6/26/2017
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`A real tear-jerker: Team creates device to alleviate dry eye | News Center | Stanford Medicine
`
`News Center
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`A real tear-jerker: Team creates device to alleviate dry eye
`
`A search for medical needs in eye clinics led Stanford Biodesign fellows to develop an implantable
`neurostimulator that painlessly increases natural tear production.
`
`JAN 23
`2015
`
`Michael Ackermann, PhD, knows how to make
`you cry. 
`
`But this is a good thing for the more than 20
`million Americans who suer from a painful
`condition in which the lacrimal glands don’t
`create enough tears to lubricate the surface of
`
`the eye. 
`
`To help these patients, Ackermann, PhD, a former Stanford
`Biodesign fellow, and his new company are testing two tiny
`devices that stimulate natural tear production by delivering
`micro-electrical pulses to the lacrimal gland. One model is
`inserted into the mucous membrane in the nasal cavity, and
`the other is inserted under the skin below the eyebrow. Tear
`delivery rates can be adjusted manually with a wireless
`controller. 
`
`This wireless device is designed to stimulate natural tear
`production in patients with dry eye.
`Michael Ackermann
`
`Stanford Biodesign is a training program in medical-technology innovation and development. Each year, it admits 12 applicants
`with backgrounds in medicine, engineering and business. These Biodesign fellows work to address unmet medical needs through
`the development of new technologies and devices.
`
`Ackermann, 32, who has a boyish grin and buzz-cut hair, joined the program in 2010 aer earning a PhD in biomedical engineering
`from Case Western Reserve University and working on chronic-pain and movement-disorder devices at Boston Scientific, a
`medical device corporation. He said he enjoyed the corporate work but realized he wasn’t a big-company person.
`
`“I thought the Biodesign Program was a good opportunity to try out entrepreneurship in a safe, academic environment,” he said.
`Solving problems with fresh eyes
`
`At the start of the program, Ackermann was assigned to a four-person team tasked with looking for medical needs in eye clinics.
`His team members included Victor McCray, MD, a board-certified surgeon; Brandon Felkins, a graduate student in mechanical
`engineering at California Polytechnic State University-San Luis Obispo; and Garrett Smith, a PhD candidate in bioengineering at
`UC-San Diego.
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`https://med.stanford.edu/news/all-news/2015/01/a-real-tear-jerker-team-creates-device-to-alleviate-dry-eye.html
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`MYLAN - EXHIBIT 1049
`Mylan Pharmaceuticals Inc. et al. v. Allergan, Inc.
`IPR2016-01127, -01128, -01129, -01130, -01131, & -01132
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`6/26/2017
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`A real tear-jerker: Team creates device to alleviate dry eye | News Center | Stanford Medicine
`
`They began by observing all facets of a busy ophthalmology practice, shadowing the doctors and
`interviewing them and their patients. At the end of two months, they had documented more than 300
`clinical needs. 
`
`Early in this process, Ackermann recognized dry eye as a promising area. “Every third person visiting
`the clinic seemed to be suering from dry eye, which ranged from something that was a nuisance to a
`genuine, sight-threatening disease,” he said. “It was a huge medical need with no optimal treatments.”
`
`Michael Ackermann
`
`With every blink, healthy eyes are lubricated with tears — a mixture of oils, water, proteins and mucus.
`This fluid helps protect and moisturize the eyes, and the thin film that it creates is necessary for clear
`vision. Dry eyes become vulnerable to painful abrasions of the cornea, which can distort vision. 
`
`Dry eye can be triggered by a number of factors, including gland defects, medication side eects and hormonal changes caused by
`pregnancy or menopause. It is also associated with some immune-system disorders.
`
`“There are very poor treatment options for my dry-eye patients,” said Mark Blumenkranz, MD, professor and chair of
`ophthalmology, who was a mentor for the fellows on this project.
`
`The two most common dry-eye treatments are lubricating eyedrops and cyclosporine, a topical emulsion, but both have
`drawbacks. The eyedrops require refrigeration, making them diicult to apply when needed, and they don’t replicate all the vital
`components of natural tears. The topical ointment treats the inflammation associated with dry eye but not the root cause of the
`condition.
`
`“
`
`There are very poor treatment options for my dry eye patients.”
`
`“We’ve observed that more than half of our dry-eye patients stop taking cyclosporine aer a few months,” Blumenkranz said.
`“This high dropout rate led the team to believe that patients and physicians would be open to new treatment options.”
`
`Paul Yock, MD, director of Stanford Biodesign, said, “The key to biomedical technology innovation is getting the need right.
`Michael and his team appreciated that dry eye was a latent need, in that these patients were being inadequately treated, with no
`real breakthroughs in years. In this kind of situation, the need quietly recedes into the background, as patients and providers
`become complacent with the status quo.”  
`Aiming for a market blind spot
`
`Once the fellows focused on dry eye, they spent the next few months coming up with hundreds of treatment ideas. Then, they
`systematically analyzed each for technical feasibility, the ability to fit into a physician’s workflow and the potential to generate
`revenues. During this phase, the Biodesign community — faculty mentors, working physicians and venture capitalists — provided
`invaluable feedback, Ackermann said.
`
`“Because of my background in neuromodulation, I wondered if we could stimulate the nerves in the lacrimal gland to generate
`tears,” Ackermann said.
`
`It was a radically dierent idea, but aer conducting extensive research, they thought this concept was worth a try. But their first
`product configuration was poorly received by clinicians. 
`
`“Initially, we envisioned a large implanted device with a wire coming up inside the neck, similar to a pacemaker,” said Ackermann.
`“We took it to eye specialists, who said, ‘That is never going to happen.’” 
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`A real tear-jerker: Team creates device to alleviate dry eye | News Center | Stanford Medicine
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`So they went back to the drawing board and built several versions of a much smaller model out of plastic and clay. They took
`these prototypes back to the eye specialists, who thought the devices, when actually made, could be injected under the eyebrow
`with a large-gauge needle in a doctor’s oice.
`
`“At first, I thought their solution was quirky,” Blumenkranz said. “But nobody was thinking about the neurological basis of dry eye.
`I recognized that it had the potential to be a breakthrough product.”
`Building the business
`
`Between March and June of 2011, the team entered its business plan into a number of startup competitions. The team placed in
`six of them, earning more than $32,000 in prizes and thousands more in business-development services. This was enough to fund
`a prototype eort.
`
`As the fellowship year came to a close, Ackermann was accepted as a second-year Biodesign fellow. During that year, he decided
`to launch a company, called Oculeve, to develop tear-stimulation devices and bring them to market. For help with the technical
`challenges, he teamed up with Daniel Palanker, PhD, professor of ophthalmology at Stanford, and Jim Loudin, PhD, a
`postdoctoral scholar in Palanker’s lab and an expert in stimulator design who is now Oculeve’s vice president of research and
`development.
`
`McCray and Felkins decided to launch another startup, Ocular Dynamics, which is developing a fluid that helps prevent the drying
`of contact lenses. Smith went on to earn a PhD and is now co-founder and chief technology oicer of Nasseo, a startup developing
`a novel dental implant technology.
`
`Oculeve caught the attention of Brook Byers, a founding member of the distinguished Silicon Valley venture-capital firm Kleiner
`Perkins Caufield & Byers. “Oculeve was aer a large market with weak competition,” Byers said. “They had a clever new invention,
`a good economic model and a strong starting team.” 
`
`Byers then convinced the firm to commit $100,000 in seed funding, and this enabled Oculeve to test a prototype for eicacy and
`safety in animals.
`
`“
`
`The first time I saw our device actually working in a real patient, it was out of this
`world.”
`
`In October 2012, aer proof-of-concept testing, Byers and Ackermann assembled a group of health-care venture capitalists —
`KPCB, Versant Ventures and New Enterprise Associates — and convinced them to invest $7.6 million into the startup. With this
`funding, they were able to hire much-needed employees and launch clinical trials in Australia, New Zealand and Mexico. 
`
`“The first time I saw our device actually working in a real patient, it was out of this world,” Ackermann said.
`
`In May 2014, Oculeve investors contributed an additional $16.6 million to the company. That money will hopefully carry the
`company through the expensive, time-consuming process of getting a medical device through its European and Canadian round
`of regulatory approvals, Ackermann said. U.S. regulatory approvals are in progress, and patients interested in participating in
`future clinical trials can visit http://www.clinicaltrials.gov (and search for “Oculeve”). 
`
`Today, Ackermann runs his 20-person company from a corner oice with a panoramic view of the San Francisco Bay. When asked
`about the challenges of launching a company, Ackermann points to a quarter-sized patch of gray hair on the crown of this head:
`“This wasn’t here before I started. It’s incredibly hard managing a company where the money only flows out. I won’t consider it a
`success until the products are on the market, treating patients and profitable.”
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`6/26/2017
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`A real tear-jerker: Team creates device to alleviate dry eye | News Center | Stanford Medicine
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`And when this happens, there probably won’t be a dry eye in the house.
`
`Early support for this project came from Biodesign, which is part of the university’s interdisciplinary Bio-X institute; and Spectrum,
`the Stanford Center for Clinical and Translational Research and Education.
`
`Blumenkranz sits on the board of Oculeve.
`
`By
`KRIS NEWBY
`Kris Newby is the communications manager for Spectrum, the Stanford Center for Clinical and Translational Research and Education.
`Email her at krisn@stanford.edu.
`
`Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of
`Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. For more
`information, please visit the Oice of Communication & Public Aairs site at http://mednews.stanford.edu.
`
`©2017 Stanford Medicine
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