Eli Lilly Invests Another $600M in Gene Editing, Bringing Its 3-Year Total to Over $10 Billion

Nov 02, 2023 15:53 CST Updated 15:53

As the world’s first pure-play pharmaceutical company to surpass a $500 billion market capitalization, Eli Lilly can rightly be called the “leader” in the global pharmaceutical industry. This “leader,” with roots tracing back to the mid-to-late 19th century, has recently shown strong confidence in gene editing, the “rising star” of the medical field. Just now, the “leader” invested another $600 million to forge partnerships with two star gene-editing companies, Beam Therapeutics and Verve Therapeutics.

On October 31 local time, base editing company Beam Therapeutics (Nasdaq: BEAM) announced an agreement with Eli Lilly, under which Lilly will acquire Beam’s cardiovascular disease base editing therapy pipeline developed in collaboration with gene editing company Verve. The portfolio includes programs targeting PCSK9, ANGPTL3, and an undisclosed liver-mediated cardiovascular target.

Under the terms of the agreement, Beam will receive a $200 million upfront payment and a $50 million equity investment. Upon the achievement of certain clinical, regulatory, and alliance milestones, Beam is also eligible for potential future development-stage payments of up to $350 million, bringing the total potential transaction value to as much as $600 million.

Prior to the announcement of this transaction, Beam, the first base-editing company to list on Nasdaq, had just restructured and streamlined its pipeline and announced plans to lay off approximately 100 employees. The cash flow generated from this collaboration will help alleviate some of the crises facing Beam’s development.

$10 Billion Spent in 3 Years

In fact, Eli Lilly’s $600 million investment in gene-editing therapies is merely a prominent highlight of its significant endeavors in the gene-editing arena in recent years.

Eli Lilly’s earliest foray into the gene-editing sector dates back to 2020.That year, American scientist Jennifer Doudna and French scientist Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for their contributions to the development of methods for genome editing. This gene-editing method is the third-generation gene-editing technology, known as CRISPR/Cas technology.

Perhaps recognizing the vast potential of gene editing, in November 2020, Eli Lilly entered into a collaboration worth up to $2.7 billion with Precision BioSciences to advance gene therapy for Duchenne Muscular Dystrophy (DMD).

This collaboration also signals Eli Lilly’s formal entry into the gene-editing sector. Previously, the company had maintained a cautious, wait-and-see stance toward gene editing, even exhibiting a degree of “resistance.” In a 2019 interview, Eli Lilly CEO Dave Ricks went so far as to state, “Gene editing is not an area of interest for Eli Lilly at the moment.”

One month later, in December 2020, Eli Lilly reached a $1.04 billion acquisition agreement with gene therapy company Prevail Therapeutics to strengthen its portfolio of gene therapies for neurodegenerative diseases.

In December 2022, ProQR Therapeutics announced an expansion of its licensing and research collaboration agreement with Eli Lilly. Through this expanded partnership, the two companies will explore further applications of the Axiomer platform, focusing on the discovery, development, and commercialization of RNA-editing therapeutics. The collaboration originally commenced in September 2021. Under the original agreement dated September 2021 and this expansion, ProQR is eligible to receive approximately $3.75 billion in research, development, and commercialization milestone payments, as well as tiered royalties on product sales. The total potential value of the agreement amounts to up to $3.9 billion.

In May this year, Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly, and gene-editing company Scribe Therapeutics announced a collaboration to jointly develop in vivo gene-editing therapies for specific neurological and neuromuscular diseases. Under the agreement, Prevail will make an upfront payment of $75 million to Scribe to secure exclusive rights to Scribe’s “CRISPR X” editing technology. Additionally, Scribe is eligible to receive up to $1.5 billion in milestone payments.

In June this year, Eli Lilly entered into a collaboration with Verve Therapeutics, valued at over $500 million in total, to advance Verve’s preclinical in vivo gene editing therapy targeting lipoprotein(a) [Lp(a)]. Under the agreement, Verve will be responsible for driving the development of the Lp(a)-targeted in vivo gene editing therapy through completion of Phase I clinical trials, while Eli Lilly will oversee subsequent development, manufacturing, and commercialization activities. According to the terms, Verve will receive a $60 million upfront payment, and Eli Lilly will cover the costs of the research and development program up to the completion of Phase I clinical trials. Additionally, Verve may be eligible for milestone payments totaling up to $465 million.

As previously mentioned, Eli Lilly recently entered into collaborations with Beam Therapeutics and Verve Therapeutics, totaling $600 million, to jointly develop a pipeline of base editing therapies for cardiovascular diseases.

In terms of potential deal value, Eli Lilly’s cumulative commitments have exceeded $10 billion since it began positioning itself in the gene-editing sector in late 2020. The industry leader’s strong preference for gene editing is self-evident.

The Industrialization of Gene-Editing Drugs Is Imminent

It is not only Eli Lilly, the global leader in the pharmaceutical industry, that has shown strong favor for gene-editing therapies; other well-established multinational companies, including Novo Nordisk, AstraZeneca, Pfizer, Novartis, Sanofi, and Kyowa Kirin, are also engaged in collaborative research projects with gene-editing firms or have their own in-house gene-editing programs under development.

In China, the field of gene editing is also developing rapidly, with multiple companies such as WuXi AppTec, Biocytogen, Huida Gene, Rayful Biotech, Bangyao Biotechnology, Bendao Gene, Qihan Biotechnology, and Shali Biotechnology making strategic investments.

In addition to the small number of companies mentioned above, there are many more “underwater” enterprises also leveraging this foundational tool to develop a broader pipeline of innovative drugs. However, as most companies in this sector reach the industrialization stage, they tend to prioritize publicizing tangible milestones related to the drug candidates themselves. Consequently, the majority of these companies maintain a notably “low-key” approach to the development and optimization of their gene-editing tools.

Gene editing, as the cornerstone of the cell and gene therapy industry, has been advancing rapidly in recent years alongside the sector’s swift growth. This once “low-profile” foundational technology has recently begun to take center stage, with the FDA gradually relaxing its regulatory policies.

Recently, several major events have occurred in the field of gene editing.

On October 23, nearly a year after the initial hold, Verve announced that the FDA had lifted the clinical hold on its core product, VERVE-101. Verve plans to begin enrolling U.S. patients in its Phase Ib trial of the gene-editing therapy VERVE-101. Andrew Bellinger, Chief Scientific Officer at Verve, stated in a press release, “This authorization marks the first time an in vivo base editing candidate has been permitted to proceed with clinical development in the United States.”

Previously, the FDA has always been cautious in its approach to gene editing, with even greater concerns regarding base editing. The FDA’s recent decision to lift the clinical hold signifies a shift in its stance on approving gene-editing projects and will provide valuable experience for other gene-editing companies conducting clinical trials.

On October 27, the FDA will review exa-cel (exagamglogene autotemcel), the first-ever CRISPR-based gene-editing therapy, with final results expected on December 8.This drug is the first CRISPR-based gene-editing gene therapy product, indicated for sickle cell anemia.

The FDA has issued a document announcing that it will hold an Advisory Committee (AC) meeting on October 31 local time (which is today in China) to evaluate the safety of the exa-cel therapy.According to the briefing documents released by the FDA on October 27, FDA reviewers have noted the safety data submitted by the two companies, and the potential impact of off-target editing in the exa-cel therapy will be a key topic for advisors when discussing the risks and benefits of exa-cel.

What are the final outcomes of the world’s first CRISPR gene-editing drug? What does the future hold for the gene-editing arena, into which major pharmaceutical companies have poured hundreds of millions? Let us wait and see.