Eyedrop Kallikrein Inhibitor Shows Promise for Diabetic Macular Edema

MedicalResearch.com Interview with:
Dr. David Kita, PhD Founder and Head of R&D Verseon Corporation Dr. David Kita, PhD
Founder and Head of R&D
Verseon Corporation

MedicalResearch.com: What is the background for this study?

Dr. Kita: The preclinical data presented at the 2017 BIO International Conference provided details about Verseon’s plasma kallikrein inhibitors for the treatment of diabetic macular edema (DME).

DME affects millions of people worldwide and is a major cause of vision loss in patients with diabetes mellitus. Upregulation of the kallikrein-kinin system in response to diabetes can result in retinal vascular permeability, which can damage the retina and eventually lead to the central vision loss associated with DME.

The current treatment options for DME include intravitreal injections of anti-VEGF agents or corticosteroids into the eye and surgical laser treatments. Long-term use of intravitreal injections is associated with side effects such as inflammation, infections, and cataracts. For anti-VEGF drugs in particular, there is also a growing concern about geographic atrophy. In addition, about 50% of patients reported at most moderate vision improvements following anti-VEGF therapy in clinical trials. This highlights the need for a new treatment that can serve as a monotherapy or as an adjuvant to current therapies.

At Verseon, we are working on inhibitors of the serine protease plasma kallikrein (KLKB1) that can be administered either topically or orally. Verseon’s unique computer-driven drug discovery platform allows us to design potent, selective drug candidates that are unlikely to be found using traditional approaches. We have generated a number of chemically distinct series of KLKB1 inhibitors and optimized multiple lead candidates, which show good activity, permeability, and solubility.

MedicalResearch.com: What are the main findings?

Dr. Kita: Verseon’s drug candidates target a validated disease pathway, the kallikrein-kinin system, and in particular inhibit plasma kallikrein at the top of the kallikrein-kinin cascade.

At the 2017 BIO International Conference, we presented an in vivo study in which our drug candidates significantly reduced retinal vascular permeability and decreased mean circulation time when dosed systemically. This demonstrates the preclinical efficacy of our compounds and suggests a slowing of the disease progression.

In addition, we presented intraocular pharmacokinetics for two series of drug candidates. Both series showed good exposure in the relevant tissues of the eye when administered topically, which is an important step in the development of eye drops. Alternatively, some of our DME candidates show high oral bioavailability, indicating that they may be suitable for oral administration.

MedicalResearch.com: What should readers take away from your report?

Dr. Kita: There is an unmet medical need for new diabetic macular edema treatments to complement or replace current VEGF-based therapies delivered through injections into the eye. The preclinical efficacy study presented at BIO 2017 shows that our drug candidates can have a positive effect on the disease progression. Furthermore, our pharmacokinetic data indicates that Verseon’s novel class of plasma kallikrein inhibitors spans compounds suitable for either eye-drop or oral delivery, which could be of great benefit for millions of patients worldwide.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Kita: In addition to the established diabetic macular edema treatment options, several companies are currently also targeting kallikrein. However, to the best of our knowledge, these drug candidates must still be administered through injections into the eye.

At Verseon, we believe that there is a substantial patient benefit associated with alternate routes of administration, even if achieving efficacy can pose a significant challenge. To address this challenge, we continue to develop combinations of compounds and formulations that will give us the best safety and efficacy profile after either topical ophthalmic or oral dosing.

MedicalResearch.com: Is there anything else you would like to add?

Dr. Kita: We believe that the preclinical results in our diabetic macular edema program also demonstrate the capabilities of our proprietary computer-driven drug discovery platform. The platform allows us to identify novel classes of compounds and advance multiple high-quality candidates, representing different chemotypes, into the clinic. In addition to the DME program, we currently have drug programs in anticoagulation and oncology. The anticoagulation program is the furthest along, with a first development candidate approaching phase I clinical trials.


Abstract presented at BIO 2017

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