Small Or Large Molecule: Unifying Essentials For Development

By Louis Garguilo, Chief Editor, Outsourced Pharma

One biopharma startup. Two assets – the first a small molecule (SM); the second a biologic.

Both assets were being developed via a fully outsourced strategy – the CDMO for the first was a small molecule specialist in China, called Xianju Pharmaceutical; the other is at a leading biologics CDMO, Lonza.

It added up to an informative discussion on outsourcing with Context Therapeutics CEO, Martin Lehr, at the helm of Context since 2015.

Among other positions, prior to his current role Lehr was part of the founding team at Osage University Partners, a VC fund focused on spinouts from leading research institutions.

Earlier, he conducted research at the Sloan Kettering Institute, in DNA repair, and at the Children’s Hospital of Philadelphia, in thrombosis and hemostasis. Lehr holds an M.A. in biotechnology from Columbia University and a B.A. in economics from the University of Pennsylvania.

Context is developing novel treatments for solid tumors. The operational model is based on the selective and strategic acquisition of assets that can potentially be developed and directed to that focus.

The initial asset was onapristone extended release (ONA-XR), an investigational medicine to prevent progesterone (PR) signaling by blocking the interaction between progesterone and its binding partner, progesterone receptor. Onapristone is the only known full PR antagonist. 

Sometime after my discussion with Lehr, Context announced it had decided to discontinue the development of ONA-XR, due to “the challenging market conditions for emerging companies, the increasingly competitive landscape for breast cancer treatments, and recent study findings.”

Lehr said the company is shifting development focus to its second asset, “the compelling preclinical candidate CTIM-76, a CLDN6 x CD3 bispecific antibody.

As we’ve discussed in many Outsourced Pharma editorials over the past months, the economy is having an impact on our industry.

Nonetheless, Lehr described some overriding and important best practices on outsourcing drug development and manufacturing across modalities.

Quality Costs

Lehr chuckles when I ask him what he had to learn about drug development and manufacturing outsourcing when the company got started with its small-molecule candidate.

“I’m laughing a bit here because my background’s molecular biology, so I know virtually nothing about chemistry, let alone manufacturing of chemicals,” he says.

“I learned early on to hire really good people. That means consultants, and good consultants are incredibly expensive. You have to get comfortable with the fact you're paying for quality, and in the long run it saves you so much time and money. Just get the right people on the bus early.”

There’s s second application to Lehr’s “pay up” philosophy.

“If you're an emerging biotech, manufacturing is pretty much all outsourced, so you have to rely on the best vendors. For example, we learned – and have relearned time and time again – picking the second to lowest bid likely leads to a bad situation.”

“Actually, the highest or close to the highest bid is often the best route.”

Putting it altogether, and to repeat: “You have to pay for quality. Embrace that.”

PAY NOW, PLAY NOW

Lehr has discovered that a small biotech or start-up typically finds itself fighting to get a good place, or to move up in line to get projects initiated in a timely manner at CDMOs.

But there’s a weapon to help you succeed at that. If you offer to pay more upfront, and you take on a more aggressive payment-at-risk approach, “you can move up in that line real fast, even as a small customer.”

“It’s also critical to get the CDMO excited about your project,” he says.

“Context is developing cancer drugs, so it’s helpful for the CDMO to appreciate that this little program in their really big company can potentially have a meaningful impact for a cancer patient.”

Therefore, he says, “waiting for slots has never been a material issue at Context. We've always paid the bulk of the money upfront, and worked hard to get the CDMO excited about our programs. That really does save an enormous amount of time.”

Fast payment and full communication fosters good feelings about your organization at the CDMO that can be utilized when challenges arise, and for future projects.

Lehr says you can approach the pay-now strategy in a number of ways.

One is “out of the gate,” at the very beginning of discussions. Or you can move towards an agreement, and ask about a realistic starting date.

“If you get a reasonable start time, you are set. If they say six months from now, the counter is, ‘Well, if we pay you 50% upfront, does that turn into next week?’”

Often enough, he says, start times do collapse.

“Our biologics partner is a great example of a large CDMO trying hard to change the perception they focus on larger customers,” says Lehr. “Now, whichever the reality, the truth is we need them more than they need us.”

“So you always have to keep that in mind when working with a company of that size. You have to be flexible on your end.”

That includes this willingness to pay on the front end. “If you do that, you help them support small companies. I understand the elevated risk of a small company relative to the risk of a large-cap pharma customer. It’s not anywhere near the same.”

Don’t Discount Capabilities

Lehr in no means suggests outsourcing is all about hard currency. There are indeed a variety of factors to consider.

ONA-XR had a steroid component to it, and most all Outsourced Pharma readers recognize this may be the most difficult chemistry to try to outsource to a CDMO. Parenthetically, I’ve heard it is becoming harder still to find CDMOs willing to devote facilities, personnel, and time to this pursuit. Particularly, I’ll add, in the U.S., due also to environmental and other restrictions.

Xianju in China was recommended to Lehr by a highly trusted source as one of the largest, if not the largest, manufacturer of steroid based drugs in the world. Their reputation was there; the years of knowledge and track record commendable.

In fact, in part two we’ll look more closely at how Lehr and Context selected both Xianju and Lonza.

Here’s a hint to noodle on until next time: Rolodexes and consultants.