After watching and listening to Dr. Rahhal's many episodes hosting the OIS Retina Podcast we joined him in this week's installment. Firas was having so much fun talking ophthalmic innovation with his other guests we wanted to get in on the action. 
Our wide-ranging discussion touched on everything from the history and formation of ExSight, how we operate with two very busy vitreoretinal surgeons, our investment process, a pair of portfolio companies, and much more. The conversation lasted nearly an hour but it wasn't enough to mention all of the outstanding portfolio companies and teams, our investors, advisors, and founding members. Hopefully we'll have a chance to do a deeper dive at some point. We hope you enjoy the conversation. 

The below is taken from an update we shared with our investors, portfolio companies, and friends as 2020 came to a close. We share some of these reflections here as well. We're hopeful and optimistic that 2021 will bring much more positivity and wish everyone well in the new year. 
​
As so many of us do today, we are reflecting on the past year. 2020 was a historic and tragic year by any measure though not without silver linings. We're  focusing on several positive accomplishments and critical milestones as we enter a new year.

• We began the year by announcing an investment in DTx Pharma. DTx is developing technology that will utilize RNA-based therapeutics as the preferred modality for personalized treatment across many therapeutic areas. DTx was able to leverage its technology to improve outcomes in a rodent model of Retinitis Pigmentosa. DTx had a very productive year. They announced prestigious funding awards and grants, added team members, appeared at numerous virtual events, and much more. While 2020 was momentous, 2021 should be even more so. 
• In February we announced a follow-on investment in Envision Diagnostics. Envision has had several significant accomplishments this year that we hope to share with you soon. 
• We announced our investment in Re-Vana Therapeutics, a specialty therapeutic and drug delivery company developing sustained-release therapeutics for significant sight-threatening ocular diseases. This was the first round we led and we were grateful to have participation from our colleagues at InFocus Capital Partners and Visionary Ventures. The Re-Vana investment was the first time we utilized an AngelList Syndicate to amplify our investment. 
• June saw ExSight Ventures mentioned alongside other specialized venture firms in the Wall Street Journal. 
• Dr. Rahhal added "podcast host" to his many titles. Firas began hosting the OIS Retina Podcast this summer. The podcast presents "a unique offering of information, discussion, education, and possibly debate, in the form of small group dialogue or interview between myself and many of the individual stakeholders in this space," Dr. Rahhal commented at launch. His guests have included the prolific Dr. Mark Humayun, ONL Therapeutics CEO David Esposito, and many, many more. It is a must-listen for anyone interested in ophthalmic innovation. 
• Trefoil Therapeutics began their first clinical trial of regenerative treatment for patients with corneal endothelial dystrophies. This is a massive accomplishment for which all involved should be proud. 
• LensGen maintained momentum in their work toward an Investigational Device Exemption ("IDE") approval by closing additional financing and adding James (Jim) Mazzo to the board.
• ONL Therapeutics helped us finish the year on a high note with a successful  $46.9 million Series B financing. The proceeds will take ONL's lead candidate beyond retinal detachment and into the chronic conditions of glaucoma and dry age-related macular degeneration. ExSight continued our support and participation in the round. 

These accomplishments helped us find many silver linings and remain positive throughout the year. We thank the teams of each of these companies and all of our portfolio companies for their tenacity, perseverance, and dedication to advancing ophthalmic innovation. 

Beyond retinal detachment, lead candidate ONL1204 will also advance into the chronic conditions of glaucoma and dry age-related macular degeneration

ONL Therapeutics, Inc. (“ONL”), a clinical-stage biopharmaceutical company and ExSight Ventures (“EV”) portfolio company, announced it closed a $46.9 million Series B financing. EV syndicated $3.75 million. ONL is developing novel therapies for protecting the vision of patients with retinal disease. This funding will enable the completion of the company’s Phase 1 study in retinal detachment with ONL’s lead compound ONL1204 while advancing ONL1204 programs in two chronic indications, glaucoma and dry age-related macular degeneration.
 
ONL1204 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 critical retinal cells is the root cause of vision loss and is implicated in a wide range of retinal diseases, including glaucoma, age-related macular degeneration (AMD), and inherited retinal degeneration (IRD; also known as retinitis pigmentosa).
 
Bios Partners led the round with additional participation from new investors Johnson & Johnson Innovation – JJDC, Inc., Kaitai Capital, PSQ Capital, and Michigan Capital Network Venture Fund III. Bios Partners has been an excellent partner and lead investor for another EV portfolio company, Trefoil Therapeutics. We’re gratified by their investment in ONL and have immediately seen the impact of their non-financial support. “Bios Partners has been instrumental in working with our team to build the syndicate and strengthen our plans,” stated David Esposito, ONL CEO.  

Dr. Rahhal is quickly becoming a prolific podcaster. In this week's roundup Firas hosts three podcasts with another impressive list of guests offering different perspectives on ophthalmic innovation. 

In this third OIS Retina Podcast, host Firas Rahhal, MD, sat down with Paul Hallen, VP, Global Head, Retina and Glaucoma, at Alcon, who talks about how he grew with the company over 31 years and provides an engineer’s perspective on how far innovation in retina surgery has come, and where it’s heading. ​
Watch the conversation on YouTube. 

In the fourth installment of the OIS Retina Podcast guest is French-born Patricia Zilliox, who boomeranged back to her homeland to become president and CEO of Eyevensys. Before that she’d spent 25 years with Alcon before joining the Foundation Fighting Blindness as chief drug development officer. Having spent so much time evaluating new therapies at FFB, she was intrigued by Eyevensys’ unique platform to enable the sustained intraocular production of therapeutic proteins to treat a broad range of ophthalmic disease. Listen to hear Patricia share more details on Eyevensys’ lead product: a gene therapy to treat uveitis. 
Watch the conversation here. 

In this episode of the OIS Retina Podcast, Firas is joined by legendary vitreoretinal specialist and serial entrepreneur, Mark Blumenkranz, MD, MMS. It hasn’t always been smooth sailing in the start-up ship, but Dr. Blumenkranz persevered and now shares his proven recipe for ophthalmic innovation. (Hint: It starts with an unmet need.) Dr. Blumenkranz also talks about his investment/incubation firm Lagunitas Biosciences and drug delivery start-up Kedalion Therapeutics. 
​Watch the conversation here. 

LensGen maintains momentum in their work toward an Investigational Device Exemption ("IDE") approval by closing additional financing and adding James (Jim) Mazzo to the board. Jim brings over 40 years of ophthalmic industry experience. The $10 million is an important step toward the company's Series B financing that will fund LensGen through approval of Juvene IOL pivotal FDA study. 
Read the full announcement here. 
​

LensGen CEO Ram Rao sits down with Dr. Ehsan Sadri on the OIS Podcast to discuss his entrepreneurial journey, the recent financing, and the history of LensGen. Listen here and see below for a video of the discussion. 

Phase 1/2 “INTREPID” trial to evaluate safety and ability of engineered FGF-1 to regenerate corneal endothelial cells San Diego, CA – August 19, 2020 – Trefoil Therapeutics today announced it has initiated the first clinical trial of its engineered Fibroblast Growth Factor-1 TTHX1114 for the regenerative treatment of people with corneal endothelial dystrophies (CED), including Fuchs Endothelial Corneal Dystrophy. The Phase 1/2 trial (“INTREPID”) is designed to evaluate TTHX1114’s safety and ability to stimulate the regeneration of corneal endothelial cells lost due to CED when administered by intracameral (back of the cornea) injection. Continue reading

Watch CEO David Eveleth at OIS@AAO.

ExSight founding partner, Dr. Firas Rahhal, is no stranger to the OIS stage and has even had a turn as host of OIS TV. Firas discusses this new role below.

It has been an honor and a privilege to be invited to host the new OIS-Retina Podcast.  The OIS has become one of the best and most important meetings in Ophthalmology over the last decade or so.  I have been attending regularly, along with my partners at ExSight Ventures, since 2014, and have become a more active participant in the last few years.  It is the meeting place for innovators, industry professionals, clinical scientists, clinicians, and investors.  There is no other meeting with this great constellation of professionals in the field of ophthalmology. 

So the OIS-Retina Podcast seeks to mimic this unique offering of information, discussion, education, and possibly debate, in the form of small group dialogue or interview between myself and many of the individual stakeholders in this space.  Of course, given the name of the Podcast itself and my particular clinical expertise, many of the discussions will revolve around the posterior segment of the eye, but will certainly not be exclusively so.

I will attempt to have a mixture of guests from all parties in the previously mentioned fields, namely the innovators/founders, the CEOs and CMOs of the “small” start-up companies, the upper management personnel from the “big” corporations, as well as individuals from leading investment groups.  With my busy clinical vitreoretinal surgery practice (Retina Vitreous Associates in LA), significant involvement in clinical trials, and role at ExSight Ventures as a background and hopefully lending some context, I will ask questions probing all aspects of the innovation and development process. Topics will range from first de novo ideas in the lab, all the way to commercialization, and ultimately market acceptance.  We will cover drugs, devices, and diagnostics in the retina space.  I hope to explore in some detail the thoughts of our experts on topics including basic science, clinical trials, team-building, business management, fundraising, career decision-making, and of course, issues around work-life balance. I will be speaking to a group of highly successful, hard-working people, and it will be great to get a sense of who they are and learn a bit about their personal histories.
​​
I would also like to thank my friend and colleague, Craig Simak, Co-Founder of OIS, for entrusting me with the OIS-Retina Podcast, and will do my best to simply stay out of the way while we hear from these amazing leaders and innovators in our field.

ExSight Ventures ("ExSight") is pleased to announce our investment Re-Vana Therapeutics, Ltd, ("Re-Vana") to support pre-clinical development of sustained-release biologic and small molecule therapeutics. ExSight is proud to have led the $3.25 million pre-Series A financing with participation from InFocus Capital Partners (“InFocus”) and Visionary Ventures (“Visionary”). Leading this round represents a significant milestone in ExSight's maturation as a firm. Not coincidentally, a technology capable of sustained release biologic therapeutics has been a priority for ExSight from day one. 
 
Re-Vana is a specialty ocular therapeutic and drug delivery company developing sustained-release therapeutics for significant sight-threatening ocular diseases. The technology was spun out from Queen's University Belfast, Northern Ireland. Re-Vana's sustained release ophthalmic therapeutics promise to reduce the frequency of intravitreal injections required to treat a wide range of retinal diseases, including neovascular age-related macular degeneration. The Re-Vana platform has the potential to deliver at least 4 to 6 months sustained delivery of a large molecule biologic, including anti-VEGF therapies. Re-Vana's technology could spur a new generation of glaucoma medications that may reduce or eliminate the need for eye drops by delivering small molecules for 6 to 9 months or longer. Re-Vana has also secured the rights to a novel nanoparticle polymer-based drug delivery technology for ophthalmic applications.
 
ExSight's Re-Vana investment is the culmination of over two years of our team's efforts. Working closely with Re-Vana's founders and leadership team we were able to lead this round and build a syndicate of other respected existing and new investors. ExSight led the first tranche closing of $2.08 million with participation from InFocus Capital Partners and existing U.K. investors, including TechStart Ventures, Clarendon Fund Managers, and Qubis Ltd. ExSight added to our investment with an AngelList Syndicate. Visionary Ventures led the second closing of $1.17 million. 
 
With the second closing, Re-Vana became the first company in which all three specialized U.S. ophthalmic funds have invested in the same company. Re-Vana's President and Chief Executive Officer Michael O'Rourke said, "We are especially fortunate to have participation from three highly respected U.S. ophthalmic-focused investors." ExSight echoes Mr. O’Rourke’s sentiments and we are grateful to have substantial participation from InFocus and Visionary. The proceeds will advance proof-of-concept development for Re-Vana's proprietary photocrosslinked EyeLief™ and OcuLief™ biodegradable technologies for the delivery of biologic and small molecule therapeutics, as well as enable expansion of the company's research and development team.
 
Dr. Rahhal first met Re-Vana's CEO, Michael O'Rourke at OIS@ASRS in August 2017 and was immediately impressed with the promise of Re-Vana's technology and Mr. O'Rourke's in-depth ophthalmic industry knowledge and experience. The ExSight team had grown skeptical of drug delivery technologies due to limitations in several underlying technologies. An initial conversation with Dr. Raj Thakur, CSO and Co-Founder, established our confidence in Re-Vana's approach. Reflecting on the experience, Dr. Rahhal said, "Joining up with Re-Vana is very gratifying because we are so confident in the clinical relevance and, ultimately, direct and profound impact on patient care, something we have felt since first meeting Michael O'Rourke and Dr. Thakur and learning about the technology over two years ago."
 
As part of this financing ExSight's James Murray will join Re-Vana's Board of Directors along with representatives from InFocus and Visionary. Dr. Rahhal commented, "James, as a result of our deep understanding and confidence in Re-Vana, has done an amazing job putting together the syndicate needed for the current round. It is a terrific blend of experience and talent. I look forward to working with this great team in the coming months and years to bring Re-Vana's products to patients." Dr. Rahhal and Dr. Nissen will join the Re-Vana Scientific Advisory Board. Dr. Nissen added, “Supporting important drug delivery technology has been a major goal at ExSight since the firm’s inception. Re-Vana is a clear standout of all the companies we have studied.  Michael O’Rourke and the Re-Vana team have the experience and the vision bring their products to market and have a significant positive impact on patient’s lives. We are proud to partner with Re-Vana in developing EyeLief™ and OcuLief™.”

We are grateful to join Mr. O'Rourke, Dr. Thakur, the Re-Vana team, and a remarkable group of investors in bringing this much needed therapeutic technology to the clinic and improving patient care.
​
See also:
Full Press Release

​ExSight Ventures ("EV") is pleased to announce our continued involvement and additional investment in Envision Diagnostics, Inc. ("Envision"). EV joined existing investors and new investors in Envision’s recent Series A financing. Envision is developing diagnostic devices that capture eye exams digitally. Envision's all-in-one box solution enables faster, cheaper, and more accurate readings of an eye exam. The Envision device will translate into higher quality and more efficient eye exams.
 
EV has committed additional capital in this Series A financing. Proceeds from this Series A round will fund the development of the company's Version 4 Instrument and allow Envision to execute its FDA strategy.
 
Envision recently successfully completed a clinical trial that compared Envision’s results to standard of care.
 
Envision continues to develop and iterate on its current prototype at Dr. Rahhal's clinic. Envision's data collection and standardization will revolutionize the standard of care for ophthalmology patients "by enabling consistent, reproducible testing and robust reference ranges that facilitate identification of abnormalities."
 
Envision's automation will reshape the ophthalmology by decreasing cost, increasing efficiency, improving quality, and standardizing eye exams.
 
We expect strong demand and a steep adoption curve based on clinical insights by the ExSight team and others. Funding was the single biggest challenge facing the company. With this issue now resolved, we are confident in Envision's ability to deliver on their promise of revolutionizing eye care.