During the initial Phase I trial, a yearlong first-in-humans test, researchers will study the drug's safety and pharmacology of multiple doses of VTX-2337 in patients with late-stage cancer. If successful, a Phase II trial will test the drug's effectiveness on tumours.
Dr. Ramesh Ramanathan, Medical Director of TGen Clincal Research Services at Scottsdale Healthcare, said the new drug appears to be quite promising. ‘VTX-2337 is a new, novel, small molecule aimed at stimulating the immune cells in the blood, lymph nodes, and in and around the tumour. It represents an exciting new class of agents for cancer therapy with good preclinical evidence of activity.’
VentiRx Pharmaceuticals, founded in June 2006 by Michael Kamdar and Robert Hershberg, M.D., Ph.D, is committed to the development of novel medicines for the treatment of cancer, infectious, respiratory, and autoimmune diseases. The medical research team of experienced biotechnology professionals, is excited to be working on this new drug. Michael Kamdar, Executive Vice President and Chief Business Officer at VentiRx : ‘Entering Phase I clinical trials represents a significant milestone for VentiRx and our TLR efforts in that we have rapidly advanced into a clinical development company with a novel molecule that may play an important role and have broad application in the treatment of cancer.’
Role of the immune system
A weakened immune system is often the result of advanced cancer. 'We hope that this new drug will actually help enable the immune system to slow down the growth of tumours, and perhaps even shrink them,' Ramanathan explained.
Toll-like receptors (TLRs) play an important role in stimulating innate and adaptive immunity and TLR ligands have become interesting targets to use as stand-alone immunotherapeutics or vaccine adjuvants for cancer treatment.
VTX-2337 is a small molecule TLR8 agonist that is expected to be used in combination with standard of care for the treatment of patients with cancer. Preclinical evaluation of VTX-2337 suggests that it may play a key role in augmenting the innate arm of the immune system.
There are two broad components of the immune system, the innate arm, and the adaptive arm. Both generally aim to eliminate viruses and bacteria.
- The innate arm senses infectious agents as they infect the body by recognizing structures they have in common, such as lipids, proteins, sugars, and nucleic acids (DNA and RNA). This is an initial rapid response, which is not precise but potent.
- The adaptive arm of the immune system is instructed by the innate arm to devise more specific responses to unique components of the invading pathogens. This is a more precise response and takes longer, especially when an infectious agent is encountered for the first time.
‘VTX-2337 is the first selective TLR8 compound to reach the clinic, and we are hopeful that modulation of the innate immune response will provide a benefit to patients in a number of oncology indications,’ said Dr. Robert Hershberg, Executive Vice President and Chief Medical Officer at VentiRx.
Also read PubMed abstracts:
- Smits EL, Ponsaerts P, Berneman ZN, Van Tendeloo VF. The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 2008 Aug;13(8):859-75. Epub 2008 Aug 13
- Zhang SY, Jouanguy E, Sancho-Shimizu V, von Bernuth H, et al
Human Toll-like receptor-dependent induction of interferons in protective immunity to viruses.
Immunol Rev 2007 Dec;220:225-36 - Uematsu S, Akira S
Toll-like receptors and Type I interferons
J Biol Chem 2007 May 25;282(21):15319-23. Epub 2007 Mar 29 - Ghosh TK, Mickelson DJ, Fink J, Solberg JC, et al
Toll-like receptor (TLR) 2-9 agonists-induced cytokines and chemokines: I. Comparison with T cell receptor-induced responses.
Cell Immunol 2006 Sep;243(1):48-57. Epub 2007 Jan 23
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