From The Editor | June 24, 2024

Power Of Attorney For Cell Therapy Outsourcing


By Louis Garguilo, Chief Editor, Outsourced Pharma

Keir Loiacono

“I always say I’ve brought a little New Jersey litigator to Pittsburgh biotech,” says BlueSphere Bio CEO Keir Loiacono.

And to the CDMOs he works with.

Today, his attorney-informed focus is applied to T cell receptor (TCR) technology.

“I learned as a practicing lawyer that if you have a ‘bet-the-company’ trial coming up, you never have enough time,” he says, “so you need people in the trenches as hyper-focused, and almost obsessive about attention to detail, as you are.”

With that attitude and a team in place, when there is an unexpected occurrence, “which can happen in a courtroom or any day in cell-therapy development and manufacturing outsourcing, you’ve set the cadence to take action quickly.”

Loiacono isn’t quite advocating for “litigating” your CDMOs. As we’ll see here and later in part two, he considers them vital partners, critical to the success of the entire industry. But he has insights on how to keep everyone motivated and on alert.

“Nobody cares as much about your objectives as you. It’s your team who needs to closely manage the relationship with your external partner.”

In And Out Support

BlueSphere possesses some wet labs for research based on the company’s proprietary TCR platform, and significant process development capabilities. It outsources all its cell manufacturing needs, and utilizes vendors for scaled development and testing assistance.

BlueSphere is the first translational sciences stand-alone company formed by UPMC Enterprises, the venture capital arm of the Pittsburgh-based health system.  

Founded in 2017, BlueSphere utilizes proprietary technology platforms for novel T cell therapies aimed at hematologic malignancies and solid tumors. Surpassing CAR-T solutions today, the thinking is that TCRs will be more effective in treating various cancers, and with fewer side effects.

BSB-1001, targeting the minor histocompatibility antigen-1 (HA-1), is its first TCR-based T cell clinical candidate for the treatment of high-risk leukemias, including acute myeloid leukemia (AML). Loiacono anticipates opening a first-in-human clinical trial for BSB-1001 later this year.

Loiacono became CEO in 2022. He’s built a strong management team filled with industry veterans.

Among its 40 employees, the company has technical expertise in research, discovery, and product development. While key product development activities are performed in-house, Loiacono estimates 95% of “making the product” takes place at a handful of major CDMOs.

One of those is a plasmid manufacturer; another does the gene editing required for BioSphere’s products; a third supplies “gene-editing materials”; and, says, Loiacono, “we're using lentiviral transduction, so we have a company that does that.” All components “get shipped to our cell-therapy manufacturer,” where the actual BSB-1001 product is then made.

Apart from BlueSphere’s lentiviral vector manufacturer in Europe, current external partners are U.S based. “We have used vendors in China in the past – and there are very good ones – but right now we're not using anybody there,” he clarifies.

BSB-1001 requires a complicated supply chain with multiple moving parts that need coordinating. Emerging companies without experience in this arena would be seriously challenged trying to manage similar development and manufacturing needs.

“There's this thought that what makes a successful biotech is the underlying technology and discovery capabilities, and that is what gets people excited initially,” says Loiacono.

However, the organization’s ability to succeed in the clinic “is all about operational execution.”

“If you can’t execute every step in the cell-therapy world, getting new therapies to patients is impossible.” The keys, he says, are tenacity, working 24/7 to oversee each aspect of the business, and dedicated and smart people working alongside you.

Loiacono mentions his chief development officer held senior positions at CDMOs and a cell therapy operation at Big Pharma. His head of operations is “a brilliant project manager, but also a PhD scientist who ran R&D at a clinical-stage biotech.”

They may not have been lawyers like Loiacono, but they know what it takes to execute on cell-therapy contracts. “You need that internal bench with different expertise and perspectives,” says Loiacono.

CDMO Resources

Loiacono describes the “traditional biotech model” is an attempt to maintain a handful of employees, and perhaps grow slowly as programs progress.

“What do these companies do in that case?” he asks. “They pick one of the CDMO names we've all heard of, invest significant capital and resources, and hope that provider is going to execute.”

But that rarely happens so smoothly in development and manufacturing. Challenges arise, delays occur – sometimes enough to put biotech startups out of business.

“It is a hyper-vigilant managing of the outsourcing processes that’s necessary, both internally and externally,” he says.

Prior to working out the logistics of any program with a CDMO, Loiacono focuses on getting his own house in order. Project management and operations work side-by-side with the development, clinical and manufacturing teams.

He’s preparing a case to bring to the CDMO, you might say.

“Sponsors need integration – people working together towards the common objective,” he advises. “Cell therapy can be more complicated with more obstacles than other areas of drug development.”

When Loiacono took over as CEO, among his initial priorities was to improve the internal organization at BlueSphere.

“We didn't have a manufacturing process we knew we could move forward with, let alone think about an operational plan to file an IND,” he recalls.

“I focused on allocating team members towards our intentions,” and “hired the best regulatory team I could find – and who we pay a lot of money for.”

Steps To Successful Outsourcing

Today, BlueSphere is staffed "appropriately" – with CMC, project management, regulatory, and clinical resources. It's, a team that can answer this question:

What are all the steps that must happen to outsource successfully?

That question, Loiacono says, should be addressed before going out to CDMOs or other external partners.”

“Communication around expectations and goals is our responsibility. Communication at BioSphere starts ahead of transfer to a CDMO, with three to four separate meetings at regular intervals.”

These meetings are multidisciplinary “working sessions,” followed by correspondence with the CDMOs to relay information and strategic direction.

“Equally important,” he adds, “early correspondence is used to understand where the CDMOs stand with their activities and deadlines.”

Currently, some 10 BlueSphere employees are “mostly dedicated” to overseeing the CDMO relationships. Project management is “centralized,” and application software employed for real-time updating.

Often, he’ll have a person-in-plant at a CDMO for important manufacturing runs at BlueSphere’s cell-therapy manufacturers.

“They have been good partners to us,” he adds, but you can be sure he’ll stay on their case until the final gavel.