|Q&A: SNS01-T is a new approach to treating B-cell cancers that can be modified for all cancers|
|By Staff and Wire Reports|
|Tuesday, 05 June 2012 06:38|
SNS01-T is a novel approach to cancer therapy that is designed to selectively trigger apoptosis in B-cell cancers such as multiple myeloma, and, mantle cell and diffuse large B-cell lymphomas. Senesco is the sponsor of the Phase 1b/2a study that is actively enrolling patients at Mayo Clinic in Rochester, MN, the University of Arkansas for Medical Sciences in Little Rock, and the Mary Babb Randolph Cancer Center in Morgantown, WV. What caused the excitement is the fact that so far one patient has completed the 6 week dosing schedule. This patient’s disease was considered stable, no disease progression, based on key disease markers including monoclonal protein when evaluated at the end of weeks 3 and 6.
Les Browne, Ph.D., President and Chief Executive Officer of Senesco was asked to comment further on the surprising findings.
Question: How significant is having one “stable disease” in your study? Isn’t this a small sample size?
Les Browne, CEO of Senesco: We think that it is significant because the starting dose in a first-in-humans study is chosen with safety as the priority. So seeing a tumor response is not necessarily expected. A response in just one patient needs to be kept in perspective. However we are pleased to see an effect and encouraged that higher doses might be even more effective.
Question: Assuming that the low dose patient cohort completes dosing at the end of June how soon are you able to escalate up to the next higher dose level? Do you have to wait months before enrolling the next cohort?
Les Browne, CEO of Senesco: No, we only have to wait till our data review committee has reviewed the safety data and gives the go ahead to escalate to the next higher dose. This is expected to take 2-4 weeks after the last dose in each cohort. There may have been some confusion over this. Our clinical protocol anticipates monitoring patients for up to 6 months after completion of dosing; however we don’t have to wait this long to start the next higher dose level.
Question: What is the significance for your development program that two patients have dropped out of the first cohort?
Les Browne, CEO of Senesco: We are concerned for the patient’s well-being. However seeing patients drop out due to their disease getting worse is not unusual. Unfortunately the patients’ disease progressed before the end of the 6 week treatment period and the reason for their dropping out was not considered to be related to SNS01-T. Recall that the patients who are eligible to enroll in the study have relapsed from, or, have become refractory to at least two standard multiple myeloma treatment regimens, and, are not eligible for any other approved treatment. They have a poor prognosis so seeing disease progression is not unexpected.
Question: It seems that most cancer patients are on multiple drugs at the same time. Why are you not investigating SNS01-T in combination with other approved multiple myeloma drugs?
Les Browne, CEO of Senesco: You’re right. However we wanted to assess whether SNS01-T alone is effective in patients before combining with approved products. SNS01-T represents a new approach to treating B-cell cancers like multiple myeloma and mantle cell lymphoma so we did not want to cloud the picture by doing a combination study. If the ongoing Phase 1b/2a study is successful, it seems likely that it would be best to follow up with a Phase 2 multiple myeloma study comparing the Celgene drug, REVLIMID® with the combination of REVLIMID and SNS01-T.
Question: Why compare to REVLIMID rather than VELCADE®.
Les Browne, CEO of Senesco: We are interested in looking at VELCADE also. In fact we have a preclinical comparison study running in mice. However we recently reported compelling results with lenalidomide, the active ingredient of REVLIMID. In a mouse cancer model study SNS01-T alone performed well by completely eliminating tumors in 40% of the animals. Complete tumor eradication was achieved in over 80% of the treated animals that received SNS01-T combined with the optimal study dose of lenalidomide. When the study was terminated the effect had lasted for 8 weeks after the end of the 6 week treatment and the tumors did not regrow. It seems like our first combination study should be with REVLIMID.
Question: To finish up why don’t you remind us how SNS01-T works?
Les Browne, CEO of Senesco: OK. We have impressive and growing evidence that modulating the eIF5A pathway, our platform technology, is highly conserved and critically involved in regulating cell growth and cell death in all eukaryotic cells from plants to people. Of the numerous potential applications of our eIF5A technology we are focused on cancer in general and B-cell cancers specifically at present. SNS01-T is designed to induce apoptosis, a natural process that our bodies employ regularly to eliminate defective cells, in B-cell cancers like multiple myeloma and mantle cell lymphoma. SNS01-T is a nanoparticle which contains two active components that are responsible for modulating eIF5A. The nanoparticle protects the active ingredients till they are taken up and released inside the cancer cell where they trigger the production of a stable eIF5A protein that signals the cancer cell to die. We have shown that SNS01-T shrinks human tumors in mice. The study that we reported at ASCO sets out the show a similar outcome in multiple myeloma patients. If SNS01-T is effective in myeloma, it would be expected to work more broadly in non-Hodgkin’s B-cell lymphomas and in many other types of cancer by making a small change to one of the active components.