Exclusive: David Esposito in an Illuminating Discussion with PharmaShots

Shots:

Our recent Spotlight interview with David Esposito, CEO at ONL therapeutics became a major hit on the internet. We were moved by the overwhelming response from the netizens
Here we have again, David Esposito in an engaging conversation with PharmaShots. David discusses in great length about the company’s lead candidate ONL1204, currently being evaluated in P-II for retinal detachment and expects result in Q2’24
David explains the mechanism of Fas pathways current and current partnership with Novai, a UK-based company with an innovative technology, and potential collaborations that ONL may enter in future

Himanshu: Welcome again, David! Our recent Spotlight interview has garnered immense praise on the internet. People are curious to know more about your lead product ONL Therapeutics’ lead product ONL1204. Do you mind sharing some insights from the ongoing trials of ONL1204?

David: ONL’s lead candidate, ONL1204, is currently in clinical trials for retinal detachment, open angle glaucoma and geographic atrophy.

We plan to release top-line results from our Phase II retinal detachment trial in the second quarter of 2024. If these results are positive, and we believe they will be, we will initiate our Phase III retinal detachment trial in late 2024 or early 2025. We anticipate a Phase II/III registrational geographic atrophy trial and a Phase III glaucoma study to follow three to four years later.

Himanshu: The incidences of rhegmatogenous retinal detachments (RRD) have registered a significant spike in both males & females. Could you apprise our viewers of the condition and how threatening it can be to the vision?

David: A retinal detachment is a serious medical emergency, and if not addressed quickly, it can lead to permanent vision loss

Retinal detachment is an eye condition where the retina, found in the back of the eye, detaches from the surrounding tissue. The retina has light-sensitive cells responsible for converting light into neural impulses. 

These impulses communicate with your optic nerve and brain, allowing them to process what you’re seeing. When the retina separates from the supportive tissue, it no longer receives the nourishment it requires. 

Consequently, your eyes may experience irreversible damage in a short period. 

A rhegmatogenous retinal detachment happens when a tear in the retina enables fluid to get under it. When fluid accumulates under the retina, it separates it from the cell layer that provides nourishment. 

There are nearly 100,000 retinal detachment repairs annually in the US. The primary objective of ONL’s Phase 2 study is to evaluate the safety and efficacy of two doses of a single injection of ONL1204 Ophthalmic Solution as an adjunct to standard-of-care surgical repair in patients with a macula-off RRD.

Himanshu: Can we delve a little on how Fas pathway works and how it could be the reason behind various ophthalmic disorders?

David: The core of ONL Therapeutics’ biotechnology lies in inhibiting the Fas receptor, one of the body’s cornerstone mechanisms for triggering death of retinal cells in various eye diseases. The death of vital cells in the retina is a root cause of vision loss and is associated with a number of retinal diseases.

Our primary scientific focus is Fas-mediated signaling initiated by the activation of the Fas receptor at the cell surface and implicated in a variety of diseases. Inhibition of Fas signaling at the receptor represents the most direct and upstream approach to preventing its negative impact. The therapeutic benefits of blocking Fas activation and its subsequent signaling may have wide-ranging clinical value for patients suffering from retinal diseases.

Himanshu: ONL is partnering with a UK company that has a unique biomarker technology.

David: Yes. The partnership is with Novai, a UK-based company with an innovative technology. Nova’s Detection of Apoptosing Retinal Cells (DARC) technology introduces a novel dimension to the clinical assessment. DARC fluorescently labels stressed or sick retinal cells, providing a biomarker for evaluating treatment efficacy. The collaboration with Novai empowers ONL Therapeutics to leverage DARC in identifying stressed cells in eye diseases, offering a glimpse into the potential of early intervention.

Himanshu: What exactly does ONL1204 consist of?

David: ONL1204 is a small 12–amino acid peptide designed to inhibit the Fas receptor and block the Fas-mediated activation that triggers cell death, thereby protecting retinal cells from disease development. What sets ONL1204 apart is not only its role in protecting retinal cells from cell death but also its ability to block the inflammatory response that the body typically induces in response to eye disease. ONL1204 achieves a dual effect: cell protection and a reduced inflammatory response. This translates into clinical outcomes in terms of a better efficacy profile in slowing disease progression across different diseases.

Himanshu: ONL1204 is also being explored across other indications as well?

David: ONL may look to expand the drug’s use in the future to include more eye diseases such as acute glaucoma, central retinal vein occlusion or central retinal artery occlusion, and wet age-related macular degeneration.

Himanshu: ONL is preparing for a Series D and or strategic partnerships?

David: Yes, we are currently seeking investor capital or strategic partnerships to raise $75 –$100 million to run Phase II studies in geographic atrophy and open-angle glaucoma.

We are open to financing with our current investors and partners, as well as those with larger pharmaceutical partners

Himanshu: Audience, potential investors and potential partners would love to know about what is more in the pipeline of ONL.

David: We are pursuing numerous indications in the eye given the broad impact of inhibiting the Fas receptor provides the potential to impact several acute and chronic eye diseases.

Himanshu: If there are any other molecules in discovery or undisclosed stage (if yes, what could be the potential focus)

David: Yes, we do have multiple back up compounds focused on inhibiting the Fas receptor.

Image Source: Canva

About the Author:

David Esposito

David who is presently leading ONL therapeutics, also formerly served as the CEO of Armune Bioscience where he led the development and commercialization of blood-based diagnostics to improve the early detection of cancer (prostate cancer). Armune Bioscience was acquired by Exact Sciences (EXAS) in 2017. 
 
David Esposito is an experienced healthcare executive who has built and scaled multiple companies that resulted in successful exits to strategic buyers. 
 
He was President of Phadia US Inc. (allergy and autoimmune diagnostics) and played a pivotal role in the sale of the business to Thermo Fisher Scientific (TMO) in 2011. David began his career as a sales representative with Merck & Co. Inc. and rose through the ranks of sales, marketing and commercial strategy for the US Division. 
 
David is a combat veteran, led an infantry platoon with the 101st Airborne Division through several combat operations, and was recognized with a Bronze Star for combat action in Iraq in 1991. David earned his B.S. degree in Civil Engineering from the United States Military Academy at West Point and his MBA from Syracuse University. 