Multispecific Trial Supply Stability Hinges On CDMO Agility
A conversation with Dr. Daniel Teper, Naya Therapeutics
Not long ago, developing bi- and trispecific antibodies was fraught with complications, including process impurity and stability issues. Now, more companies can enjoy the fruits of a well-characterized modality still ripe with unexplored therapeutic potential.
At the product level, the heightened confidence comes down to picking the right manufacturer, says Daniel Teper, Pharm.D., founder and chief executive at Naya Therapeutics.
Naya recently completed a spinoff from their reverse merger partner Invo Fertility, a strategic decision that enables Teper’s team to accelerate clinical development of its immuno-oncology portfolio and begin recruiting patients for its lead candidate, NY-303, a GPC3/NKp46/CD16 trifunctional antibody to treat hepatocellular carcinoma (HCC), approved to proceed with a Phase 1/2a in Israel.
Teper, who is leading the company through its decoupling, said the move gives them freedom to pursue an ambitious pipeline of immuno-oncology assets leveraging two disruptive modalities: multifunctional antibodies and radioimmunotherapy.
As the company approaches a few key milestones, we had questions about how it is addressing legacy challenges related to multispecifics and new obstacles in the increasingly hot radiotherapy field. Teper offered to help clear up some of them.
We learned that, for Naya and its partners, making multispecifics has become routine. Radiotherapy, on the other hand, is where the growing pains are happening. His answers have been edited for clarity.
What obstacles have you encountered concerning adequate supply and waste prevention? What concerns do you have around cold chain, storage, and staff training?
Teper: In a world of uncertainty, we chose to manufacture in the United States. We're working with a boutique CDMO, STC Biologics, which has known our technology for several years.
Not only are they in the U.S., they're flexible — probably more flexible than larger CDMOs — and they can produce on demand with no surprises. I think that's important.
I respect the larger CDMOs, but they're probably more appropriate for Big Pharma or later stages of development. Working with someone who has the same standards, at least the same standards as Big Pharma and the larger CDMOs, but has a more entrepreneurial and more flexible approach, with whom we’ve built a close partnership over the years — I think those elements are critical to maintaining and managing a reliable clinical supply.
They're doing our first lead GPC3/NKp46 candidate, and they're also doing the other antibodies, which are moving toward clinical trials. They have the flexibility and speed, and that is important because we're able, within 12 months, to go from designing the sequence of the product to IND and patient enrollment.
And why is it so important? Because we have more and more competition from China, and China goes very fast in preclinical and clinical CMC. We believe that the only way the U.S. can compete is to shorten the timelines — the timelines for preclinical development, CMC development, and early clinical trials.
The choice of a CDMO is extremely strategic. You have to make sure that you have slots reserved in advance and that you have flexibility in those slots. It does happen, including in the larger CDMOs, that an early batch fails to meet quality standards. If you must redo it and you lose your spot to a Big Pharma company, it could mean a year or two years of delay. If you're a small private or public company, it is very problematic with investors.
I would encourage biotechs to consider establishing close partnerships with boutique CDMOs. They don’t have to be small, but they have to be sufficiently experienced to deliver GMP and commercial or pre-commercial quality, and they must be true partners.
Now, about managing supply and cold chain — I think that for bispecifics, this has become really routine and not so different from mAbs. As recently as five years ago, everybody was concerned about bispecific manufacturing. For example, I remember we were in due diligence, and a senior executive at the large pharma company was describing how they had licensed a product from another biotech, and they had to completely redo the CMC because of manufacturing issues.
I think that dynamic has changed. At least in our hands and the hands of a number of other companies, it is no more difficult to do a bispecific than it is to do a monoclonal antibody.
Are you concerned about capacity when you reach commercial phase?
Teper: Boutique doesn't necessarily mean tiny. There are some midsize CDMOs that have capacity to do a commercial product.
At the same time, you have to think that the products most likely are going to be licensed to Big Pharma, and Big Pharma is going to do a tech transfer from the CDMO, either internally or to their favorite larger CDMO.
There's no point choosing a large CDMO, which may not necessarily be what the licensee is looking for.
How are you approaching these issues for NY-700, the radioimmunotherapy? Is your strategy different compared to the multispecifics in your pipeline?
Teper: Radiopharmaceuticals are new, even for Big Pharma. Recently, we've seen acquisitions that have been driven in part by access to the supply chain. We've seen acquisitions like RayzeBio by BMS in which a lot of the value was in the supply chain access.
Many radioisotopes, such as, for example, actinium-225, which is a good radionuclide, are in limited supply. This is why there are only a small number of players.
We chose a novel radionuclide, which hasn't been disclosed yet, that is potentially safer than actinium-225, but it has a shorter half-life. That means you cannot transport it from China to the U.S. or even from Canada to the U.S. It requires a production infrastructure on a regional level, so we're currently securing a network for the supply of the radionuclide that can deliver in multiple locations in the U.S., Europe, and Asia.
What has your experience been in identifying trial sites equipped and staffed with technical expertise to handle the drug? Is there additional cooperation required based on the nature of the drug?
Teper: For bispecifics, it's not really an issue in 2025. For radiopharmaceuticals, it's a different matter.
There are fewer sites with expertise, so you have to take that into consideration. When we begin clinical trials with our first radiopharmaceutical, we're not going to take risks on unexperienced sites, so we will have fewer sites.
What about some of the other issues that come along with more complex molecules, like aggregation and process-related contaminants? Are you encountering these kinds of things? And if so, how are you addressing them?
Teper: I think we've learned a lot. I remember working on monoclonals 10 years ago, and we had significant aggregation. And moving into bispecifics, we had even more aggregation; we had molecules breaking and all those kinds of issues.
With the processes that we've perfected with STC, we don't see any of those issues anymore.
Productivity has also improved dramatically. We see titers with bispecifics that we couldn't see with monoclonals, even before optimizing.
Typically, the product you take into Phase 1 is not fully optimized. You still have the Phase 1/2 long before you get into pivotal trials where you can optimize the process. And it's only when you enter the pivotal trials that the FDA requires you to lock up the manufacturing process.
What has changed in the last 10 years is that the product you're taking into Phase 1/2 could be commercially viable by earlier productivity standards. Five years from now, the standards are going to be higher, including from an economic standpoint. Everyone’s seeking to develop a high-quality product while lowering the cost of goods.
About The Expert:
Daniel Teper is founder and chief executive officer of Naya Therapeutics. Previously, he was chairman and CEO of Cytovia Therapeutics and before that, CEO of Immune Pharmaceuticals. He was a managing partner at Bionest partners, now Accenture, and he was a partner at ISO Healthcare Group, now Deloitte. He began at Novartis and has filled management roles at GlaxoSmithKline and Sanofi. He received his Pharm.D. from Paris Saclay University and an MBA from INSEAD.