– Successful generation of functional Nanobodies to an ion channel
– In vivo proof-of-concept for GPCR targeting Nanobody in hematopoietic stem cell mobilization programme
GHENT, Belgium | January 11, 2010 | Ablynx [Euronext Brussels: ABLX] announced today two significant advances achieved within its R&D portfolio. In the first, it has demonstrated the successful generation of functional Nanobodies against an ion channel. In the second, Ablynx has demonstrated in vivo proof-of-concept for a GPCR targeting stem cell mobilization programme. The target, CXCR4, is a validated chemokine receptor that plays an important role in cell movement, tumor growth and metastasis.
Nanobodies against an ion channel*
Ablynx has generated functional Nanobodies in the sub-nanomolar range, against an ion channel. The Nanobodies can block the ion channel function irrespective of whether it has been indirectly or directly activated. The ion channel drug class is technically very challenging and only a few functional research reagent monoclonal antibodies exist. Ion channels are highly relevant therapeutic targets especially in areas such as neuropathic pain, neurological disorders, inflammation and cardiovascular disorders.
In vivo proof-of-concept in CXCR4 stem cell mobilisation programme
Ablynx has successfully generated functional Nanobodies against the clinically validated chemokine receptor, CXCR4. Two types of Nanobody have been identified: highly potent antagonistic Nanobodies, as well as anti-CXCR4 Nanobodies with inverse agonist function. Ablynx has demonstrated in vivo proof-of-concept in a hematopoietic stem cell model. A single, intravenous administration of formatted anti-CXCR4 Nanobody resulted in rapid mobilization of stem cells in vivo. The antagonistic Nanobodies are now being further evaluated for their ability to mobilize hematopoietic stem cells in certain types of cancers.
Edwin Moses, CEO and Chairman of Ablynx, commented:
“Raising functional Nanobodies against two very challenging drug classes, ion channels and GPCRs, further demonstrates the strength and broad applicability of the Nanobody platform. These breakthroughs may open up important routes to innovative new therapies. I am also extremely pleased with the progress made in the last 12 months, with four Nanobodies now in clinical development, two of which are in Phase II. Our lead programme in thrombosis, ALX-0081, reached proof-of-concept by biomarker at the end of last year. We look forward to building on this success with primary endpoint data anticipated for both Phase II trials during 2010.”
About Ablynx [Euronext Brussels: ABLX] – http://www.ablynx.com
Founded in 2001 in Ghent, Belgium, Ablynx is a biopharmaceutical company focused on the discovery and development of Nanobodies, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious and life-threatening human diseases. The Company currently has over 230 employees. Ablynx completed a successful IPO on Euronext Brussels [ABLX] on 7 November 2007.
Ablynx is developing a portfolio of Nanobody-based therapeutics in a number of major disease areas, including inflammation, thrombosis, oncology and Alzheimer‟s disease. Nanobodies have been generated against more than 150 different disease targets. Efficacy data have been obtained in over 26 in vivo models for Nanobodies against a range of different targets.
Ablynx has an extensive patent position in the field of Nanobodies for healthcare applications. It has exclusive and worldwide rights to more than 50 families of granted patents and pending patent applications, including the Hamers patents covering the basic structure, composition, preparation and uses of Nanobodies.
Ablynx has ongoing research collaborations and significant partnerships with several major pharmaceutical companies, including Boehringer Ingelheim, Merck Serono, Novartis and Pfizer (previously Wyeth Pharmaceuticals). Ablynx is building a diverse and broad portfolio of therapeutic Nanobodies through these collaborations as well as through its own internal discovery programmes.
The Company‟s lead programme, ALX-0081, an intravenously administered novel anti-thrombotic entered a Phase II study in patients undergoing percutaneous coronary intervention (PCI) in September 2009. Ablynx demonstrated proof-of-concept by biomarker for ALX-0081 in December 2009. ALX-0681, a subcutaneous formulation of the novel anti-thrombotic Nanobodies that also selectively targets von Willebrand factor (vWF) has concluded Phase I. In December 2009, Ablynx initiated a double-blind, randomised, placebo-controlled Phase I study with ALX-0141, a Nanobody targeting Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), in healthy postmenopausal women. ALX-0061, an anti-IL6R Nanobody is in preclinical development for the treatment of autoimmune and inflammatory diseases. In addition, in September 2009, Ablynx‟s partner Pfizer entered a Phase II study in RA patients, with an anti-TNF-alpha Nanobody.
Nanobody® is a registered trademark of Ablynx NV.
*This work was carried out in collaboration with Professor Koch-Nolte, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
About ion channels
Ion channels are present in the membranes that surround all biological cells. They are proteins that sit within the membrane that surrounds each cell, acting as a „doorway‟ through which ions – charged atoms such as potassium (K+), sodium (Na+) and calcium (Ca2+) – can pass. Channels differ with respect to the ions they allow through, and to the way they regulate the flow of these ions. In the search for new drugs, ion channels have become a favourite target since they provide the ability to regulate many physiological processes, and they could potentially be used to treat a wide range of diseases including incontinence, diabetes, epilepsy, migraine, pain, allergy and asthma, glaucoma, stroke, irregular heart beat and cancer.
About GPCRs
G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors (7TM receptors), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. These proteins are active in just about every organ system and present a wide range of opportunities as therapeutic targets in areas including cancer, cardiac dysfunction, diabetes, central nervous system disorders, obesity, inflammation, and pain. The GPCR target class is one of the most important in drug discovery and about 40% of all prescription pharmaceuticals on the market target this protein class.
About stem cell mobilization
Successful bone marrow transplant (BMT or blood and marrow transplant), requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. These hematopoietic stem cells can come from the patient, a donor or from umbilical cord blood. The stem cells can be separated from the blood via a procedure called leukapheresis after they have been mobilized from the bone marrow into the peripheral blood circulation. Haematopoietic growth factors such as G-CSF (granulocyte colony stimulating factor) or chemotherapeutic agents often are used to stimulate the mobilization.
Mozobil® is a hematopoietic stem cell mobilizer targeting the chemokine receptor CXCR4. It was approved in the United States in December 2008 where it is indicated for use in combination with G-CSF to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin‟s lymphoma and multiple myeloma. In Europe, Mozobil® was approved in August 2009 and is indicated in combination with G-CSF in patients with lymphoma and multiple myeloma whose cells mobilize poorly.
SOURCE: Ablynx
Post Views: 39
– Successful generation of functional Nanobodies to an ion channel
– In vivo proof-of-concept for GPCR targeting Nanobody in hematopoietic stem cell mobilization programme
GHENT, Belgium | January 11, 2010 | Ablynx [Euronext Brussels: ABLX] announced today two significant advances achieved within its R&D portfolio. In the first, it has demonstrated the successful generation of functional Nanobodies against an ion channel. In the second, Ablynx has demonstrated in vivo proof-of-concept for a GPCR targeting stem cell mobilization programme. The target, CXCR4, is a validated chemokine receptor that plays an important role in cell movement, tumor growth and metastasis.
Nanobodies against an ion channel*
Ablynx has generated functional Nanobodies in the sub-nanomolar range, against an ion channel. The Nanobodies can block the ion channel function irrespective of whether it has been indirectly or directly activated. The ion channel drug class is technically very challenging and only a few functional research reagent monoclonal antibodies exist. Ion channels are highly relevant therapeutic targets especially in areas such as neuropathic pain, neurological disorders, inflammation and cardiovascular disorders.
In vivo proof-of-concept in CXCR4 stem cell mobilisation programme
Ablynx has successfully generated functional Nanobodies against the clinically validated chemokine receptor, CXCR4. Two types of Nanobody have been identified: highly potent antagonistic Nanobodies, as well as anti-CXCR4 Nanobodies with inverse agonist function. Ablynx has demonstrated in vivo proof-of-concept in a hematopoietic stem cell model. A single, intravenous administration of formatted anti-CXCR4 Nanobody resulted in rapid mobilization of stem cells in vivo. The antagonistic Nanobodies are now being further evaluated for their ability to mobilize hematopoietic stem cells in certain types of cancers.
Edwin Moses, CEO and Chairman of Ablynx, commented:
“Raising functional Nanobodies against two very challenging drug classes, ion channels and GPCRs, further demonstrates the strength and broad applicability of the Nanobody platform. These breakthroughs may open up important routes to innovative new therapies. I am also extremely pleased with the progress made in the last 12 months, with four Nanobodies now in clinical development, two of which are in Phase II. Our lead programme in thrombosis, ALX-0081, reached proof-of-concept by biomarker at the end of last year. We look forward to building on this success with primary endpoint data anticipated for both Phase II trials during 2010.”
About Ablynx [Euronext Brussels: ABLX] – http://www.ablynx.com
Founded in 2001 in Ghent, Belgium, Ablynx is a biopharmaceutical company focused on the discovery and development of Nanobodies, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious and life-threatening human diseases. The Company currently has over 230 employees. Ablynx completed a successful IPO on Euronext Brussels [ABLX] on 7 November 2007.
Ablynx is developing a portfolio of Nanobody-based therapeutics in a number of major disease areas, including inflammation, thrombosis, oncology and Alzheimer‟s disease. Nanobodies have been generated against more than 150 different disease targets. Efficacy data have been obtained in over 26 in vivo models for Nanobodies against a range of different targets.
Ablynx has an extensive patent position in the field of Nanobodies for healthcare applications. It has exclusive and worldwide rights to more than 50 families of granted patents and pending patent applications, including the Hamers patents covering the basic structure, composition, preparation and uses of Nanobodies.
Ablynx has ongoing research collaborations and significant partnerships with several major pharmaceutical companies, including Boehringer Ingelheim, Merck Serono, Novartis and Pfizer (previously Wyeth Pharmaceuticals). Ablynx is building a diverse and broad portfolio of therapeutic Nanobodies through these collaborations as well as through its own internal discovery programmes.
The Company‟s lead programme, ALX-0081, an intravenously administered novel anti-thrombotic entered a Phase II study in patients undergoing percutaneous coronary intervention (PCI) in September 2009. Ablynx demonstrated proof-of-concept by biomarker for ALX-0081 in December 2009. ALX-0681, a subcutaneous formulation of the novel anti-thrombotic Nanobodies that also selectively targets von Willebrand factor (vWF) has concluded Phase I. In December 2009, Ablynx initiated a double-blind, randomised, placebo-controlled Phase I study with ALX-0141, a Nanobody targeting Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), in healthy postmenopausal women. ALX-0061, an anti-IL6R Nanobody is in preclinical development for the treatment of autoimmune and inflammatory diseases. In addition, in September 2009, Ablynx‟s partner Pfizer entered a Phase II study in RA patients, with an anti-TNF-alpha Nanobody.
Nanobody® is a registered trademark of Ablynx NV.
*This work was carried out in collaboration with Professor Koch-Nolte, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
About ion channels
Ion channels are present in the membranes that surround all biological cells. They are proteins that sit within the membrane that surrounds each cell, acting as a „doorway‟ through which ions – charged atoms such as potassium (K+), sodium (Na+) and calcium (Ca2+) – can pass. Channels differ with respect to the ions they allow through, and to the way they regulate the flow of these ions. In the search for new drugs, ion channels have become a favourite target since they provide the ability to regulate many physiological processes, and they could potentially be used to treat a wide range of diseases including incontinence, diabetes, epilepsy, migraine, pain, allergy and asthma, glaucoma, stroke, irregular heart beat and cancer.
About GPCRs
G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors (7TM receptors), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. These proteins are active in just about every organ system and present a wide range of opportunities as therapeutic targets in areas including cancer, cardiac dysfunction, diabetes, central nervous system disorders, obesity, inflammation, and pain. The GPCR target class is one of the most important in drug discovery and about 40% of all prescription pharmaceuticals on the market target this protein class.
About stem cell mobilization
Successful bone marrow transplant (BMT or blood and marrow transplant), requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. These hematopoietic stem cells can come from the patient, a donor or from umbilical cord blood. The stem cells can be separated from the blood via a procedure called leukapheresis after they have been mobilized from the bone marrow into the peripheral blood circulation. Haematopoietic growth factors such as G-CSF (granulocyte colony stimulating factor) or chemotherapeutic agents often are used to stimulate the mobilization.
Mozobil® is a hematopoietic stem cell mobilizer targeting the chemokine receptor CXCR4. It was approved in the United States in December 2008 where it is indicated for use in combination with G-CSF to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin‟s lymphoma and multiple myeloma. In Europe, Mozobil® was approved in August 2009 and is indicated in combination with G-CSF in patients with lymphoma and multiple myeloma whose cells mobilize poorly.
SOURCE: Ablynx
Post Views: 39
