pidilizumab (CT-011) / CureTech - LARVOL DELTA

Tetramethylpyrazine-caffeic Acid Hybrid CT-011 Exerts Dopaminergic Neuroprotection Through Inhibiting Microglia-mediated Neuroinflammation. (PubMed, Mol Neurobiol) - "Additionally, CT-011 protected primary neurons against microglial-mediated neurotoxicity in vitro, and ameliorated dopaminergic neuronal damage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice with a consistent anti-neuroinflammatory effect in vivo. These results demonstrate that CT-011 effectively inhibits microglia-mediated neuroinflammation and exerts neuroprotective effects on dopamine neurons, thus making it a promising therapeutic candidate for PD."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Movement Disorders • Parkinson's Disease • MYD88 • NLRP3 • TLR4

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Beth Israel Deaconess Medical Center | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Adrenal insufficiency in patients on immune checkpoint inhibitors: An All of Us Data study. (ASCO 2023) - "We identified participants in the cancer cohort without or with at least one exposure to immune checkpoint inhibitors nivolumab, pembrolizumab, cemiplimab, ipilimumab, atezolizumab, avelumab, durvalumab, tremelimumab, relatlimab, tremelimumab, pidilizumab. Our result suggests a higher incidence of adrenal insufficiency in cancer patients on immune checkpoint inhibitors compared to cancer patients, not on immune checkpoint inhibitors. Future prospective studies will be needed to confirm this finding. Physicians, particularly oncologists and endocrinologists, should have a high index of suspicion for adrenal insufficiency in patients on immune checkpoint inhibitors."

Checkpoint inhibition • Clinical • Endocrine Disorders • Immune Modulation • Nephrology • Oncology • Renal Disease

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Beth Israel Deaconess Medical Center | Trial primary completion date: Jul 2022 ➔ Jul 2023

IO biomarker • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

"So what became of the Teva/Curetech CT-011. Quick search suggests deal was terminated in 2014, Curetech was acquired by InSight Biopharma in 2018 which was itself bought by Gencor Pacific in 2019. No trace since?" (@RobinDavison2)

Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission (clinicaltrials.gov) - P2; N=63; Active, not recruiting; Sponsor: Beth Israel Deaconess Medical Center; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation (clinicaltrials.gov) - P2; N=35; Active, not recruiting; Sponsor: Beth Israel Deaconess Medical Center; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: Jul 2021 ➔ Jul 2022

IO biomarker • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Safety, Pharmacokinetics, and Neutralizing Activity of SYN023, a Mixture of Two Novel Antirabies Monoclonal Antibodies Intended for Use in Postrabies Exposure Prophylaxis. (PubMed, Clin Pharmacol Drug Dev) - "Anti-CTB011 and anti-CTB012 antibodies occurred with no apparent effect on PK or safety. These data support the potential use of SYN023 in antirabies postexposure prophylaxis."

Clinical • Journal • PK/PD data

Computationally-obtained structural insights into the molecular interactions between Pidilizumab and binding partners DLL1 and PD-1. (PubMed, J Biomol Struct Dyn) - "The unprecedented structural data on Pidilizumab's interactions provided novel evidence that its legitimate target is the DLL1 protein and offered structural insight on how these molecules interact, shedding light on the pathways that could be affected by the use of this essential immunobiological. Communicated by Ramaswamy H. Sarma."

Journal • Hematological Malignancies • Lymphoma • Melanoma • Oncology • Solid Tumor • PD-1

Blockade of PD-1 in Conjunction With the Dendritic Cell/Myeloma Vaccines Following Stem Cell Transplantation (clinicaltrials.gov) - P2; N=35; Active, not recruiting; Sponsor: Beth Israel Deaconess Medical Center; Trial primary completion date: Dec 2019 ➔ Jul 2021

IO Biomarker • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Safety, pharmacokinetics and pharmacodynamics of SYN023 alone or in combination with a rabies vaccine: An open, parallel, single dose, phase 1 bridging study in healthy Chinese subjects. (PubMed, Antiviral Res) - "SYN023 at 0.3 mg/kg is relatively saf e and effective and can be selected for further clinical trials in Chinese subjects. The clinical trial registration number is CTR20190281. http://www.chinadrugtrials.org.cn/eap/clinicaltrials.searchlist?a=a&reg_no=CTR20190281."

Clinical • Combination therapy • Journal • P1 data • PK/PD data

Risk of gastrointestinal complications in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. (PubMed) - "Our meta-analysis has demonstrated that immune checkpoint inhibitors are associated with a significantly increased risk of all grade and high-grade colitis."

Journal • Biosimilar • Immunology • Inflammation • Oncology

Gemcitabine and CT-011 for Resected Pancreatic Cancer (clinicaltrials.gov) - P2; N=29; Suspended; Sponsor: Georgia Regents University; Recruiting -> Suspended

Trial suspension • Biosimilar • Oncology • Pancreatic Cancer • Reperfusion Injury

Blockade of PD-1 in Conjunction With the Dendritic Cell/AML Vaccine Following Chemotherapy Induced Remission (clinicaltrials.gov) - P2; N=63; Active, not recruiting; Sponsor: Beth Israel Deaconess Medical Center; Trial primary completion date: Jun 2020 ➔ Jun 2021

Clinical • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] The combination of PARP inhibitor talazoparib with low-dose temozolomide results in increased cell lethality in BRCA1/2 wild-type melanoma, small cell lung cancer, ovarian, and colon cancer cell lines and mouse xenografts via the formation of DNA double-strand breaks during S-phase (AACR-II 2020) - "In April 2016, my colleague Dr Zev Wainberg presented Phase I safety and efficacy data at AACR (abstract CT011) with PARP inhibitor talazoparib in combination with alkylating agent temozolomide in cancer patients without gBRCA1/2+, demonstrating this to be a promising combination. We evaluated the molecular mechanisms underlying cancer cell lethality with talazoparib plus temozolomide in melanoma, small cell lung, ovarian, and colorectal cancer cell lines and mouse xenografts. Taking into consideration both the molecular data demonstrating efficacy of talazoparib plus temozolomide therapy in BRCA1/2 wild-type cell lines and mouse xenografts and the Phase I trial data showing safety and efficacy with this combination, PARP inhibitors likely have utility beyond treatment of gBRCA1/2+ patients. Use of the alkylating agent might be particularly important, as it is recognized during S-phase and trapping of PARP on the DNA could result in collapse of a stalled replication..."

Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • BRCA1 • BRCA2

Gemcitabine and CT-011 for resected pancreatic cancer (clinicaltrials.gov) - P2, N=32; Completed; Recruiting -> Completed; Completion: Dec’12->Oct’11

Completion date • Trial completion • Oncology • Pancreatic Cancer

Anti-PD-1 Therapy in Melanoma. (PubMed) - "Long-term survivors already have been reported with these therapies. In this review, we discuss the current state of anti-PD-1 agents, the evidence in the literature to support the combination of anti-PD-1 antibodies with other anti-cancer agents and discuss the future directions for rational design of clinical trials that keep on increasing the number of long-term survivors."

Review • Biosimilar • Head and Neck Cancer • Immunology • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma

Lenalidomide and pidilizumab in treating patients with relapsed or refractory multiple myeloma (clinicaltrials.gov) - P1/2, N=53; Not yet recruiting -> Recruiting.

Enrollment open • Multiple Myeloma • Oncology

CT-011 and p53 genetic vaccine for advanced solid tumors (clinicaltrials.gov) - P1, N=0; N=27 -> 0; Completed -> Withdrawn

Enrollment • Trial withdrawn • Oncology • Pancreatic Cancer

Anti PD1 antibody in diffuse intrinsic pontine glioma and relapsed glioblastoma multiforme (clinicaltrials.gov) - P1/2, N=30; Not yet recruiting -> Recruiting.

Enrollment open • Oncology

Study to evaluate the safety, tolerability and efficacy of FOLFOX + CT-011 versus FOLFOX alone administered intravenously to patients with colorectal adenocarcinoma previously untreated for metastatic disease (clinicaltrials.gov) - P2, N=168; Active, not recruiting; Completion date: Dec '10 → Sep '12; Primary completion date: Oct '10 → Aug '12; Study design: Active deleted

Completion date • Protocol • Trial delayed • Oncology

Anti PD1 Antibody in Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov) - P1/2; N=50; Recruiting; Sponsor: Hadassah Medical Organization; N=30 ➔ 50; Trial primary completion date: Nov 2015 ➔ Nov 2018

Enrollment change • Trial primary completion date • Biosimilar • Hepatitis C Virus • Oncology

Medivation buys into PD-1, picking up where Teva left off (FierceBiotech) - "The prostate cancer experts at Medivation...are getting into the hot field of checkpoint inhibitors for cancer, agreeing to pay Israel's CureTech as much as $335 million for the full rights to a promising Phase II asset. Under the agreement, Medivation will pay $5 million up front to get its hands on pidilizumab..."

Licensing / partnership • Oncology • Prostate Cancer

Safety, tolerability and efficacy study of the monoclonal antibody, CT-011, in patients with metastatic melanoma (clinicaltrials.gov) - P2, N=100; Not yet recruiting -> Recruiting; Start date: Oct ‘11→ Nov ‘11

Enrollment open • Start date • Melanoma • Oncology