Schizophrenia and the Future of Long-Acting Therapeutics

Long-acting injectables help improve patient adherence in schizophrenia, but many patients dislike needles. Lyndra Therapeutics hopes to bring an oral long-acting medicine to market based on technology from MIT. Clinical trials have shown positive results to date, and the company has signed Thermo Fisher Scientific as a manufacturing partner. We spoke with Richard Scranton, President of Global Product Development and Chief Medical Officer at Lyndra Therapeutics to find out more.

What’s the story behind Lyndra?
 

Lyndra Therapeutics was founded in 2015 with technology from the Traverso and Langer Labs at MIT. The labs had been working on an approach that would extend dosing periods of oral therapies beyond 24 hours. Robert Langer, Giovanni Traverso, Andrew Bellinger, and Amy Schulman founded the company to develop and expand the technology that would ultimately become the LYNX drug delivery platform. In its early stages, Lyndra received funding from the NIH and the Gates Foundation. The early funding from NIH supported the preclinical research that proved the platform worked. 

Why focus on conditions such as schizophrenia?
 

The team thought about medical conditions where reducing medication dosing frequency would provide significant benefits to patients, caregivers and society. People living with CNS disorders, particularly those relating to mental health, have unique challenges adhering to their prescribed medications. In schizophrenia, for example, maintaining adherence to therapy is a treatment priority because non-adherence often contributes to episodes that lead to worsening of the condition. This is one reason why long-acting injectables are sometimes prescribed to individuals with schizophrenia. A long-acting oral therapy could help increase adherence further because we know people prefer this over injectables.

There’s also another potential benefit. Our technology can enable stable and sustained delivery of medicine in a target therapeutic window for a week or longer in a single oral dose. This means there are fewer peaks and troughs of drug levels, as is typical from daily dosing, and may lead patients to avoid issues relating to dose-related toxicities or side effects.

But we aren’t just focused on schizophrenia and bipolar disorders. Our platform is suitable for a variety of compounds, and we have clinical proof of concept research in five therapeutic areas: psychiatry, Alzheimer’s disease, opioid use disorder, cardiometabolic diseases and infectious disease. We have developed 25 API formulations.

What are the challenges of developing a dosage form suitable for patients with schizophrenia and other mental health conditions?
 

These conditions directly affect a person’s ability to maintain consistent treatment. For example, during a period of paranoia, patients may refuse medication; during stable periods, they may believe they no longer need it. The dosage form must, therefore, be simple to administer and highly reliable. Long-acting injectables have traditionally been used in individuals with known challenges adhering to their schizophrenia medication, but they require regular clinic visits and can be associated with injection site reactions, stigma and a feeling of a lack of control, making a long-acting oral alternative particularly valuable for this patient population.

Tell us about your drug delivery platform…
 

The LYNX drug delivery platform is designed to deliver long-acting therapies in oral form through an easy-to-swallow 00EL capsule. Once the capsule reaches the stomach, it dissolves, and the dosage form unfolds, moving freely within the stomach. Drug is continuously released at the desired level for the intended dosing duration. Time-dependent layers soften, enabling exit of the drug from the stomach and out of the body.

This approach differs from conventional oral medications by focusing on physical retention in the stomach in addition to chemical release mechanisms. In addition to lasting significantly longer than “extended release” pills, the LYNX platform has the potential to perform better in terms of pharmacokinetics by maintaining target drug levels over the dosing period.

The platform's novelty means we've had to rethink traditional approaches at every step. This includes designing specialized analytical methods to build and test the technology, establishing new quality control parameters and building expertise in areas that bridge mechanical engineering with pharmaceutical sciences. For example, Lyndra created an artificial stomach that mimics the stomach’s gastric waves and developed specialized manufacturing processes.

How would LYN-005 build on current risperidone treatments?
 

Oral weekly risperidone (LYN-005) represents an important advance in risperidone delivery as the potential first long-acting oral treatment for people with schizophrenia and bipolar 1 disorder. The development program recently achieved a significant milestone with the pivotal STARLYNG-1 (LYN-005-C-301) study, which demonstrated the efficacy of oral weekly risperidone compared to daily risperdal by meeting the primary endpoint, which included the geometric mean ratio of week 5 oral weekly risperidone drug levels compared to baseline immediate-release risperdal drug levels. The study also met its secondary endpoints for safety and Positive and Negative Syndrome Scale (PANSS) score, which is used for measuring symptom severity in schizophrenia. With these positive results, the study was stopped early according to the pre-defined stopping criteria.

A phase III pivotal safety study is planned to start in the first half of 2025 and we have agreed to a collaboration with Thermo Fisher Scientific, who will provide both manufacturing and clinical research services to streamline the development process.

We are also pursuing partnerships with developers and manufacturers of branded, generic and emerging therapeutics interested in developing long-acting oral therapies using the LYNX platform. Oral weekly therapies have the potential to transform the lives of patients living with many different conditions.

A drug in development for schizophrenia was recently listed in Clarivate’s top drugs to watch for 2025 list, which demonstrates that there is huge interest in this area. Why do you feel it’s so important for companies to innovate in areas such as mental health?
 

Innovation in mental health treatment demonstrates the broader imperative for pharmaceutical advances across complex chronic conditions. When patients require consistent, long-term medication management – whether for psychiatric conditions, diabetes, cardiovascular disease, or other conditions – optimized drug delivery and patient experience are critical factors in treatment success. We’ve heard from patients and family members that a long-acting oral medication option for schizophrenia would be valuable.

In addition to improving the patient experience through improved adherence and clinical outcomes, in schizophrenia and bipolar disorder, long-acting oral medications could also potentially deliver value to the healthcare system by reducing relapses (and therefore disease progression), hospitalizations and health costs.

In terms of the big picture, we think that developing new therapeutic approaches should be about more than creating new drug compounds. As an industry, we must improve the patient experience, supporting patients to take their medicines as prescribed and experience the full benefits of their medications.