Naheed Kurji, President and CEO

During the past four years, closely-held Cyclica has developed and validated a patented structure-based and AI-augmented proteome-screening platform, known as Ligand Express. 

“The platform enables critical insights into the polypharmacology of small molecules, which is useful in identifying novel targets, target deconvolution, lead prioritization, and drug repurposing,” president and CEO, Naheed Kurji, says in an interview with BioTuesdays.

“We believe that AI will undeniably play a future in the role of Pharma R&D, but that it is one piece of a much bigger puzzle,” he adds.

With the Ligand Express platform, Mr. Kurji says scientists can filter and sort data, and visualize and interact with protein-ligand structures in real-time to gain a panoramic view of their small molecules.

“We have built an enabling platform that when used by bench scientists enhances their R&D productivity by helping them take more steps in the right direction, and fewer steps in the wrong direction,” he adds.

The team at Cyclica, which was founded in 2014, consists mainly of biophysicists and computational physicists.

According to Mr. Kurji, the pharmaceutical sector is facing a productivity issue. Cyclica, together with its partners, has the opportunity to reduce the risk of pharmaceutical R&D to get life-saving drugs to the market faster and cheaper, he contends.

He also suggests that the problem with conventional drug discovery is that the focus is on how a given drug candidate interacts with one biological target. “It’s like one lock and millions of keys, and trying to find the key that opens the lock.”

Drug Development Pain Points

In reality, he says a given drug candidate can interact with up to 300 biological targets, many of which are considered off-target interactions, so the key can open more than one lock. “Understanding these off-target interactions is important in understanding potential downstream side-effects, which is why many drugs fail,” he adds.

Mr. Kurji points out that the scientific value proposition of Ligand Express is that it enables the discovery of proteome-wide drug polypharmacology, or off-target effects, for any disease, providing critical insights for R&D.

“By identifying off-target effects through an in silico [computational] approach, Ligand Express can save significant R&D time and cost, which can then be allocated to other drug development initiatives.”

Ligand Express™ Workflow in Action

Cyclica operates in the pharmaceutical, nutraceutical and personal/beauty care markets, with the latter two largely untapped by in silico to date, he adds.

Looking forward, he says Ligand Express is not just a technology platform that is used to solve a few important R&D problems, “Instead it is a cloud-based infrastructure that enables us to innovate and integrate novel solutions to create and capture significant value.”

Cyclica's Vision to Redefine Drug Discovery

Cyclica’s vision is to offer an integral-enabling platform to transform pharma R&D. “We will achieve this by deploying an integrated network of technologies that design, screen and stratify/personalize drug discovery and development.”

To this end, Mr. Kurji explains that Cyclica has expanded the “functionality of Ligand Express downstream to investigate the effect that sequence variants and mutations have on protein structure, thereby providing insight into structural pharmacogenomics.”

Cyclica also has launched an alpha version of its second-generation differential drug design (DDD) technology to select Pharma partners. “DDD extends our value to the market upstream into multi-targeted drug design.”

Mr. Kurji says the company has adopted a multi-pronged business model, which includes fee-for-service for small pharma companies and licensing and partnership arrangements with larger pharma companies. For smaller, venture-backed pharma companies, Cyclica has taken equity positions and structured other creative deals.

For example, Cyclica recently partnered with an oncology company, Tieös Pharmaceuticals, as well as with ophthalmology company, Translatum Medicus, to advance a small molecule discovery for dry age-related macular degeneration.

“We are driving towards our vision by bridging technology, chemistry and biology to more efficiently discover novel medicines to treat human diseases,” he adds.

Peter Wolpert, CEO and founder

Sweden’s Moberg Pharma (OMX:MOB) is focused on maximizing the potential of its market leading position in over-the-counter sales of topical dermatology products to drive development of new therapies for the treatment of nail fungus and mouth pain, especially in cancer patients.

“Our aspiration is to continue as a market leader in niche categories as we make the company strategically larger through our innovation engine and bolt-on acquisitions,” CEO and founder, Peter Wolpert, says in an interview with BioTuesdays.

Moberg has a number one positions in U.S. OTC sales of its topical nail fungus product, Kerasal Nail; pain relief spray, Dermoplast; and an antiseptic liquid bandage, New-Skin. “We are expecting double-digit growth from these brands,” he adds.

a leader in topical niche categories

For the fourth quarter of 2017, retail sales for Kerasal Nail grew 17%; New Skin was up 21%; and Dermoplast up 14%. Moberg acquired Dermoplast at the beginning of 2017 and generates 60% of its sales from hospitals and 40% from retail. “We are launching a targeted marketing plan for Dermoplast, with a digital focus this year,” Mr. Wolpert says.

Regarding Kerasal Nail, he says the company expects favorable market conditions in the U.S. to continue after the product’s main competitor was forced to discontinue its current marketing and change its packaging design and advertising. 

Mr. Wolpert says that in 2018, Moberg plans to test launch Kerasal Nail to a totally new target group: patients suffering from nail psoriasis, for which there is no OTC treatment currently available. Clinical data published in 2017 demonstrated a 76% visible improvement after one week and 94% improvement after eight weeks with Kerasal Nail in psoriasis patients with nail problems, he points out. 

17% growth for Kerasal Nail in the U.S. in Q4

“Our ambition from the start was to make the U.S. our home market, and now some 90% of our sales are in the U.S.,” Mr. Wolpert says, noting that he and his family moved to the U.S. from Sweden in August 2017. In addition to direct sales, Moberg uses distributors to sell its nail fungus products in more than 40 countries.

Net sales for 2017 rose 31% to 439 Swedish krona (about US $50-million) with underlying EBIDTA growth of 108% to 89 Swedish krona. Kerasal Nail, New Skin and Dermoplast accounted for more than 80% of net sales last year.

“We believe there is plenty of value in Moberg Pharma,” Klas Palin, an analyst with Sweden’s Redeye, wrote in a research report last month after the quarterly results.

“However, the shares continue to trade at a significant discount to our fair value, as investors seem unwilling to pay for the opportunities in the pipeline assets,” he added. Reaching full recruitment in two Phase 3 trials in the U.S. and EU in 2018 with MOB-015 for the treatment of onychomycosis, or nail fungus, will be the next important catalysts for the share price, Mr. Palin said. “We believe they will serve as a starting point for a growing interest in MOB-015.”

MOB-015 is an internally developed topical formulation delivering high concentrations of terbinafine through the nail for the treatment of onychomycosis. Oral terbinafine is the gold standard for treating onychomycosis, but is associated with safety issues, including drug interactions and liver damage.

Mr. Wolpert says Moberg is building on its leading OTC product, Kerasal Nail, to demonstrate rapid visible improvement, superior cure rates and safety with MOB-015, which has patent protection in the U.S., Europe and Japan until 2032. “This is our most valuable asset,” he adds.

The two Phase-3 studies in North America and Europe are expected to enroll a total 800 patients. The company hopes to complete enrollment in the North American study in the summer of 2018 and the European study in the second half of 2018 and report data 14-to-15 months thereafter.

In a previous Phase 2 study, MOB-015 demonstrated delivery of high microgram levels of terbinafine into the nail and through the nail plate into the nail bed. Mycological cure of 54% and significant clear nail growth was observed in patients who completed the Phase 2 study. 

Phase 2 – results demonstrated efficacy and safety

In addition, 100% of patients were culture-negative at 60 weeks, “which is something I don’t think has ever been reported in this area before,” Mr. Wolpert contends.

The results were “remarkable, particularly when taking into account the severity of the nails included in the study, because on average, approximately 60% of the nail plate was affected by the fungal infection.” 

In addition, he says plasma levels of terbinafine with MOB-015 were 1,000 times lower than after oral administration, reducing the risk of liver toxicities observed with oral terbinafine.

According to Mr, Wolpert, approximately 10% of the general population suffer from onychomycosis and a majority of those afflicted go untreated. The global market opportunity is significant with more than 100 million patients worldwide, including 35 million to 40 million in the U.S.

Mr. Wolpert figures that if approved, a conservative assumption is that MOB-015 has the potential to achieve 5% to 7.5% market share of some five million total prescriptions for onychomycosis. Assuming an annual selling price of $1,700 a year and trade discounts of 50% to 60%, he says the potential for net sales of MOB-015 in the U.S. would be $170-million to $300-million-plus.

Including prescription markets in Japan and Canada, and OTC markets in Europe and the rest of the world, the total net sales potential would be $250-million to $500-million, he adds.

Moberg’s other pipeline asset is BUPI, a taste-masked lozenge containing bupivacaine that is designed to provide better pain relief in the mouth for the treatment of oral mucositis, a debilitating side effect of radio- and chemotherapy for cancer patients, causing severe pain which can prevent patients from eating and swallowing solid food.

Mr. Wolpert says that in a Phase 2 study with 39 patients, BUPI provided 50% better pain relief in the mouth than standard pain treatments. Each lozenge has the potential to provide two-to-five hours of pain relief, he adds.

Moberg’s partner, Cadila Pharmaceuticals of India, has agreed to fund one Phase 3 trial of BUPI in exchange for distribution rights in India and parts of Africa. Discussions with Indian regulators are underway and Cadila hopes to begin the pivotal study in 2018.

Mr. Wolpert says Moberg would like to find a U.S. partner to conduct pivotal trials of BUPI in the U.S. “This could be a company that would distribute the product in the U.S. or a joint venture investor.”

Rob Thornhill, CEO

Closely-held Tear Film Innovations plans to formally launch at two upcoming medical conferences its iLux medical device to treat Meibomian gland dysfunction, the leading cause of dry eye disease. 

The company will be exhibiting to ophthalmologists at the American Society of Cataract and Refractive Surgery (ASCRS) this weekend and optometrists at Vision Source: The Exchange 2018 during the first weekend in May.

“By ASCRS, we’ll have initiated the integration of iLux at 25 eye practices, where they’ll have the proper tools and processes in place to identify dry eye patients, discuss iLux with patients and perform procedures,” CEO, Rob Thornhill, says in an interview with BioTuesdays.

“We designed iLux so patients will say yes to a dry eye treatment without a significant financial commitment and provide doctors with a business model that would benefit their practice,” he adds.

According to Mr. Thornhill, the root cause of dry eye is Meibomian Gland Dysfunction (MGD), which is a blockage or some other abnormality of the meibomian glands, causing them to not secrete enough oil to cover the tear film. This oil (lipid) layer is the key to a healthy ocular surface and 86% of dry eye patients have an insufficient lipid layer. 

iLux® Treats The Leading Cause Of Dry Eye Disease

“Any blockage of meibomian glands can lead to evaporative dry eye, resulting in unstable tear film and associated symptoms,” he adds. “iLux is designed to treat the leading cause of the disease.”

Tear Film Innovations was founded in 2014. The technology, resulting in a handheld device designed to unclog meibomian glands with heat and compression, was invented and developed in-house by Brian Kelleher, a co-founder and currently COO of the company, and Kabir Gambhir, another co-founder. 

Mr. Thornhill explains that a clinician can view the meibomian gland orifices through a magnifier on the iLux instrument and assess the impact of the heat and compression from the iLux system on the glands. The compression force and heat is controlled by a thumb-operated switch that gives a clinician tactile feedback.

After the meibum is melted, the clinician gently massages the eyelid between the two pads, expressing the melted meibum through the gland orifices, which are monitored through the magnifier.

Unlike other treatments for MGD, the iLux device is designed to accomplish this procedure usually in less than a minute per treatment zone for most patients. 

Mr. Thornhill points out that safety features incorporated in the device ensure that the energy delivered is within the therapeutic range, and that the compression force is well tolerated by patients.

While the treatment relieves dry eye symptoms, it is not a cure and he says most doctors want to see patients every six months on average. iLux may improve cataract and LASIK surgical outcomes and complement dry eye medications, including Restasis and Xiidra.

Dry eye disease affects more than 20 million people in the U.S. and 300 million worldwide, with the incidence growing above 5% a year because of an aging population, use of electronic devices, diabetes, contact lens wear and cataract and LASIK surgery. 

“Because people blink less while using computers, tablets and smartphones, for example, meibomian glands are not activated to secrete enough oil onto the tear film,” Mr. Thornhill suggests.

Common symptoms of dry eye include dryness, grittiness, soreness, irritation and burning, watering, sensitivity to light, blurred vision and eye fatigue. These symptoms, which often worsen throughout the day, can significantly diminish quality of life. The symptoms of dry eye disease are one of the most common reasons people visit the eye doctor. 

Why iLux is Needed

Mr. Thornhill says patients in a randomized clinical study had similar outcomes with the iLux and the TearScience LipiFlow. However, the price paid by patients for iLux handheld treatments will be roughly one-third of the price paid by patients for LipiFlow.

iLux also differentiates itself from LipiFlow by allowing doctors to offer customized treatments to patients and to verify outcomes at the time of treatment, he adds.

For clinics, Mr. Thornhill says the iLux instrument is one-third the cost and the disposable one-fourth the cost of the LipiFlow instrument and disposables.

iLux recently received 510(k) clearance from the FDA after completing a pivotal study, including LipiFlow, with 142 patients at eight clinical sites in the U.S. last August. 

The study demonstrated that iLux’s meibomian gland score, and measurements of tear breakup time and ocular surface disease index all exceeded the FDA’s requirement for clinical significance. iLux also was found to be non-inferior to LipiFlow. There were no adverse events and iLux was proved to be safe for patients.

 “We have a seasoned management team, with a successful track record, and an opportunity to build a cash flow positive company by the end of 2019,” Mr. Thornhill suggests.

Paul Gudonis, chairman and CEO

Myomo (NYSE American:MYO) is moving from a controlled introduction over the past few years to a scale up sales and distribution of its MyoPro product line of lightweight, non-invasive, powered arm braces to restore function in paralyzed or weakened arms.

“This is the reason we went public last year and raised about $20-million for sales and marketing, and expansion of the business,” Paul Gudonis, chairman and CEO, says in an interview with BioTuesdays.

“Our mission is to conquer paralysis with our patented myoelectric technology and show that the conventional wisdom of upper limb paralysis, where an arm hangs limp or is in a sling, doesn’t apply any more,” he adds.

According to Mr. Gudonis, MyoPro is the only commercially available upper limb medical device, with the largest home user base in the wearable robotics market, including more than 700 devices shipped.

“It is the only device that, sensing a patient’s own neurological signals through non-invasive sensors on the arm, can restore their ability to use their arms and hands so that they can return to work, live independently and reduce their cost of care,” he explains.

Only Commercially Available Upper Limb Product Line to Restore Function

Mr. Gudonis says MyoPro also is supported by a growing body of clinical evidence, including academic studies about home use, safety and efficacy, functional benefits, and studies with victims of stroke, brachial plexus injury and traumatic brain injury.

Myomo was spun out of MIT in 2006 and after receiving FDA approval in 2007. It then set out on a controlled release of the MyoPro device, adding wrist and grasp components to the elbow only device, and working with the VA and leading institutes, such as Cleveland Clinic and Mayo Clinic.

The company went public in 2017 and began to scale up its commercial focus. “Our four pillars to grow revenue include sales and marketing, product development, clinical studies and reimbursement and international expansion all designed to broaden adoption around the world and establish MyoPro as the standard of care for upper limb paralysis,” Mr. Gudonis contends.

The strategy seems to be working. Revenue for 2017 rose 41% to $1.6-million from $1.1-million a year earlier. The company also continued the roll out of its MyoPro Centers of Excellence at orthotics and prosthetics (O&P) practice organizations, reaching 36 U.S. locations offering the MyoPro line of powered orthosis at the end of 2017.

Last summer, the company introduced its next-generation MyoPro 2 with significant enhancements, including an upgraded user interface, improved sensors and improved harness and finger grasp orthosis for more reliable and comfortable long-term wear.

MyoPro 2 is available in three models to match patient-specific needs: the Motion E features a powered elbow with static rigid wrist support; Motion W has a powered elbow and a multi-articulating wrist, with flexion/extension and supination/pronation; and Motion G offers a powered elbow, a multi-articulating wrist and a powered 3-jaw-chuck grasp.

The company also plans to roll out a miniaturized and lighter weight MyoPro for younger children. According to Mr. Gudonis, there are 150,000 children under the age of 18 in the U.S. with some form of upper limb paralysis.

Overall, there are some three million cases of upper limb paralysis in the U.S., with more than one million new cases a year caused by stroke, brachial plexus injury, spinal cord injury, multiple sclerosis, traumatic brain injury and ALS.

Mr. Gudonis says the average selling price of a MyoPro device is $13,400, which generates gross margins of 65%. “Assuming an addressable market of 25% of existing cases and new incidences a year, the potential U.S. market opportunity is more than $10-billion, which can reach $30-million, including Europe and the rest of the world,” he figures. MyoPro was CE marked in Europe last year.

Large Market Opportunity*

Myomo’s business model involves outsourcing manufacturing of the robotic components and fabrication while it focuses on sales and distribution to VA hospitals and O&P clinics. Ottobock, a global prosthetics group, distributes MyoPro in Germany, Canada and certain regions of the U.S.

Mr. Gudonis says Myomo is expanding its direct sales force to 10 regional managers from three this year. “Our goal is to be in the top 50 markets by the end of 2018, with reasonable access to 90% of the U.S. population.”

Last month, analyst Scott Henry of Roth initiated coverage of Myomo, saying the impetus for his “buy” rating is a belief that the company has a favorable opportunity to capitalize on its position as the first company commercializing a myoelectrically-powered orthotic solution for upper extremity partial paralysis.

“We believe that the device is now commercial-ready, following multiple improvements, and we anticipate meaningful sales growth going forward driven by a multi-faceted distribution strategy,” Mr. Henry said.

The VA, private insurers and worker’s compensation on a case-by-case basis are currently reimbursing O&P clinics in ranges from $20,000 to $50,000, depending on the MyoPro model. The company recently applied to CMS for a Healthcare Common Procedure Coding System code to expand coverage to patients who are covered by Medicare and motivate additional O&P clinics to offer the device.

“We have a reimbursement team that works with patients and O&P clinics because like any prosthetic, MyoPro is a medical necessity designed to restore function in one or both limbs,” Mr. Gudonis says. “We’ve had patients avoid amputations, reduce pain medication and therapy sessions because they are able to use our device at home and at work.”

Moving from Controlled Introduction to Scale Up