Considerations For Licensing Platforms From Universities
By Tyler Menichiello, contributing editor
The symbiotic relationship between biotech and academia is as old as medicine itself. Great discoveries come out of universities all the time, and sometimes serve as the seeds for revolutionary therapies. However, as Coeptis Therapeutics’ director and VP of operations, Dan Yerace, tells me, even the most promising platforms don’t come out of universities IND-ready.
Such is the case for SNAP-CAR, an adaptable CAR-T platform that Coeptis licensed from the University of Pittsburgh (Pitt) in August. Developed in the laboratories of Jason Lohmueller, Alexander Deiters, and Olivera Finn, this novel platform uses antibodies to target T cells to tumors. This not only allows for a dose-responsive approach to CAR-T therapy, but one that’s flexible since it can be retargeted post-infusion. While it may potentially become the first approved “universal” CAR-T, SNAP-CAR has a way to go before reaching the clinic. I spoke with Yerace and Coeptis’ CEO, Dave Mehalick, about their experience licensing this platform and the challenges of preparing for an IND application.
Why SNAP-CAR?
The basis of SNAP-CAR is the T-cell receptor’s extracellular SNAPtag enzyme. This SNAPtag on the receptor covalently binds to benzylguanine (BG)-conjugated antibodies that are designed to target specific tumor antigens. This pairing of the engineered T cells with antigen-specific antibodies “activates” the T cells and directs them to cancer cells. Unlike regular CAR-T, this allows for a dose-dependent response where T-cell activation can be modulated by adjusting the antibody dosage. The T cells can also be targeted to different tumor types post-infusion — just by changing the antibody. This adaptability, Yerace says, is what makes SNAP-CAR more of a platform than “just another targeted therapy.”
With Pitt’s reputation and proximity to Coeptis’ Pittsburgh-based office, it made sense to look there. What really piqued Coeptis’ interest in the platform, Mehalick tells me, was Finn’s connection to the work. One of Coeptis’ lead scientific advisors, Evren Alici, MD, PhD, told Mehalick and Yerace how he had worked with Finn in the past. “He said he’d love to work with her again; that she was brilliant,” Mehalick says. After the ball started rolling on the licensing agreement, Yerace says Finn similarly advised Lohmueller to work with Alici. “There were these background conversations happening that made us want to work with Pitt, and made Pitt want to work with us on a science level,” Yerace says. He thinks Coeptis' size also appealed to the scientists at Pitt; its narrow pipeline makes SNAP-CAR a priority.
Identify GMP Gaps Before Licensing
While SNAP-CAR stood out as an innovative platform, it was nowhere near ready for IND upon licensing. “University labs aren’t GMP labs,” Yerace explains. Platforms developed in a university can’t automatically be manufactured at scale or in-line with GMP. This is partly because academic researchers usually aren’t familiar with FDA requirements. Even if the technology is incredible, if it wasn’t developed with GMP in mind, it won’t be considered for an IND. “You can’t take something from an academic lab and have it be perfect,” he says. “If you did, it would be a $50 million licensing fee.”
This disconnect in manufacturing practice is important to keep in mind when licensing from a university. Understanding how far removed the manufacturing process is from meeting FDA requirements can save you a lot of time. Yerace explains the importance of performing a “gap analysis” to identify these discrepancies early on. A gap analysis involves comparing a platform’s current manufacturing process to GMP regulations and identifying incongruities to evaluate the platform’s maturity. “Make sure the platform is far enough along that you’re not spending five or seven years in the preclinical phase,” he says.
Coeptis partnered with IQVIA to evaluate the gaps in SNAP-CAR’s process and prepare for an IND submission. “They’re basically our regulatory and clinical advisors through this whole process,” Yerace explains. IQVIA performed a thorough gap analysis comparing Pitt’s process to the FDA’s requirements for an IND. “They highlighted all the gaps for us, so the next 18 months or so are going to be checking off all those boxes,” he says.
Fill In The Gaps, Prepare For IND
For SNAP-CAR, Yerace says the next steps are closing these gaps and transferring the process to a GMP manufacturing site. He explains how this transfer involves replacing things like raw materials with those that are GMP-approved. Essentially, he says, “you have to reproduce or repeat a lot of the same tests that they already did, but in the GMP setting, to put together your pre-IND.”
Together, Coeptis, IQVIA, and Pitt are working to not only prioritize SNAP-CAR’s initial indication (HER2-expressing ovarian cancer), but to expand the capabilities of the platform. Yerace says working with IQVIA guides process development to ensure everything is done with GMP in mind. Moving forward, this will make it easier to gather FDA-friendly preclinical data for future indications.
Yerace says the nature of SNAP-CAR is prolonging the IND preparation. “It’s not just a gene-edited cell,” he says, “it’s the antibody piece as well, which is really the slowest factor here.” Mehalick thinks partnering with another company on this front can expedite the process. “To get some big partner behind it would not only validate it, but also assume a lot of the cost,” he adds. After SNAP-CAR reaches clinic, Mehalick tells me Coeptis intends to maintain its relationship with Pitt. “I think their science team will always be working with ours,” he says.
Leave Manufacturing To The Pros
Though large-scale manufacturing isn’t an immediate concern at the preclinical stage, it’s never too early to strategize. Mehalick and Yerace both agree that in-house manufacturing isn’t in Coeptis’ plan, at least not with SNAP-CAR. “I don’t ever see it being required,” Yerace says. “For a company like us, or any company that only has a handful of products, I don’t think it makes sense,” he says. Both Mehalick and Yerace agree that the company’s valuable dollars should go towards R&D, not building a manufacturing facility. After all, Yerace says, that’s what CDMOs are for. “They’re good at what they do,” he says, “and they’re well-funded.”
Yerace explains how four years ago, a shortage of manufacturing space created a major bottleneck in clinical studies. “There was an 18-month wait just for suite space, so a lot of companies decided they were going to build their own facilities,” he says. “In the meantime, tons of venture capital money got poured into contract manufacturers.” Now that the bottleneck is gone, he says, costs are down, and suite space is abundant. “We have companies begging us to fill their suites,” he says.
For small companies like Coeptis, working with a CDMO makes sense. However, as cell therapies advance, Yerace thinks we may see an increasing trend of hospitals building their own GMP manufacturing facilities. “I think some of these forward-thinking hospitals are starting to build different suites where they can produce autologous cell therapies in-house for pennies on the dollar,” he says. “It’s faster, and it’s better for the patient.” He thinks this would especially benefit university hospitals involved in autologous cell therapy trials, like the University of Pittsburgh Medical Center (UPMC). For these institutions, in-house GMP manufacturing could save time and make these treatments more accessible to patients.
Invest In Commercial Viability, Not Science Projects
While big-name universities produce a lot of great science, good technology can come from schools of all sizes. “Don’t be afraid to look at smaller universities,” Yerace says. “There are small schools that are churning out really good, interesting technology,” he says. “Look at schools like that — don’t just focus on the Pitts and Johns Hopkins of the world.”
When licensing from a university, Mehalick says, don’t rush to purchase IP just because it’s inexpensive. He says universities are generally more concerned with recouping their IP costs than they are with the product’s commercial viability. While an IP may not cost much initially, you have to consider how much capital it takes to get a product into clinic. The cost of clinical development is one of many reasons why groundbreaking science doesn’t always translate into a feasible product. Ultimately, Yerace says, it’s important to recognize what’s worth licensing and what’s “just a science project.”