Lilly targets kidney disease with Ascidian’s RNA exon editors for up to $1.9B

Eli Lilly Inks Up To $1.9B Deal With Ascidian For RNA Exon Editing Platform

Eli Lilly has entered into an RNA-focused alliance with Ascidian Therapeutics, involving an investment of up to $1.9 billion. This deal grants Lilly access to Ascidian’s RNA exon editing platform, which is designed to remove mutated exons from mRNA molecules to prevent the expression of disease-causing proteins. The collaboration aims to develop assets for undisclosed kidney indications. The financial terms include an upfront payment, development and commercial milestone commitments, and tiered royalties on worldwide sales. Ascidian will manage discovery and early lab work, while Lilly will handle preclinical and clinical development, manufacturing, and commercialization.

• The strategic alliance between Eli Lilly and Ascidian Therapeutics is valued at up to $1.9 billion, encompassing an undisclosed upfront payment, substantial development and commercial milestone commitments, and tiered royalties on global sales. This significant financial outlay highlights Lilly's aggressive strategy to expand its pipeline, leveraging its robust financial performance, particularly from its successful GLP-1 franchise.
• Ascidian Therapeutics' innovative RNA exon editing platform utilizes DNA constructs that are transcribed into mutation-free, exon-only RNA molecules. These molecules specifically target and replace mutated exons within pre-mRNA, thereby preventing the synthesis of disease-causing proteins. A key advantage of this technology is its reliance on the patient's native cellular machinery, eliminating the need for introducing foreign enzymes.
• Under the terms of the agreement, Ascidian Therapeutics will be responsible for the discovery phase and initial laboratory work for the targeted kidney indications. Following this, Eli Lilly will assume full responsibility for all subsequent preclinical and clinical development, manufacturing, and global commercialization efforts. Ascidian retains the flexibility to pursue other kidney disease targets or engage in collaborations with different partners using its proprietary platform.

Ascidian's RNA Exon Editing: A Novel Target in Kidney Disease

Recent research has identified several promising therapeutic targets that are advancing through clinical development for kidney disease treatment. SGLT2 inhibitors and GLP-1 receptor agonists, originally developed for hyperglycemia management, have demonstrated transformative effects in diabetic kidney disease by consistently reducing cardiovascular events, albuminuria, and glomerular filtration rate decline. The combination of finerenone and empagliflozin has shown particularly significant nephroprotective benefits, while nonsteroidal mineralocorticoid antagonists have emerged as a dedicated kidney-protective drug class.

Disease-specific therapeutic approaches are gaining traction across multiple nephropathies. Atrasentan, an endothelin type A receptor antagonist, has demonstrated efficacy in IgA nephropathy, while iptacopan, an oral factor B inhibitor, has shown therapeutic benefit in both IgA nephropathy and C3-deposit glomerulopathy. For lupus nephritis, obinutuzumab, a humanized anti-CD20 antibody, has proven effective. In sickle cell disease-related kidney disease, researchers are investigating endothelin receptor antagonists, pyruvate kinase activators, and APOL1 inhibitors, with inaxaplin advancing to phase 3 studies for APOL1-associated kidney disease.

Novel mechanistic targets are expanding the therapeutic landscape beyond traditional approaches. Researchers are exploring soluble guanylate cyclase stimulators, aldosterone synthase inhibitors like baxdrostat, and interventions targeting mitochondrial dysfunction and cellular senescence. Pharmacological agents that restore endoplasmic reticulum-mitochondria communication, including AMPK activators and mTOR inhibitors, have shown promise in experimental models. Additionally, emerging research focuses on achieving complete arrest or reversal of chronic kidney disease progression through precise targeting of mitochondrial senescence and age-related pathogenic mechanisms.

The Unmet Needs Driving Lilly's Investment in Kidney Disease

Despite the availability of multiple approved therapies with proven kidney and cardiac benefits, significant barriers prevent optimal management of chronic kidney disease (CKD). These challenges span from early detection and diagnosis to treatment implementation and coordination across healthcare systems.

Implementation and Awareness Gaps:
• Uptake of evidence-based therapies remains lower than expected in clinical practice, particularly for sodium-glucose cotransporter 2 inhibitors (SGLT2is), despite strong guideline recommendations
• Medical awareness initiatives suffer from five key deficiencies: lack of metric-driven goals, limited peer-to-peer engagement, insufficient emphasis on serious outcome prevention, inadequate targeting of high-risk populations, and general lack of primary care physician-focused interventions
• A persistent gap exists between accumulated knowledge about prevention and treatment versus actual clinical implementation

Screening and Early Detection Challenges:
• Systematic strategies for CKD screening and diagnosis remain inconsistent globally, with limited adoption of best practices across healthcare systems
• Cost-effectiveness of screening programs continues to be debated, hindering widespread implementation
• Suboptimal prevention strategies and failure to implement detection protocols may contribute to CKD's overall impact on cardiovascular mortality

Diagnosis and Recognition Deficiencies:
• CKD frequently goes unrecognized even in hospital settings, with correct diagnosis documented in only 38.1% of discharge reports for patients with stage 3 or higher CKD
• It remains unclear whether uniform strategies for early CKD identification can be applicable across diverse socioeconomic populations
• Delayed recognition leads to missed opportunities for early intervention and disease modification

Underrecognized Symptoms and Comorbidities:
• Complex concerns in older adults with CKD, including frailty, malnutrition, sarcopenia, and cognitive dysfunction, are poorly understood and inadequately addressed
• Chronic pain perception, particularly in elderly dialysis patients, may be greatly underrecognized
• Management of pain, depression, and other physical and mental symptoms receives insufficient attention in primary care settings

Blood Pressure Management Issues:
• Blood pressure measurement remains unstandardized across clinical settings, with practitioners frequently failing to follow basic recommendations to avoid measurement errors
• Inconsistent monitoring practices lead to misdiagnosis and inappropriate management of hypertension, particularly problematic in CKD patients where precise control is critical

Resource and Access Limitations:
• CKD poses a major threat to public health in low-income and lower middle-income countries where resources for treating advanced disease are scarce
• Global challenges of access and affordability prevent optimal application of proven therapies for people with CKD
• Limited research infrastructure in many countries hampers understanding of local disease burden and treatment needs

Current Standard of Care and the Evolving Kidney Disease Landscape

Current standard of care for chronic kidney disease has evolved significantly with the release of comprehensive 2025 guidelines and emerging evidence supporting multimodal therapeutic approaches. The treatment landscape now emphasizes early intervention, combination therapies, and integrated primary care management to optimize patient outcomes and delay disease progression.

• 2025 VA/DoD Clinical Practice Guidelines provide 23 evidence-based recommendations using GRADE methodology, covering diagnosis, monitoring, management strategies, hypertension control, pharmacotherapy for cardiovascular risk reduction, and kidney replacement therapy considerations

• Triple therapy approach combining renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) represents the current gold standard, with potential to delay kidney replacement therapy by up to a decade

• Primary care-centered management is recommended for over 90% of eligible patients, emphasizing lifestyle interventions and rapid initiation of evidence-based pharmacotherapy in collaboration with specialty services when needed

• SGLT2 inhibitor integration has become standard across CKD populations regardless of diabetes status, with empagliflozin demonstrating cost-effectiveness and significant reductions in kidney disease progression and cardiovascular death risk

• Enhanced monitoring protocols require regular assessment of both urine albumin-to-creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR) in at-risk populations to enable early therapeutic intervention

• Implementation gaps persist despite robust evidence, with suboptimal albuminuria testing rates and delayed triple therapy initiation limiting the potential benefits of current guideline-directed care

• Personalized treatment strategies are increasingly emphasized given the expanding therapeutic pipeline and need to optimize individual patient outcomes across diverse CKD populations and comorbidity profiles