Eli Lilly Bets on AI and RNA in Drug Discovery

The field of RNA-based therapeutics has witnessed significant advancements, particularly with the development of oligonucleotide-based therapies. These therapies offer a novel approach to modulating gene expression, presenting new avenues for treating diseases previously deemed intractable. Eli Lilly has strategically positioned itself at the forefront of this evolving landscape by integrating AI into its drug discovery processes, forging collaborations with innovative biotech firms, and investing in infrastructure to support RNA research.

Oligonucleotide Therapeutics: Mechanisms and Clinical Applications

Oligonucleotide therapeutics encompass a class of drugs designed to interact with RNA molecules, thereby influencing gene expression. These agents include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), which can modulate splicing, inhibit translation, or induce degradation of target mRNA. The specificity of these molecules allows for the targeting of genes that are otherwise challenging to modulate with traditional small-molecule drugs.

Clinically approved oligonucleotide therapies include:

• Nusinersen (Spinraza): an ASO approved for spinal muscular atrophy (SMA), it enhances the production of functional SMN protein by modulating SMN2 pre-mRNA splicing.
• Tofersen (Qalsody): targets SOD1 mRNA to reduce the production of mutant SOD1 protein in amyotrophic lateral sclerosis (ALS) patients with SOD1 mutations.
• Inclisiran (Leqvio): a siRNA that inhibits PCSK9 synthesis, leading to reduced LDL cholesterol levels in patients with hypercholesterolemia.

Despite these successes, challenges persist, including efficient delivery to target tissues, stability against nucleases, and minimizing off-target effects. Addressing these issues is crucial for the broader application of oligonucleotide therapeutics.

Integration of AI in RNA Therapeutics Discovery

The complexity of RNA biology and the need for precise targeting have made the integration of AI into RNA therapeutics discovery increasingly valuable. AI and machine learning algorithms can analyze vast datasets to predict RNA structures, identify potential binding sites, and optimize oligonucleotide sequences for efficacy and safety.

Companies like Creyon Bio and Genetic Leap exemplify this integration:

• Creyon Bio employs AI-driven platforms to design tissue-specific oligonucleotides, aiming to enhance safety and efficacy profiles. Their approach combines computational modeling with high-throughput screening to expedite the development process.
• Genetic Leap utilizes AI to identify and validate RNA targets, focusing on diseases with unmet medical needs. Their platform enables the rapid discovery of oligonucleotides that can modulate gene expression at the RNA level.

These AI-driven methodologies promise to accelerate the discovery and optimization of RNA therapeutics, potentially reducing development timelines and costs.

Eli Lilly’s Strategic Collaborations and Investments

Eli Lilly has recognized the transformative potential of RNA therapeutics and AI integration, leading to several strategic initiatives:

• Partnership with Creyon Bio: In April 2025, Lilly entered into a collaboration with Creyon Bio to develop RNA-targeted oligonucleotide therapies. The deal includes a $13 million upfront payment, with potential milestones and commercialization payments exceeding $1 billion. Creyon’s AI platform will be instrumental in designing therapies for both rare and common diseases (see news here).
• Collaboration with Genetic Leap: In September 2024, Lilly partnered with Genetic Leap in a deal valued up to $409 million. This collaboration leverages Genetic Leap’s AI platform to discover RNA-targeted drugs, focusing on high-priority therapeutic areas (see news here).
• Engagement with Alchemab: Lilly licensed an early-stage ALS program (ATLX-1282) from Alchemab in May 2025, building upon a prior collaboration initiated in January 2025. Alchemab’s AI-driven approach to antibody discovery complements Lilly’s focus on neurodegenerative diseases (see news here).
• License Agreement with QurAlis: In June 2024, Lilly secured global rights to develop and commercialize QRL-204, an ASO targeting UNC13A for the treatment of ALS and frontotemporal dementia. The agreement includes a $45 million upfront payment, with potential total payments up to $577 million (see news here).

In addition to these collaborations, Lilly has invested $700 million in a nucleic acid research facility in Boston, aimed at advancing the delivery and development of RNA and DNA-based medicines.

Conclusion

The convergence of RNA therapeutics and AI represents a paradigm shift in drug discovery and development. Oligonucleotide therapies offer targeted approaches to modulate gene expression, while AI enhances the precision and efficiency of identifying and optimizing these therapies. Eli Lilly’s strategic collaborations and investments underscore its commitment to leading in this innovative space, with the potential to address unmet medical needs across a spectrum of diseases.