Discovery is a complex and high-risk process in drug development, as researchers strive to identify and advance promising therapeutic candidates. It requires scientific prowess, advanced technologies, and strategic vision to navigate through potential obstacles with agility. With this episode, Big4Bio is kicking off an occasional series on discovery sciences with Charles River Labs, which, over the past five years, has contributed to more than 80 percent of novel FDA-approved drugs. We spoke with Charles River Labs' chief scientific officer of discovery Justin Bryans, and Charles River Labs' vice president and chief scientific officer for discovery and safety assessments, Steve Bulera, about the challenges of drug discovery, why every moment matters, and the benefits of the collaborative approach Charles River takes in working with its partners.

With government funding cuts to research in the United States and an uncertain and erratic policy environment, stability is emerging as a strength Europe is seeking to leverage to attract scientific investment and talent. As the industry readies to gather in Vienna for Bio-Europe 2025, we spoke to Director of the European Portfolio for EBD Group Claire Macht and BioXconomy Partnering and Investment Editor Millie Nelson, about the state of the European biotech industry, the landscape for finance and dealmaking, and what to expect when 5,700 investors and biotech executives gather for 30,000 meetings Vienna.

The IPO market remains unwelcoming to biotechs and venture investors are reticent to back younger companies. In the absence of reliable funding sources, many biotechs are trying to advance their most promising programs while keeping their operations lean until they can get to a fundable milestone. We spoke to Kevin Sarney, Life Sciences Practice Leader for Charles River CFO, about the current uncertainty biotechs face, the need for capital efficiency, and how companies can best prepare for future opportunities.

In 2022, Charles River Laboratories acquired the vivarium operation services provider Explora BioLabs. The acquisition both complemented and expanded the operations of CRADL (Charles River Accelerator and Development Lab), which is part of Charles River’s Insourcing Solutions business. Now, three years later, the company has built a consistent brand, set of services, and unified offering across its North American locations based on the best of both companies. And, Explora BioLabs clients now have direct access to Charles River’s other products and services. We spoke to Charlie Cook, Senior Director of Operations for Charles River Labs, and Julie Freebersyser, Executive Director NA Insourcing Solutions for Charles River Labs, about the merger, the benefits it has brought, and the greater flexibility it provides its clients.

Biotech companies are more prone than most to shareholder lawsuits because single events can often cause sharp and sudden price drops in their shares. While they buy insurance to protect their officers and directors from financial exposure, companies often do poorly to understand their actual risks. C3 Risk & Insurance Services has created “The Answer,” a proprietary database of 13,000 shareholder suits with 80 data points around each to guide companies in their coverage decisions. We spoke to Mike Milligan, managing director at C3 Risk & Insurance Services, about its shareholder lawsuit database, the insights it provides, and why who owns a stock is a much better indicator of a company’s risk of being sued than the size of a price drop.

With the JPMorgan Healthcare Conference on the horizon, biotech CEOs are wondering whether the new year will bring a more welcoming IPO market. But Gregg Beloff, co-founder and managing director of Danforth Advisors, said rather than focus on an IPO, companies should prepare themselves to capitalize on a range of financing options that may present themselves. We spoke to Beloff about what CEOs should do now to get their companies positioned for different financing options, how they can de-risk themselves, and the things it is never too early to do so they can capitalize on opportunities when they arise.

The recently released update to the International Council for Harmonisation M12 guidelines provides a consistent approach to drug-drug interaction studies across different regulatory agencies. The new guidelines replace regional and local ones and set a global standard for addressing drug-drug interactions. We spoke to Michael Templin, Senior Principal Scientific Advisor for Charles River Laboratories; and Marko Andric, Senior Business Development Director, Late Discovery, for Charles River Laboratories; about the new guidelines, changes drug developers will need to make in their approach to pre-clinical development, and the tools and technologies that might help them comply. A related webinar on the guidelines can be found at www2.criver.com/l/60962/2024-11-05/n5wj6y

Partnering has long been a critical engine to drive companies’ success in the life sciences. In the current difficult financing environment, executives and business development leaders need to take advantage of opportunities to meet with organizations around the world to ensure they have the capital, resources, and expertise they need to achieve their goals. We spoke to Patrik Frei, CEO and founder of Venture Valuation, about the role partnering plays in the life sciences, The Pre-JPM Partnering Week that will run virtually December 2 through 6, and how companies can best position themselves for a productive JPM Week.

Ultra-rare neurological diseases are often without any treatment options. Even if a biopharmaceutical company decided to pursue one of these conditions, it’s unlikely that a child already diagnosed would be able to get treatment in time to prevent irreversible damage. Charles River Laboratories has embarked on a three-pronged strategy to work with families of children with these conditions to rapidly develop customized therapies. This involves the simultaneous pursuit of drug repurposing, antisense oligonucleotides, and gene therapies customized to individual patients. The company is using induced pluripotent stem cells to create differentiated cells with a patient’s genetics to study the disease and screen treatments. We spoke to Roxana Redis, Associate Science Director of Advanced Modalities for Charles River Laboratories, about the potential to rapidly develop so-called N-of-1 therapies, how Charles River does this, and why its pursuit of multiple modalities at once is designed to meet the urgency of these patients.

One of the challenges for drug discovery for new therapies to treat neurological conditions has been the need for better models of the various cells within the human brain and the interaction between different cell types. Charles River Laboratories, through a partnership with Bit Bio, has been able to access a consistent and scalable supply of a variety of induced pluripotent stem cell-derived human brain cells that have enabled the development of multi-cell cultures that can model various neurological diseases. We spoke to Malika Bsibsi, research leader at Charles River Laboratories International, about the challenges of developing treatments for neurological diseases, the limitations of animal models and single cell type cultures, and how this new approach promises to improve drug discovery in what has been a difficult area for therapeutic developers.

The emergence of TechBio takes center stage at this year’s BioFuture conference, which will be held in New York City, one of the emerging centers of this new breed of companies. The conference will explore the transformative forces from AI to digital medicine that are reshaping healthcare. The conference, which will be held October 28 to 30, brings together innovators and investors to exchange ideas, discuss trends, and do business. We spoke to event organizer Sara Demy, co-founder and CEO of Demy-Colton, about BioFuture, how innovative technologies are transforming the healthcare landscape, and why it is unlike other biotech conferences.

AI is increasingly being integrated into the drug discovery process and promises to not only increase efficiency, but expand the chemical space for drug developers to explore. Even though it is still early days for the technology, it is already demonstrating its ability to be a powerful tool across a broad set of applications from testing molecules in silico to designing new molecular entities. We spoke to David Clark, Senior Research Leader in UK Small Molecule Drug Discovery at Charles River Laboratories, about the potential to harness the predictive powers of AI to improve drug discovery, how generative AI can get us to better drugs faster and cheaper, and how this technology is reshaping the drug discovery process.

For drug developers, hit identification is a critical part of the discovery of new medicines, but the proliferation of therapeutic modalities, new biological targets, and screening technologies has meant that there’s not a one-size-fits-all strategy for drug developers to pursue. We spoke to Rob Howes, Head of Discovery Sciences UK for Charles River Labs, about the need for pairing the right hit Identification strategy to a target, how hit identification is gaining importance as funding activity picks up and biopharmaceuticals turn their attention to rebuilding their early-stage pipelines, and why compelling hit identification data can attract fresh capital to a drug developer. You can learn more about Charles River Labs Hit Identification work at https://www.criver.com/products-services/discovery-services/integrated-drug-discovery/hit-identification?utm_source=big4bio&utm_medium=podcast®ion=3701

One of the reasons that drug development is so expensive and time consuming is the cost of clinical trial failures. A critical means of accelerating drug development and reducing its cost lies in identifying candidates during preclinical development that have risks that outweigh their benefits and eliminating them from the pipeline before they advance to the clinic. We spoke to Sarah Gould, Director and Senior Principal Scientific Advisor for Charles River Labs, about the types of risks that can be detected through preclinical testing, strategies that can be used to de-risk programs, and why doing so in the current environment can take on growing importance for companies seeking funding or licensing agreements.

Cryo electron microscopy, or Cryo-EM, enables high-resolution screening for small-molecules or biological ligands, particularly for targets that are challenging to crystallize. One area that technology is proving to be a valuable tool for is the development of lipid nanoparticles, which have emerged as important vectors for mRNA and other genetic medicines. Cryo-EM can be used to analyze the size, shape, payload characteristics and other aspects of LNPs. We spoke Tim O’Bryan, director of discovery partnerships and commercial integration for Charles River Labs; and Karl Bertram, co-founder and managing director for ATEM Structural Discovery; about ATEM’s Cryo-EM technology, its incorporation of machine learning, and how it fits in with Charles Rivers’ broader drug discovery offerings.

Despite significant advancements, the field of Synthetic Biology has yet to fully deliver on its promise of a world where we can overcome the challenges we face in human health and the environment by programming biology. Elegen has developed innovative, cell-free technologies that allow it to synthesize DNA with unprecedented speed, length, and quality. We spoke to Matt Hill, founder and CEO of Elegen, about Elegen’s ENFINIA DNA technology, the need it addresses, and how it has disrupted the status quo for DNA synthesis.

Biomarkers can provide insights into experimental therapies, identify patients who are likely to benefit from them, and improve chances for clinical success. Charles River Laboratories offers a range of early biomarker discovery services, leveraging the expertise of its scientists to identify biomarkers in the early stages of drug development programs. We spoke to Stefan Kostense, director of biology at Charles River Laboratories, about the benefits of conducting biomarker discovery early in the drug development process, how it can drive development decisions in the preclinical phase and beyond, and how it benefits patients.

Earlier this year, Charles River Laboratories acquired SAMDI Tech, a provider of proprietary mass spectrometry technology that enables label-free, high-throughput screening for drug discovery. The technology cuts cost and accelerates the time it takes to identify a lead drug candidate, enabling drug developers to make critical go-no-go decisions earlier. We spoke to Zack Gurard-Levin, science director in discovery for Charles River Laboratories about the advantages SAMDI’s mass spectrometry offers over alternative technologies, how it enables the study of a broad range of modalities, and how it fits into a comprehensive set of Charles River offerings.

Chief Financial Officers in the biotech industry operate in a complex and ever-changing financial landscape. In addition to being charged with traditional financial duties, they must navigate regulatory uncertainties, manage risks, and adjust to evolving market dynamics. We spoke to Kevin Sarney, Life Sciences Practice Leader for Charles River CFO, about the current financial environment for biotech companies seeking to raise money, how CRCFO works with biotech clients, and how the use of an outsourced CFO can allow younger biotechs to cost-effectively tap deep industry experience.

The high cost of drug development is linked to the high rate of therapies that fail in the clinic. Safety concern relating to the ability for an experimental therapy to bind to more than a target of interest is one major reason drugs fail in development. Charles River Labs is working with its clients to detect off-target binding early in the drug development process using its Retrogenix platform, cell microarray technology that can identify potential safety problems of an experimental therapy (https://www2.criver.com/l/60962/2024-01-31/n4wrxz). We spoke to Mark Aspinall-O’Dea, associate director of U.K. advanced modalities for Charles River Labs, about the risks of off-target binding, how its Retrogenix platform technology works to detect potential problems, and its ability to work across therapeutic modalities.