Phosplatin Therapeutics LLC, a clinical stage pharmaceutical company focused on oncology drug development, announced it has enrolled the first cohort of patients into its phase I/II study of PT-112 as a single agent in relapsed or refractory multiple myeloma. The company further announced having received FDA Orphan Drug Designation for PT-112 in the treatment of multiple myeloma.
PT-112 is currently under advanced phase I development in solid tumors. As reported at the ASCO 2017 Annual Meeting, PT-112 displays an attractive tolerability profile and signals of a broad, positive therapeutic index, with RECIST partial responses and clinical benefit observed across a range of dose levels in heavily pre-treated patients. PT-112 engenders a form of apoptosis that results in damage associated molecular patterns (DAMPs) that activate immunological effects, such as T-cell recruitment to the tumor microenvironment.
PT-112 also displays an affinity to target certain compartments within the bone (a property known as "osteotropism"). This unique property, together with data from a suite of genetically engineered mouse models of multiple myeloma derived at Mayo Clinic, suggests PT-112 could be efficacious in hematological malignancies. Phosplatin Therapeutics' research detailing these properties was the subject of an abstract and poster session presented at the 2017 American Society of Hematology (ASH) Annual Meeting.
"Given PT-112's successful clinical development track record in solid tumors, its mechanism of immunogenic cell death (ICD), and its unique osteotropic properties, it is exciting to build upon our successful translational research and to expand the clinical research of PT-112 into treating patients with relapsed or refractory multiple myeloma," said Robert Fallon, president & chief executive officer of Phosplatin Therapeutics.
The principal investigator of the phase I / II clinical trial in multiple myeloma is P. Leif Bergsagel, MD, the David F. and Margaret T. Grohne Research Professor in Therapeutics for Cancer Research at Mayo Clinic. Further information on this clinical trial, now open at Mayo Clinic and other sites, can be found at the clinicaltrials.gov registry under NCT 03288480.
PT-112 is a novel small molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage associated molecular patterns (DAMPs), leading to downstream T-cell recruitment in the tumor microenvironment. As such, it represents a potential best-in-class small molecule inducer of immunogenic cell death. The first-in-human PT-112-101 phase I study was the subject of a poster discussion session at the ASCO 2017 Annual Meeting, in which a positive therapeutic index was reported among heavily pre-treated advanced solid tumor patients.
Additional research findings were presented at the 2017 American Society of Hematology (ASH) Annual Meeting that demonstrate a particular affinity for PT-112 to localize in bone compartments, along with demonstrable accumulations in other target organs, offering a compelling logic to treat disease that metastasizes to, or originates in bone, such as multiple myeloma.