Peptide therapeutics are being introduced into ophthalmology

(Image Credit: AdobeStock/Christoph Burgstedt)

Reviewed by Robert Yu

YP-P10 (Yuyu Pharma), a novel, patented synthetic peptide, is being evaluated for safety, tolerability, and efficacy in the phase 2 clinical trial ICECAP 1 (NCT05467293). Yuyu Pharma describes the treatment as an ophthalmic solution with anti-inflammatory properties and the potential to manage dry eye disease (DED).

Peptide therapy has already been explored in other medical specialties such as cardiology, endocrinology, gastroenterology, oncology, orthopedics, and pain management. It is a new treatment entity being introduced into ophthalmology.

Robert Yu, president and CEO of Yuyu Pharma, which is based in South Korea, explained that although relatively new to the eye care armamentarium, peptides are increasingly becoming a larger part of the pharmaceutical conversation, and they offer the potential for significant advantages over existing treatment modalities. Interest and investment in peptides have increased over time, and eye care is joining other specialties as targets for peptide drug development.

Peptide research has grown exponentially because of innovations in processing technology and the ability to mimic natural pathways; in addition, peptides can serve as replacement therapies to augment low levels of natural peptides.^1-3

Yuyu Pharma received clearance in April 2022 from the FDA for its investigational new drug application for YP-P10 ophthalmic solution, which enabled the company to start the phase 2 clinical trial in patients with DED. Patient enrollment began in July 2022.

Dry eye in the spotlight

Dry eye is a highly prevalent disease that can range from 5% to 50% of a given population, with women affected more frequently.⁴ Surveys of patients have shown that low percentages of patients find long-term relief.⁵

One of the main challenges of developing dry eye therapeutics is that they should be water soluble for ease of use; YP-P10 is highly water soluble. Toxicology studies so far have shown a good safety profile. The next step is evaluation of the efficacy through the ICECAP 1 clinical trial.

Another challenge, he explained, is developing technologies that can prolong the drug’s presence in the eye. Thus far, in vitro and in vivo studies have suggested that the formulation decreases cytokines and chemokines, a finding that needs further evaluation. “If we see that keeping the drug on the eye longer makes sense, then we will explore options,” he commented.

Raising the question: What is a peptide?

A company news release explained that peptides are short amino acid chains that are linked by peptide bonds. Chains of fewer than 20 amino acids are called oligopeptides and include dipeptides, tripeptides, and tetrapeptides. Peptides, such as insulin, can occur naturally or be created synthetically.

Like anything else, peptides have associated advantages and disadvantages. Because of their short half-life, rapid clearance, and lack of oral availability, peptides have not been popular choices in the past for pharmaceutical companies to develop into potential therapeutics. However, innovations in technology and manufacturing have led to increased interest in peptide development because of the introduction of new formulations, alternative delivery methods, and better stability.^3,6 The published literature on the topic has shown exponential growth spanning 6 decades, with most of it occurring during the past 20 years.

As Yu explained, when compared with small molecules, peptides potentially offer a better safety profile and improved tolerability with efficacy.^6,7 Other advantages include a broad range of targets because of stronger binding affinity and specificity to the target compared to small molecules, high chemical and biologic diversity, high selectivity, low tissue accumulation, standard synthetic protocols, and lower production complexity and costs.^3,8

Yu also pointed out that peptides do not have the disadvantages associated with biologics, such as low stability, expensive manufacturing costs, difficulty for patients to take, low tissue penetration, and limited shelf life. Peptides have the potential to provide more targeted therapy because they usually exert strong binding affinity and specificity to the target compared to small molecules. Approved peptide therapeutics have shown advantages over small molecules without the previously mentioned drawbacks of biologics.

Preclinical data

Yu reported that studies conducted in animal models of dry eye have shown dose-dependent decreases in several dry eye-associated inflammatory mediators and improvement in corneal damage. “These findings indicate that YP-P10 ophthalmic solution may have corticosteroid-like anti-inflammatory activity on dry eye-induced ocular surface inflammation,” he said.

The multicenter ICECAP 1 study is the company’s first pharmaceutical trial in the US and includes 240 participants. The first results are expected to be reported in the middle of 2023.

Robert Yu

E: wsyu@yuyu.co.kr

Yu is the president and CEO of Yuyu Pharma.

References:

1. Wang L, Wang N, Zhang W, et al. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. 2022;7(1):48. doi:10.1038/s41392-022-00904-4

2. Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26(10):2700-2707. doi:10.1016/j.bmc.2017.06.052

3. La Manna S, Di Natale C, Florio D, Marasco D. Peptides as therapeutic agents for inflammatory diseases. Int J Mol Sci. 2018;19(9):2714. doi:10.3390/ijms19092714

4. Chern KJ, Nettesheim ER, Reid CA, Li NW, Marcoe GH, Lipinski DM. Prostaglandin-based rAAV-mediated glaucoma gene therapy in brown Norway rats. Commun Biol. 2022;5(1):1169. doi:10.1038/s42003-022-04134-w

5. Kang JM, Tanna AP. Glaucoma. Med Clin North Am. 2021;105(3):493-510. doi:10.1016/j.mcna.2021.01.004

6. Goodwin D, Simerska P, Toth I. Peptides as therapeutics with enhanced bioactivity. Curr Med Chem. 2012;19(26):4451-4461. doi:10.2174/092986712803251548

7. Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M. Synthetic therapeutic peptides: science and market. Drug Discov Today. 2010;15(1-2):40-56. doi:10.1016/j.drudis.2009.10.009

8. Recio C, Maione F, Iqbal AJ, Mascolo N, De Feo V. The potential therapeutic application of peptides and peptidomimetics in cardiovascular disease. Front Pharmacol. 2017;7:526. doi:10.3389/fphar.2016.00526