Panelists Sam Chuang, Jesse McCool, and Ian Wyllie, with moderator Nicholas Ostrout

On Wednesday afternoon, 5 June 2024, contract research organization (CRL) Charles River Laboratories (CRL) held a panel discussion as part of the BPI Theater at the Biotechnology Innovation Organization’s (BIO’s) annual convention in San Diego, CA. Moderator Nicholas Ostrout (CRL’s senior director of strategic accounts and partnerships) led the conversation with panelists Jesse McCool (cofounder and chief executive officer of Wheeler Bio), Ian Wyllie (CRL’s director of RightSource operations), and Sam Chuang (senior director of the scientific advisory services group at CRL).

In March of this year, CRL and contract manufacturer Wheeler Bio announced a partnership “to help clients expedite their drug development journey from discovery and CMC [chemistry, manufacturing, and controls] development to manufacturing” of antibody-based biotherapeutics. The alliance combines CRL’s experience in discovery, safety, and analytics with Wheeler’s “Portable CMC” platform for biotherapeutics discovery to investigational new drug (IND) submission.

The Road from Discovery to Clinical Testing

New companies starting out on the road of drug development need service providers that can help them throughout that journey. Ostrout emphasized beginning each program with end goals in mind, whether a developer is working with monoclonal antibodies (mAbs) or advanced therapies. CRL works with clients from early stages of discovery, and Wheeler provides a platform approach to manufacturing identified lead candidates. Meanwhile, CRL serves as the single point of contact for the shared clients.

The company’s RightSource program provides a fully equipped and staffed quality control (QC) laboratory on site to help sponsors get up and running quickly. “Instead of having to bring in experts, equipment, and instrumentation, you have a drop-in testing lab,” Ostrout said. “We run and manage it.”

Wyllie elaborated: “We provide the Charles River testing platform on site. It includes a quality management system [QMS], some assays, and standard operating procedures [SOPs] to run as if a client had outsourced the testing to one of our legacy sites — brought right up to the manufacturing floor. That allows companies such as Wheeler Bio to focus on their biomanufacturing and what they do best.”

Wheeler Bio is a contract development and manufacturing organization (CDMO) focused on “early biotechs and providing services to bridge the translational gap,” McCool explained. Rather than small- or large-scale services, he said, the company provides the “right scale” needed for CMC development of early stage molecules, with a digital platform for good manufacturing practice (GMP) biomanufacturing. It’s “exactly the right scale needed for first-in-human” test materials.

Chuang described his group’s work with business-development colleagues at CRL in developing effective IND-enabling strategies to help clients achieve defined milestones in their projects. “These strategies can start as early as target validation, new drug creation, and development of a target product profile [TPP] to select a lead candidate for development.”

He said that CRL’s antibody-discovery program is “built on an extensive platform of over 76 billion unique epitopes that can be screened to find ideal binding fragments.” Clients then leverage protein engineering to create a biotherapeutic candidate. Once a drug format is established, translation efforts become critical to saving time in characterization and producing material for early safety studies. Partners such as Wheeler Bio are central to those efforts.

McCool pointed out that his company’s Chinese hamster ovary (CHO) cell platform epitomizes a turning point in the industry: CMC efforts are “getting away from transient expression” in human embryonic kidney (HEK) cells and toward development of stable CHO cells for early production. “Materials may be of suitable quality, but you actually never know until you get to the clinic.” Alternatively, he said, companies can “hedge their bets” and get into a scalable platform the sooner the better — as long as it’s not going to kill your budget.” To facilitate that, Wheeler offers CRL customers a stepwise move into its turn-key production platform. “We use transposon technology and leverage pools to keep the cost down, and we go fast” at a US$10 million development laboratory in Oklahoma City, OK.

There, high-throughput technologies enable programs to move quickly. McCool’s company spent its first 18 months developing workflows and supporting data sets by working on internal projects. “Those data sets are what we used to develop our model, and we make it all open source so that customers have access to transferable knowledge.” Once the platform has been applied to a client project through phase 1, the resulting Portable CMC process is customer-owned, “so they can take that on forward to their next partner or [use it] in house.”

Ostrout pointed to the also-portable RightSource model. CRL’s market analysis suggests that such an approach “makes more sense financially” for small manufacturers than would building, equipping, and staffing a QC laboratory in house. Wyllie said that the company wanted to design a program to enable its scientists and partners to work together seamlessly, leveraging the technical expertise of both. Both CRL and Wheeler Bio understand the value of portable platforms.

Speaking from his long experience with CDMOs, McCool said that partnering can be frustrating “because you’re on the critical path to get your material into the clinic. It’s a high-pressure point in the life cycle and very capital-intensive.” His goal in founding Wheeler was to change the customer experience. “CRO partnerships made a lot of sense to us. We are partnered with three different CROs that help us to connect with early stage companies developing antibodies and related products.”

In creating its Portable CMC platform, Wheeler was more interested in process development than building a QC laboratory, staff, and laboratory information management systems (LIMS). Leveraging the RightSource concept helped to help keep costs down. “We have to be really capital efficient as a CDMO, and CRL has this turn-key solution.” Bringing a RightSource laboratory into Wheeler’s GMP facility also allows for valuable collaboration, with scientists from both companies working together.

Serving an Evolving Market

Ostrout next asked the panelists why how their partnership benefits the current biopharmaceutical market. Looking back at >17 years with CRL, Chuang described a changing business model from providing services to providing relationships. Clients are becoming wiser about their money and more strategic about how they use it.

“They’re keeping their teams strategically small,” he said, “which means relying on external resources. If you’re using 12 different service providers, that’s 12 different relationships and communication streams.” CRL’s integrated model helps companies “transition seamlessly from one phase of a drug-development journey to the next very quickly.”

Manufacturers such as Wheeler provides clients with the confidence of knowing when to expect materials for the next study. “You need quality materials to generate safety data that regulatory agencies need to review before allowing drugs to advance into clinical trials.” Connections built among partners provide a strategic advantage. “You actually save months of time at each stage of a drug-development journey that you’d normally waste working through and navigating different relationships.”

McCool added, “This integration is not just focused on certain services and pricing and offering deliverables and cutting deals. It’s really about going to a partner that can offer progress through key milestones through a development journey.”

He emphasized the value of alliances such as CRL–Wheeler to small, early stage sponsors that don’t have the capital to hire all the people they need. “Giving those customers access to resources helps them move faster. As a CDMO in the middle of the country, our cost of operations enables us to be competitive on price. We’ve also automated workflows and done a lot of work to derisk manufacturing, including using predictive models and some artificial intelligence [AI].” Especially for new product modalities, he said, “you need partners that will be agile and flexible. It’s never a one-size-fits-all offering.”

Wyllie highlighted the teamwork aspect. “With Wheeler tied to our discovery group, you’re not done with discovery and handed off; you’ve already been working with them. Then as you go from manufacturing with Wheeler and to a later-stage provider (or doing it yourself), you already have the assays. It’s beyond customer-centric.” The partners — client included — work together to drive biotherapeutic candidates forward to success. “There are so many providers right now and so many options,” he concluded, “but to have it integrated and pulled all the way through in a way that saves you time, that’s a little bit different.”

Chuang brought up the engineering conundrum of balancing quality, speed, and cost-effectiveness. “With an integrated model, you can achieve all three, whereas often you hear that you can get only two. And you can transition quickly. The communication process is established, and the team works together. Then to produce materials at the right quantity gives you the predictability of when to start activities.”

He explained that CROs must schedule preclinical studies, for example, around other projects. “Being able to deliver materials on time, order the animals, conduct the studies, and deliver the reports puts your filing and interactions with regulatory agencies on track.”

Investment groups scrutinize how young companies manage their time and resources. Some provide money in installments rather than in one lump sum. “It’s spread out over four different milestones, and you’d better hit each one if you want the next tranche of money so that you can carry on with your work.”

Cheryl Scott is cofounder and editor in chief of BioProcess International (part of Informa Connect Life Sciences); 1-212-600-3429; [email protected].

Watch Online

See the full panel discussion online at https://bioprocessintl.com/category/bpi-theater/bpi-theater-bio-2024.