A careful calibration: balancing small molecule needs and biologic innovation

CPHI Europe isn’t just a massive annual pharmaceutical trade show, though with upwards of 60,000 people passing through the Frankfurt Messe doors when it came to Germany in October the event certainly does offer an impressive scale. But what Informa’s flagship pharma exhibition can also provide are glimpses into the current and future direction of the industry.

One major trend is the significant growth of the contract development and manufacturing organisation (CDMO) sector, with Informa’s Executive Vice President of the Pharma Portfolio Orhan Caglayan noting that where pre-pandemic CPHI Europe had two halls devoted to CDMOs, in 2025 that number had doubled, driven by the huge level of interest in outsourced services. Alongside the growth of CDMOs, Caglayan sees the biopharmaceutical landscape evolving, as the small molecules side of the industry becomes increasingly stable and commoditised, while biopharma gets bigger and bigger as more of the companies coming to CPHI look to tap into it.

One of those with a front row seat for this evolution is Alex Del Priore, who is Head of Large Molecules at Syngene, an integrated research, development and manufacturing services company.

“The base business in large molecules of biologics has been growing at a pace of 10-15 percent per year and it’s forecast that will continue to do so over the next five years,” he told EPR. “It’s an area that continues to see growth from its core as more and more applications are being rewarded in the industry for their effectiveness – whether it’s from oncology, whether it’s from inflammation – there are a number of indications that have traditionally been solved with small molecules and are now [done] with large molecules.”

Scaling pharma manufacturing to support scientific advances

Driving this is how “the complexity of molecules is increasing and increasing”, said Martin Meeson, Chief Executive Officer at CDMO and API manufacturer Axplora. Sat at his company’s stand, with its appropriate space age theme, he said the nature of that molecular complexity brings important handling and contamination control strategy considerations for companies such as the one he leads.

“We have seen some investment recently into our highly potent API handling capabilities, because as they become more complex, the ability to operate at OEB4 is increasingly evident – and even now the ability to offer up to OEB5 is needed and it’s important to make sure that you’ve got those capabilities for the clients that need them.”

It certainly makes for an exciting time for pharmaceutical advances, with antibody-drug conjugates (ADCs) being just one of the areas generating a lot of industry interest.

“There’s some cool treatments in that [ADC] space,” Meeson said. “I was literally just talking with a client about how they’re looking to put bispecifics in there, so they’re actually targeting how to activate the tumour and then the target is unmasking it [for] the body’s immune system. I know we’ve got a space theme, but some of this stuff is like sci-fi. So we’re excited about what we can do there.”

With this come considerations of scale for pharma manufacturing. “Four or five years ago, when people said we were going to need kilos and kilos of payload, we were like, ‘no’,” Meeson said, “and we have had to recently expand – we’re just up to a workshop that can make kilos at a time and even that is under quite high demand. It’s cool; it’s cool for patients – particularly with the potential for secondary treatments, but it is quite a lot [of investment].”

Although ADCs and personalised medicine have been around for some time, the materials they require are also becoming more complex, not least when you consider the bispecifics, trispecifics or even multi-specifics that they could be combined with. However, it’s useful to see this in context.

“There’s thousands of APIs, small molecules, that are approved – [but] we just crossed 100 mAbs not that many years ago,” said Syngene’s Del Priore. “The ADCs, there’s like 14. When you look at cell therapies, they’re in the 10 range and gene therapies are similar. So, you’re on that emerging side of the product lifecycle, which is a great place to be if you’re a science-based company.”

The biotech sector bounces back

Aiding those emerging treatment modalities has been the recent surge of interest in biotech investments from big pharma. As Campbell Bunce, Chief Scientific Officer at the CDMO and CRO Abzena, told EPR.

“The biotech sector [has blossomed], in particular over the last 3-4 years, when obviously there was the record investments going into biotech through the early to back-end of COVID. But of course that dried up significantly, so when we saw the massive drop in that through late 2022 and 2023, a lot of businesses suffered. But because of our expertise and the services and platform technologies that we offer, we’ve been really [well] placed to take advantage – especially more recently, over the last 12-15 months, as we’ve seen that investment coming back. And it’s coming back into these complex biologics and bioconjugates. So we’re seeing ADCs, and there’s no lack of investment there, in terms of pharma buying their way into this area, whether it’s acquisitions or licensing of ADCs themselves.”

Looking to take advantage of the current “fair wind of investment” in the newer modalities, “the challenge is keeping up with that”, Bunce noted.

In terms of the future of biologics, Bunce said: “Antibodies of course are still there, very much so, and there are two aspects to antibodies. One is the continuation of pure-play antibodies, and with AI coming along – particularly AI platforms that are looking to mine for, and find, new targets, when AI [can] develop or identify new targets. [UK biotech] Alchemab, for example, has this really interesting approach where they look at healthy patients within disease populations and they mine for antibodies that could be associated with a better outcome.

“There’s [also] a lot of interest in these biologics – bi‑specifics, next-generation antibody formats [and] there’s going to be a combination of AI feeding back into antibodies and bi-specific development.

“From the technology side, we’re looking at a bit of an AI approach to more automating the design of the biologics piece; so we’re just starting to do that and we’re talking to a bunch of other folks about their AI approaches and whether there’s synergy with what we do.”

Small molecules vs large molecules

Coming back to the idea of where to place emerging modalities in the overall landscape, it is clear that the growth of, and excitement in, large molecule biologics can obscure the foundational place occupied by small molecules and that requires a balancing act from many CDMOs.

As Axplora’s Martin Meeson said: “It’s human nature a little bit to turn your gaze onto the new and the shiny thing.”

He added: “Across our different business units we’re operating in the generic medicines space, we’re crossing over to do CDMO-type projects, both in the small molecule and in the emerging modalities that we talk about. For me, what’s important is that we focus our energies on both of them. Sometimes, small molecule – people don’t get excited about it, but people get very passionate when they go to the pharmacy and they can’t pick up the medicine that they picked up ten, twenty years ago. So, for us, I see it not with a level of ‘these are a little bit boring and old’, for me, actually, they are still very much the present and the future.

“The only way that you can treat millions and millions of people is using the technologies that you have around small molecules. So the new modalities around the biologics are all very exciting, I love the impact that they can have on treatments and peoples’ lives, but they’re not scalable to that level of treatment you can reach with small molecules. So we still are investing [in small molecules] to make sure that we’ve got that ability to supply our core generic medicines.

“We recently expanded our Italian site to make sure that we can increase the amount of steroids that we can get out into the market – it’s just a key treatment area that everybody uses and goes into a lot of things that people take. But then we are also focusing on those emerging modalities.”

Another of the many companies carefully calibrating this balance between established and emerging products is the CRDMO Quotient. Its Chief Executive Officer Thierry Van Nieuwenhove was clear where the business currently is and how it has been changing.

“For me, the majority for the market is in small molecules and [for] Quotient, as a consequence, the majority of the business that we do is in small molecules – oral solid dose mainly, but also some liquid forms or sterile forms. Over the past years we’ve done some biologics, we do clinical pharmacology on monoclonal antibodies, on peptides, on ‘oligos’. In just the last three years we’ve probably done 10 trials based on large molecules. Today, it still represents a minor portion of the activities that we do [but] we continue to develop that approach to monoclonal antibodies, peptides and so on.”

Pharma’s future biologic bets

“We are in an interesting time right now,” President and CEO at the CDMO Fujifilm Biotechnologies Lars Petersen told EPR. “If you go three or four years back, everybody wanted to go into biology therapy. Now everybody wants to go into cell therapy, but everybody also understands now this is more complicated, and it’s maybe not always mature; whereas many companies often default back to mammalian cells because it’s so predictive.

“I’ve been 35 years in this industry, there’s always great things about it, but sometimes things take scientists 10 years or more to solve. I was at Genentech when ADCs came out first time 20 years ago. Then it stopped for 10 years, and now it’s big. mRNA was discussed in the 2000s, but it took COVID for that to take off.”

Meanwhile, in times that provide the industry with a lot of uncertainty – whether politically, regulatory or clinically – companies in pharma, biopharma and biotech, and their outsourcing partners, must chart a way through this that works best for them.

“There’s a lot of technical risk that you manage as you go through clinical,” said Syngene’s Del Priore. “So that’s technical risk (‘can you make it?’), clinical risk (‘does the drug actually work?’) and as a CDMO there’s an ownership risk, because many of these biotechs with these fantastic ideas the pipelines of our large pharma clients are often filled through acquisition. So you have an ownership change – you might have a relationship with Customer X and then they are bought [by] a large pharma and you have to re-establish a relationship; or perhaps they have their global network that they prefer. The fourth risk then becomes actual demand – when you launch a product, sometimes you estimate high, sometimes you estimate low, but you always estimate wrong.

“In any growth area you’ve got to decide where you place your bets.”