GEM 640 / Aceragen, Pharmascience - LARVOL DELTA

[VIRTUAL] Beyond BCL-2 Inhibition in Acute Myeloid Leukemia: Other Approaches to Leverage the Apoptotic Pathway (SOHO 2021) - "However, 10–50% of newly diagnosed patients with AML may not respond to venetoclax and HMA or LDAC, and 3–15% patients may not respond to venetoclax with intensive or non-intensive chemotherapy.1–6 In addition, up to 40% of responding patients may relapse with low rates of response of 20% to salvage therapy and poor overall survival of 2 months after relapse.7 Clinical and biological factors associated with primary and acquired resistance to venetoclax include secondary AML, monocytic differentiation, complex cytogenetics, mutations in TP53, BAX, dependence on other anti- apoptotic proteins, altered metabolism of nicotinamide, fatty acids, and oxidative phosphortylation.3,8–14 Several novel inhibitors of BCL-2 are currently being tested in clinic, including BGB 11417, APG-2575, LP-108 and others...There is strong pre-clinical rationale for targeting MCL-1 alone as well as in conjunction with BCL-2 inhibition in AML.15 Recently several selective and highly potent MCL-1..."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • BCL2L1 • BIRC5 • CFLAR • MDM2 • TNFRSF10A • TNFRSF10B • XIAP

XIAP antisense therapy with AEG 35156 in acute myeloid leukemia (Expert Opin Investig Drugs) - PMID: 23586880; “Role of XIAP in apoptosis pathways, structure of AEG 35156, mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy and review of clinical trials in AML.”

Review • Acute Myelogenous Leukemia • Oncology

Randomized phase II study of the x-linked inhibitor of apoptosis (XIAP) antisense AEG35156 in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC) (ASCO 2012) - Presentation time: Monday Jun 4, 8:00 AM to 12:00 PM; P2, N=51; AEG35156-205; PFS for the combination arm was 4.0 months & 2.6 months for control arm; OS for the combination arm was 6.5 months & 5.4 months for the control arm; There were 3 PRs (Choi’s criteria) in the combination arm & none (0%) in the control arm

P2 data • Hepatocellular Cancer • Oncology

Randomized phase II study of the X-linked inhibitor of apoptosis (XIAP) antisense AEG35156 in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC) (Am J Clin Oncol) - P2, N=51; NCT00882869; Sponsor: Aegera Therapeutics; "At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm."

P2 data • Hepatocellular Cancer • Oncology

AEG35156 in combination with high-dose cytarabine and idarubicin in aml following failure of a single standard dose cytarabine based frontline induction regimen (clinicaltrials.gov) - P2, N=60; Active, not recruiting → Terminated (Failed to reach endpoints); Completion date: Oct ’11 → Oct ‘10

Completion date • Trial terminated • Oncology