Scientific work spanning drug discovery and development programs, published research, and community engagement.

In an increasingly complex drug development landscape, scientific rigor alone is no longer sufficient - what matters is the ability to translate data into timely, defensible decisions. At A2-Ai, our scientific work in 2025 focused on applying strategic, quantitative thinking to answer the most consequential questions at each stage of drug discovery and development.

An Approach Focused on Meaningful Outcomes

Over the past year, scientific work at A2-Ai has been guided by a core principle: using strategic, quantitative thinking to answer the most critical questions at each stage of drug discovery and development. This approach has been applied across a broad range of therapeutic areas and modalities, enabling teams to tackle the layered scientific and regulatory challenges that emerge as programs move from early discovery through clinical development and life-cycle management.

Each indication and modality brought unique pharmacological complexities and distinct translational considerations. Accordingly, our approach emphasized tailoring analyses to the question at hand, applying data-driven methods, and clearly framing development and regulatory objectives. This focus on relevance and clarity translated directly into outcomes: 100% of submissions supported by A2-Ai in 2025 were accepted by regulatory agencies, reflecting both the rigor of the underlying analyses and the effectiveness of communication. The following sections highlight how our ethos was applied across pharmacometrics, clinical pharmacology, and broader scientific engagement.

Pharmacometrics in Practice

Pharmacometrics played a central role in supporting decisions across various stages of drug development, particularly when complex datasets needed to be translated into actionable insights. By integrating data across studies, our analyses provided sponsors with a comprehensive understanding of drug exposures, their relation to pharmacological responses, and key intrinsic and extrinsic factors, ultimately supporting critical program decisions related to dose selection, clinical trial design, patient eligibility, and overall benefit-risk assessment.

Across programs, the selection of pharmacometric approaches was based on both the scientific question needing answers and the totality of data available. This work included population pharmacokinetic (PK) and PK/pharmacodynamic modeling, exposure-response analyses, and targeted safety evaluations such as concentration-QTc and concentration-blood pressure assessments.

Where appropriate, analyses were conducted longitudinally to characterize the full time course of response rather than relying on isolated landmark analyses. Throughout these efforts, the emphasis remained on interpretability and regulatory relevance, ensuring that results could be clearly communicated and directly applied to inform development strategies and meet critical timelines.

Clinical Pharmacology in Context

Clinical pharmacology strategy complemented pharmacometrics efforts by placing quantitative results into a broader clinical and regulatory context. One example was applying guidance-driven and integrated approaches to enhance cardiac safety assessments, including thoughtful planning and considerations to replace standalone thorough QT (TQT) studies through TQT waiver application. Close collaboration between the clinical pharmacology and pharmacometrics teams ensured that the strategy and analyses were compelling and coherent to facilitate regulatory decision-making.

In parallel, a substantial focus was placed on delivering regulatory-compliant noncompartmental analyses (NCA) across preclinical and clinical studies, supported by high quality scientific interpretations. NCA often represented the first opportunity to quantitatively assess emerging data, support real-time trial dosing decisions, and establish a foundation for subsequent modeling and regulatory strategy development. Clinical pharmacology efforts also extended into scientific writing, including support for Investigational New Drug (IND) applications and briefing documents for global regulatory agencies. The collective work helped clients navigate key discovery and development milestones while maintaining consistency across technical reports and submissions.

Engagement with the Scientific Community

Engagement with the broader scientific community remained a core component of A2-Ai’s work throughout the year. In parallel with client-focused and scientifically driven efforts, A2-Ai remained actively involved in the research community through peer-reviewed publications and participation in key scientific forums, reflecting the same principles applied across development programs.

In 2025, members of A2-Ai’s leadership team contributed to peer-reviewed publications spanning clinical pharmacology and pharmacometrics. Jack Cook, SVP Clinical Pharmacology, co-authored publications in the European Journal of Pharmaceutical Sciences and the British Journal of Clinical Pharmacology addressing global bioequivalence harmonization, the clinical relevance of therapeutic drug monitoring, and considerations for clinical trials in aging populations. Additionally, Rosa Luo, SVP Clinical Pharmacology, contributed to applied clinical pharmacology research published in the British Journal of Clinical Pharmacology.

Within pharmacometrics, Ryan Crass, Executive Director of Pharmacometrics, authored and co-authored publications covering exposure–response and disease progression analyses (CPT: Pharmacometrics & Systems Pharmacology), population PK/PD modeling in the Journal of Clinical Pharmacology, and a high-impact study in The Lancet Infectious Diseases examining antibiotic pharmacokinetics in patients with obesity.

Beyond publications, A2-Ai team members were actively engaged in key scientific forums, including the American Conference on Pharmacometrics and the American Society for Clinical Pharmacology and Therapeutics. These engagements fostered ongoing dialogue around emerging scientific challenges, evolving methodologies, and best practices in drug development, helping ensure that A2-Ai’s approaches remained aligned with current thinking across the field.

Looking Ahead

Reflecting on a year of tremendous growth in 2025, we are grateful for the opportunities and collaborative efforts among clients, partners, and internal teams advancing the development of life-changing therapies. This progress underscores the value of a scientific approach grounded in clarity, rigor, and outcomes that matter in practice. As we build on this foundation in 2026, A2-Ai is committed to supporting our clients while continuously identifying new ways to accelerate drug development programs and strengthen our engagement with the broader scientific community.