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The Pipeline | Jan/Feb '14

Kala Pharmaceuticals, Inc.

Tackling the challenge of drug delivery in the eye is a daunting task, with limited treatments available to eye care professionals in terms of bioavailability and convenience. For example, current treatments for retinal diseases involve intravitreal injections, laser therapy, or implants. Recognizing the need for improved drug delivery in ophthalmology, Kala Pharmaceuticals, Inc., is building a diversified pipeline of innovative products that rapidly and effectively penetrate the mucosal barrier to treat ocular disease. The company, formed in 2009, was founded on a breakthrough mucus penetrating particle (MPP) nanotechnology based on decade-long work at Johns Hopkins University. It is now advancing treatments for five ocular diseases, four of which are entering clinical development early next year.

Kala counts one of history’s most prolific inventors in medicine, Massachusetts Institute of Technology’s Robert Langer, ScD, as a cofounder and director. The recipient of more than 220 major awards, Dr. Langer has received many accolades, including being named one of the most important people in America and one of the top 18 people in science or medicine in America by Time Magazine and CNN. He is one of only seven individuals to receive both the United States National Medal of Science and the United States National Medal of Technology and Innovation. Dr. Langer is also cofounder of InVivo Therapeutics Holdings Corp., a developer of technologies for the treatment of neurotrauma conditions, and Blend Therapeutics, a biopharmaceutical company dedicated to novel drug discovery and nanotechnology. Kala is venture backed by leading investors, including Lux Capital, Polaris Venture Partners, Third Rock Ventures, and Crown Venture Fund, LLC.

With its proprietary MPP nanotechnology, Kala has already achieved impressive bioavailability for a variety of therapeutic agents, including their lead products, into ocular tissue in animal models.1 MPPs uniquely evade the defense mechanisms protecting the eye by diffusing drug carrier through the mucus layer of the tear film. Nanotechnology, the science of manipulating materials on a scale smaller than 1 μm,2 has been on the verge of revolutionizing the approach to therapeutic challenges in eye care for years. It is finally making an impact on ophthalmology with Kala’s technology.

Kala’s scientists engineer drug nanoparticles to allow drug delivery, which improves drug penetration and retention and, therefore, provides opportunity for more efficacious ocular treatments. Possessing the unique ability to evade the mucus barriers protecting the eye, Kala’s MPPs reach mucus-protected tissue targets to a much higher extent than traditional delivery systems.1 Mucus consists of a heterogeneous mesh of mucin fibers, which serves as a primary defense mechanism in the body; it protects against pathogens and other foreign material by excluding particles larger than pore sizes with the mucin mesh and binding to foreign particles via glycosylated macromolecules within the mucus network. Furthermore, particles trapped in the surface mucus layer of the tear film are cleared away with blinking, which occurs approximately every 10 seconds. This has greatly limited the delivery and therapeutic efficacy of ocular drugs.

MPP technology allows therapeutic agents to avoid being trapped by the tear film and cleared via blinking, thereby extending the duration and enhancing the penetration of drugs to the site of disease. MPP combines nanometric particle size and proprietary surface engineering to achieve particles that can freely diffuse through the mucus layer of the tear film. The process features the creation of a nanoparticle crystalline core consisting of the therapeutic agent, surrounded by surface-engineered polymers that allow the drug to be inert to the mucin fibers. MPP platform technology can deliver a wide variety of molecules and could also be amenable to the delivery of biologic agents and controlled delivery.

Loteprednol etabonate ophthalmic suspension (Lotemax; Bausch + Lomb) is a popular medication for reducing postoperative ocular inflammation. Together with Kala’s MPP technology, it has revealed record levels of bioavailability. Preclinical data have demonstrated clear efficacy results for Kala’s 1% formulation of loteprednol etabonate (1% LE-MPP) in preclinical models that are on par with the current standard of care (data on file with Kala). Other ocular surface disease indications, such as dry eye and meibomian gland dysfunction, are also in development.

LE-MPP for postoperative ocular inflammation and pain is expected to enter a pivotal phase 2/3 trial in 2014, followed by a second phase 3 trial to be completed in 2015. Kala will initiate clinical trials in the United States with 0.25% LE-MPP in dry eye and blepharitis in 2014. A 0.25% loteprednol etabonate-MPP formulation for dry eye and blepharitis is also expected to enter clinical trials in 2014.

In addition, Kala plans to test the platform’s ability to deliver drugs to the back of the eye when topically applied; this trial could open a vast array of possibilities for LE-MPP use, such as for diabetic macular edema and cystoid macular edema. A research phase program featuring a topical RTKi-MPP for the treatment of wet age-related macular degeneration is advancing toward selection of a clinical candidate in 2014, with the investigational new drug submission expected in 2015.

1. Schopf L, Enlow E, Popov A, et al. Enhanced Topical Delivery of a Small Molecule Receptor Tyrosine Kinase Inhibitor (RTKi) via Mucosal- Penetrating Particle Technology. Poster presented at: ARVO 2013; May 5, 2013; Orlando, FL.

2. Zarbin MA, Montemagno C, Leary JF, Ritch R. Nanotechnology in ophthalmology. Can J Ophthalmol. 2010;45(5):457-476.

John Berdahl, MD

John Berdahl, MD, is an Assistant Professor of Ophthalmology at the University of South Dakota and in practice at Vance Thompson Vision in Sioux Falls, South Dakota. He may be reached at john.berdahl@vancethompsonvision.com.