By Terry Cochrane
Founder and President | BrevisRefero
Large molecule (biologic) drug target discovery is a complicated and critical step in the development of biopharmaceuticals that involves identifying a specific molecular target associated with a disease or condition that can be modulated by the drug, whether it be a therapeutic or vaccine. As part of understanding the disease/condition and the associated medical need the biotech researcher pours time and energy into assessing the physiopathology as well as the disease molecular and cellular mechanisms. This results in the selection of specific targets which can include a protein, enzyme, nucleic acid, or other biologically relevant molecules. Advancement of the identified target through the discovery stage typically involves genomic and proteomic analysis, pathway analysis, target validation, biomarker discovery, functional characterization, preliminary in vitro and in vivo testing, and many more supporting activities. Once through this discovery process, which can take up to five or more years to complete, how should you plan for continued drug development success?
" In the current environment early-stage biotech companies outsource a significant portion of all activities related to the readying of their biologic drug target for clinical trials while still requiring some internal resources to manage all aspects of drug development outsourcing. "
It may be surprising to know that while target discovery is the most crucial step in the development of biopharmaceutical products, it’s seldom the longest timeline nor the most resource and cost intensive part of drug development in biotech. The pathway from preclinical to First in Human (FIH) Phase 1 clinical trials that gives the initial signal of the drug target being safe and tolerable begins with the identification of funding, which is typically a significant challenge for early-stage biotech companies. Common sources of early-stage development funding for a newly discovered biologic drug target includes seed and angel investors, venture capital investment, strategic partnerships, and non-dilutive government grants and awards. Every avenue of potential funding needs to be investigated and pursued to push the drug development program forward. But how much exactly should an early-stage biotech company budget to complete all activities associated with their Phase 1 human clinical trials?
In the current environment early-stage biotech companies outsource a significant portion of all activities related to the readying of their biologic drug target for clinical trials while still requiring some internal resources to manage all aspects of drug development outsourcing. Accordingly, the budget to enable Phase 1 clinical studies not only needs to account for internal overheads, consultants, research and development labs, and general/administrative expenses, but also for the outsourced actives comprising:
o Chemistry, Manufacturing, & Controls (CMC)
Costs related to the development and manufacturing of the biologic drug target including process development, formulation development, assay development, scale-up, engineering runs, product characterization, GMP manufacturing of drug substance, GMP manufacturing of drug product, stability studies, etc.
Included within this bucket are the costs of materials and consumables which can be a significant cost that should not be overlooked during the budgeting exercise.
o Preclinical Laboratory Studies
A clear demonstration of the mechanism of action of the target candidate is necessary for continued development and investment of time and resource.
Typical practice is to perform several supporting lead-up animal studies as part of target identification and initial readouts on safety before initiating GLP toxicology studies to provide added assurance.
o Good Laboratory Practice (GLP) Toxicology Studies
These costs are related to generating the first safety data in animal models which provides regulatory authorities like Health Canada, US Food and Drug Administration, European Medicines Agency, etc. assurance that the biologic drug target is preliminarily safe ahead of the FIH Phase 1 clinical study.
" Depending on the complexity of the clinical study protocol, and the disease indication, it can be anticipated that between 40-100 subjects may be required, which is a major driver of study costs. "
o Clinical Studies & Supporting Clinical Sample Analysis
The primary objective of the Phase 1 trial is to evaluate the safety and tolerability of the biologic drug in humans. Additionally, the trial may also aim to establish preliminary dosage levels and assess the drug's pharmacokinetics and pharmacodynamics. Depending on the complexity of the clinical study protocol, and the disease indication, it can be anticipated that between 40-100 subjects may be required, which is a major driver of study costs.
Additionally, the costs associated with analysis of samples from the study must be factored into the budget as it includes analysis such as blood for immune response monitoring, urine for drug processing, and other fluids and samples, depending on the nature of the biologic drug.
Finally, a Contract Research Organization (CRO) is typically contracted to manage all aspects of the clinical study including the clinical protocol writing and approval, site selection, subject enrollment, study monitoring, data compilation, statistical analysis and more.
o Regulatory Filings & Support
Crucial to all aspects of the overall clinical development plan is the identification and contracting of a competent regulatory organization that will compile all aspects of the preclinical, CMC, and clinical sections for submission to the regulatory agency.
Also, the regulatory group must act asf agent (key point of contact) for all interactions with the regulatory authority. Regulatory activities should not be underestimated as they are several months of work which requires appropriate budgeting in advance.
"An approximation of this timeline is typically from two to four years depending on the factors mentioned above that influence complexity of the program. "
The timeline for moving a biologic drug candidate from discovery to the completion of FIH Phase 1 clinical trials can vary significantly based on several factors including the complexity of the drug, manufacturing challenges, regulatory requirements, and unforeseen hurdles which all contribute to the overall cost to getting the candidate into clinical trials. An approximation of this timeline is typically from two to four years depending on the factors mentioned above that influence complexity of the program. With such a wide range in timeline and recognizing that biologic drug development timeline equates to burn rate, there is a significant variation on the estimated costs ranging from $10-25 million or more to achieve the finalized data readout from a Phase 1 clinical study.
" An approximate range of $10-25 million or more to achieve the finalized data readout from a Phase 1 clinical study can be anticipated. "
Paramount to establishing a timeline and budget to advance a biologic drug candidate through preclinical to completion of Phase 1 clinical is managing the expectations of investors as to the required time and costs, since few small biotech companies have the financial resources to tackle the gauntlet on their own internal funding. The very important activity of selecting reputable contract service provider organizations (CDMOs, CROs, CTOs) cannot be understated and should be carefully considered to ensure a successful Phase 1 outcome.
BrevisRefero Corporation is a collection of biologics drug development experts utilizing its collective 100+ years of experience in advancing our clients outsourcing objectives through its RFP>Navigator® portal to accelerate drug candidates efficiently into clinical trials.
If you would like a free, no-obligation consultation to talk about your biologic drug development outsourcing, planning, budgeting, or execution then please reach out to us at:
email@example.com or call us at (905) 636 - 6559.
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By Terry Cochrane
Founder and President | BrevisRefero