Navigating a Growing Field of New Biotherapeutic Modalities

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The field for next-generation biotherapeutics boasts a myriad of innovative molecules thanks to extensive R&D and technological breakthroughs, such as gene editing. As researchers come to better understand the underlying biology of both molecule and immune system, and with the success of next-generation biotherapies on the market (e.g., cell and gene therapies [CGTs], bispecific antibodies, antibody-drug conjugates [ADCs], and others), the biopharma industry is preparing for a new wave of therapies expected to enter the market during the next decade. However, these next-generation therapies come with challenges.

Where the challenges lie

One of the most recent challenges the industry has faced on the road to developing next-generation biotherapies has been funding, especially post-COVID-19 and especially for small companies, says Benoit Gourdier, executive vice-president and head, Bioscience Production Segment, Avantor. Gourdier observes that funding available for smaller players had decreased significantly after the pandemic and may just now be starting back up. “This is one element that we cannot ignore, for sure, and we have seen the drop. Now we are in a modest recovery,” Gourdier states. Another challenge he is seeing is the pace of innovation, especially in terms of which platform technology to choose, for example.

On the technical side, adds Nandu Deorkar, senior vice-president, Bioscience Production Research & Development, Avantor, many of these next-gen therapies are targeting small populations for rare diseases. This means there is strong unmet need. However, because the patient populations are small, the development and manufacturing challenges for these therapies must be addressed at that level.

Typically, with monoclonal antibodies (mAbs), a developer or biomanufacturer has years to figure out scale-up: clinical trials involve a significant number of people, and a commercial launch can involve thousands, giving a reasonable window within which to solve challenges, Deorkar notes. However, with a next-gen therapy aimed at treating a small population, the developer or biomanufacturer needs to solve these challenges in the clinical phase itself to make the treatment viable, because in the case of a clinical trial for a small patient population, the clinical trial may involve only 10 or 20 people, and then the treatment is launched to maybe 100 people, Deorkar observes.

“That’s why having some platform technologies that you can adopt from one molecule of rare disease to another molecule of rare disease makes the process easily scalable,” Deorkar says. “So that’s the challenge. How do you develop the scalable technologies that can apply from one molecule to other molecules? And this challenge has even been recognized by FDA now, so [the agency] added a platform technologies designation. If you come up with a technology used by one molecule, then [the agency] will designate that as a platform technology. Then that company can use that technology for another molecule without having to validate again and again. That has been another challenge—to reduce the complexity and challenges from having to undergo validation each time.”

The FDA document, Platform Technology Designation Program for Drug Development, was released as a draft guidance in May 2024 (1) to provide details about the implementation of the platform technology designation program, which was established in section 506K of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The guidance contains eligibility factors for receiving a platform technology designation and outlines the potential benefits of receiving such a designation. The guidance also describes how to leverage data from designated platform technologies and having discussion about a planned designation request as part of a milestone meeting, among other information. The platform technology designation program aims to increase efficiencies in drug development, manufacturing, and drug application review processes (1).

From complex to simple?

The evolution of more sophisticated molecules has translated to increasingly complex manufacturing processes, partly due to the evolution of starting material as well. “They all start from complex biology,” notes Deorkar, who explains that early on in the drug development process, everyone wants to get to market fast, so they will use that complex biology; however, that translates into complex manufacturing, which can slow things down and add significant costs.But if one sits back and thinks about it, Deorkar emphasizes, those biologic processes can actually be simplified in the manufacturing process.

“For example, look at 30 years ago, when the monoclonal antibody first came; that was also very complex. People had 0.1 gram per liter titer. Now, [they] can make tons of antibody. So, [there are] similar challenges [with next-gen biotherapeutics], because you’re starting with complex biology as you develop the understanding,” Deorkar says.

Deorkar highlights the position Avantor plays in this scenario, where the company focuses on taking this complex biology problem and makes it simpler for the industry. “So, the way we do it [is] you can keep the biology complex, but anything around the biology, [we] make it simple. Your unit operation, your use of solutions, materials, etc., we supply around it. So, you don’t have to make everything complex, you can make some things simple around it,” he explains.

“And, associated with the complexity of the process, you have the cost that leads to this [manufacturing] complexity,” adds Gourdier. “And one of the things [to consider] is that … the raw material … is quite limited versus the total cost of the drug. One of our roles is to have discussions with the technical people—could be the developers, could be the engineers, could be the manufacturers—and, to build on what [Deorkar] said, give options [on how] to simplify the process, to reduce your cost, and give you flexibility.”

Navigating regulatory standards

Another area that continues to evolve is the regulatory space around next-generation biotherapeutics. With new modalities, there is still some opaqueness in regulatory standards, says Deorkar. He explains that some of the regulatory standards are not clearly defined and contain general statements about what can be done.

“Those regulatory standards are written that way, and there is a purpose why they are written that way,” Deorkar emphasizes. “It’s because regulators don’t want to create an artificial boundary, because they also don’t have experience. However, when an application goes to them, they are still going to look at it based on the risk. So, although the regulations [themselves are] not very clear, the intent [behind them] is clear: we want to make the drug as safe as possible and demonstrable efficacy.”

A future of innovation

The biopharma industry’s future may boast much more opportunities based on continued innovation in the way drug modalities are conceived and how biology is harnessed. Twenty-five or 30 years ago, Gourdier says, the industry was all about mAbs and traditional vaccines. “We grew up in this environment, with the mAbs. Now, we have this diverse portfolio of modalities, so [there will be] lots of opportunities to go after,” he states.

Meanwhile, new challenges, particularly for a service provider, will entail ensuring that one’s company is well equipped to tackle this diversity of new modalities, from a chemical standpoint for fluid handling to offering the right support to navigate regulatory requirements, says Gourdier.

To add to that, Deorkar points to personalized medicines influencing a distributed manufacturing network. “If you look at cell and gene therapies (for example), [patients] are treated with these on a personal basis. [This will require] distributed manufacturing, and then considerations of how do we do this more locally? So, I think one of the things we’ll talk about is geographically adjacent innovation centers or support centers,” Deorkar explains. Furthermore, because some of these personal therapies have a 72-hour or 48-hour injection requirement after manufacturing, location is going to be very important, he adds.

Collaboration is key

At the end of the day, bringing new next-generation therapeutics to market will require industry collaboration. For instance, EvolveImmune Therapeutics, a Branford, Conn.-based immunotherapy platform company focused on developing next-generation biotherapeutics, formed an agreement with AbbVie in October 2024 to develop novel multispecific therapeutic antibodies against cancer (2). The agreement involves a $65 million upfront fee and equity investment made by AbbVie. In addition, EvolveImmune is eligible to gain up to $1.4 billion in aggregate option fees and milestones and is eligible for tiered royalty payments on net sales, a hefty financial commitment overall by AbbVie, which has an option-to-license stipulation as part of the agreement.

In the agreement, EvolveImmune’s T-cell engager platform, EVOLVE, will be used to develop novel antibody-based therapies for solid and hematologic malignancies. This platform is designed to deliver “potent, selective, and integrated T-cell co-stimulation to amplify and sustain the tumor killing capacity of the T-cells,” as stated in a company press release (2). With this approach, the company aims to bypass low tumor immunogenicity while conditionally activating adaptive immunity and reducing T-cell dysfunction, which have been difficult challenges to overcome in solid and hematologic tumors.

“We believe that EVOLVE, with its differentiated CD2 co-stimulation strategy, represents a potential next-generation, best-in-class T-cell engager platform and that our technology may offer clinically meaningful benefits for patients,” Stephen Bloch, MD, chief executive officer of EvolveImmune, stated in a press release (2).

Meanwhile, another collaboration gaining attention is Charles River Laboratories’ partnership with Ori Biotech, in which Charles River gained access to Ori Biotech’s next-generation cell and gene therapy (CGT) manufacturing platform, IRO (3), and conducted head-to-head comparison runs over the course of two years between it and a legacy CGT manufacturing technology previously optimized by Charles River. In September 2024, the companies jointly announced the fruits of their labor: the comparison evaluation between IRO and the legacy CGT manufacturing platform showed that IRO generated, on average, 51% chimeric antigen receptor positive (CAR+) expression and 2.1 billion total CAR+ cells in a seven- to eight-day process, compared with 1.6 billion CAR+ cells generated by the legacy CGT manufacturing technology (3).

Such collaborations, whether to develop new modalities with superior therapeutic efficacy or to push the envelope with manufacturing technologies and processes, will play central roles in the future shape of the next-gen biotherapeutics market.

References

1. FDA. Draft Guidance for Industry, Platform Technology Designation Program for Drug Development (CDER, CBER, May 2024).
2. EvolveImmune Therapeutics. AbbVie and EvolveImmune Therapeutics Announce Collaboration and Option-to-License Agreement to Develop Next-Generation Cancer Biotherapeutics. Press Release. Oct. 31, 2024.
3. Ori Biotech. Ori Biotech and Charles River Laboratories Collaborate to Accelerate Life-Saving Cell and Gene Therapy Development and Manufacturing. Press Release. Sept. 18, 2024.

About the author

Feliza Mirasol is science editor at BioPharm International®.

Article details

BioPharm International®
Vol. 38, No. 1
January/February
Pages: 13–15

Citation

When referring to this article, please cite it as Mirasol, F. Navigating a Growing Field of New Biotherapeutic Modalities. BioPharm International 2025, 38 (1) 13–15.