Lead Optimization

Our expert team provides tailored solutions to streamline lead optimization, transforming promising leads into clinic-ready candidates. By leveraging decades of experience, we deliver innovative, efficient, and precise optimization processes that differentiate us in the drug discovery space.

We focus on enhancing novelty, potency, and safety while achieving the perfect balance of ADMET properties, such as exposure, duration, and target engagement. With a clearly defined target candidate profile guiding our work, we help you save valuable time and resources during this critical stage of drug development.

Our approach to lead optimization

Our approach integrates cutting-edge methodologies and technologies to ensure the optimal progression of lead compounds. The iterative process involves the design, synthesis, testing, and analysis of numerous analogues to explore the structure-activity relationship (SAR). This allows us to identify compounds with the ideal balance of potency, exposure, and safety to achieve the desired pharmacological effect and safe dosing regimens.

Driving efficiency with advanced computational tools

CADD plays an essential role at this stage by refining models with advanced calculations and enabling the prioritization of the most promising targets. This lean and focused approach ensures laboratory resources are used effectively, driving efficiency and accelerating progress.‍

Biological screening in lead optimization

Biological screening is a critical component of the lead optimization phase, enabling the precise evaluation of compound efficacy, selectivity, and mechanism of action. By employing high-throughput screening and advanced cellular assays, we ensure that lead compounds demonstrate strong activity against their targets while minimizing off-target effects. This comprehensive screening approach also allows us to identify and validate key biomarkers, which are essential for monitoring drug activity and refining therapeutic strategies. Our ability to integrate biological insights with chemical optimization ensures a seamless progression toward clinical success.‍

Seamless integration between medicinal chemistry, PR&D and GMP

Our medicinal chemistry services are at the core of the lead optimization phase, driving the creation of high-quality, innovative compounds. Our medicinal chemists design and synthesize tailored molecules to address specific challenges in drug discovery, such as optimizing chemical structures to improve target engagement, enhance ADMET properties, and overcome potential drug resistance issues. This process ensures the generation of compounds that meet the desired target candidate profile while advancing discovery efforts efficiently.

In parallel, we seamlessly integrate medicinal chemistry with process research and development (PR&D), providing a vital link between discovery chemistry and GMP manufacturing. PR&D ensures that optimized lead candidates transition smoothly into scalable processes suitable for clinical and commercial production.

PK/PD modeling and biomarker identification

PK/PD modeling is central to our lead optimization strategy. Our teams excel at identifying suitable biomarkers, optimizing dosing regimens, and ascertaining in vivo efficacy in appropriate models. By meticulously optimizing these parameters, we maximize the chances of clinical success and ensure robust therapeutic outcomes. 

Comprehensive ADME and toxicity assessments

We also conduct thorough investigations into absorption, distribution, metabolism, and excretion (ADME) properties. Our multidisciplinary teams analyze the pharmacokinetic profiles of lead compounds, ensuring favorable ADME characteristics essential for success. Additionally, we assess potential toxicity issues to select candidates with acceptable safety profiles.

As candidates are finalized, our experienced ADMET & DMPK team evaluates routes of administration, establishes PK/PD correlations, and predicts optimal human dosing. This holistic approach ensures the selection of the best candidates for clinical trials, accelerating your path to success.