Lilly Partners with Genetic Leap in $409M AI-Driven RNA-Targeted Drug Discovery Deal

On September 5, Eli Lilly and Company reached a research and development cooperation agreement with Genetic Leap, an AI pharmaceutical company. Eli Lilly will utilize Genetic Leap's RNA-targeting AI technology platform to generate gene drug candidates for selected targets. Eli Lilly will select targets in high-priority areas, and Genetic Leap will focus on finding RNA drugs for these targets.

Genetic Leap, founded in 2016, is committed to disrupting traditional thinking in RNA drug development. It aims to address the undruggable bottlenecks in the pharmaceutical field by building a customized AI platform and exploring small-molecule drugs targeting RNA for the treatment of difficult-to-treat diseases. In this collaboration, Genetic Leap will receive up to $409 million (approximately 2.9 billion yuan) in upfront and milestone payments, as well as tiered royalties.

At present, many complex genetic diseases lack effective drug treatments, and there are two fundamental reasons for this:

First, the pharmaceutical field is unable to establish effective predictive models for such diseases, leading to a lack of sufficiently validated genetic targets. Over 99% of the genes or genetic traits responsible for polygenic diseases remain unknown. The absence of effective tools to analyze the entire genome and uncover the role of these non-coding genes in diseases results in conditions being "untreatable."

Secondly, the pharmaceutical field mainly develops new drugs through three dimensions: DNA, RNA, and proteins, but each has its drawbacks. Current drug treatment methods limit their ability to regulate gene targets in a safe, effective, and minimally off-target manner to treat diseases.

Based on these two major issues, Genetic Leap was established, dedicated to exploring the yet unknown 99% of the genome, identifying therapeutic targets for difficult-to-treat diseases, and designing drugs targeting RNA transcription using small molecules or oligonucleotide modalities.

Genetic Leap addresses these two challenges by pioneering a whole-genome analysis platform. They start from four key dimensions: target discovery, disease cause analysis, drug design, and candidate drug confirmation, to build an interconnected AI model—Genetic Intelligence.

This platform combines biological genetic principles with AI algorithms to identify actionable disease targets that can be used for effective treatment. It then designs oligonucleotide- or small molecule-based drug modalities to modulate these targets at the RNA transcription level, bypassing the inherent limitations of protein targeting and enabling any genetic target to be addressed effectively and safely. For diseases with validated targets that are undruggable at the protein level, Genetic Intelligence will directly oversee RNA-targeted drug discovery and screen candidates.

Genetic Intelligence relies on four key components: Bergspitze, Franklin, Orisha, and Lea. Bergspitze is primarily used for target discovery, precisely locating the genes responsible for causing diseases. Franklin serves as Genetic Leap’s Deep-traces™ platform, which conducts detailed and rigorous analysis of disease-causing genetic variations through biomolecular networks, providing coherent etiological models of diseases and confirming the necessary therapeutic targets. Orisha is utilized for drug design and consists of two sub-modules: Orisha-SM focuses on designing drugs targeting RNA structures using small molecules—identifying optimal regions with unique structures on RNA, predicting the structure of selected regions, and docking small molecules to the predicted structures. Orisha-oligo designs drugs targeting RNA sequences using oligonucleotides, identifying the most accessible yet unique regions on RNA and designing ASO sequences to facilitate drug development. Lea employs cell assays and animal models related to disease etiology and human biology to experimentally validate the previously screened targets and drug candidates.

Currently, based on this innovative AI technology platform, Genetic Leap has launched seven product pipelines targeting new and undruggable targets, focusing on multiple fields such as cancer, autoimmune diseases, and neurodegenerative diseases.

In March 2022, Genetic Leap also entered into a research collaboration agreement with Astellas. According to the terms of the agreement, Genetic Leap will utilize its platform to discover and validate RNA-targeting small molecule therapies for undisclosed tumor targets selected by Astellas.

Now, Genetic Leap has caught the attention of Eli Lilly and Company.

The collaboration with Genetic Leap reflects Eli Lilly's future strategic direction, showing not only confidence in the development prospects of AI-driven drug discovery but also a continuous increase in investment in RNA-targeted therapies. Only in 2024, Eli Lilly has already achieved multiple investment arrangements in related fields.

In June 2024, Eli Lilly and Company partnered with OpenAI, a world-leading artificial intelligence lab, to jointly develop novel antibacterial drugs in response to the growing threat of antimicrobial resistance (AMR). AMR is one of the most significant threats in the field of global public health and development, particularly severe in regions plagued by poverty and inequality. Eli Lilly stated that this collaboration marks a crucial step in combating the AMR threat, as OpenAI's generative AI technology can accelerate the discovery of new antibacterial drugs and develop specialized technologies to target drug-resistant pathogens.

In addition, Eli Lilly and Company has committed to providing $100 million to the AMR Action Fund to support clinical research for new antibiotics. The AMR Action Fund, a $1 billion fund initiated by more than 20 biopharmaceutical companies, aims to deliver 2 to 4 new antibiotics to patients by 2030. This collaboration and investment demonstrate Eli Lilly's determination to combat AMR and also affirm the potential of AI technology in healthcare innovation.

In the field of RNA therapy, Eli Lilly has also made significant investments. In August 2024, Eli Lilly invested $700 million to open a nucleic acid drug research and development center in Boston Harbor, a key part of its efforts to develop novel RNA and DNA drugs. Eli Lilly aims to push the boundaries of delivery technology and create innovative new drugs in key strategic areas such as neurodegenerative diseases, diabetes, and obesity.

In September 2024, Eli Lilly and Company entered into a collaboration agreement with HAYA Therapeutics worth up to $1 billion. HAYA Therapeutics is a precision medicine company dedicated to developing programmable therapies that target regulatory RNAs of non-coding proteins to reprogram pathological cellular states in various diseases, including cardiovascular disease, metabolic disorders, and cancer. The company is leveraging its innovative platform to gain new insights into the biology of disease cellular states and related long non-coding RNAs (lncRNAs). Its lead program, HTX-001, is being developed for the treatment of heart failure. HAYA is also developing a series of precision therapies targeting lncRNAs for cell-specific treatments aimed at other tissue-related diseases.

It is reported that HAYA's proprietary gene regulation discovery platform can identify tissue-, disease-, and cell-specific lncRNA targets and develop corresponding RNA-targeted therapies, which can reprogram cells and potentially restore them to a healthy state. Compared with existing therapies, these therapies may be more effective and less toxic.

Under the terms of the agreement, the two companies will apply HAYA's RNA-guided gene regulation platform to support preclinical drug development efforts for obesity and related metabolic diseases. They will identify multiple RNA drug targets capable of modulating gene expression to treat these chronic conditions.