Dose Escalation Studies are the cornerstone of early-stage drug discovery, critical for defining the therapeutic window and identifying the Maximum Tolerated Dose (MTD) of novel compounds. By systematically increasing dosage levels in preclinical models, researchers can characterize the safety profile, assess pharmacokinetics (PK), and establish preliminary dose-response relationships. BOC Sciences offers flexible, non-GLP dose escalation services designed to support rapid lead optimization and candidate selection. Our approach integrates rigorous observation with advanced bioanalytical monitoring, providing the high-quality data needed to confidently advance your small molecules, biologics, or conjugates into further development stages.
We conduct SAD studies to assess the acute tolerability and PK profile of a compound after a single administration. This foundational service helps identify the initial toxicity threshold and informs the dosage range for subsequent multiple-dose studies.
Our MAD studies evaluate the effects of repeated administration over time. We monitor drug accumulation, steady-state pharmacokinetics, and delayed-onset toxicity, providing a comprehensive view of the compound's safety during chronic exposure.
We focus on accurately defining the MTD and the No-Observed-Adverse-Effect Level (NOAEL). These critical parameters are essential for designing subsequent efficacy models and ensuring animal welfare in downstream research.
BOC Sciences delivers data-driven dose escalation strategies to accelerate your drug discovery pipeline with precision and speed.
The classic algorithmic approach where cohorts of three subjects are treated at increasing dose levels. It is a conservative and well-understood method ideal for compounds with unknown toxicity profiles, prioritizing safety during the escalation process.
Doses are increased based on the Fibonacci sequence (e.g., 100%, 67%, 50%, 33% increments). This method allows for rapid escalation at lower doses while slowing down as doses approach the predicted toxic range, balancing speed with caution.
An adaptive design where the dose for the next subject is adjusted up or down based on the response of the previous subject. This statistical approach is highly efficient for estimating the median lethal dose (LD50) or specific toxicity thresholds with fewer animals.
We combine dose escalation with toxicokinetics (TK) sampling. By correlating plasma concentration levels with observed physiological effects, we provide a deeper understanding of the exposure-response relationship rather than relying on external dose alone.
Beyond in-life observations, we incorporate blood chemistry, hematology, and histopathology endpoints. This multi-dimensional analysis detects sub-clinical toxicity markers that might be missed by visual observation alone.
For compounds with extensive preliminary data, we offer accelerated titration designs involving single-subject cohorts and intra-subject dose escalations. This minimizes animal usage and shortens the timeline to reach the target dose range.
BOC Sciences optimizes dose finding strategies for a wide variety of therapeutic modalities, ensuring the specific properties of each molecule type are considered.
Submit your compound information, and our experts will design a scientifically robust escalation strategy tailored to your research goals.
We define the starting dose, escalation factors (e.g., Fibonacci), and stopping rules based on your compound's mechanism of action and existing literature.
Research models are selected and acclimatized. Baseline health parameters are established to ensure data accuracy during the escalation phase.
Compounds are administered according to the protocol. We conduct real-time health monitoring, wellness scoring, and collection of bio-fluids for PK/PD analysis.
We compile toxicity data, body weight changes, and PK profiles to determine the MTD. A detailed research report with "Go/No-Go" recommendations is delivered.
Partner with BOC Sciences to uncover the true safety limits of your compounds. Our expert dose escalation services provide the critical insights needed to de-risk your program and select the best candidates for development.
We move beyond rigid protocols by offering adaptive designs (e.g., Up-and-Down, Accelerated Titration) that fit your compound's specific toxicity profile and material availability, saving time and resources.
Our on-site bioanalysis capabilities ensure rapid turnaround of PK samples between cohorts. This allows dose escalation decisions to be driven by actual systemic exposure data, not just clinical observations.
We maximize the value of every study by capturing multi-dimensional data, including clinical chemistry, hematology, and histopathology, to identify subtle, sub-clinical toxicity signals early.
Our study directors provide more than raw data; we offer expert interpretation of the therapeutic window and "Go/No-Go" recommendations to guide your transition to efficacy models.
Client Needs: A biotech company needed to determine the MTD of a highly potent cytotoxic small molecule to design a subsequent tumor efficacy study.
Challenges: The compound had a narrow therapeutic index with predicted bone marrow toxicity. Standard rapid escalation could risk losing subjects too early, while overly conservative designs would waste valuable compound and time.
Solution: BOC Sciences' toxicology team devised a bespoke modified Fibonacci escalation protocol. We integrated continuous hematological analyzing using automated counters and conducted bone marrow smear evaluations at peak and trough drug levels. The study also employed a "rolling 6" design adaption to balance safety with the need for statistical significance in the MTD estimation.
Outcome: Successfully identified the MTD where efficacy was maximized without irreversible myelosuppression. The data allowed the client to set precise dosing for the efficacy model, resulting in significant tumor regression with manageable weight loss.
Client Needs: A developer of ADCs required a dose escalation study to assess off-target toxicity and payload stability in vivo.
Challenges: ADCs often exhibit complex toxicity profiles driven by both the antibody and the free payload. The client needed to differentiate between on-target effects and toxicity caused by premature linker cleavage.
Solution: We executed a sophisticated, multi-arm escalation study utilizing LC-MS/MS for dual-analyte quantification (total antibody vs. free payload). Our pathologists performed targeted immunohistochemistry (IHC) on liver and kidney sections to visualize payload accumulation, while real-time cytokine profiling was used to monitor potential infusion reactions distinct from direct tissue toxicity.
Outcome: The study revealed that high doses led to liver toxicity correlated with free payload spikes, indicating linker instability. The client used this data to re-engineer the linker chemistry before proceeding to further development.
Client Needs: To support a formulation change, a client needed to compare the safety profile of a lead candidate when administered orally versus intravenously.
Challenges: The oral formulation had unknown bioavailability, making it difficult to predict the starting dose based on IV data. There was a risk of gastrointestinal toxicity confounding the systemic safety results.
Solution: Our experts designed a crossover escalation strategy. We utilized microsampling techniques to obtain high-resolution PK profiles from individual animals, allowing for intra-subject comparison. The oral dosing regimen was dynamically adjusted using a pharmacokinetic-guided escalation algorithm, ensuring systemic exposure (AUC) remained within safe limits established by the initial IV bolus phase.
Outcome: We established that the oral formulation had 40% bioavailability and identified a GI-specific dose-limiting toxicity. This helped the client optimize the oral formulation to improve tolerability.
Dose escalation studies primarily assess the in vivo behavior of new compounds or biologics at different doses, including pharmacokinetics, pharmacodynamic responses, and safety trends. These studies incrementally increase doses in phases to establish dose-response relationships, providing critical data to guide subsequent dose optimization and early-stage development strategies.
Designing a dose escalation scheme requires integrating compound characteristics, expected pharmacological range, and safety data to determine starting dose, escalation steps, and observation periods. Typically, gradient or staged escalation strategies are used with real-time monitoring, allowing dose adjustments based on in vivo responses. Proper design enhances data reliability while minimizing unnecessary risk and resource use.
Common models include single-dose escalation, multiple-dose escalation, and crossover designs. Model selection considers drug half-life, accumulation potential, and study objectives. For example, single-dose escalation is suitable for initial pharmacokinetic exploration, while multiple-dose escalation evaluates accumulation and steady-state concentrations, informing subsequent dose selection.
Analysis focuses on dose-response curves, blood concentration profiles, and biomarker responses. Statistical and modeling approaches help identify dose-related trends, maximum effective doses, and potential nonlinear effects, providing quantitative guidance for dose optimization and supporting strategic decisions in development.
Risk control relies on staged monitoring, real-time data analysis, and flexible dose adjustment strategies. Safety thresholds, observation windows, and key indicator checkpoints enable timely intervention when abnormal trends occur. Simulation using predictive models further evaluates potential risks, supporting both study safety and data reliability.
BOC Sciences' team helped us navigate a difficult dose escalation for our lead kinase inhibitor. Their suggestion to use an Up-and-Down procedure saved us significant time and compound. The report was clear and helped us immediately set doses for our xenograft models.
— Dr. Arthur, Director of Biology, Emerging Biotech
We appreciated the seamless integration of PK sampling during the escalation study. Getting exposure data alongside toxicity observations allowed us to understand the poor tolerability of our initial formulation and fix it quickly.
— Dr. Lucas, Principal Scientist, Drug Discovery Firm
Although we are in the early discovery phase, the quality of data provided by BOC Sciences was exceptional. Their detailed observation logs and pathology reports gave us the confidence to select our top candidate for further development.
— Dr. Thomas, VP of R&D, Biopharma Startup
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