Illimis and Lilly partner on ARIA-free Alzheimer’s therapy

The development of new Alzheimer’s disease drugs has long been considered a major challenge for the pharmaceutical and biotech industries.

While recent approvals of antibody therapies targeting amyloid beta (Aβ), such as lecanemab and donanemab, have opened new possibilities, limitations in efficacy and the side effect of amyloid-related imaging abnormalities (ARIA) still constrain broader use.

Illimis Therapeutics, a Korean bioventure, has taken on this challenge through its GAIA platform, which utilizes the TAM (Tyro3, Axl, Mer) receptor. This platform offers a novel approach to removing amyloid beta without triggering an inflammatory response. By expanding collaborations with global pharmaceutical companies, Illimis aims to shift the paradigm in Alzheimer’s disease treatment.

Korea Biomedical Review met with CEO Park Sang-hoon to discuss the technology strategy for Alzheimer’s drug development, global collaborations, and the company’s future vision.

Question: You have extensive experience as a researcher in the investment and industrial sectors. You co-founded Illimis with Professor Kim Chan-hyuk of Seoul National University, a co-founder of Curocell. Senior managers’ resumes are also quite impressive.

Answer: I majored in immunology and contemplated an academic career after my Ph.D. Even during my degree program, I developed an interest in immunotherapy development, so I decided to pursue a career in industry rather than academia. Starting in 2013, I worked at a venture capital firm, where I gained experience in biotech investing. At that time, VC investment analysts with doctoral degrees were rare. Through investing, I realized that “to become a true investor, one must directly experience entrepreneurship and new drug development.”

Later, I oversaw business development and operations at various companies, co-founding the Alzheimer’s startup Amyloid Solution in 2017. This process led me to begin serious Alzheimer’s research, culminating in the 2021 founding of Illimis Therapeutics with KAIST Professor Chung Won-suk and Seoul National University Professor Kim Chan-hyuk. The startup was born from the ambition that “Korea must also produce a true innovative new drug platform company.”

Q: You mentioned the need for a truly innovative drug platform. Is the GAIA platform the result? Could you explain this platform?

A: Existing antibody therapies rely on Fc receptors to activate microglia to remove amyloid beta. However, this process induces inflammation, leading to ARIA side effects such as brain edema or microbleeds. Additionally, the cognitive improvement effects are limited.

The GAIA platform utilizes the TAM receptor and its ligand, GAS6. The TAM receptor is involved in efferocytosis (effector cell-mediated phagocytosis), which removes dead cells without inflammation. Applying this mechanism allows for the safe removal of amyloid beta aggregates without triggering an inflammatory response. Unlike existing antibody approaches, the GAIA platform uniquely enables clearance of pathological proteins without causing neuronal damage or synaptic loss.

Q: What are the characteristics of ILM01, the first pipeline based on the GAIA platform?

A: ILM01 (GAIA-Aβ) is a fusion protein that removes amyloid beta aggregates while simultaneously protecting neurons. It induces stronger phagocytosis by utilizing not only microglia but also astrocytes. Preclinical studies showed lower inflammatory responses and significant cognitive improvement compared to aducanumab (sold as Aduhelm), while markedly reducing ARIA side effects.

The goal is to develop ILM01 as the “ARIA-free standard treatment for Alzheimer’s disease.” Preparations are underway for phase 1 clinical trials in 2027, with the secured Series B investment of 58 billion won ($41 million) also slated for concentrated allocation to this project.

Q: CMC (Chemistry, Manufacturing, and Control) issues are also a critical challenge in Alzheimer’s drug development. What strategy do you have for this aspect as you approach clinical trials?

A: CMC is a hurdle that must be overcome to enter global clinical trials. However, many Korean biotech companies struggle during the CMC development phase after candidate discovery because of limited experience in this area. We also experienced the limitations of relying solely on external outsourcing in the early stages, which led to extended development timelines and increased costs.

To address these issues, we began directly strengthening our internal CMC development capabilities with specialized personnel starting last year. This approach is not just about developing the drug; it will be a key factor in enhancing credibility when discussing technology transfer with global big pharma.

Q: I understand your collaboration structure with Eli Lilly differs significantly from other Korean drug developers. What kind of collaboration framework have you established with Lilly?

A: Following our 2022 paper publication in Nature Medicine, we held seminars with Biogen, Genentech, and others. Most significantly, our collaboration with Eli Lilly holds great meaning. Lilly is a leading research team that elucidated the ARIA side effect mechanism of antibody therapeutics, and they highly evaluated our approach utilizing the TAM receptor.

Notably, Lilly is moving beyond a simple technology review to conduct joint research in which they directly manufacture our material. We believe this exemplifies the urgent needs of global pharmaceutical companies and the technological potential of our approach. Furthermore, starting in September, we have been working at Lilly Gateway Labs in Boston, U.S., to strengthen collaboration with Lilly researchers.

We view the collaboration with Lilly as more than just a research partnership; it is a crucial process for validating our technology in the global new drug development arena. We will advance our new platform alongside world-class researchers at the heart of drug discovery.

Q: What is the pipeline expansion strategy using the GAIA platform?

A: The GAIA platform is not limited to specific targets. Beyond Alzheimer’s, we are currently developing diverse pipelines, including ILM02 (tauopathy), targeting the tau protein; ILM22 (inflammatory bowel disease), targeting TNF-α; and ILM21 (multiple sclerosis), targeting myelin debris removal. Our drug development strategy focuses on expanding into neurological and immune diseases, based on the principle of “removing causative proteins without inflammation.”

Q: What is Illimis’ long-term goal?

A: We aim to demonstrate that we can create a baseline therapy for Alzheimer’s disease in Korea, comparable to Keytruda (pembrolizumab), rather than merely discovering candidate compounds.

We also aspire to present diverse collaboration models, including IPOs and M&A, through partnerships with global pharmaceutical companies. Ultimately, we aim to change the paradigm for treating intractable brain diseases, including Alzheimer’s, and establish ourselves as a company that contributes to Korea’s biotech ecosystem.