Treating immune-mediated diseases with nanoparticles

How does COUR Pharmaceuticals’ immune-modifying nanoparticle platform differ from traditional approaches to treating immune-mediated diseases?

Most traditional approaches for treating autoimmune and inflammatory diseases treat the inflammatory mediator by trying to either remove or suppress it, for example removal of B cells non-specifically or killing T cells non-specifically that ultimately lead to broad immunosuppression. COUR nanoparticles (CNPs) induce antigen-specific immune tolerance by harnessing the body’s peripheral immune system. The underlying cause of autoimmunity is the body mistakenly identifying self-antigens as foreign and the ideal approach to treat autoimmunity is to reintroduce (re-establish) tolerance to self-antigens. By encapsulating specific self-antigens within our biodegradable nanoparticles, we enable the targeted delivery of the CNPs to antigen-presenting cells (APCs) primarily in the spleen and liver. Through phagocytosis of the CNP, these APCs are reprogrammed to present the antigens to T cells with a tolerogenic signal, leading to T cell tolerance. This process results in anergy, deletion, production of regulatory T cells and downregulation of the antigen-specific T cell response.

Essentially, our CNPs reprogramme the immune system by restoring balance and returning the body to a homeostatic state, offering a precise approach to treating immune-mediated diseases.

Could you give an overview of the candidates currently at the preclinical stage of COUR Pharmaceutical’s pipeline?

We have several candidates at the preclinical stage of development, including CNPs for type 1 diabetes (T1D), vitiligo, and are evaluating several undisclosed autoimmune diseases in which there is a significant unmet need and the disease-specific antigens have been identified.

Our most advanced preclinical program, CNP-103, targets T1D by addressing the immune-mediated destruction of pancreatic islet cells stopping disease progression.

In preclinical studies to date, treatment with CNP-103 in the NOD mouse model of diabetes has shown the ability to significantly increase the regulatory T cell phenotypes of both antigen-specific Tregs and TR1 cells. It also increased the number of tolerogenic PD-L1+ and CD206+ macrophages, a population of APCs that induces antigen specific Treg/TR1 cell differentiation and/or decreases inflammatory T cell function. The observed increases in Treg and TR1 populations resulted in a general downregulation of inflammatory cells and an increased pro-regulatory environment.

Additional preclinical studies have shown statistically significant differences in CNP-103 treated NOD mice in preventing onset and progression of diabetes by reducing the amount of immune cell infiltration within the pancreatic islets compared to the control group. Results from these preclinical studies were published in the peer-reviewed publication, Journal of Immunology in August 2022 as a “Top Read” article.

Notably, we anticipate initiating the first clinical study of CNP-103 in late 2024, on the heels of our Series A announced earlier this year on January 30.

Could you explain the development of CNP-108 for T cell immunogenicity in gene therapy, and how it induces the immune system to build a tolerance to gene therapy treatments?

CNP-108 is currently in early-stage evaluation but conceptually is similar to treating autoimmune disease. CNPs can encapsulate both AAV capsid protein and/or the target protein of the gene therapy with the goal of stopping the T cell response directed against both the target protein and the cells making the protein. It was published by Pfizer and Sarepta that the T cell component is responsible for toxicity in humans within gene therapy trials. By delivering the AAV protein in a targeted manner, CNP-108 harnesses the immune system’s learning power to induce tolerance. This process helps mitigate T cell immunogenicity associated with gene and protein therapies, potentially enhancing their safety, durability, and efficacy.

How does COUR Pharmaceuticals envision expanding the application of its nanoparticle platform to address other immune and inflammatory conditions?

We aim to expand the application of our nanoparticle platform to address a wide range of conditions beyond those currently highlighted in our pipeline. Due to the unique versatility of our platform, we can simply swap the antigens encapsulated within our nanoparticles as we target different diseases. As a result, we are confident that our technology can be leveraged to treat a wide range of immune-mediated diseases.

How does COUR Pharmaceuticals plan to mitigate potential risks associated with reprogramming the immune system using its nanoparticle platform, and what are the anticipated challenges in bringing these therapies to market?

As mentioned above, our nanoparticle platform is highly versatile. We can easily switch the disease-specific antigen(s) that are encapsulated within our CNP depending on the disease that we are targeting. To date, this interchangeability has made it possible for us to create a strong foundation of platform toxicology and Phase 1 safety and tolerability data and have safely treated over 70 human patients with autoimmune disease. This allows us to compress preclinical development and go directly into proof-of-concept Phase 2 studies.  It also has significant positive impacts on our clinical development timelines and de-risks the development of new CNPs.

In bringing our technology to the market, we expect our biggest challenge to be the acceptance of our novel technology by doctors and patients where the standard of care for decades has been focused on immune-suppressant approaches. Our nanoparticle approach is the first of its kind to clinically show antigen-specific immune reprogramming, leading to improvement in patient health. This was demonstrated in our Phase 1/2a POC in Celiac disease (now licensed to Takeda), the results of which were published in the peer-reviewed publication, Gastroenterology, in March 2021. As such, we are working diligently to educate the scientific community on how our CNPs have the potential to be an innovative new treatment option for those suffering from autoimmune diseases.

About the author

John Puisis, CEO, COUR Pharmaceuticals

John is a senior executive with over 25 years’ experience at transforming technology-based companies into product-based organisations. He combines a unique set of strategic, financial, talent management, and operating skills to identify unmet medical needs optimising an organisation to translate cutting–edge technology into products that address our most pressing hard to treat diseases to enhance people’s lives.

Prior to co-founding and joining Cour, John was Co-Founder and CEO of Tolera Therapeutics. He led the company from initial startup through manufacturing optimisation, pre-clinical, completion of a Phase 2 clinical trial, and filing of a Phase 3 Special Protocol Assessment (SPA) with the FDA. The company built significant barriers to entry by achieving several orphan drug designations and issuance of composition of matter patents utilising a unique patent strategy.

John was also instrumental to the startup of Cleveland Heart Labs (sold to LabCorp). He has served on the boards of Third Wave Technologies (NASDQ:TWTI) and ProNAi Therapeutics (NASDQ:DNAI), Tolera Therapeutics. John is a current board member at Cour Pharmaceuticals and advisory board member of NewCures of Northwestern University. He is also a member of the Economic Club of Chicago.

Prior to Tolera, he was President and CEO of Third Wave Technologies (NASDAQ: TWTI), a biotechnology company, where he led the transformation of a non-sustainable genomics tools business into a robust growth-driven molecular diagnostics company primarily by leading the development of hard to detect infections and cancers. Third Wave was eventually sold for $600 million. John also served as a strategic consultant to DEKALB Genetics Corporation (NYSE) that was ultimately sold for $3.2 billion. Earlier in his career, John was with Spencer Stuart and Egon Zehnder International, in their life sciences practice groups where he consulted with biotech and pharmaceutical firms. After receiving his BS in Accounting from Northern Illinois University, John started his career at Arthur Andersen and also worked for Price Waterhouse. He received his MBA from the Kellogg School of Management at Northwestern University.