Elixirgen Therapeutics’ Innovative Approach to mRNA Therapeutics

Aki Ko, Co-Founder and CEO,
Elixirgen Therapeutics

In the rapidly evolving biotech landscape, Elixirgen Therapeutics distinguishes itself through its clear vision and innovative approach. Aki Ko, Co-Founder and CEO of Elixirgen Therapeutics, has steered the company into a mission to use mRNA technologies to unlock new therapeutic avenues for diseases currently deemed incurable.

Xtalks spoke with Ko to learn about Elixirgen Therapeutics’ cutting-edge mRNA platforms and research.

“We started in 2017… we’re basically an mRNA innovation company with roots in the aging and stem cell fields originally,” shares Ko.

Founded in Baltimore, Maryland, a vibrant science hub, Elixirgen Therapeutics emerged from a vision to harness the untapped potential of mRNA technology. In a field quickly gaining attention for its role in vaccine development and personalized medicine, Elixirgen Therapeutics stands out through its pursuit of innovation and safety.

The company is currently testing its lead candidate, EXG-34217 — an autologous cell therapy in Phase I/II trials for treating telomere biology disorders (TBDs), conditions known to cause bone marrow failure with treatments mainly limited to complicated bone marrow transplants.

“We’re doing cutting-edge mRNA, and we deeply care about patient safety, which is why we design patient safety directly into the core of the therapies.”

— Aki Ko

Additionally, Elixirgen Therapeutics has unveiled promising preclinical results for its Bobcat mRNA technology at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Orlando, Florida. This innovative technology, capable of carrying large protein payloads, has demonstrated potential in restoring muscular function in a mouse model of Duchenne muscular dystrophy (DMD) through the delivery of a full-length dystrophin protein.

Through this exclusive interview with Ko, we gain unprecedented insights into the journey of Elixirgen Therapeutics — the innovative mRNA platforms they’ve developed and the future they envision.

XTALKS CLINICAL EDGE: Issue 2 — Elixirgen Therapeutics’ Interview

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Elixirgen Therapeutics’ Revolutionary mRNA Platforms

Elixirgen Therapeutics’ suite comprises three advanced mRNA platforms, each designed to address unmet medical needs with precision and safety. These platforms — Bobcat mRNATM, controllable self-replicating RNA (c-srRNA) and ZSCAN4 delivered by an RNA virus — represent the forefront of genetic therapy, harnessing the power of mRNA to combat diseases at their genetic roots.

Bobcat mRNATM: Targeting Rare Diseases

Elixirgen Therapeutics’ Bobcat mRNATM platform gives hope in the fight against rare diseases, particularly those caused by deficiencies in large proteins. This innovative technology represents an advancement in genetic therapy, offering the potential to deliver therapeutic proteins previously considered too large for effective treatment.

This capability is crucial for diseases like DMD, where the absence or malfunction of the dystrophin protein — a protein larger than 13 kilobases in size — leads to progressive muscle degeneration and weakness. By enabling the delivery of full-length dystrophin, Bobcat mRNATM offers a promising approach to treating DMD, a condition that has long challenged the medical community.

The preclinical data of Bobcat mRNATM in a mouse model of DMD underscores its potential to restore muscular function and significantly improve the quality of life for patients. This breakthrough is not just a step forward in treating DMD; it’s a proof of concept that large protein delivery via mRNA is feasible, opening the door to potentially addressing a wide array of genetic disorders previously deemed untreatable at the genetic level.

c-srRNA: A Temperature-Controllable Innovation

Elixirgen Therapeutics’ c-srRNA platform offers a novel approach to controlling gene expression through temperature sensitivity.

The essence of the c-srRNA platform lies in its innovative use of temperature as a regulatory mechanism. By engineering self-replicating RNA that is most active at lower temperatures — specifically, those mimicking the human skin’s temperature (30°C to 35°C) — and that deactivates at higher temperatures (core body temperature of 37°C and above), Elixirgen Therapeutics has crafted a system that combines the expression capabilities of self-replicating RNA with control over gene expression. This temperature controllability aims to ensure that therapeutic proteins are produced only when and where needed, thereby minimizing potential side effects and maximizing efficacy.

Initially applied to the development of a vaccine for SARS-CoV-2, the c-srRNA platform has demonstrated its potential for broad applicability in other therapeutic areas, including cancer vaccines. The ability to fine-tune the expression of antigens or therapeutic proteins based on temperature can not only enhance the safety profile of these treatments but also open the door to personalized medicine applications where treatments can be tailored to the specific conditions of individual patients.

ZSCAN4 and Telomere Biology Disorders

The ZSCAN4 gene produces a protein that plays a crucial role in maintaining telomeres. Telomeres, the protective caps at the ends of chromosomes, naturally shorten as cells divide and as people age, but in TBDs, this process accelerates, leading to the early onset of diseases such as bone marrow failure. Elixirgen Therapeutics’ ZSCAN4 platform specifically targets TBDs and their pioneering work with ZSCAN4 aims to counteract this accelerated shortening, offering a potential lifeline to patients with few other options.

The ZSCAN4 technology, initially discovered by the company’s Chief Scientific Officer Minoru Ko at the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), can play a crucial role in stabilizing and protecting the genome.

Elixirgen Therapeutics leverages this technology in their lead candidate, EXG-34217, for treating TBDs. EXG-34217 is an autologous cell therapy, meaning it uses the patient’s own cells, modified to express ZSCAN4 and thereby extend their telomeres. This approach presents a groundbreaking step forward in treating TBDs, diseases that have had no cure beyond complex and risky bone marrow transplants.

“We extend the telomeres of the patient’s hematopoietic stem cells…kind of like adding sand back into the top of the hourglass,” says Ko. This metaphor captures the essence of their therapeutic approach.

Elixirgen Therapeutics’ ongoing Phase I/II clinical trial for EXG-34217 is not just a test of efficacy but an important moment in regenerative medicine, potentially setting a new standard for treating age-related genetic disorders. By focusing on the root cause of TBDs — the degradation of telomeres — this therapy could offer a significant improvement in quality of life and longevity for patients who currently face a grim prognosis.

Looking Ahead: The Future of Elixirgen Therapeutics

As Elixirgen Therapeutics looks to the next five to ten years, the focus remains on accelerating the development of their mRNA platforms and fulfilling their pledge to deliver transformative therapies to patients.

“Delivering on the promise to the patients is the one and only goal that we have,” Ko asserts, highlighting their dedication to making a tangible impact on patient care.

At the heart of Elixirgen Therapeutics’ mission is a deep commitment to patient safety and well-being. This commitment shapes their R&D strategies, with patient experiences and feedback playing a crucial role in therapy design.

And their journey is not without its hurdles, particularly in the complex regulatory landscape of innovative therapies. Ko emphasizes the importance of staying current with regulatory changes and engaging with clinical and regulatory programs to navigate these challenges effectively.

Through Ko’s insights, it’s clear that Elixirgen Therapeutics has a steadfast commitment to innovation, patient safety and therapeutic efficacy. The company stands ready to redefine the possibilities of mRNA technology for treating rare and challenging diseases.

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