Strategic Services

Clinical Pharmacology & Drug Development



During the drug discovery process, ADME/DMPK characterization is very important to ensure that the identified lead or the chosen candidate has the right absorption, distribution, metabolism and elimination properties in preclinical species to enable translation of the promised biology (i.e., in vitro potency and in vivo efficacy) of the target into human proof of concept.

IntiQuan helps in a phase dependent, balanced and well-thought out approach to render the appropriate qualification of the preclinical characteristics for key Go and No Decisions during discovery and early transition into development.

IntiQuan believes in creating a research based target product profile to guide the initial small molecule drug development with right biopharmaceutics/formulated related support to achieve the desired concentrations of the drug. Alongside, the pharmacokinetic characterization, IntiQuan provides an option for integration of the biology (in vitro and in vivo efficacy data) to PK/PD aspects by application of Pharmacometric principles as deemed appropriate.

IntiQuan believes in tackling some fundamental questions that often plague the early drug discovery to developmental transition of key assets:

Some frequently asked questions:

  • My small molecule drug is highly potent (i.e., nanomolar potency in the in vitro assays) and provides right target engagement, however, the in vivo dose to render efficacy is too high?
  • Should I chose a small molecule drug that shows good ADME properties but moderate potency for target inhibition vs a drug that has high potency for target inhibition with mediocre ADME properties?
  • During the initial screening, the small molecule drug had a tendency to show (drug) cytochrome P450 inhibition in the in vitro assays – should I discard the small molecule and look for another chemical scaffold?
  • I realized that our small molecule drug has a chiral centre; however, the initial discovery and development work has focussed on the racemic drug. What should I do now?
  • Based on the pharmacokinetic and metabolic disposition of the lead compound, have I chosen the right toxicology species for evaluation of nonclinical safety?

Nonclinical Drug Development

Toxicology and Toxicokinetics (TK)

Toxicology studies are an integral part of drug development as the molecule is advanced into Phase 1 through Phase 3 clinical development. Toxicology studies are aimed at understanding the adverse effect level the drug imposes on the body system and organs. Appropriate toxicokinetics data are gathered to obtain exposure data of the drug. The exposure data of the drug would help in establishing NOAEL (No Observed Adverse Effect level) or LOAEL (Low Observed Adverse Effect Level] which are needed for making dosing decisions in early human studies.

ADME, PK, and PKPD Studies

Prior to IND filing, as part of discovery to development transition of the drug, it is customary to characterize the  absorption, distribution, metabolism and excretion profile of the drug in animals. Such data are gathered by performing plethora of in vitro studies and in vivo studies, as deemed appropriate. Also, it may be possible to identify potential gender differences, identify primary routes of excretion, enzymes responsible for metabolism, drug-drug interactions arising from enzymatic and/or transporter systems either due to inhibition or induction mechanisms.

Integration of Pharmacology and Pharmacokinetics

The in vitro potency data and/or in vivo preclinical efficacy data may help in the generation of appropriate PK/PD models that would aid in projection of likely therapeutic dose in humans for achieving the translation of the in vitro or in vivo pharmacological effects of the drug. While toxicology studies would aid in establishing a starting dose with adequate safety in humans, PK/PD modeling would aid in projecting the likely doses in humans where a potential pharmacological activity of the drug would be expected.

We at IntiQuan can help you design an appropriate nonclinical package to support the small molecule drug development leading to IND filing and subsequent Phase 1 evaluation. The integrated service includes:

  • Due diligence of the package and gap analysis
  • Recommend appropriate PK/TK studies
  • Suggest CROs/Partners to perform PK/TK and/or pharmacology studies (if required)
  • Data review, interpretation and finalization of the reports by the CROs
  • Prepare summary documents for the Pre-IND meeting
  • Outline Pre-IND strategy include Company’s questions
  • Prepare Company’s position for questions in the Pre-IND
  • Support Pre-IND meeting

Clinical Pharmacology

The gateway to clinical development is a successful initiation and completion of the Phase 1 First in Human study, let it be in healthy subjects or an appropriate patient population.

Clinical Pharmacology is the heart of clinical development, probing the drug actions/effects with drug/metabolite(s) concentrations achieved in the system. The early and complete understanding of Clinical Pharmacology aspects renders a successful design of the overall drug development package.

IntiQuan has experience in the proper design of Phase 1 Clinical Pharmacology studies –  where emphasis is placed on the collection of right biomarker/pharmacodynamic data alongside the relevant pharmacokinetic data. The proper analysis and interpretation of the gathered data would support key decisions and in planning of the next study/studies.

Based on your requirement and the existing data package, IntiQuan will appropriately structure the Clinical Pharmacology program for answering the critical questions.

Some of these questions include:

  • Is the Phase 1 dose range chosen appropriate for evaluating my drug?
  • What is the minimum threshold concentration to establish the pharmacodynamic activity?
  • Do I have to change my delivery system to achieve the desired threshold concentration to ensure pharmacologic activity?
  • What additional biomarkers can I include in the study design to fully understand the pharmacodynamic effects of my drug?

Clinical Drug Development

We aspire to be your ideal partner to enable seamless development of your programs. We can help in transitioning of your asset to the next decision step by supporting design, study conduct, and data interpretation of a single study or multiple studies. We believe in creating a research-based target product profile deemed appropriate to the phase of development. Our integrated approach of evaluating data carries a greater impact on the overall development, supporting understanding, gap analysis, risk mitigation, and proactive development of contingency plans.

Our knowledge across various therapeutic areas of small molecule therapeutics and biologics/biosimilar enables development of tailored comprehensive strategies that encompass route of administration (intravenous, oral, subcutaneous, intramuscular, intranasal, etc.), biopharmaceutics/formulation options for ensuring that the drug is delivered with right pharmacokinetic attributes to the target site for its purported action.

Furthermore, the interplay of strategic advice, pharmacokinetic and pharmacometric tools enables us to evaluate the key issues in a development program and counter these with remedial plans.

Regulatory Advice & Interactions

Our Regulatory Advice begins with laying out a clear strategy and framework to ensure the program meets the requirements of the Regulatory Agencies. Furthermore, we dissect-out the various components of the program and weigh-in the chosen option(s)/methodology with a razor-sharp scrutiny, since the data package will be submitted to the Regulatory Agency. We believe that interactions with the regulators is of paramount importance because it will provide an opportunity to further strengthen the program while understanding the deficiencies.

We can provide guidance with respect to the FDA expectations and tease out issue(s) of criticality from the FDA perspective. We can articulate a strategy and help in preparing Company’s position to ask the relevant question to the FDA for getting the right advice pertaining to the issue at hand.

The meetings with the Regulatory Agency is an important milestone for drug development. We can take part in such meetings with our clients for example: Pre-IND, end of Phase 1 [EoP1], end of Phase 2 [EoP2], etc.

We have experience and can represent clients in FDA meetings such as teleconferences, face-to-face meetings, and written correspondence with the various FDA’s divisions.

  • Design of individual TK/PK study (dose levels, number of animals, PK time points etc.)
  • Conduct of NCA analysis of TK/PK data, data interpretation and report preparation
  • Review of ADME/DMPK package for gap-analysis
  • Comparison of the nominated candidate with the comparator drug for differentiation strategies
  • Performance of allometry or PKPD modelling relevant for human dose projections
  • Opinion and strategic advice on drug-drug interaction
  • Review and data interpretation of select PK/ADME non-clinical studies
  • Justification of toxicology species
  • First-in-Human/Patients (FIH/FIP)
  • Single Ascending Dose (SAD)
  • Multiple Ascending Dose (MAD)
  • Food Effect
  • Drug-Drug Interaction (DDI) include CYP and Transporter cocktail probe studies
  • Thorough QT (TQT) Study
  • Special population (renal, hepatic, age and gender studies)
  • Mass balance studies with 14C labelled drug

Our overarching Clinical Pharmacology/Development support includes:

  • Translational Medicine – interplay of pharmacometric tools
  • Clinical pharmacology strategy development/review
  • Risk assessment and creation of contingency planning
  • Study design and protocol development including collaboration with study centers and/or CROs
  • Study startup activities, SIV – study initial visits
  • Robust PK analysis and standalone PK Report
  • Summary presentations
  • First-in-Humans (FIH) – healthy subjects or patients
    • These studies encompass assessments of safety, tolerability, pharmacokinetics with or without evaluation of pharmacodynamics and/or target engagement
      • Single Ascending Dose (SAD)
      • Multiple Ascending Dose (MAD)
  • Food effect studies & drug-drug interaction studies
  • Evaluation of human proof of concept studies
    • Part of the extension of Phase 1 program
    • Separate Phase 2a program

Our collaboration can provide a helping hand in developing comprehensive frameworks for the following:

  • Translational Research
    • Exploring preclinical efficacy (in vitro & in vivo) for human translation
    • Providing a Starting Dose rationale
  • Early and Late development for advice in clinical pharmacology and PK/PD
  • Study designs, protocol review, selection of CRO
  • PK and/or PD sampling strategy, Robust PK & PK/PD analyses and standalone PK reports
  • Strategy and clinical development outlines and presentations
  • Comprehensive Pre-IND strategy and gap analysis for data sufficiency
  • Pre-IND related Briefing Book contents development and assistance in preparation
  • IND CTD / eCTD Module 2 – related to ADME, DMPK and Clinical Pharmacology
  • 2.5 Clinical Overview, 2.6 Nonclinical Written and Tabulated Summaries, 2.7 Clinical Summary (2.7.1 and 2.7.2 Biopharmaceutics and Pharmacology)
  • Strategy and Frame-work for FDA / EMA / PMDA Meetings, teleconferences and written correspondence
  • Briefing book contents, review and strengthening Company’s position
  • Attend FDA / EMA / PMDA meetings as a subject matter expert (clinical pharmacology/PK, PKPD, Pharmacometrics, development representation at regulatory meetings)
  • Review of Investigator’s Brochure and provide right insights for data integration
  • Review of Clinical trial protocols and Clinical Study Reports (CSRs)
  • Review of IND / NDA / BLA submissions (clinical pharmacology modules)

We can perform due diligence and provide a gap analysis report on the feasibility of the 505(b)(2) program. Following which, we can provide an end-to-end solution for a comprehensive 505(b)(2) strategy as outlined below:

  • Positioning
  • Key Product Differentiation
  • Target Product Profile
  • Key Challenges
  • Development plan (Preclinical and Clinical POC)
  • Clinical Pharmacology and Pharmacometrics Integration
  • Pre-IND Strategy – FDA meeting
  • IND planning

Some examples of our experience include:

  • Conversion of an immediate release drug product to extended-release product (i.e., reducing the dose frequency of daily administration)
  • Conversion of an intravenous drug product to oral drug product