Tagworks reports the development of a new and highly reactive Click-to-Release reaction in the Journal of the American Chemical Society. Great collaboration between Tagworks and SyMO-Chem, Syncom, TU/e , Avipep and Levena. https://pubs.acs.org/doi/abs/10.1021/jacs.0c00531
Tagworks is pleased to announce that on the 10th of October, it won the World ADC Award for Best Publication during the 10th World ADC Summit 2019 in San Diego. The World ADC Awards exist to commend excellence across nine categories within antibody-drug conjugate research and development.
Tagworks applies its Click-to-Release platform for the selective release of anticancer drugs in the tumor microenvironment. The publication Rossin et al. Nature Comm. 2018, 9, 1, 1484, is the result of a collaboration between 5 companies (Tagworks, Avipep, SyMO-Chem, Syncom, Levena) and the Radboud University & Medical Center. It demonstrates strong therapeutic proof of concept of a first in class click-cleavable ADC, expanding the scope of ADC therapy to non-internalizing cancer receptors. Tagworks and partners are pleased that the jury recognised the impact of this novel approach.
“Click chemistry targets antibody-drug conjugates for the clinic”. Nature Biotechnology news reports on the current scope and status of the use of click chemistry in vivo, including Tagworks programs, and concludes that bioorthogonal chemistry, already a workhorse of drug discovery research, is ready for the leap into human testing.https://www.nature.com/articles/d41587-019-00017-4
Tagworks reports that the scope of its proprietary click-to-release reaction can be expanded from the cleavage of carbamates to ethers, potentially allowing more drug types to be released from their click-cleavable ADCs.
In mouse models of ovarian and aggressive colon cancer, Tagworks Pharmaceuticals has demonstrated the potent antitumour effect of the company’s ‘click-to-release’ bioorthogonal chemistry approach. The results are published in the journal Nature Communications
Raffaella Rossin, et al., Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice, Nature Communications (2018), doi:10.1038/s41467-018-03880-y
In a recent publication in the scientific journal Bioconjugate Chemistry, Tagworks Pharma describes its success in using a bioorthogonal reaction for the selective cleavage of tumor-bound ADCs in mice. This represents a powerful new tool for ADC therapy as it does not rely on the currently used biological activation mechanisms, thereby potentially expanding the scope of ADC therapy to noninternalizing cancer targets.
Read the full paper – doi:10.1021/acs.bioconjchem.6b00231
A consortium of five European partners, among which Tagworks Pharmaceuticals, has secured a €6 million grant from the EU Horizon2020 program for their research action entitled In Vivo Click PET Imaging Agents: Improving clinical companion diagnostics – Click-It. Coordinator of the Click-It consortium is the University of Copenhagen and next to Tagworks, the other partners are the Technical University of Vienna, the Austrian Institute of Technology and the Johannes Gutenberg University in Mainz (Germany).
Companion diagnostics are crucial for drug development and disease management with regard to patient selection, therapy planning and monitoring. Antibodies have been proven to be optimal disease-targeting and -modulating agents. However, to date, nuclear imaging of antibodies has been limited to the use of long-lived isotopes to be compatible with their slow pharmacokinetics. Major drawbacks include high radiation doses, precluding routine and repeated companion imaging procedures.
The Click-It consortium aims to circumvent this issue by using a pretargeting approach, which centers on the administration and target binding of a tagged antibody followed by administration and binding of a small, fast-clearing, short-lived radiolabeled probe to the tag of the antibody. This results in lower absorbed radiation doses and in a boost in target-blood ratios, which in turn leads to a superior imaging contrast. PET scan snapshots at multiple time-points provide long-term imaging information by applying short-lived nuclides. So far, only the fastest click reaction, the tetrazine ligation, has demonstrated potential in clinically relevant conditions. Tagworks has shown in SPECT imaging studies that this click reaction can be applied for the imaging of non-internalizing antibodies in vivo. This project aims at expanding the scope of click-pretargeted imaging to 18F-labeled tetrazines for PET imaging and to internalizing antibodies.
In a recent paper in the Journal of Nuclear Medicine, Tagworks, in collaboration with Austrialian biotech company Avipep, describes an alternative radioimmunotherapy strategy based on separate administration of the tumor-homing agent and a fast clearing radioactive probe. This way, the unwanted high renal retention of low-molecular weight radiometal tumor-homing agents can be overcome.
The Tagworks and Avipep researchers show that a pretargeting strategy with a small protein may be an attractive approach in radioimmunotherapy to reduce kidney uptake while maintaining high tumor targeting. An effective tumor-targeting agent, a TAG72 diabody that had a high kidney uptake as a directly radiometal-labeled analog, showed complete retention of its properties upon TCO-modification. Administration of a radiometal-labeled tetrazine in a second step, showed efficient tumor uptake and most importantly low kidney uptake. This pretargeting strategy could be an important alternative platform, superseding the use of peptides and small proteins as metal-chelate conjugates for imaging and therapy.
Read the full paper: doi:10.2967/jnumed.115.159145
Tagworks Pharmaceuticals has received two valorization grants, €180,000 total, from NanoNextNL, the Dutch research and innovation program on nanotechnology. The grants will be used to take two of the company’s core programs to the next level.
One grant concerns Tagworks’ antibody drug conjugate (ADC) technology and will be applied to further demonstrate the benefits of the use of click chemistry to activate ADCs on the tumor. The other grant will be dedicated to further development of a novel liver-targeted clearing agent. Through a chemical reaction, this agent enables instantaneous clearance of tagged nanomedicine from the blood at any desired time. Such an agent offers promising perspectives for boosting the therapeutic window of ADCs or drug containing liposomes by controlling and minimizing off-target toxicity. Furthermore, when used in combination with directly labelled antibodies in companion diagnostic applications, use of this agent will improve the target/blood ratio and thus enhance image quality.