Targeted & controlled bone healing

CYT003 is a product that can be applied in different indications and hence not a platform. The concept of packaging Oligos into Qbeta could be seen as a platform but this would than not be CYT003.

CYT003 is a biological carrier filled with an activating ligand (agonist) of Toll-like receptor 9 (TLR9), a key mediator of innate immunity. TLR9 is the receptor that detects the presence of microbial DNA and induces the immune system’s first line of defense against bacterial infection. The TLR9 agonist of CYT003 is a synthetically produced oligonucleotide containing non-methylated CpG motifs as found in bacterial DNA and belongs to the class of A-type CpGs.

Toll-like receptors are expressed in a subset of immune cells called antigen-presenting cells (APCs; e.g. dendritic cells, macrophages, B-cells). APCs are typically found in tissues in contact with the external environment (skin, lining of the nose, lungs, stomach and intestines) and serve as an important element of the immune defense. APCs, and in particular dendritic cells, communicate with T-cells to orchestrate the immune response when challenged by bacteria or viruses.

TLR9 is predominantly expressed in plasmacytoid dendritic cells (pDCs) and B-cells in humans. CYT003 is actively taken up by pDCs, activates TLR9, and induces the production of type 1 helper T cell (Th1) cytokine IFN-alpha and the co-stimulatory molecule ICOS-Ligand.

CYT003 has been tested in multiple clinical studies and was shown to have a good safety and tolerability profile in more than 700 patients.

Checkmate Pharmaceuticals Inc. of Cambridge, MA, USA, acquired an exclusive license to develop CYT003 in the field of oncology. In April 2016, a first melanoma patient was dosed in a Phase 1b clinical trial with CMP-001, formerly known as CYT003. The trial is designed as a multi-center, open-label study of CMP-001 in combination with pembrolizumab for patients with advanced melanoma who have either progressed on anti-PD1 therapy or have failed to respond to at least 12 weeks of therapy.

 

 

Publications on CYT003 Technology

Casale TB, Cole J, Beck E, Vogelmeier CF, Willers J, Lassen C, Hammann-
Haenni A, Trokan L, Saudan P, Wechsler ME. CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.
Allergy. 70(9):1160-8. 2015 Beeh, KM, Kanniess, F, Wagner, F, Schilder, C, Naudts, I, Hammann-Haenni, A, Willers, J, Stocker, H, Mueller, P, Bachmann, MF, Renner.
The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma
J Allergy Clin Immunol, Vol. 131 (3) pp 866-874, 2013 Klimek, L, Willers, J, Hammann-Haenni, A, Pfaar, O, Stocker, H, Mueller, P, Renner, WA, Bachmann,
MF Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study.
Clin Exp Allergy, Vol. 41(9) pp. 1305-1312, 2011 Senti, G, Johansen, P, Haug, S, Bull, C, Gottschaller, C, Müller, P, Pfister, T, Maurer, P, Bachmann, MF, Graf, N, Kündig,
TM Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial.
Clin Exp Allergy, Vol. 39(4) pp. 562-570, 2009 Manolova, V, Flace, A, Bauer, M, Schwarz, K, Saudan, P, Bachmann, MF
Nanoparticles target distinct dendritic cell populations according to their size.
Eur J Immunol, Vol. 38(5) pp. 1404-1413, 2008

Publications on VLP Technology

Low JG, Lee LS, Ooi EE, Ethirajulu K, Yeo P, Matter A, Connolly JE, Skibinski DA, Saudan P, Bachmann M, Hanson BJ, Lu Q, Maurer-Stroh S, Lim S, Novotny-Diermayr V.
Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized Phase I clinical trial in healthy Asian volunteers.
Vaccine, 32(39):5041-8, 2014 Jegerlehner, A, Zabel, F, Langer, A, Dietmeier, K, Jennings, GT, Saudan, P, Bachmann, MF
Bacterially produced recombinant influenza vaccines based on virus-like particles.
PLoS One, Vol. 8(11) pp. e78947, 2013 Skibinski, DA, Hanson, BJ, Lin, Y, von Messling, V, Jegerlehner, A, Tee, JB, Chye, de H, Wong, SK, Ng, AA, Lee, HY, Au, B, Lee, BT, Santoso, L, Poidinger, M, Fairhurst, AM, Matter, A, Bachmann, MF, Saudan, P, Connolly,
JE Enhanced Neutralizing Antibody Titers and Th1 Polarization from a Novel Escherichia coli Derived Pandemic Influenza Vaccine.
PLoS One, Vol. 8(10) pp. e76571, 2013 Saudan, P, Bachmann,
MF Noninfectious disease vaccines.
Vaccines 6th Ed., Plotkin, SA, Orenstein, W and Offit, PA (Eds.) Chapter 54, 2012 Schmitz, N, Beerli, RR, Bauer, M, Jegerlehner, A, Dietmeier, K, Maudrich, M, Pumpens, P, Saudan, P, Bachmann, MF.
Universal vaccine against influenza virus: Linking TLR signaling to anti-viral protection.
Eur J Immunol, Vol. 42(4) pp. 863-9, 2012 Wiessner, C, Wiederhold, KH, Tissot, AC, Frey, P, Danner, S, Jacobson, LH, Jennings, GT, Lüönd, R, Ortmann, R, Reichwald, J, Zurini, M, Mir, A, Bachmann, MF, Staufenbiel, M
The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects.
J Neurosci, Vol. 31(25) pp. 9323-31, 2011 Bachmann, MF, Jennings, GT.
Therapeutic vaccines for chronic diseases: successes and technical challenges.
Philos Trans R Soc Lond B Biol Sci, Vol. 366(1579) pp. 2815-22, 2011. Bachmann, MF, Jennings, GT.
Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns.
Nat Rev Immunol, Vol. 10(11) pp. 787-96, 2010 Zou, Y, Sonderegger, I, Lipowsky, G, Jennings, GT, Schmitz, N, Landi, M, Kopf, M, Bachmann, MF
Combined vaccination against IL-5 and eotaxin blocks eosinophilia in mice.
Vaccine, Vol. 28(18) pp. 3192-200, 2010 Link, A, Bachmann, MF.
Immunodrugs: breaking B- but not T-cell tolerance with therapeutic anticytokine vaccines.
Immunotherapy, Vol. 2(4) pp. 561-74, 2010 Jennings, GT, Bachmann, MF
Immunodrugs: therapeutic VLP-based vaccines for chronic diseases.
Annu Rev Pharmacol Toxicol, Vol. 49 pp. 303-26, 2009 Schmitz, N, Dietmeier, K, Bauer, M, Maudrich, M, Utzinger, S, Muntwiler, S, Saudan, P, Bachmann, MF
Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy.
J Exp Med, Vol. 206(9) pp.1941-55, 2009 Tissot, AC, Maurer, P, Nussberger, J, Sabat, R, Pfister, T, Ignatenko, S, Volk, HD, Stocker, H, Müller, P, Jennings, GT, Wagner, F, Bachmann, MF
Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.
Lancet, Vol. 371(9615) pp. 821-7, 2008 Jennings, GT, Bachmann, MF.
The coming of age of virus-like particle vaccines.
 Vol. 389(5) pp. 521-36, 2008 Spohn, G, Keller, I, Beck, M, Grest, P, Jennings, GT, Bachmann, MF
Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis.
Eur J Immunol, Vol. 38(3) pp. 877-87, 2008 Maurer, P, Bachmann, MF
Vaccination against nicotine: an emerging therapy for tobacco dependence.
Expert Opin Investig Drugs, Vol. 16(11) pp. 1775-83, 2007 Sonderegger, I, Röhn, TA, Kurrer, MO, Iezzi, G, Zou, Y, Kastelein, RA, Bachmann, MF, Kopf, M
Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis.
Eur J Immunol, Vol. 36(11) pp. 2849-56, 2006 Röhn, TA, Jennings, GT, Hernandez, M, Grest, P, Beck, M, Zou, Y, Kopf, M, Bachmann, MF
Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis.
Eur J Immunol, Vol. 36(11) pp. 2857-67, 2006
Kuros Biosciences AG
Wagistrasse 25, 8952 Schlieren, Switzerland
Tel: +41 44 733 47 47   Fax: +41 44 733 47 40   Email: info@kurosbio.com

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Immune Modulation

CYT003 is a product that can be applied in different indications and hence not a platform. The concept of packaging Oligos into Qbeta could be seen as a platform but this would than not be CYT003.

CYT003 is a biological carrier filled with an activating ligand (agonist) of Toll-like receptor 9 (TLR9), a key mediator of innate immunity. TLR9 is the receptor that detects the presence of microbial DNA and induces the immune system’s first line of defense against bacterial infection. The TLR9 agonist of CYT003 is a synthetically produced oligonucleotide containing non-methylated CpG motifs as found in bacterial DNA and belongs to the class of A-type CpGs.

Toll-like receptors are expressed in a subset of immune cells called antigen-presenting cells (APCs; e.g. dendritic cells, macrophages, B-cells). APCs are typically found in tissues in contact with the external environment (skin, lining of the nose, lungs, stomach and intestines) and serve as an important element of the immune defense. APCs, and in particular dendritic cells, communicate with T-cells to orchestrate the immune response when challenged by bacteria or viruses.

TLR9 is predominantly expressed in plasmacytoid dendritic cells (pDCs) and B-cells in humans. CYT003 is actively taken up by pDCs, activates TLR9, and induces the production of type 1 helper T cell (Th1) cytokine IFN-alpha and the co-stimulatory molecule ICOS-Ligand.

CYT003 has been tested in multiple clinical studies and was shown to have a good safety and tolerability profile in more than 700 patients.

Checkmate Pharmaceuticals Inc. of Cambridge, MA, USA, acquired an exclusive license to develop CYT003 in the field of oncology. In April 2016, a first melanoma patient was dosed in a Phase 1b clinical trial with CMP-001, formerly known as CYT003. The trial is designed as a multi-center, open-label study of CMP-001 in combination with pembrolizumab for patients with advanced melanoma who have either progressed on anti-PD1 therapy or have failed to respond to at least 12 weeks of therapy.

 

 

Publications on CYT003 Technology

Casale TB, Cole J, Beck E, Vogelmeier CF, Willers J, Lassen C, Hammann-
Haenni A, Trokan L, Saudan P, Wechsler ME. CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.
Allergy. 70(9):1160-8. 2015 Beeh, KM, Kanniess, F, Wagner, F, Schilder, C, Naudts, I, Hammann-Haenni, A, Willers, J, Stocker, H, Mueller, P, Bachmann, MF, Renner.
The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma
J Allergy Clin Immunol, Vol. 131 (3) pp 866-874, 2013 Klimek, L, Willers, J, Hammann-Haenni, A, Pfaar, O, Stocker, H, Mueller, P, Renner, WA, Bachmann,
MF Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study.
Clin Exp Allergy, Vol. 41(9) pp. 1305-1312, 2011 Senti, G, Johansen, P, Haug, S, Bull, C, Gottschaller, C, Müller, P, Pfister, T, Maurer, P, Bachmann, MF, Graf, N, Kündig,
TM Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial.
Clin Exp Allergy, Vol. 39(4) pp. 562-570, 2009 Manolova, V, Flace, A, Bauer, M, Schwarz, K, Saudan, P, Bachmann, MF
Nanoparticles target distinct dendritic cell populations according to their size.
Eur J Immunol, Vol. 38(5) pp. 1404-1413, 2008

Publications on VLP Technology

Low JG, Lee LS, Ooi EE, Ethirajulu K, Yeo P, Matter A, Connolly JE, Skibinski DA, Saudan P, Bachmann M, Hanson BJ, Lu Q, Maurer-Stroh S, Lim S, Novotny-Diermayr V.
Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized Phase I clinical trial in healthy Asian volunteers.
Vaccine, 32(39):5041-8, 2014 Jegerlehner, A, Zabel, F, Langer, A, Dietmeier, K, Jennings, GT, Saudan, P, Bachmann, MF
Bacterially produced recombinant influenza vaccines based on virus-like particles.
PLoS One, Vol. 8(11) pp. e78947, 2013 Skibinski, DA, Hanson, BJ, Lin, Y, von Messling, V, Jegerlehner, A, Tee, JB, Chye, de H, Wong, SK, Ng, AA, Lee, HY, Au, B, Lee, BT, Santoso, L, Poidinger, M, Fairhurst, AM, Matter, A, Bachmann, MF, Saudan, P, Connolly,
JE Enhanced Neutralizing Antibody Titers and Th1 Polarization from a Novel Escherichia coli Derived Pandemic Influenza Vaccine.
PLoS One, Vol. 8(10) pp. e76571, 2013 Saudan, P, Bachmann,
MF Noninfectious disease vaccines.
Vaccines 6th Ed., Plotkin, SA, Orenstein, W and Offit, PA (Eds.) Chapter 54, 2012 Schmitz, N, Beerli, RR, Bauer, M, Jegerlehner, A, Dietmeier, K, Maudrich, M, Pumpens, P, Saudan, P, Bachmann, MF.
Universal vaccine against influenza virus: Linking TLR signaling to anti-viral protection.
Eur J Immunol, Vol. 42(4) pp. 863-9, 2012 Wiessner, C, Wiederhold, KH, Tissot, AC, Frey, P, Danner, S, Jacobson, LH, Jennings, GT, Lüönd, R, Ortmann, R, Reichwald, J, Zurini, M, Mir, A, Bachmann, MF, Staufenbiel, M
The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects.
J Neurosci, Vol. 31(25) pp. 9323-31, 2011 Bachmann, MF, Jennings, GT.
Therapeutic vaccines for chronic diseases: successes and technical challenges.
Philos Trans R Soc Lond B Biol Sci, Vol. 366(1579) pp. 2815-22, 2011. Bachmann, MF, Jennings, GT.
Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns.
Nat Rev Immunol, Vol. 10(11) pp. 787-96, 2010 Zou, Y, Sonderegger, I, Lipowsky, G, Jennings, GT, Schmitz, N, Landi, M, Kopf, M, Bachmann, MF
Combined vaccination against IL-5 and eotaxin blocks eosinophilia in mice.
Vaccine, Vol. 28(18) pp. 3192-200, 2010 Link, A, Bachmann, MF.
Immunodrugs: breaking B- but not T-cell tolerance with therapeutic anticytokine vaccines.
Immunotherapy, Vol. 2(4) pp. 561-74, 2010 Jennings, GT, Bachmann, MF
Immunodrugs: therapeutic VLP-based vaccines for chronic diseases.
Annu Rev Pharmacol Toxicol, Vol. 49 pp. 303-26, 2009 Schmitz, N, Dietmeier, K, Bauer, M, Maudrich, M, Utzinger, S, Muntwiler, S, Saudan, P, Bachmann, MF
Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy.
J Exp Med, Vol. 206(9) pp.1941-55, 2009 Tissot, AC, Maurer, P, Nussberger, J, Sabat, R, Pfister, T, Ignatenko, S, Volk, HD, Stocker, H, Müller, P, Jennings, GT, Wagner, F, Bachmann, MF
Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.
Lancet, Vol. 371(9615) pp. 821-7, 2008 Jennings, GT, Bachmann, MF.
The coming of age of virus-like particle vaccines.
 Vol. 389(5) pp. 521-36, 2008 Spohn, G, Keller, I, Beck, M, Grest, P, Jennings, GT, Bachmann, MF
Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis.
Eur J Immunol, Vol. 38(3) pp. 877-87, 2008 Maurer, P, Bachmann, MF
Vaccination against nicotine: an emerging therapy for tobacco dependence.
Expert Opin Investig Drugs, Vol. 16(11) pp. 1775-83, 2007 Sonderegger, I, Röhn, TA, Kurrer, MO, Iezzi, G, Zou, Y, Kastelein, RA, Bachmann, MF, Kopf, M
Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis.
Eur J Immunol, Vol. 36(11) pp. 2849-56, 2006 Röhn, TA, Jennings, GT, Hernandez, M, Grest, P, Beck, M, Zou, Y, Kopf, M, Bachmann, MF
Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis.
Eur J Immunol, Vol. 36(11) pp. 2857-67, 2006