DUBLIN – Shares in Polyphor AG gained as much as 12% during early trading Aug. 31 on news of a deal in China for its lead drug, balixafortide, which is currently undergoing a phase III trial in HER2-negative locally recurrent or metastatic breast cancer.
Allschwil, Switzerland-based Polyphor is getting $15 million up front, no more than $19 million in development milestones, as well up to $148 million in sales-based milestones from its new partner, Shanghai Fosun Pharmaceutical (Group) Co. Ltd. It would also receive tiered percentage royalties, ranging from low-double-digits to midteens, on product sales in China. Polyphor retains rights in all other territories. Company CEO Gokhan Batur told BioWorld that the deal terms are actually better than those for comparable oncology transactions in China, which typically involve a median of $10 million up front and total deal value of $120 million, with high-single-digit to low-double-digit royalties. “We’re starting at 12%, so that’s a pretty good starting point,” he said.
As it requires the establishment of an additional development program, analysts had not included the program’s potential in China, despite projections that it will become the world’s second largest market for breast cancer therapies, said Batur. “This is a pure upside addition,” he said.
The up-front payment also buys the company some precious time. It had previously guided that its existing cash balance would get it to the end of the first quarter next year, which coincides with the objective response rate (ORR) readout for the Fortress pivotal phase III trial of balixafortide. “It was creating a lot of anxiety on the analyst and investor side,” Batur said. The additional cash runway will now get the company to the progression-free survival (PFS) readout.
The study is still enrolling. It had recruited 273 of its 384-patient target by May 14. The company will disclose a further update when it reports its interim results on Thursday. “Despite COVID, we did really well. We are on schedule,” Batur said. The trial has already successfully navigated two interim safety assessments from the study’s independent safety data monitoring board.
Polyphor has been pretty much in salvage mode since July last year, when it terminated its then-lead program, first-in-class cyclic peptide antibiotic murepavadin, which had been in development in pneumonia, following the emergence of acute kidney injury in a large fraction of phase III trial participants. That setback wiped out much of the company’s market cap, which it has yet to recover. The company is currently valued at about CHF80 million (US$87 million). “It’s difficult to comment on valuation,” Batur said. “It takes time to transition the company from an antibiotic lead to an oncology lead.” Trading volumes are low. “People are waiting on the data,” he said.
The Fortress study is comparing a combination of balixafortide, a CXC chemokine receptor type 4 (CXCR4) antagonist, and the microtubule inhibitor Halaven (eribulin) with Halaven only. The primary endpoint is progression-free survival, assessed 12 months after the last patient undergoes randomization, but Polyphor may be able to file for accelerated approval six months after completing recruitment based on ORR data.
In a single-arm phase I study, reported at the virtual American Society of Clinical Oncology (ASCO) meeting in May, the combination attained an ORR of 38% and 6.2 months median PFS at the dose levels that are being employed in the Fortress trial. But even attaining an ORR of 30% – which it reported for the entire study population – with a high degree of statistical significance would support an accelerated filing. In two pivotal trials in metastatic breast cancer, Eisai Co. Ltd. reported ORRs of 12% and 11% for Halaven.
CXCR4, a G protein-coupled receptor, is best known as a target for hematopoietic stem cell mobilization. Mozobil (plerixafor), marketed by the Sanofi Genzyme arm of Paris-based Sanofi SA, gained FDA approval back in 2008. Interest in the receptor as a cancer target was spurred by a recognition of the role of CXCR4 overexpression in promoting tumor growth, invasion, angiogenesis, metastasis, relapse and drug resistance. Despite many attempts, drug developers have largely failed to obtain significant efficacy signals. Batur attributed most of the failures to insufficient dose levels – balixafortide is administered intravenously whereas most other pipeline drugs are delivered orally or by subcutaneous injection and do not result in the same level of exposure. “The benefit really comes from the higher dose,” he said. Antibody-based programs at Bristol Myers Squibb Co., of New York, and Eli Lilly and Co., of Indianapolis, foundered for other reasons, possibly linked to the induction of apoptosis of healthy cells, Batur said.
Meanwhile, murepavadin, the company’s former lead asset, is by no means dead. A long-trailed clinical study of an inhaled formulation of the drug is slated to get underway this year, with a view to developing an antibiotic for Pseudomonas infection in patients with cystic fibrosis. Because of the significantly lower systemic exposure, the safety margin of the inhaled version of the drug has been enhanced five- to 10-fold. The company hopes to start the study before the year-end, having conducted safety studies in multiple animal species. “We saw no organ toxicity,” Batur said.
Polyphor’s stock (POLN:Zurich) shed most of its gains during trading Monday, to close at CHF7.16, up 2% on its previous close.