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:
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:
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:
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.
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.
Our overarching Clinical Pharmacology/Development support includes:
Our collaboration can provide a helping hand in developing comprehensive frameworks for the following:
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:
Some examples of our experience include: