OR WAIT null SECS
The biopharma industry is seeing more merit in strategizing clinical and commercial drug development as early as the preclinical phase.
There is a strong inclination in the biopharmaceutical industry today to begin key drug development tasks early on in the drug development lifecycle. In some cases, clinical and commercial manufacturing discussions begin as early as the preclinical phase. Preclinical strategies can be used to facilitate and improve drug development timelines and outcomes for biologics. Securing expertise in preclinical studies is an important aspect of optimizing the commercial potential for a biologic.
At the fundamental level, preclinical studies need to prepare drug development programs with clinical trials in mind, according to Armin Spura, PhD, CEO of Crown Bioscience. Preclinical studies aim to inform trial design and satisfy regulatory requirements for regulatory filings, such as an investigational new drug or clinical trial application. It is therefore essential that preclinical trials inform candidate selection to ensure that one’s strongest program goes into clinical trials. The data should also generate documentation for a comprehensive safety profile, including robust toxicology data, and provide enough pharmacokinetic and pharmacodynamic information to inform optimal dosage, in terms of both potency and timing. Finally, preclinical data must also prepare the selected drug development program for clinical manufacturing with chemistry, manufacturing, and controls information, Spura asserts.
“Beyond these key tasks, in today’s era of drug discovery and development, robust preclinical studies also offer your program the greatest chance of success by identifying and defining programs with the greatest potential benefit for patients, or by identifying patients most likely to benefit from a particular candidate,” Spura says.
The key outcomes of preclinical studies are to determine target identification, efficacy, mechanism of action (MoA), and to some extent toxicity/safety, says Matthew M. Hewitt, PhD, senior director, Scientific Services Cell and Gene Therapy, Charles River Laboratories. Hewitt explains that, typically, target identification, efficacy, and MoA can be initially confirmed using in-vitro studies. During late preclinical in-vivo studies, research models are used to assess efficacy as well as address safety questions. “In many research models, efficacy is many times overestimated, and safety is hard to evaluate. This is due to the imperfect nature of these models and their current inability to predict clinical outcomes in patients,” he states.
It can be beneficial to start strategizing clinical and commercial development tasks early on as well. “We are seeing this type of strategizing in the cell and gene therapy (CGT) space,” says Hewitt. The primary reason for this early strategizing in CGT involves the timeline to clinic and potentially compressed commercialization timeframe of CGT compared to traditional therapeutics.
“In gene therapy, commercialization can be attained in as little as two years, and in three to five years for cell therapies, so a viable clinical and commercial strategy must be mapped out earlier in the development process,” Hewitt explains. Key to this is the ability to scale-up a therapeutic’s manufacturing process from one suitable for preclinical work to one able to operate within a certified current good manufacturing practices environment. This is coupled with defining a robust, consistent manufacturing process and analytical assays to ensure a smooth transition from preclinical to clinical to commercial, Hewitt adds.
“It is imperative to take advantage of every facet of drug development for which we can reasonably optimize the quality and speed to move the candidate programs forward, and improve their chances for success in the clinic,” says Spura.
It is therefore essential to start planning as early as possible for the long-term needs of one’s program, especially given recent pressures on supply chain materials and labor, as well as manufacturing capacity, to ensure the program doesn’t experience avoidable logistical delays. “These needs are heightened in particular if your program is novel, specialized, or leverages advanced technologies that are rare in the industry,” Spura states.
“We have long been working through the balance of providing enough time to adequately plan for and execute clinical development and commercial launch, alongside the realities of limited resources,” Spura adds. Starting with a preclinical program that increases response predictability in human populations, or better defines human patient characteristics in which a drug candidate is more likely to be viable, shifts this balance. Having advanced preclinical results could also support expanded investment to secure materials, capacity, and the workforce to translate the science into a solution for patients.
Outsourcing preclinical studies or partnering on them is an important strategy, particularly for small firms with little experience in dealing with the regulatory pathways for drug approval or little experience in commercializing a therapeutic.
“One of the major advantages of outsourcing drug discovery is access to specialized technology and expertise that can ultimately help advance stronger programs into the clinic. Drug development has an extremely high attrition rate. But we know that better information on, and characterization of, your preclinical program can put you in a much stronger position to identify patients and design the clinical program, ideally suited for your drug candidate,” Spura explains.
Generally, outsourcing enables therapeutic developers to operate more efficiently, especially if they are a small startup with multiple pipeline products, says Hewitt. Hewitt finds this to be especially true if specialized assays and/or research models are needed to advance programs. “We are seeing this more and more in the cell and gene therapy space where specialized analytical methods (i.e., identity and potency assays) and/or models (i.e., Crigler Najjar animal models) are required,” he states.
Hewitt points out that there are two primary types of preclinical studies to outsource, in-vitro and in-vivo preclinical studies. The key benefits to outsourcing these studies include removing the need for large numbers of employees (particularly to support in-vivo studies) as well as building/maintaining large research facilities. “This is especially critical for startups in large biotech clusters where space, particularly for in-vivo studies, is at a premium (think Boston, San Francisco, Seattle, etc). Outsourcing enables startups to operate more-or-less virtually, extending their funding runways to reach a program and/or company value inflection point,” Hewitt explains.
Once that value inflection point is reached, startups can make better informed decisions about whether to build out internal preclinical capabilities, Hewitt adds. Additionally, therapeutic developers can take advantage of other capabilities with an outsourcing partner, such as process scale-up, optimization, analytical development, and qualification. “The primary challenge to outsourcing is losing control of quality and timeline. Generally, quality and timeline are linked in that preclinical service providers may require time to master unique assays and models for studies. These are generally challenges which can be mitigated by interviewing then choosing the a preclinical partner with the appropriate experience,” Hewitt says.
“Solving the challenges in preclinical research are what dedicated contract research organization (CRO) teams do all day every day,” Spura adds. “A broad range of specialized technologies are often easier for CROs to identify, develop, and match with sponsor programs.”
Capacity issues are also a key challenge today with the life sciences sector experiencing strong growth right now, Spura emphasizes. This type of growth can cause bottlenecks. Furthermore, the initial investment in preclinical work can be substantial; however, if a drug developer is using novel technologies and leveraging a partner’s expertise to help improve the predictability of the drug candidate, then the investment pays itself off multiple times over in the long run, Spura states.
Feliza Mirasol is the science editor for BioPharm International.
Vol. 34, No. 11
When referring to this article, please cite it as F. Mirasol, “Biopharma Industry is Seeing Merit in Early Preclinical Strategies,” BioPharm International 34 (11) 36–37 (2021).