Bachem is participating in the DCAT Week 2017, the pharmaceutical industry’s premier event for innovator and generic drug manufacturers and suppliers of ingredients, development and manufacturing services.
The 2017 edition will take place on March 20 – 23, 2017 in New York City, USA.
http://www.bachem.com/service-support/newslet...uary-2017/
Preclinical Candidates
Amarantus BioScience is developing AMRS001, a growth factor known as mesencephalic astrocyte-derived neurotrophic factor (MANF). The lead indication for AMRS001 is retinitis pigmentosa and other indications include Parkinson’s disease, Wolfram’s syndrome, diabetes and retinal arterial occlusion (3). MANF has been granted Orphan Drug designation for the treatment of retinitis pigmentosa from both the US Food and Drug Administration and the European Medicines Agency (2). Celtic Biotech Iowa, a subsidiary of Spotlight Innovation, is developing Cardiotoxin, a membrane-disruptive peptide from Naja naja atra venom, for the treatment of chronic kidney disease (CKD) and cancer. This cobra venom peptide is a Caspase-9 activator. Positive preclinical study data has been published showing that Cardiotoxin has the ability to reduce the effects of CKD (4). CVXL0103 is a cell-penetrating peptide and caspase-9 inhibitor that induces apoptosis. This peptide was in preclinical studies for the treatment of her2-negative breast cancer and ovarian cancer by Clevexel Pharma SAS. No recent development has been reported by Clevexel Pharma and the product’s status is currently unknown (2). F573 is a dipeptide caspase inhibitor in preclinical development. GNI Group and its subsidiary, Shanghai Genomics, are developing this dipeptide for the treatment of acute liver failure. In 2011, Shanghai Genomics filed an IND for F573 in China. In 2012, GNI Group published results from a research study in mice concluding that F573 had a therapeutic effect on mice with acute liver injury (2). PEP-010 is being developed by PEP-Therapy for oncology indications. This 30-mer peptide contains DPT, a shuttle sequence that delivers the active peptide into the cell and an interfering active peptide sequence that blocks caspase-9/PP2A interaction. Preclinical studies showed that PEP-010 induced death in human tumor cell lines and in B-cells of patients with lymphocytic leukemia without affecting healthy cells. As a next step, the PEP-Therapy plans to initiate toxicity studies (5).
Phase I Candidate
VRCTC310 contains the snake venoms crotoxin and cardiotoxin. Celtic Biotech Iowa, a subsidiary of Spotlight Innovation, is developing VRCTC310 for the treatment of hematological cancers and pancreatic cancer (2). The company is preparing for Phase II studies and plans to submit an IND for VRCTC310 to the US Food and Drug Administration in 2017 (4).
Phase II Candidate
Neuren Pharmaceuticals is developing a peptide product candidate, designated NNZ-2566 (trofinetide), for Rett syndrome, Fragile X syndrome and traumatic brain injury. This candidate is a synthetic analog of glypromate, a neuropeptide derived from insulin-like growth factor-1 (IGF-1). In 2015, Neuron reported results from Phase II trials in Fragile X syndrome in which improvements were seen across the core symptoms of Fragile X syndrome. In 2016, Neuron announced that it started a Phase II trial in children and adolescents with Rett syndrome, a neurological disorder. The US Food and Drug Administration and the European Medicines Agency have both granted Orphan Drug status to trofinetide for Rett Syndrome. In addition, the FDA has granted Fast Track designation to trofinetide (2).
Conclusion
The development of therapeutics that target caspases has been of great interest and caspase inhibitors and substrates have been used to help define the role of caspases in apoptosis and other biological processes. To assist researchers and organizations that are active in this field of research, Bachem offers 85 different caspase inhibitors and substrates from stock at shop.bachem.com. In addition, comprehensive custom peptide synthesis services and the production of peptide-based New Chemical Entities are offered.
References
(1) J. Kudelova et al. Pharmacological Caspase Inhibitors: Research Towards Therapeutics Perspectives, J. Physiol. Pharmacol. 66, 473-482 (2015)
(2) Medtrack (2017)
(3) MANF, Amarantus Bioscience (2017)
(4) Spotlight Innovation Company Overview, Spotlight Innovation (2016)
(5) Products, PEP-Therapy (2017)
The 2017 edition will take place on March 20 – 23, 2017 in New York City, USA.
http://www.bachem.com/service-support/newslet...uary-2017/
Preclinical Candidates
Amarantus BioScience is developing AMRS001, a growth factor known as mesencephalic astrocyte-derived neurotrophic factor (MANF). The lead indication for AMRS001 is retinitis pigmentosa and other indications include Parkinson’s disease, Wolfram’s syndrome, diabetes and retinal arterial occlusion (3). MANF has been granted Orphan Drug designation for the treatment of retinitis pigmentosa from both the US Food and Drug Administration and the European Medicines Agency (2). Celtic Biotech Iowa, a subsidiary of Spotlight Innovation, is developing Cardiotoxin, a membrane-disruptive peptide from Naja naja atra venom, for the treatment of chronic kidney disease (CKD) and cancer. This cobra venom peptide is a Caspase-9 activator. Positive preclinical study data has been published showing that Cardiotoxin has the ability to reduce the effects of CKD (4). CVXL0103 is a cell-penetrating peptide and caspase-9 inhibitor that induces apoptosis. This peptide was in preclinical studies for the treatment of her2-negative breast cancer and ovarian cancer by Clevexel Pharma SAS. No recent development has been reported by Clevexel Pharma and the product’s status is currently unknown (2). F573 is a dipeptide caspase inhibitor in preclinical development. GNI Group and its subsidiary, Shanghai Genomics, are developing this dipeptide for the treatment of acute liver failure. In 2011, Shanghai Genomics filed an IND for F573 in China. In 2012, GNI Group published results from a research study in mice concluding that F573 had a therapeutic effect on mice with acute liver injury (2). PEP-010 is being developed by PEP-Therapy for oncology indications. This 30-mer peptide contains DPT, a shuttle sequence that delivers the active peptide into the cell and an interfering active peptide sequence that blocks caspase-9/PP2A interaction. Preclinical studies showed that PEP-010 induced death in human tumor cell lines and in B-cells of patients with lymphocytic leukemia without affecting healthy cells. As a next step, the PEP-Therapy plans to initiate toxicity studies (5).
Phase I Candidate
VRCTC310 contains the snake venoms crotoxin and cardiotoxin. Celtic Biotech Iowa, a subsidiary of Spotlight Innovation, is developing VRCTC310 for the treatment of hematological cancers and pancreatic cancer (2). The company is preparing for Phase II studies and plans to submit an IND for VRCTC310 to the US Food and Drug Administration in 2017 (4).
Phase II Candidate
Neuren Pharmaceuticals is developing a peptide product candidate, designated NNZ-2566 (trofinetide), for Rett syndrome, Fragile X syndrome and traumatic brain injury. This candidate is a synthetic analog of glypromate, a neuropeptide derived from insulin-like growth factor-1 (IGF-1). In 2015, Neuron reported results from Phase II trials in Fragile X syndrome in which improvements were seen across the core symptoms of Fragile X syndrome. In 2016, Neuron announced that it started a Phase II trial in children and adolescents with Rett syndrome, a neurological disorder. The US Food and Drug Administration and the European Medicines Agency have both granted Orphan Drug status to trofinetide for Rett Syndrome. In addition, the FDA has granted Fast Track designation to trofinetide (2).
Conclusion
The development of therapeutics that target caspases has been of great interest and caspase inhibitors and substrates have been used to help define the role of caspases in apoptosis and other biological processes. To assist researchers and organizations that are active in this field of research, Bachem offers 85 different caspase inhibitors and substrates from stock at shop.bachem.com. In addition, comprehensive custom peptide synthesis services and the production of peptide-based New Chemical Entities are offered.
References
(1) J. Kudelova et al. Pharmacological Caspase Inhibitors: Research Towards Therapeutics Perspectives, J. Physiol. Pharmacol. 66, 473-482 (2015)
(2) Medtrack (2017)
(3) MANF, Amarantus Bioscience (2017)
(4) Spotlight Innovation Company Overview, Spotlight Innovation (2016)
(5) Products, PEP-Therapy (2017)
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