Check The Rolodex: China For Steroids, Europe For Biologics

By Louis Garguilo, Chief Editor, Outsourced Pharma

We left off part one of our discussion with Philadelphia-based Context Therapeutics CEO, Martin Lehr, as he was providing us key learnings for selecting and working with CDMOs.

At the time of our discussion, Context was utilizing a CDMO in China to help with a steroidal small-molecule program; and a second CDMO, for his biologic program, in the U.K.

Lehr's process for deciding on his partners starts out rather traditionally – with an RFP issued to seemingly qualified CDMOs. "Qualified" by gathering information, including via consultants and internal investigation and deliberations.

Pretty normal stuff. However, there are some notable comings-and-goings surrounding Context's practicing of this otherwise usual process.  

Concentric Contacts

Just after my discussion with Lehr, Context announced it would discontinue work on that steroidal small-molecule program, ONA-XR, to prioritize its second asset, CTIM-76, a CLDN6 x CD3 bispecific antibody clinical candidate.

Nonetheless, it’s instructive to take a look at how Context selected its CDMO for both programs.

Lehr says the company received six CDMO replies to the ONA-XR RFP.

That was a positive return. Services for a steroidal compounds targeting solid tumors are hard to come by.

“Xianju Pharmaceutical [a China-based CDMO] was by far the best fit, with the technical capabilities, and a specialty in steroid chemistry,” explains Lehr of the final decision to go offshore.

Moreover, Context had already established a partnership with an emerging Chinese pharmaceutical company, Tyligand Bioscience, and a close relationship with the company’s CEO, Tony Zhang.

Context had licensed Greater China rights to Tyligand, effectively giving Context boots on the ground in China. “Having Tony and his team in China to monitor and coordinate activities with Xianju was invaluable,” says Lehr.

It didn’t hurt that Zhang had been head of CMC at Eli Lilly for some 25 years.

“He has wonderful connections, not just in China, but globally,” Lehr says. “That’s a key component of the relationship with Xianju – having someone with Tony’s experience, and the fact that he is a Chinese national, makes trouble shooting a breeze.”

So there's more to it than RFPs ... readers will want to note their "set process" and how it interacts with special situations and relationships ...

Dial Up, Pay Up

How much did Lehr, as CEO, drive the decision-making process to select this CDMO? 

“Well, I was not that involved," he says with a smile, "because I don't have the technical skills for this specific program.”

On the other hand, he did have the skills he brought to Context from his prior job in venture capital – specifically investing in biotechs.  

“One of the core components of being a young biotech investor is you have to build a Rolodex very quickly,” he explains. “You do this to support your portfolio companies, find new deals, and find people to work at your companies. And so, I built a network.”

From the very formation of Context, Lehr rolled through that Rolodex to hire professional advisors to drive the company forward, and maintain their all-outsourcing, virtual strategy.

“I was able to bring in a full CMC [consultant] team very early on,” he says. He refers to theese early advisors as "contractors" – many still in his employ. 

The ONA-XR program, for example, Context had a nominal head of CMC leading the small-molecule consulting team; there was a drug substance and product lead, a quality and PK tox lead, and while they made up "the core team to support that function, there were others as well.”

Readers may recall in part one Lehr shared that the best consultants are, well, expensive, and he advises getting used to paying up for them.

Like Context, readers may be at smaller organizations, but you can still surround yourself with highly experienced drug and therapy developers – and those who know how to best work with CDMOs – if you are willing to take on those costs.

But back to Context, if Lehr has a Rolodex full of options, how does he select among those?

“It becomes easier over time,” he replies.

“You get one good consultant, and when you need a professional for another capability or role, that consultant will say, ‘I have this buddy I’d recommend.’”

In other words, you start to use your consultant's Rolodex.

Finally, commenting on the importance of key professional-to-professional relationships, Lehr adds that on the ONA-XR program, “it was largely ex-Eli Lilly people who used to work for Tony [Zhang]!”

Bigger Biologics 

This January, Context and Lonza entered a manufacturing agreement for the development and manufacturing of CTIM-76, Context’s CLDN6 x CD3 bispecific antibody clinical candidate.

Lonza will provide manufacturability assessment, gene and cell line construction, and process development. Deliverables will include drug substance and drug product, with services centered in the U.K.  

Not nearly as restricted as the ONA-XR program was (because of the steroid compotent), but with CTIM-76 as well, Lehr mentions outsourcing is not a cake walk here either.

“Bispecific antibody-drug candidates targeting cancer signaling pathways pose unique challenges, related to both their development and manufacturing,” he explains.

At the onset of the CDMO search, he continues, “Our assumption was two-fold. Bispecifics are by nature hard to manufacture, so you need supporting technical expertise; and we wanted a vendor that could do everything from initial cell-line development to GMP manufacturing.”

The team at Context had expected there would be varying expertise within the bispecific field.

“Some companies do it more than others,” Lehr says. “We did assume, though, that most every company would tag their capabilities as ‘end-to-end.’ However, we were surprised that while theoretically they had all these capabilities, often it was through a subsidiary or another outsourced partner.”

“That was eye-opening,” Lehr says, “because while every company is looking to mitigate risk, particularly because we have so few products, Lonza seemed like a safer bet in this case.”

One pre-selection box Context did not check during the selection process was a site visit.

“We could have gone,” says Lehr. “But there was still somewhat of a risk with COVID at the time.”

Months later and that risk reduced, he recently took a trip to visit the U.K. facilities.

“While I'm not terribly involved in the outsourcing operations,” he says, “this is a very large contract for us.”

“If you are a Pfizer, perhaps you don't necessarily need to send people to your CDMO, but maybe it is good for everyone just to remind them of your existence,” he says.

“But seriously, a visit is an important part of the relationship building … as well as fighting those potential risks you have as the smaller fish in a large pond."

With a sizable Rolodex, we might add.