PMD-026 demonstrates 70% inhibition of ribosomal S6 kinase (RSK) signaling, blocking TNBC tumor growth in mice
VANCOUVER, British Columbia and SAN DIEGO, May 25, 2017 /PRNewswire/ — Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, announced today that it has made a significant research breakthrough in the development of a novel therapy for the treatment of triple negative breast cancer (TNBC) with new preclinical data for its lead asset, PMD-026, an oral small molecule that selectively targets RSK (p90 ribosomal S6 kinase) in TNBC and suppresses tumor growth.
In preclinical studies using the MDA-MB-231 TNBC model, PMD-026 was administered orally over a 28 day time course and demonstrated 70% inhibition of RSK signaling, blocking the growth of TNBC, and importantly, no adverse effects were observed. Within 30 min, PMD-026 was rapidly taken up by tumors whereby it shuts down the central signaling network needed for TNBC to grow. The preclinical model selected is resistant to a wide range of targeted therapies in which tumors do not respond to EGFR or mTOR inhibitors. In addition, a head to head comparison of PMD-026 versus standard of care (doxorubicin) in the same mouse model showed equal inhibition of tumor growth – and most importantly – PMD-026 demonstrated a more favorable safety profile than doxorubicin.
“The need for new targeted therapies to help patients suffering with TNBC is urgent, but unfortunately novel treatments are extremely scarce. We are addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK, known to be involved in the progression of numerous cancer indications,” said Sandra Dunn, Ph.D., Chief Executive Officer of PhoenixMD. “Our recent favorable preclinical data on PMD-026, coupled with our robust intellectual property estate and leading research collaborations, give us greater confidence in our novel approach to treating cancer. We look forward to building upon these preclinical results and initiating first-in-man studies with PMD-026 in 2018.”
“Disruptive therapies require thinking outside the box. PhoenixMD has taken a differentiated approach to developing inhibitors for TNBC by relying on functional screens to guide the selection of the fundamental kinase that drives the disease. In the case of TNBC, RSK appears to be an essential kinase. RSK inhibitors are new to the kinase scene and PMD-026 is headed for a first-in-class designation,” said Alan Lewis, Ph.D., Chair of the Scientific Advisory Board at PhoenixMD and CEO of Diavacs. “The therapies being developed at PhoenixMD are designed to treat the most difficult cancer indications. They are also promising for strategic combinations with check point inhibitors and/or standard of care therapies. I look forward to working with the established team at PhoenixMD to advance PMD-026 into the clinic.”
Dr. Lewis has led biotech companies focused on developing kinase inhibitors including Signal, Celgene, and Ambit. Further, he serves on the Board of numerous companies involved with the development of kinase inhibitors including BioMarin.
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, while RSK3 and RSK4 are associated with drug resistance.
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. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer 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.
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