Executive Summary / Key Takeaways

• Verve Therapeutics is pioneering a novel approach to cardiovascular disease treatment using single-course in vivo gene editing, aiming to replace chronic therapies with permanent genetic modifications.
• Initial data from the Heart-2 Phase 1b trial for VERVE-102 targeting PCSK9 show promising dose-dependent reductions in LDL-C (up to 69% maximum reduction) and a potentially favorable safety profile, supporting the potential for durable efficacy.
• The recent definitive agreement for Eli Lilly and Company (LLY) to acquire Verve significantly de-risks the company's funding needs and provides access to Lilly's extensive resources and expertise in cardiometabolic disease and genetic medicines, fundamentally altering the investment landscape.
• Verve's pipeline includes additional programs targeting ANGPTL3 (VERVE-201) and Lp(a) (VERVE-301), leveraging its proprietary GalNAc-LNP delivery technology, positioning it against both traditional and gene editing competitors in the large cardiovascular market.
• While the technology is novel and clinical development carries inherent risks, the acquisition by Lilly validates Verve's platform and provides a clear path forward, subject to closing conditions and continued clinical success.

A New Era for Cardiovascular Care: Verve's Gene Editing Ambition

Cardiovascular disease (CVD) remains the leading cause of death globally, imposing a significant burden despite decades of therapeutic advancements. The current standard of care often relies on chronic, lifelong therapies requiring strict patient adherence and extensive healthcare infrastructure. Verve Therapeutics, founded in 2018, emerged with a bold vision: to transform CVD treatment from this fragile, chronic paradigm to single-course gene editing medicines. The company's strategy centers on leveraging breakthroughs in human genetic analysis, gene editing, mRNA technology, and lipid nanoparticle (LNP) delivery to target genes predominantly expressed in the liver that drive atherosclerotic cardiovascular disease (ASCVD).

Verve's historical journey reflects the typical trajectory of an early-stage biotechnology company, focused initially on foundational research and capital raising through private placements. A pivotal moment was its initial public offering in June 2021, providing significant funding but also introducing the complexities and costs of operating as a public entity. The company's strategic evolution has included navigating early clinical challenges, such as the discontinuation of the Heart-1 trial for VERVE-101 due to observed laboratory abnormalities potentially linked to the LNP delivery system, while simultaneously advancing its pipeline and forging key collaborations.

The competitive landscape in CVD treatment is vast and well-established, dominated by major pharmaceutical companies offering proven chronic therapies like statins, ezetimibe, and PCSK9 inhibitors (e.g., Amgen (AMGN)'s Repatha, Sanofi (SNY)/Regeneron (REGN)'s PRALUENT, Novartis (NVS)'s Leqvio). Within the burgeoning field of gene editing, Verve competes directly with companies like Beam Therapeutics (BEAM), CRISPR Therapeutics (CRSP), Editas Medicine (EDIT), and Intellia Therapeutics (NTLA), many of whom also have gene editing programs, some targeting similar indications or genes. While these competitors possess varying strengths in specific gene editing modalities (e.g., Beam in base/prime editing, CRISPR/Editas/Intellia in CRISPR-Cas9) and stages of development, Verve aims to differentiate itself through its specific focus on in vivo liver gene editing for cardiovascular targets and its proprietary delivery technology.

The Technological Engine: Base Editing and GalNAc-LNP Delivery

At the heart of Verve's approach is its gene editing technology, primarily utilizing base editing, and its proprietary delivery system. Base editing allows for precise, single-letter changes in DNA without creating double-strand breaks, which are associated with higher risks of unwanted edits. This precision is crucial for safety in a therapeutic setting.

Verve's lead programs employ a proprietary GalNAc-LNP delivery technology. This system is designed to encapsulate the base editor and guide RNA and deliver them specifically to liver cells. The GalNAc ligand facilitates uptake via the asialoglycoprotein receptor (ASGPR) on hepatocytes, offering a targeted delivery mechanism alongside potential uptake via the LDL receptor (LDLR). The tangible benefit of this targeted in vivo delivery is the potential for a single intravenous infusion to achieve durable, potentially lifelong, gene modification in the liver, thereby permanently disrupting the production of disease-causing proteins. This contrasts sharply with chronic therapies requiring daily pills or intermittent injections.

Early clinical data from the Heart-2 trial of VERVE-102, targeting PCSK9, provides initial validation of this approach. In 14 participants across three dose cohorts, VERVE-102 demonstrated dose-dependent reductions in both blood PCSK9 protein and LDL-C levels. In the highest dose cohort (0.6 mg/kg), mean time-averaged reductions from baseline were 53% for LDL-C and 60% for PCSK9 protein. Notably, one participant in this cohort achieved a 69% LDL-C reduction. Analysis by total RNA dose showed a mean LDL-C reduction of 59% in participants receiving 50-60 mg total RNA. These figures suggest that VERVE-102 has the potential to achieve LDL-C lowering comparable to or exceeding currently available PCSK9 inhibitors, but with the potential for a single-dose administration. The safety profile observed so far has been favorable, with no treatment-related serious adverse events or dose-limiting toxicities, although the prior experience with VERVE-101 highlights the importance of continued safety monitoring, particularly concerning LNP-related effects.

Verve's R&D efforts extend beyond its lead programs, including the development of novel gene editing technologies and delivery systems. The stated goal is to expand the applicability of their platform to a wider range of genetic targets and diseases, further solidifying their competitive moat in the in vivo gene editing space. For investors, the "so what" of this technological foundation is the potential for Verve to create highly disruptive, high-value therapies that could capture significant market share by offering a fundamentally different, potentially superior, treatment modality for widespread conditions like ASCVD.

Pipeline Progression and Strategic Positioning

Verve's pipeline is strategically focused on the three key lipoprotein pathways implicated in ASCVD. Beyond the lead PCSK9 program (VERVE-102), the company is advancing VERVE-201, designed to turn off the ANGPTL3 gene, a target validated for lowering both LDL-C and triglycerides. VERVE-201 is currently in the Pulse-1 Phase 1b trial, targeting patients with refractory hypercholesterolemia and homozygous familial hypercholesterolemia (HoFH). An update on this program is anticipated in the second half of 2025.

The third key program, VERVE-301, targets the LPA gene to reduce elevated levels of lipoproteina (Lp(a)), an independent risk factor for ASCVD. This program is being developed in collaboration with Eli Lilly and Company. In January 2025, VERVE-301 was designated as the initial development candidate under the Lilly agreement, triggering a $20.0 million milestone payment to Verve. Preclinical studies are underway to support future clinical trial applications.

Verve's competitive positioning is significantly influenced by its strategic collaborations. The partnership with Lilly, initially focused on the Lp(a) program, also includes an opt-in right for Lilly on the PCSK9 program (VERVE-102). Verve expects to deliver the opt-in package to Lilly and receive their decision in the second half of 2025. This collaboration provides not only potential funding and shared development costs but also access to Lilly's vast expertise and resources in cardiometabolic drug development and commercialization. While the termination of the Vertex (VRTX) agreement in April 2025 highlights the inherent risks in collaborations, the Lilly partnership represents a more substantial validation of Verve's platform and pipeline.

Financially, Verve's performance reflects its stage of development as a clinical-stage biotech. For the three months ended March 31, 2025, the company reported collaboration revenue of $33.0 million, a significant increase from $5.7 million in the same period of 2024. This surge was primarily driven by the recognition of $20.0 million in deferred revenue from the terminated Vertex agreement and $11.6 million from the Lilly collaboration, including the $20.0 million milestone payment. Operating expenses remain substantial due to ongoing R&D. Research and development expenses increased by $6.1 million to $54.5 million in Q1 2025, reflecting increased headcount, clinical trial costs for Heart-2 and Pulse-1, and manufacturing/preclinical expenses. General and administrative expenses also rose to $15.2 million. The net loss for Q1 2025 was $31.0 million, an improvement from the $48.7 million loss in Q1 2024, largely due to the higher collaboration revenue.

As of March 31, 2025, Verve held $497.1 million in cash, cash equivalents, and marketable securities. The company estimates this is sufficient to fund operations into mid-2027. However, operating cash flow remains negative, using $27.8 million in Q1 2025. The company acknowledges the need for substantial additional funding beyond its current runway to support ongoing clinical development, potential commercialization, and further pipeline expansion. Future financing is expected through equity offerings (including the remaining capacity under its ATM program), debt, and additional collaborations.

Outlook, Risks, and the Lilly Acquisition

The outlook for Verve is now inextricably linked to the recent definitive agreement for Eli Lilly to acquire the company. While the 10-Q was filed prior to this announcement, the news significantly alters the investment thesis. The acquisition, reportedly valued at $1.3 billion, represents a major validation of Verve's gene editing platform and its lead programs, particularly VERVE-102. Lilly's stated rationale for the acquisition is to advance one-time treatments for people with high cardiovascular risk, highlighting the strategic alignment and perceived potential of Verve's approach.

This development fundamentally changes Verve's financial outlook, effectively addressing the need for substantial additional funding beyond mid-2027 that was a prominent risk factor. Integration into Lilly's larger organization provides access to greater financial resources, extensive R&D capabilities, and established commercial infrastructure, potentially accelerating the development and eventual commercialization of Verve's pipeline candidates.

However, significant risks remain, albeit within the context of a larger, more stable parent company. The core technological risk associated with in vivo gene editing persists; it is a novel modality that is not yet clinically validated for widespread human therapeutic use, and the long-term safety and efficacy of permanent genetic changes are still being studied. Clinical trials, even under Lilly's stewardship, are inherently uncertain and may not yield positive results or support regulatory approval. The risk of serious adverse events or unexpected characteristics from the gene editor or delivery system remains, as evidenced by the VERVE-101 experience. Manufacturing complexity, intellectual property challenges (including ongoing disputes in the gene editing field), and intense competition from both existing therapies and other emerging modalities are also factors that will continue to influence the success of Verve's programs within Lilly.

Regulatory uncertainty surrounding novel genetic medicines, potential changes in healthcare policy and pricing regulations (such as those introduced by the IRA), and the need to obtain broad market acceptance from physicians, patients, and payors are additional hurdles. While Lilly's expertise mitigates some of these risks, they are not eliminated.

From a competitive standpoint, being part of Lilly positions Verve's programs with significantly enhanced resources compared to smaller, independent gene editing biotechs like Editas Medicine or even larger ones like Beam Therapeutics or Intellia Therapeutics, potentially accelerating development timelines and strengthening market access capabilities. This could allow Verve's programs to compete more effectively against both traditional therapies and other gene editing approaches.

Conclusion

Verve Therapeutics' journey from an early-stage biotech with a bold vision to a company poised to be acquired by a pharmaceutical giant like Eli Lilly and Company underscores the significant potential perceived in its single-course gene editing approach for cardiovascular disease. The initial clinical data for VERVE-102 provides promising early validation of the technology's ability to achieve meaningful and potentially durable LDL-C reduction with a seemingly manageable safety profile, leveraging its differentiated base editing and GalNAc-LNP delivery platform.

The acquisition by Lilly represents a transformative event, addressing the critical long-term funding requirements and providing the substantial resources and expertise needed to navigate the complex path from clinical development to potential commercialization in the large and competitive cardiovascular market. While the inherent risks associated with novel gene editing technologies, clinical trials, and regulatory pathways persist, the backing of a major pharmaceutical company fundamentally strengthens the investment thesis. The focus now shifts to the successful integration into Lilly and the continued execution of the clinical development programs, particularly the advancement of VERVE-102 into Phase 2 and the progress of the ANGPTL3 and Lp(a) programs, as Verve aims to deliver on its promise of a one-dose future for cardiovascular health.