John Friend
Analyst · Ladenburg Thalmann. Please proceed
Thank you, Jim and good afternoon everyone. As you know, multiple myeloma is an incurable malignancy of plasma cells, which is part of the B-cell lineage of immune cells and an important component of our immune system. As a rare cancer, approximately 30,000 Americans will be diagnosed with mild myeloma and 12,500 deaths will be attributable to this disease in 2017. This hematologic cancer is characterized by both diffuse distribution and radio sensitivity suggesting systemically delivered targeted radio therapeutics such as CLR 131 may have a role in the treatment of this formidable disease. In spite of continued advances and expansion of treatment options or combinations of therapies for multiple myeloma, this disease remains an area of high unmet medical need without a cure on the horizon, the natural course of the disease results in nearly all patients experiencing multiple rounds of relapse or the development of disease which is resistant or refractory to treatments. Frequently the time to progression accelerates after each successive round of therapy. The greatest need continues to be the development of therapies that can improve overall survival while maintaining quality of life of each patient during their cancer journey. Given this current treatment paradigm and based on the clinical data already observed with a single infusion of CLR 131 in heavily pre-treated relapse refractory patient population, we remain optimistic regarding potential benefits of CLR 131 made provide to patients with this relapse refractory multiple myeloma and other B-cell cancers. As Jim stated earlier, I would like to provide you with a review of the top line data from Cohort 3 of our ongoing Phase 1 study. As a reminder the current Phase 1 study is an open label dose escalation study in relapsed or refractory multiple myeloma patients. The primary objective of this study is to determine the safety and tolerability of a single 30 minute infusion of CLR 131 with and without dexamethasone. These early studies help us and guide us in terms of a choice of dose regimen to move forward into Phase 2 and frequently provide us with the hint of potential efficacy such as M-protein progression free survival and of course overall survival. Based on our evaluation to-date both safety and efficacy signals are extremely encouraging. Patients in Cohort 3 were enrolled over a 2 months period of time from October to December 2016. All patients met the inclusion, exclusion criteria pre-specified in the protocol. Including prior treatment with proteasome inhibitors such as Velcade or [indiscernible] and immunomodulators such as Revlimid or pomalidomide. However, unlike previous cohorts this group was older with a mean age of 71 years had a higher average number of prior treatments including one patient who had received nine prior treatments, all patients, 100% of patients had undergone stem cell transplant and as a result these patients also had a tremendous base line tumor burden which was all greater than previous cohorts. We enroll these patients with extensive and far advanced disease by design. During drug development, it is important to test the drug in a real world setting with patients who could potentially benefit the most in terms of survival and quality of life. Each patient received a single 25 millicurie per meter squared dose of CLR 131 which was based on each patient’s body surface area. As a primary objective of this study, safety data was captured over the 85 days of the study. Although the total number of adverse events experienced by these patients increased as compared to Cohorts 1 and 2, the average grade or severity was completely in line with what was observed with single doses of the 12.5 and 18.75 millicurie per meter squared doses from Cohort 1 and 2. The adverse events experienced by Cohort 3 were as could be anticipated with a radiotherapeutic cytopenic in nature. The frequently reported off-target and toxic effects of currently available therapies such as neurotoxicity, cardio and GI toxicities and deep vein thrombosis have not been reported in patients exposed to CLR 131 to-date. We believe that this favorable adverse event profile is due at least in part to our PDC tumor targeting and sparing of healthy tissue. The cytopenias observed to-date in this study have not resulted in any clinically relevant events. As previously disclosed, the data monitoring committee determined that the dose of 25 millicurie per meter squared to be safe and well-tolerated and approved a fourth cohort with a single 30-minute infusion of 31.25 millicuries per meter squared. This fourth cohort is enrolling now and we plan to provide an update later this year. As a secondary objective of this study, efficacy endpoints were collected. Progression-free survival as well as the reductions in M-protein and free light chain, also FLC levels are established surrogate markers of efficacy in patients with multiple myeloma. As one would expect with his highly advanced disease cohort, the PFS for Cohort 3 was 64 days, which is less than what was observed in previous cohorts. However, all patients in Cohort 3 achieved stable disease with single dose of CLR 131 and experiencing more substantial and sustained reduction in both M-protein and FLC. Reductions were observed as early as Day 22 with a peak reduction around Day 43. The average reduction of M-protein in Cohort 3 peaked at Day 43 and was nearly a threefold increase in the reduction seen in Cohort 1 and nearly a twofold increase in the reduction over Cohort 2. In one patient, the M-protein level reduction was just shy of 50% and continued to be well-controlled from a single 30-minute infusion of CLR 131 through Day 64 post-infusion. As a reminder, the International Myeloma Working Group considers an M-protein reduction of 50% or greater to be qualified as a partial response. Ultimately, the secondary signals that we are observing are surrogate markers of survival. The median overall survival for all evaluable patients in all cohorts continues to increase as we will continue to follow them to determine the overall survival benefit. Patients from Cohort 1 who received a single dose or 12.5 millicurie per meter squared dose have achieved a median overall survival of 19.3 months and Cohort 2 patients who received a single 18.75 millicurie per meter squared dose have a median overall survival of 9.9 months. As of March 2017, the patients from Cohort 3 who received single infusion of 25 millicuries per meter squared have a median overall survival of 4.2 months. Again, all evaluable patients from Cohort 1, 2 and 3 are alive and therefore these numbers are continuing to increase. Although these efficacy signals are extremely encouraging, very excited about the recent preclinical data we disclosed in an April 27 press release. In this release, we described a doubling of mean survival in mice receiving two doses of CLR 131 compared to mice receiving a single dose of CLR 131. A study was performed in a Capan-1 xenograft model of human pancreatic adenocarcinoma and Jarrod will provide additional details in a few minutes. The second dose provided significant survival benefit in this challenging disease model and it is possible that additional doses could further enhance these outcomes. This multi-dose schedule has been incorporated in our ongoing Phase 2 NCI supported study, where patients can receive a second dose of CLR 131. As previously announced, this is a open label U.S. base with approximately 15 sites total Phase 2 study in relapsed refractory multiple myeloma and other B-cell hematologic cancers, including chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma and mantle cell lymphoma. Similar to multiple myeloma, there is a tremendous unmet need in efficacious treatments for these B-cell malignancies. In the U.S. alone, approximately 30,000 patients will be diagnosed with these malignancies this year. In this Phase 2 trial, patients will receive a single dose of CLR 131 at 25 millicuries per meter squared infused over approximately 30 minutes, with the option of the second dose occurring between Days 75 and 180 based upon physician assessment and patient consent. The primary endpoint for this study is clinical benefit rate. Secondary endpoints include objective response rate, overall survival as well as other surrogate end points. In relapsed refractory multiple myeloma patients, efficacy responses will be determined according to the latest International Multiple Myeloma Working Group criteria or as in the select B-cell lymphomas, efficacy will be determined according to the Lugano criteria. We anticipate that preliminary safety and efficacy results will become available in the second half of 2017. With that, it’s my pleasure to turn the call over to Jim.