Abzena Discusses Novel Approaches to Bioconjugation: Part One of Three

As a contract development and manufacturing organization (CDMO), Abzena works with its partners to get molecules into the clinic and into first-in-human studies, then through the requisite regulatory stages to get drugs to market for patients.

Where novel and challenging conjugates are concerned, parts of that process may take a certain amount of time—and time is everything in a competitive environment.

In this video interview, which is presented here in the first of three parts, Abzena’s Petra Dieterich, PhD, senior vice-president and scientific leader, and Jeffrey Mocny, PhD, scientific lead, talk about those challenges and the knowledge that is needed for a CDMO to overcome them and provide representative service to customers.

“It's having the experience to know what is required, having the scientific knowledge and skill sets available to make that happen,” Dieterich says in the interview. “And then, of course, it's multidisciplinary. We're not just talking chemists. We have to have biologists on board. We have to have bioconjugation scientists on board. We mustn't forget analytical; we have to have the right analytical support. That can be complicated.”

Mocny agrees, saying that all of these elements need to come together from day one of a partnership.

“We like to get that right up front,” he adds. “Measure twice, cut once. Naturally, programs evolve with time, as the markets shift and competitor molecules come on market and treatment paradigms change, but the overarching goals need to be continuously revisited.”

The first part of BioPharm International®’s interview with Dieterich and Mocny can be viewed above.

Transcript

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Petra Dieterich

I think what we're doing very well right now is leveraging all of that experience into conjugating novel payloads. So novel, not in the sense that these are new molecules, but novel in the sense that we're creating conjugates with oligonucleotides. We can tether radioactive elements to the targeting protein. And then a lot of people are also looking at degrader proteins to, you know, get into the cells for undruggable targets.

Time is always of the essence. It's a competitive market, and we have to move rapidly. We have to make the processes that we take into manufacturing robust enough, but we don't want to overdevelop. You know, our customers want to take their molecules into the clinic, into first-in-human studies, Phase I studies, as rapidly as possible. At the same time, we need to convince the regulator that we have a molecule that's safe to use, so we know that molecule has to have the right data associated with it to make the regulator appreciate that we have indeed studied it sufficiently to enable a safe entry into human beings. So that's always important.

It's having the experience to know what is required, having the scientific knowledge and skill sets available to make that happen. And then, of course, it's multidisciplinary. We're not just talking chemists. We have to have biologists on board. We have to have bioconjugation scientists on board. We mustn't forget analytical; we have to have the right analytical support. That can be complicated. Physiochemical properties of proteins and the payloads, which can be small molecules, which can be oligonucleotides, these molecules all have significantly different physiochemical properties.

So we have to design our processes and analytical methods to take care of all of that such that we can gather that data, that's all important for our IND submissions, and then, obviously, for the entry into the clinic.

Jeffrey Mocny

The idea of fit-for-purpose at the stage of development, where our clients are naturally the stems to that, that extends to a strategy of how this asset will be developed with time, resulting from the goals that our clients have for that asset. So understanding how it all fits together in a holistic approach, like you mentioned, is the key, and then translating that to actionable work packages with purpose and explain it in a rational, logical approach so that regulators can follow is the key to success.

And it starts at day one, and kickoff with interactions with clients to frame out the objectives, frame out what the molecule needs to look like and how it should behave, and the novel critical quality attributes of the molecule, so that you can design your entire process around that, whether it be manufacturing campaign, raw material sourcing, clinical trial strategy, regulatory filing pathway. These are things that are all considered up front.

And you know, as Petra said, we like to get that right up front. Measure twice, cut once. Naturally, programs evolve with time, as the markets shift and competitor molecules come on market and treatment paradigms change, but the overarching goals need to be continuously revisited, and that's what Abzena, our focus is when we work with our clients, and you know, all this is in the backbone of satisfying the regulatory requirements on a global level. Right? We follow ICH standards because they're accepted among all countries, and we observe the peculiarities for certain markets as well, that are necessary based on our clients’ target objective market to move into.