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New interim data from the Phase 1/2 study as of May 9, 2016, demonstrated best response rates from total cardiac- (n=36) and renal- (n=35) evaluable patients of 53% and 63%, respectively, that are consistent with the interim analysis from the dose-escalation phase published February 2016 in the Journal of Clinical Oncology (Gertz, et al, 2016). In the first exploratory analysis of this kind, NEOD001 demonstrated improvement of peripheral neuropathy, evidenced by a mean 35% decrease in the NIS-LL in the expansion cohort (n=11), leading to an 82% response rate. Two patients in this cohort demonstrated complete resolution of their peripheral neuropathy, as measured by NIS-LL. The Phase 1/2 study (N=69) consists of previously-treated patients with AL amyloidosis and persistent organ dysfunction who received a mean of 2.5 prior lines of plasma cell directed therapy. NEOD001 continued to be safe and well tolerated, with study participants having received more than 900 monthly infusions with a mean treatment duration of 13.2 months.

Cardiac and Renal Responses from NEOD001 Phase 1/2 StudyIn a best response analysis of patients in the Phase 1/2 study who received NEOD001, 53% or 19 of 36 total cardiac-evaluable patients and 47% or seven of 15 prospectively defined cardiac expansion cohort patients, demonstrated a cardiac response, defined as more than 30% and 300 pg/mL decrease in levels of NT-proBNP. These cardiac best response rates compare favorably to cardiac response rates of 0% to 15% from available published historical data in patients previously-treated with plasma cell directed therapy (Palladini et al, Haematologica, 2013; Dispenzieri et al, Blood, 2012), and are consistent with the best response rate of 57% or 8 of 14 cardiac-evaluable patients reported in the interim analysis of the dose-escalation phase (n=27) of the NEOD001 Phase 1/2 study published in the Journal of Clinical Oncology. As consistently demonstrated in numerous peer-reviewed publications, the functional biomarker NT-proBNP predicts survival in patients with AL amyloidosis. Increasing levels of NT-proBNP predict higher mortality in patients with AL amyloidosis. Conversely, decreasing levels of NT-proBNP following intervention predict increased survival.The 36 cardiac-evaluable patients are comprised of 14 patients from the dose-escalation phase and 22 patients from the expansion phase, consisting of 15 from cardiac, three from renal, and four from peripheral neuropathy expansion cohorts.In a best response analysis of patients in the Phase 1/2 study who received NEOD001, 63% or 22 of 35 total renal-evaluable patients and 63% or 10 of 16 prospectively defined renal expansion cohort patients demonstrated a renal response, defined as a 30% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening. These renal best response rates compare favorably to renal response rates of 17% to 29% from published historical data in patients previously-treated with plasma cell directed therapy (Palladini et al, Haematologica, 2013; Dispenzieri et al, Blood, 2012; Reece et al, Blood, 2011), and are consistent with the best response rate of 60% or 9 of 15 renal-evaluable patients reported in the interim analysis of the dose-escalation phase (n=27) of the NEOD001 Phase 1/2 study published in the Journal of Clinical Oncology. Increased levels of proteinuria and decreased eGFR predict faster progression to dialysis whereas decreased levels of proteinuria and increased eGFR predict delayed time to dialysis.The 35 renal-evaluable patients are comprised of 15 patients from the dose-escalation phase and 20 patients from the expansion phase, consisting of 16 from renal, three from cardiac, and one from peripheral neuropathy expansion cohorts.

Additional Relevant Details Peripheral Neuropathy Expansion Cohort Data from NEOD001 Phase 1/2 StudyIn addition, an improvement in peripheral neuropathy in patients in the prospectively defined peripheral neuropathy expansion cohort was demonstrated by a mean 35% (median 23%) decrease in the NIS-LL measured at month 10, indicating improvement to a third organ system in NEOD001-treated patients. Complete resolution of peripheral neuropathy, as measured by NIS-LL, was achieved in two patients in this cohort. Improvements in patient NIS-LL scores resulted in a response rate of 82% or nine of 11 patients in the peripheral neuropathy expansion cohort of the Phase 1/2 study. A response on the NIS-LL is defined as a less than 2-point increase on the 88-point scale. NIS-LL is a composite clinical scoring scale used as a clinical endpoint in peripheral neuropathy studies and measures muscle weakness, sensation and reflexes. Peripheral neuropathy is a common and progressive component of AL amyloidosis seen in 20% to 37% of patients (Bayliss M, et al, poster P784 presented at EHA 2015), which negatively affects patient quality of life and does not improve with current treatments.

Safety, Tolerability, and Immunogenicity from NEOD001 Phase 1/2 StudyData from all patients (N=69) in the Phase 1/2 study continued to demonstrate that monthly infusions (every 28 days) of NEOD001 were safe and well tolerated. An interim analysis as of May 9, 2016 showed that a total of 69 patients received 913 infusions of up to 24 mg/kg, with a mean treatment duration of 13.2 months. The Phase 1/2 study (N=69) consists of previously-treated patients with AL amyloidosis and persistent organ dysfunction who received a mean of 2.5 prior lines of plasma cell directed therapy. No hypersensitivity reactions or drug-related serious adverse events were reported and no anti-NEOD001 antibodies were detected. The most commonly reported treatment-emergent adverse events, regardless of relationship to study drug were fatigue, upper respiratory tract infection, nausea, diarrhea, edema, anemia, and dizziness. No dose limiting toxicities have been observed and no patient discontinued treatment due to drug-related adverse events.

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