Helping Patients See the Future: ONL Therapeutics, Inc.
Vision is an amazing thing. You’re using your vision to read this right now. Think of how much you use your sight every day, how much your perception of the world relies on this key sense. You probably haven’t stopped to really think about it. Many people take their vision for granted. As is true for many things, you may not fully appreciate your vision until you’ve lost it.
Stop for a minute and ask yourself: how would your world would change if you lost your vision? How would it impact your ability to do your job? How would you get to your job? Would you be able to drive? Take the bus? Or even safely walk somewhere? At home, would you feel comfortable navigating your kitchen to cook yourself meals? What would you do for entertainment? Probably not the same things you do now. If you lost your vision, imagine how different the memories you create with your family and friends would be.
Loss of vision is a huge medical problem, as well as an emotional issue. There is a high prevalence of depression and isolation associated with vision loss. It also has a major economic impact. Billions of dollars are lost in direct costs (healthcare costs) and indirect costs (loss of productivity, family members leaving the workforce to care for loved ones).
For millions of people around the world, this isn’t just a thought exercise. There are real-life implications. Many of these people suffer from diseases and conditions that affect the retina, the back of the eye that’s responsible for capturing images you see and sending them to the brain. These people suffer from diseases like glaucoma, age-related macular degeneration (AMD), and inherited retinal degenerations (IRD).
In these diseases, as well as other retinal diseases and conditions, the root cause of vision loss is the death of retinal cells. Two key cell types that die off in disease are photoreceptors and retinal ganglion cells. The photoreceptors, which include rod and cone cells, act like the film in a camera, capturing the light and images you see. The retinal ganglion cells transmit these images to the brain, much like how a cluster of wires or cables transmit information to your television. As these cells die off in disease, the image that you see loses resolution and gets patchy. This continues until enough cells die off that you lose functional vision and become blind.
The retinal cell death seen in retinal diseases share a common biological component: the Fas receptor. This signaling receptor is on the surface of retinal cells and acts as the first domino to fall in the cell death process. Blocking this receptor from activating may prevent cells from dying, thereby protecting retinal cells and preserving vision in patients with retinal disease.
Inhibiting the Fas receptor to protect the vision of patients is the goal of ONL Therapeutics (ONL), an Ann Arbor, Michigan based biotech start up that was spun out of the University of Michigan in 2011. ONL has developed a platform of inhibitors to the Fas receptor, based on the work from the lab of Dr. David Zacks, a co-founder of ONL and a clinician-scientist at the University of Michigan’s Kellogg Eye Center. The company has generated a body of promising data showing that its Fas inhibitors protect retinal cells in a variety of retinal disease models.
Interestingly, ONL found that its Fas inhibitors not only keep retinal cells alive, but the inhibitors also had a positive effect on the retinal microenvironment. In retinal disease, the microenvironment, which includes multiple cell types in addition to the photoreceptors and retinal ganglion cells, becomes a site of inflammation.
You may be familiar with inflammation in the context of a sprained ankle or a bee sting. In these cases, you have immune cells rushing into the site of injury or disease, ready to fight off invaders and eliminate sick cells. This is similar to what happens in the retina. The diseased retina causes immune cells to traffic to the retina, and since these cells are primed to kill things, they cause additional cell death and tissue damage, impacting your ability to see. Imagine a house on fire as a stand in for a diseased and dying retinal cell. This house on fire attracts the attention of a bunch of arsonists (immune cells) who rush to the area and start pouring gasoline on neighboring houses. Without intervention, eventually the whole neighborhood is ablaze, leading to more destruction.
ONL’s preclinical data suggest that its Fas inhibitors, in addition to protecting the diseased retinal cells, will act on the retinal microenvironment and prevent retinal inflammation. In essence, the hope is to help extinguish the initial house fire, as well as prevent the whole neighborhood from going up in smoke.
Clinically, the company hopes to initially test this hypothesis in retinal detachment, a retinal condition that results in photoreceptor death. The company is initiating First-in-Human clinical trials in Australia in the fall of 2019 and is in the process of raising a Series B financing round to help fund future clinical development activities. If the company is successful, its therapeutics could have meaningful impact on the lives of patients with retinal disease, helping millions of people see the future.
To learn more about ONL Therapeutics, please visit www.onltherapeutics.com
Special thanks to:
David Esposito, CEO, ONL Therapeutics (desposito@onltherapeutics.com)
Robert Forgey, VP Operations, ONL Therapeutics (rforgey@onltherapeutics.com)