment of Leading Cause of Dry Eye Disease

Posted on November 7, 2020 at 5:55 PM

Azura Ophthalmics Ltd., a clinical-stage company developing innovative therapies for Meibomian gland dysfunction (MGD) and related eye diseases, today announced a US$20 million financing. The round was led by a syndicate of existing investors including OrbiMed, TPG Biotech, Brandon Capital’s Medical Research Commercialization Fund (MRCF) and Ganot Capital.

 

On the back of encouraging Phase 2 data to date proceeds from the funding round will be used to advance Azura’s lead product candidate AZR-MD-001 through a registration study for the treatment of MGD – an eye condition where the Meibomian glands become dysfunctional, resulting in rapid evaporation of the tear film.

 

Azura’s novel medicines in development are designed to address abnormal hyperkeratinization – the build-up and shedding of the proteins at the opening of the Meibomian gland or within the gland itself – known to be the root cause of obstructive MGD. This approach has been used safely and effectively for decades in dermatology and is based on the understanding that Meibomian glands share strong similarities with sebaceous glands, skin glands responsible for conditions like acne, including the ability to undergo keratinization.

 

Meibomian gland dysfunction is the leading cause of evaporative Dry Eye Disease, a condition known to affect more than 30 million adults in the United States alone presenting a huge unmet need globally.1,2

 

“The current options we have to treat patients with Meibomian gland dysfunction focus primarily on relieving obstruction and have not focused on the role of keratin within meibum. There are millions of patients with ocular surface disease and MGD worldwide; we need better treatments to help our symptomatic patients,” said Dr. Preeya K. Gupta, clinical medical director of Duke Eye Center at Page Road and associate professor of ophthalmology at Duke University Eye Center. “The promise of Azura’s dermatological approach lies in its ability to open the glands, increase lipid production and restore tear-layer health, as well as preventing disease progression in patients with Meibomian gland dysfunction.”

 

Azura’s lead compound AZR-MD-001 is a topical ointment applied to the lower lid that has shown a positive safety and efficacy profile in several studies in MGD. Based on these data and interactions with the U.S. Food and Drug Administration (FDA), the company plans to proceed to registration studies in 2021.

 

“We are thrilled to enter 2021 with the additional funding that will allow us to conduct the studies needed to build a strong body of clinical evidence for our approach, so we can seek FDA approval for the first ophthalmic keratolytics for the treatment of Meibomian gland dysfunction,” said Marc Gleeson, CEO of Azura. “We are grateful for the support of our investors who share our conviction that Azura’s medicines in development have the potential to transform treatment and provide hope to millions of patients suffering from unresolved eye conditions.”

 

“The investor syndicate believes in Azura and in its team’s ability to bring promising ocular products through approval and ultimately commercialization. The company is led by strong repeat entrepreneurs and industry veterans who have proven astute and resourceful in constructing an elegant pipeline and executing on efficient yet robust trials that have enabled swift progress,” said Dr. Chris Nave, managing director at Brandon Capital. “The investor syndicate is committed to continuing to support the advancement of Azura’s innovative pipeline as they create medicines to target Meibomian gland dysfunction and related conditions that impact the ocular health of millions of people around the world.”

 

 

About Meibomian Gland Dysfunction

 

Meibomian gland dysfunction (MGD) is the leading cause of Dry Eye Disease (DED), a condition known to affect more than 30 million adults in the United States alone.2 MGD is a chronic, diffuse abnormality of the Meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion.3 There are no approved prescription pharmaceutical agents that specifically treat these glandular changes. If left untreated, MGD will alter the tear film, resulting in damage to the front of the eye and severe discomfort from associated ocular surface diseases. Though there are treatments on the market for ocular surface diseases, many patients still suffer from dry eye, and research shows that hyperkeratinization of the Meibomian glands is the underlying cause of the disease.4 There are currently no approved medicines for MGD.

 

 

About AZR-MD-001

 

Azura Ophthalmics has a robust clinical development pipeline investigating the reformulated, prescription-strength SeS2 (Selenium Disulfide). The company has a pipeline of new chemical entities in pre-clinical through Phase 2 development for a number of ocular and lid margin diseases, including Meibomian gland dysfunction, acute use for Meibomian gland dysfunction, Inflammatory/Aqueous Deficient Dry Eye, Blepharitis, contact lens discomfort and ocular manifestations of Graft versus Host Disease (GvHD).

 

Azura’s lead product candidate, AZR-MD-001, is a topical ointment that has been developed to yield properties ideal for ophthalmic use. The formulation would be applied to the lower lid margin before bedtime. Azura is currently evaluating the safety, tolerability and effectiveness of AZR-MD-001, developed for ophthalmic use, in a Phase 2 study in patients with MGD and evaporative DED.

 

AZR-MD-001 leverages SeS2 as the active ingredient. SeS2 has a triple mechanism of action: it slows down keratin production; breaks down the bonds between abnormal keratin proteins; and increases the quantity of lipid produced by the Meibomian glands. If approved, AZR-MD-001 will be a first-in-class ophthalmic keratolytic for the treatment of lid margin diseases, starting with Meibomian gland dysfunction and contact lens discomfort.

 

Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol. 2014;157(4):799–806.

U.S. Census

Nichols et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary IOVS, Special Issue 2011, Vol. 52, No. 4

Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1938-78.

 

 

Media Contact:

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Sierra Smith

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References


https://azuraophthalmics.com/press-releases

Kala Pharmaceuticals Announces FDA Approval of EYSUVIS

Posted on October 27, 2020 at 9:30 AM

Kala Pharmaceuticals, Inc. a biopharmaceutical company focused on the discovery, development and commercialization of innovative therapies for diseases of the eye, today announced that the U.S. Food and Drug Administration (FDA) has approved EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease.


“The FDA approval of EYSUVIS as the first prescription therapy specifically developed to address the short-term treatment needs of people living with dry eye disease is a major accomplishment for Kala and an important moment for patients, who have been waiting for an FDA-approved, safe, effective and fast-acting therapy,” said Mark Iwicki, Chairman, President and Chief Executive Officer of Kala Pharmaceuticals. “As we prepare to launch EYSUVIS, we will leverage our strong foundation of highly experienced ophthalmology marketing, sales and market access professionals with the goal of establishing EYSUVIS as the preferred, first-line prescription therapy for dry eye disease. We’d like to thank the many patients and investigators that were involved in the clinical trials that led to this important milestone.”


Read More at: https://investors.kalarx.com/news-releases/news-release-details/kala-pharmaceuticals-announces-fda-approval-eysuvistm-short-term?fbclid=IwAR0I9eCPVS0tyD4ezU76_cszodIZc8QfoFP3sLTFEybpbWyVKk93SJmSzfc

Grafton Optical to launch new dry eye products

Posted on March 26, 2018 at 8:05 AM

Grafton Optical will launch SBM Sistemi’s Ocular Surface Analyser and the i-Pen Tear Film Osmolarity System by i-Med Pharma at Optrafair (14–16 April, Birmingham NEC).


The i-Pen is a hand-held electronic device designed to detect and indirectly measure the elevated tear film osmolarity levels associated with dry eye disease.


The in-practice screening device can be used for patients presenting with dry eye symptoms, as well as pre and post-surgery patients.


SBM Sistemi’s Ocular Surface Analyser provides a full assessment of the ocular surface through a combination of tests for dry eye disease.


It analyses the Meibomian glands and enables the practitioner to carry out tear film interferometry screening.


The integrated software allows the user to analyse the functional and non-functional areas, and to evaluate the extension of the affected areas.


For further information, visit the Grafton Optical website.

https://www.aop.org.uk/ot/industry/equipment-and-suppliers/2018/03/23/grafton-optical-to-launch-new-dry-eye-products

Can cannabis succeed where other compounds have failed

Posted on November 20, 2017 at 8:15 PM

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.

Research implications


‘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.

References


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


E: philipp.steven@uk-koeln.de


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.


Biotech startup Azura Ophthalmics raises $20 million to cure dry eye disease

Posted on October 22, 2017 at 11:30 PM

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.


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