On April 12th, the MSQ CEO Webinar Series co-hosted by MSQ Ventures and BioAroundWorld featured David Esposito, the CEO of ONL Therapeutics, as a guest speaker. The main focus of the webinar is "Developing First-In-Class Therapeutics to Protect the Vision of Patients with Retinal Disease."

Developing First-In-Class Therapeutics to Protect the Vision of Patients with Retinal Disease

Guest Speaker: David Esposito, CEO, ONL Therapeutics

Moderator: Echo Hindle-Yang, Managing Director, MSQ Ventures  

The MSQ CEO Webinar covered the progress of the company's lead compound, ONL 1204, a 12 amino acid peptide delivered via IVT injection, and its three clinical programs in retinal detachment, geographic atrophy, and open-angle glaucoma. ONL Therapeutics has raised over $60 million in four years to bring ONL 1204 to market. ONL 1204 has a unique and upstream mechanism of action, which blocks the activation of the fast receptor in retinal cells, and the inflammatory signaling that leads to the death signaling pathways within that retinal cell. ONL 1204 also blocks several of the complement pathways upstream of complement in geographic atrophy.  

The company is actively seeking investors and strategic partners to deliver phase two studies on geographic atrophy and open-angle glaucoma. ONL 1204 has shown promising results in the company's phase one study in geographic atrophy, and the company is making steady progress in its phase one studies in open-angle glaucoma. 

Presentation Highlights: 

Progress in Clinical Programs 

• ONL 1204, a 12 amino acid peptide delivered via IVT injection, has advanced across three clinical programs: retinal detachment, geographic atrophy, and open angle glaucoma. 

• Phase 1 study in retinal detachment completed successfully, and Phase 2 study in the US has begun. 

• Positive data generated in geographic atrophy and open angle glaucoma. 

• Pipeline update includes progress in acute indications and chronic diseases, as well as a gene therapy program. 

• Open label dose escalation study in geographic atrophy showed potential efficacy of ONL 1204 in 6 patients over 24 weeks. 

• Single injection of ONL 1204 at different doses monitored for 24 weeks. 

• Data shows positive results in two patients at 50 micrograms and two patients at 100-200 micrograms. 

Unique Mechanism of Action 

• ONL 1204 blocks the activation of the fast receptor, which triggers death and inflammatory signaling pathways in retinal cells. 

• Biological activity of ONL 1204 on the fast receptor confirmed in Phase 1 study in retinal detachment. 

• Fast receptor is upstream of complement, offering a unique opportunity in geographic atrophy. 

Investor and Strategic Partner Opportunities 

• ONL Therapeutics actively looking for investors and strategic partners to support Phase 2 studies in geographic atrophy and open angle glaucoma. 

• Highlight of Board of Directors and Scientific Advisory Board, including notable investors such as BIOS Partners, Johnson & Johnson, and Novartis. 

Q&A Sessions 

Current treatment challenges for NTG: Lowering intraocular pressure and adherence issues 

Echo: What are the current products on the market to treat normal tension glaucoma (NTG) in the US and Asia, and why are they not working very well? 

David: There are a number of therapeutic and surgical options to treat glaucoma, including normal tension glaucoma, which primarily involve lowering intraocular pressure. Initial therapy options for NTG often involve topical beta blockers or other therapeutics to lower intraocular pressure. However, adherence to these drops can be challenging. Surgical interventions such as laser procedures or minimally invasive glaucoma surgeries are becoming more common as first-line therapy to lower intraocular pressure. ONL Therapeutics believes that their neuroprotection therapy, ONL1204, could offer a pressure-independent treatment option for NTG patients, who may already have normal pressure or may be on a pathway to surgery. ONL1204 is currently in Phase 1B clinical trials and has shown potential as a pressure-independent treatment for glaucoma in preclinical data. 

Treatment options for OA and NTG: Managing intraocular pressure 

Echo: Can you explain the difference between OA and NTG? 

David: Open angle glaucoma (OA) is a condition where there is continued loss of visual field primarily due to increased intraocular pressure, which can be managed through various therapeutic options or surgical procedures to lower the pressure. On the other hand, in normal tension glaucoma (NTG), intraocular pressure is within the normal range, but there is still a desire to lower the pressure to protect the optic nerve and slow visual field progression. However, even with lowered intraocular pressure, there is still visual field loss and optic nerve damage, which is where neuroprotection therapy like ONL1204 can offer an opportunity for treatment. 

Changing landscape of glaucoma treatment in the US: Shift towards surgical interventions 

Echo: How has the market for glaucoma management been in the past five years and what are the new trends in the US? 

David: The market for glaucoma management has seen a shift towards surgical procedures in the last five to seven years. While generic beta blockers like timolol still serve as a baseline therapy to lower intraocular pressure, there has been a rapid progression towards surgical procedures such as laser procedures or minimally invasive glaucoma surgeries. These procedures create better outflow through the trabecular meshwork to support lowering intraocular pressure. Specialists have noticed a lack of adherence to topical therapeutics, which has led to a faster progression towards surgery as a solution. 

Innovative Approach for Long-term Success in Retinal Disease Treatments: Pressure Independent Treatment with ONL1204 via IVT Injection 

Echo: How does ONL Therapeutics plan to stay competitive in the field of retinal disease treatments and ensure long-term success? 

David: ONL Therapeutics plans to differentiate itself by using ONL1204, a pressure independent treatment for glaucoma, which can be delivered via IVT injection by a clinician, ensuring patient adherence to therapy. They believe this provides a competitive advantage over surgical procedures and ensures that patients receive the therapeutic option. They are currently focused on the Phase 2 study design for glaucoma using ONL1204. 

Targeting Patient Group and Unique Partnership Opportunities for ONL1204 in China 

Echo: Which patient group is best suited for ONL1204 treatment? 

David: The company believes that ONL1204 could be applicable to all glaucoma patients, but sees unique benefits in normal tension glaucoma patients due to ONL1204's pressure-independent treatment mechanism. The company also sees potential for a partnership in China focused specifically on normal tension glaucoma given its high prevalence in the Asian population. There is no specific therapeutic window for ONL1204, but the company believes it could offer a unique mechanism of action beyond lowering intraocular pressure and could potentially delay or reduce the need for surgical intervention in glaucoma patients. The drug is currently in Phase 1 clinical trials, and preliminary results suggest that it is safe and well-tolerated, with some early hints of efficacy. 

Early Insights from Glaucoma Study: Safety, Tolerability, and Preliminary Efficacy Signals of ONL1204 

Echo: What are the early results and insights from ONL Therapeutics' glaucoma trial so far? 

David: ONL Therapeutics has treated over 20 patients with multiple injections of ONL1204 in its glaucoma study, with a target of 25 patients. The preliminary results indicate that ONL1204 is safe and well tolerated by patients with open angle glaucoma. There are early hints of efficacy in the form of an impact on the retinal nerve fiber layer, and ONL Therapeutics is currently assessing the data on slowing visual field progression. More detailed data will be presented at the ARVO research meeting at the end of April. ONL Therapeutics is optimistic about the potential impact of ONL1204 on glaucoma and hopes to build confidence in its efficacy over the coming months. 

Potential Combination Development Plan for ONL1204 in Glaucoma: Neuroprotective and Pressure-Independent Therapeutic Option 

Echo: Does ONL Therapeutics have plans to use ONL1204 in combination with other glaucoma treatments? 

David: ONL Therapeutics sees the potential for ONL1204 to be used as a supportive, concomitant therapeutic option on top of standard of care therapeutic options such as beta blockers or Rho kinase inhibitors to lower intraocular pressure. However, ONL Therapeutics believes that ONL1204 offers a unique benefit as a neuroprotective, pressure-independent therapeutic option for glaucoma patients. ONL1204 has the potential to minimize the therapeutic burden on patients who are currently using multiple therapeutic drops and potentially slow down the progression of visual field loss, reducing the need for surgical intervention. 

Seeking an Ideal Partner for Accelerating Development in China and Beyond 

Echo: What is the ideal partner for ONL Therapeutics in terms of accelerating the development of ONL1204 across different indications? 

David: ONL Therapeutics is looking for a China partner with scientific and clinical development expertise in the China market. The ideal partner should have an active interest in the potential for ONL1204 in the acute indication of retinal detachment, chronic indications of geographic atrophy, and open angle glaucoma. The partnership structure could involve equity investment to accelerate phase two, code development partnership, or a broader cross-border collaboration of a combined US, Europe, and China patient population and study. ONL Therapeutics is open to different partnership structures as long as they can find the right partner to help them accomplish their goals. 

Accelerating Development of FAS receptor Inhibition for Impactful Patient Benefits: Exploring Global Strategies and Partnerships 

Echo: What is the company's global and exit strategy? 

David: Our goal is to move the benefits of our FAS receptor blocker through clinical trials to help patients with diseases leading to blindness. We are open to various partnership options to accelerate development, such as investing, licensing, or co-development deals. We have had success in raising capital and feel confident in finding the right partner to help us achieve our goals.