​The OIS meetings always keep us busy with a full slate of meetings. These one-day conferences occur around various ophthalmology academy and society meetings throughout the year. OIS unites key constituents in ophthalmic innovation, including industry, entrepreneurial, and clinical leaders all working to develop and commercialize products to preserve and restore vision. The meetings present an opportunity for ExSight to meet with our portfolio companies, learn about new potential investments, and network with other investors and key industry partners. Dr. Rahhal joined investors from KKR, InFocus Capital Partners, and others in a panel discussion led by OIS co-chair, William “Bill” Link of Versant Ventures and Flying L Partners. 

Trefoil Therapeutics, Inc., an early-stage biopharmaceutical company and ExSight Ventures portfolio company, announced their $28 million Series A financing. Trefoil is developing a regenerative approach to treating corneal dystrophies and other diseases. We initially invested in Trefoil's 2016 Series 1 financing and enthusiastically participated in the Series A financing. This financing is a significant milestone in bringing their treatment closer to an approved therapy.

When we first invested we wrote in a note to our investors, "Trefoil's innovations promise to improve patients' lives with a more efficacious treatment and significantly lower risk minimally invasive procedure." Since then, the company has made significant progress in bringing this treatment closer to reality for patients suffering from these disorders. Trefoil has generated preclinical data that has shown "TTHX1114's ability to accelerate corneal clearing in animal models of corneal endothelial dystrophy and enhance healing in corneal chemical injury and herpetic keratopathy." The company has also demonstrated "TTHX1114 stimulates the proliferation and migration of endothelial tissue" in human cornea organ culture models of both healthy and diseased corneas.  

Bios Partners led the round and was joined by Access Biotechnology with participation from all existing investors. The proceeds will provide for the completion of a Phase 2a proof-of-concept study in corneal endothelial dystrophy. Trefoil plans to file an Investigational New Drug (IND) application with the FDA in early 2020 and subsequently begin the clinical trial. This financing will also fund the continued development of a topical formulation of TTHX1114 for the treatment of ulcerative conditions of the cornea. The company plans a second IND submission for corneal epithelial conditions in 2021.
 
The Trefoil team's ability to plan carefully, execute effectively, and communicate clearly have advanced the company's development to this crucial stage. An exceptional and seasoned leadership team, robust preclinical data, and compelling science bode well for getting these breakthrough therapies to patients. We consider ourselves fortunate to be a small part of the Trefoil story. ​Press Release.
Other press: Fierce, Healio, PE Hub, Pro Rata, Term Sheet, and InVision. 

​ExSight is pleased to announce Qura, Inc. (“Qura”) as the fifth and final portfolio company for 8th Line Investments, LLC. Qura is developing a miniaturized pressure sensor for the measurement of intraocular pressure (“IOP”) in patients with glaucoma. Glaucoma is a common disease that typically occurs when excess fluid builds up in the eye causing increased IOP damaging the optic nerve and leading to vision loss and blindness. ExSight joins InFocus Capital Partners and Santen Ventures, Inc., a corporate venture capital fund wholly owned by Santen Holdings U.S, Inc. in Qura’s Series A financing.   The funding will be used for product development, testing, design, preclinical studies, and database development.
 
Qura’s QSmart™ wireless implantable pressure sensor (“WIPS”) technology and monitoring system promises to enable smarter treatment decisions based on better information. The miniature WIPS promises continuous monitoring and real-time IOP readings and updates. The data will then be transmitted to a tablet or other handheld device allowing physicians to evaluate glaucoma patients’ treatment in real-time. This technology will lead to better compliance within existing treatment paradigms and a better understanding of the disease. Additional insights gleaned from this data will drive drug and device developments for better treatments.
 
Qura’s CEO Doug Adams has previously remarked, “What makes this minimally invasive micro implant unique is that it will operate autonomously regardless of patient activity. The programmable device collects data based on the physician’s requirement and that data is transmitted to a handheld device or tablet. The physician will now have actionable data on which to base their treatment plans for the patient.”
    
We are excited to be part of the Qura story and their promise to improve treatments available to glaucoma patients!

ExSight is happy to announce an investment in ONL Therapeutics, Inc., an early stage biopharmaceutical company developing novel therapies for preserving sight in a range of retinal diseases. ExSight participated in a convertible note financing round with participation from existing investors. The funding will be used for IND enabling activities, clinical trial preparation and other activities.
 
ONL Therapeutics’ lead molecule, ONL 1204, is a novel, first-in class small molecule fatty acid synthase (“Fas”) inhibitor designed to protect the retina from cell death via both direct and inflammatory signaling in a range of retinal diseases. Fas is a known inducer of apoptosis, or cell death. The death of key retinal cells is the root cause of vision loss and is implicated in a wide range of retinal diseases, including retinal detachment and both the wet and dry forms of age-related macular degeneration (AMD).
 
ExSight partner and vitreo-retinal surgeon, Dr. Firas M. Rahhal stated, "No significant advances have occurred in visual results from the management of rhegmatogenous retinal detachment for the last 20 to 30 years.  ONL has developed a therapeutic agent that, along with successful surgical repair, could significantly improve the visual outcomes of this potentially devastating condition. Additionally, the same agent could be similarly useful in the visual outcomes following acute angle closure glaucoma attacks.  This too is an anatomic condition, repaired surgically, for which there have been no significant advances in treatment in recent decades." ONL’s therapeutic approach would be a transformative therapy having significant impact in an area of high unmet medical need. In other words, ONL perfectly fits ExSight’s investment thesis.
 
ExSight has been in contact with John Freshley, ONL President and CEO, and David Zacks, M.D., Ph.D., Co-Founder and CSO, for over 3 years. In that time the company has further de-risked their lead candidate, partnered with Novartis, developed a safe and ethical clinical trial protocol and identified additional potential indications. The ONL team has demonstrated tenacity, ability and significant scientific and clinical insights. The ExSight team is happy to be part of the ONL journey and look forward to contributing domain expertise to the company.  “We are thrilled to invite ExSight into the family of ONL investors. ExSight is uniquely well-qualified to understand and actively contribute to ONL’s mission of protecting the vision of patients with retinal disease,” said Mr. Freshley.
    
For all those reasons and more we are excited to make ONL Therapeutics to the ExSight portfolio. 

Dr. Rahhal later joined OIS Podcast Host Tom Salemi, Greg Grunberg, MD, and OIS Contributors Richard Mark Kirkner and Bérénice Magistretti about some of the key takeaways for investors, physicians and patients.

• OIS Podcast - Highlights from OIS Retina with Dr. Rahhal.

We're looking forward to attending the next OIS in Chicago October 25 at the American Academy of Ophthalmology meeting. 

ExSight portfolio company LensGen announced additional financing and patent grants. LensGen is developing the world's first modular, fluid-optic, curvature changing intraocular lens ("IOL"). LensGen “achieved a key clinical performance milestone which triggered the release of $11 million in funding as part of the Series A Financing.” HOYA, the lead investor, also exercised an option to invest an additional $4.4M under the terms of the Series A financing. In the same period, the US Patent Office granted LensGen two new patents that give the company comprehensive protection of its technology. The additional funding will take the Company closer to bringing the Juvene platform to market. 

We're very proud to be a part of the Company's journey. Congratulations to the LensGen team! 

Full Press Release

We’re often asked, “why ophthalmology”? We enthusiastically respond with some variation of an answer that includes a combination of our deep domain expertise, market insights, technological breakthroughs and attractive investment returns.  This specific strategy may be described by some as thematic investing in that we’ve identified eye care as a particular theme for investment. This would be an incomplete view.  We decided to publish our thesis on the site to provide a more complete picture of our approach. Publishing an investment thesis is hardly a novel concept with well-known versions coming from Union Square Ventures and Andreessen Horowitz ('a16z'). This level of transparency provides a level of accountability that we embrace and ultimately believe will make us better investors.
 
In addition to having our initial insight that ophthalmology is an attractive field in which to invest, we wanted to be sure that this insight was durable and that it would continue such that it warranted the founding of our firm. To do that, we have spent significant time over the last 4 plus years discussing where the market is going over the next ten plus years. It was not sufficient for us to merely specify ophthalmology as a field meriting investment. We wanted to define our thesis such that every investment would be filtered through our long-term outlook. This would serve two purposes: it would make sure we were staying true to our initial insights and long-range views while preventing the potential for mission drift.
 
Of course our thesis, like our outlook, isn’t static.   As the premises underlying our investment outlook continue to evolve, technology advances and markets develop we continue to revisit and revise our thesis to account for this new information. This is the fun part of our work, staying on top of breakthrough technologies and thinking critically about the future of vision care. We hope sharing this helps inform the market about our process and view. Our transparency will also keep us accountable.

​You can read the full thesis here. 

Over the last several months the press has been abuzz with the promising results of two recent, unrelated clinical studies. Each was the study of stem cell transplantation in patients with age-related macular degeneration (“AMD”). The first study to release results was conducted in London and the second was conducted in Los Angeles. The latter was performed at USC’s Roski Eye Institute at the Keck School of Medicine in conjunction with Regenerative Patch Technologies. Dr. Rahhal is a principle investigator in the USC / Regenerative Patch Technologies (funded by CIRM) and a co-author of the recent paper, covered here by the LA Times. 
 
From the LA Times:
“In a very early clinical trial, researchers have implanted a stem cell “patch” to repair failing retinal cells in four patients with a condition called dry macular degeneration.
Three of the four patients who got the bioengineered implant — all of whom had lost their central field of vision and were legally blind — reported some lightening in the previously dark center of their visual field, according to a study published this week in the journal Science Translational Medicine. The three also saw some improvement in their ability to see shapes and focus on letters or other objects directly in front of them.
In a span of roughly five months, one patient’s ability to identify letters on a vision chart improved by 17 characters.
“It is remarkable when people can start seeing again,” said the study’s lead author, Dr. Amir H. Kashani of USC’s Roski Eye Institute at the Keck School of Medicine. Kashani conducted the trial with Dr. Mark S. Humayun, also a USC ophthalmologist, and a USC team that drew from many disciplines.
The modest improvements seen in this small group of patients offer hope in a field that has had nothing to offer patients yet, said Kashani, who is both an eye surgeon and stem cell scientist.
A treatment that would allow people with dry macular degeneration to look into the faces of loved one “would be the dream,” Kashani said. “I don’t think we’re there yet.”

Our team is extremely proud of Dr. Rahhal’s contributions to this breakthrough study. Dr Rahhal's group, Retina Vitreous Associates Medical Group in Los Angeles, is also involved in many retinal/macular clinical trials, including others involving stem cell technology. The importance of this research cannot be understated. The results of the study will inform future developments in vision restoration. We look forward to covering the insights gleaned from the ongoing research on our site and in our newsletter.