In March 2018, the companies entered into a major manufacturing agreement, and have since produced a multi kilogram drug supply for PMD-026 under GMP manufacturing practices. This represents a significant milestone, accelerating PhoenixMD's Phase I readiness.
In order to further the collaboration, WuXi STA expanded its USA operations to include capsule production under GMP regulatory compliance. Dr. Minzhang Chen, CEO of WuXi STA, commented "The opportunity to enable PhoenixMD's first-in-man studies came at an opportune moment for STA's San Diego facility."
"Our partnership with WuXi STA has been critical for PhoenixMD to advance this stage of our development. Working with such a high quality, globally recognized manufacturing partner has allowed us to rapidly advance PMD-026 through IND-enabling GLP toxicology studies and has enabled us to be ready to initiate our Phase I/Ib study with high quality API in capsules," said Sandra E. Dunn, CEO of PhoenixMD. "The rapid achievement of this milestone brings us one step closer to initiating our study for women suffering from breast cancer. More specifically, metastatic triple-negative breast cancer, which is the most deadly type of breast cancer. RSK2 is a promising new drug target for the treatment of TNBC, and PMD-026 is the first drug to ever reach clinical use against this novel target."
"The secret sauce in our success – teamwork. We truly appreciate the collaborative approach and commitment that WuXi STA has brought to the PMD-026 project," notes Dr. Dunn.
The drug supply is sufficient to treat all of the patients in the Phase 1 study. This is coupled with the completion of PhoenixMD's CDx for measuring activated RSK2 in tumors signals, enabling the two key elements needed for this precisely designed clinical trial to advance.
About RSK kinases in refractory cancers such as Triple Negative Breast Cancer (TNBC)
RSK is commonly associated with refractory cancers such as TNBC, hormone-refractory prostate cancer and resistant melanoma. Beyond these cancers, it is commonly activated in ovarian and colorectal cancers. RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90% of primary TNBC express high levels of RSK1 and RSK2 mRNA and at the protein level RSK2 is activated in ~89% of primary tumors. Inhibiting RSK2 induces cell death in TNBC cells and is synergistic with standard of care chemotherapies such as paclitaxel. PhoenixMD, with its novel, targeted approach, is focused on creating patented RSK inhibitors and companion diagnostics for cancer indications - initially in breast cancer - with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.
Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. This refractory disease is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are limited targeted therapies available for TNBC making RSK a leading opportunity.
There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.
Currently, there are a limited number of approved targeted therapies for TNBC, however tumor progression continues to be eminent in most patients. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.
About PMD-026 for TNBC
PhoenixMD's lead program, PMD-026, is the first RSK inhibitor built for the treatment of triple-negative breast cancer (TNBC). PMD-026 was precisely designed for TNBC because RSK2 was specifically identified as the key kinase that drives the growth of this breast cancer subtype relative to hormone positive or Her-2 positive breast cancers. RSK2 was identified in a functional screen profiling 519 potential kinases. PMD-026 is the first drug to specifically arise from functional dependency screens in TNBC. PMD-026 is applicable to greater than 14 different types of cancers including those resistant to a wide range of therapies.
The first in human clinical trial for PMD-026 is a Phase I/Ib that is scheduled to initiate in Q3- 2019. Importantly, the clinical trial will include a companion diagnostic (CDx) that links PMD-026 to RSK2 activation in tumors, which PMD is developing in collaboration with Roche. In preclinical studies, PMD-026 shrinks tumors by over 70% as a single agent after only two weeks of treatment in tumors with high RSK2 activation using their CDx for model selection.
PMD-026 is shown to unlock the potential of tumor resistance by synergizing with chemotherapies such as paclitaxel. More recently, PMD-026 demonstrated the potential to reprogram the way that TNBC is recognized by the immune system, in part, by inhibiting PD-L1.
PhoenixMD is a privately-held biopharmaceutical company designing precise cancer therapeutics and companion diagnostics by targeting kinases, a class of highly druggable enzymes to treat a wide range of oncology indications. PhoenixMD is focused on developing first-in-class inhibitors against ribosomal S6 kinase (RSK), an important drug target for cancer, heart disease, and inflammation. Due to its emerging leadership in kinase inhibition, PhoenixMD has entered into partnerships with well-recognized academic, non-profit institutions and development companies such as the National Cancer Institute (NIH), University of Florida, Kyushu University- Japan, University of Virginia, University of Tuebingen- Germany, Mayo Clinic, University of Hawaii Comprehensive Cancer Center and MD Anderson. PhoenixMD is headquartered in Vancouver, British Columbia Canada, with U.S. operations in San Diego, Calif. For more information, visit phoenixmd.ca.
About WuXi STA
STA Pharmaceutical Co., Ltd., a subsidiary of WuXi AppTec (WuXi STA), is a leading pharmaceutical development and manufacturing capability and technology platform company serving the life sciences industry, with operations in China and the United States. As a premier Contract Development and Manufacturing Organization (CDMO), WuXi STA offers our worldwide partners efficient, flexible and high-quality solutions for Active Pharmaceutical Ingredients (APIs) and finished dosage forms. For more information, please visit: http://www.STApharma.com