PERTH, Australia – Melbourne-based Prescient Therapeutics Pty Ltd. is poised to develop next-generation CAR T therapies after signing an exclusive global licensing deal with the University of Pennsylvania for a universal immune receptor technology platform.
It also in-licensed a Spytag/Spycatcher molecular binding system from Oxford University that complements the UPenn technology to build a universal chimeric immune receptor platform, called OmniCAR.
“This has put us in front of a massive wave, and there are precious few people competing for that wave,” said Prescient CEO Steven Yatomi-Clarke during a May 26 conference call.
UPenn is a leader in the field of CAR T, having pioneered the technology that Novartis AG in-licensed for Kymriah (tisagenlecleucel), the first CAR T to be approved by the FDA.
“This is a truly transformational technology we’ve gotten from the University of Pennsylvania,” the CEO said, calling it a “stunning addition to our arsenal of personalized therapies.”
“CAR T has been a stunning success for certain types of blood cancers,” and Prescient aims to replicate that success into other cancers, such as solid tumors.
One of the problems with CAR T is that clinicians have no control of cells post infusion. Aside from safety, finding targets that work has been a problem. Price has also been an issue, and Prescient hopes to bring down the cost of those therapies as it looks at the intersection of targeted therapies and CAR T.
Going where CAR T cannot
“OmniCAR can do what conventional CAR T cannot. Conventional CAR T is only trained to hit one target that is impossible to control once deployed,” Yatomi-Clarke said.
OmniCAR can be directed against any target, including simultaneous targets, and it can be controlled at all times. “Un-armed CAR Ts are given to the patient and sit there inactive until a targeting ligand [receptor] is activated. That creates an armed CAR T that is capable and controllable on demand and switched on at will.
“For the first time, we’ll give clinicians the ability to titrate the dose by controlling the amount of binder that has the ability to switch off; it has a built-in kill switch,” he added. “If there happens to be a safety event, you stop administering the binder, and the CAR T activity switches off. If the doctor wants to recommence activity, he or she can safely do so by administering the binder alone to reactivate the T cell.”
The OmniCAR platform can target multiple antigens sequentially as well as targeting multiple antigens simultaneously to take on cancers with heterogenous antigens at the same time.
“One of the chinks in the armor of CAR T is that if the tumor sheds its antigen, all of a sudden that tumor is active again,” Yatomi-Clarke said.
“What we can do with OmniCAR is identify the target and add the binder to the cancer antigen, so if the cancer mutates, you switch out the binder. And now you have a brand new redirected antigen.”
The binder can also be controlled so that it is more dose dependent. More binder provides more of a cancer-killing punch.
“You’re combining the cell-killing cancer properties of a T cell but combining it with the control of a drug,” the CEO said.
OmniCAR has established proof of principle against several common tumor antigens, including HER2, EGFR, epithelial cell adhesion molecule (EpCAM) and B-lymphocyte antigen CD20.
It also has potential to improve cell therapy approaches for autologous cells, allogeneic T cells (off-the-shelf), as well as enhancing CARs with other cell types such as natural killer (NK) cells, macrophages, T-reg cells and stem cells.
Prescient will pursue a parallel in-house and external development strategy. It will continue to progress its lead programs – PTX-100 and PTX-200 – while broadening the OmniCAR platform with commercially attractive targets and applications.
The terms of the deal with UPenn were not disclosed, but Yatomi-Clarke said it was back-ended substantially.
Licensing payments include an up-front fee and milestones linked to clinical development and regulatory approval of products as well as sales-based royalties. The initial preclinical development program for OmniCAR will be conducted within Prescient’s current budget.
“The license agreements with Penn and Oxford align perfectly with PTX’s objective of developing personalized cell therapy medicines and complements our targeted therapy pipeline,” Yatomi-Clarke said. “We are already working on leveraging our targeted therapy expertise in other cell therapy applications.”
In the meantime, the company is progressing its lead candidates. PTX-200 is a PH domain inhibitor that inhibits the Akt pathway that plays a key role in the development of many cancers, including breast and ovarian cancers and leukemia. PTX-200 saw encouraging phase IIa results in HER2-negative breast cancer, as well as a phase Ib/II trial in relapsed and refractory acute myeloid leukemia (AML) and a phase Ib trial in recurrent platinum-resistant ovarian cancer. The FDA granted orphan drug designation for PTX-200 in AML.
Prescient's second candidate, PTX-100, blocks cancer growth enzyme geranylgeranyl transferase-1 (GGT-1) and inhibits activation of Rho, Rac and Ral circuits in cancer cells. Targeting the Ras pathway directly has proved elusive, and PTX-100 disrupts the Ras pathway downstream by inhibiting post-translational modification of Rho, Rac and Ral.
In a phase I trial in advanced solid tumors, PTX-100 was well-tolerated and achieved stable disease. Prescient plans to target Ras and RhoA mutant malignancies, such as RhoA-mutant lymphomas. It plans to develop a p27 cancer biomarker as a companion diagnostic to potentially identify those patients who are most likely to respond to PTX-100 therapy.
Taking a basket approach to trials rather than looking at specific indications for specific cancers, Prescient is targeting a number of cancers with the same mutation and bundling them into a basket study.
With an AU$19 million (US$12.6 million) market cap, Prescient's shares on the Australian Securities Exchange (ASX:PTX) were relatively flat on the deal news, trading at AU4.9 cents.