First-in-Class Candidate – Transketolase Inhibitor Benfo-Oxythiamine
Transketolase Inhibition:
Targeting Cancer with Minimal Side Effects
The sugar ribose represents the crucial building block for the DNA strand. Without ribose, there is no new formation of DNA and no repair of DNA. There is only one enzyme that produces ribose – transketolase.
Crucial Role of Ribose and Transketolase in DNA Synthesis and Repair
Transketolases are only enzymatically active when vitamin B1 (thiamine) is bound to them. Oxythiamine is a form of an inhibitory thiamine derivative that very effectively inhibits transketolases. Due to the extremely strong, almost irreversible binding of thiamine to the transketolase protein, existing transketolases cannot be inhibited by oxythiamine. As a result, only newly formed transketolases are inhibited. A high level of newly formed transketolases is found in cancer cells.
Targeting Cancer Metabolism: A New Era for Transketolase Inhibitors
Our prodrug is designed to release oxythiamine, the active inhibitor. It is the first and, to date, the only transketolase inhibitor that has been successfully evaluated in a Phase I clinical trial. This breakthrough has disproved the widespread assumption that inhibiting transketolase would result in severe side effects. Phase I results clearly show that this is not the case.
Please keep in mind, these results are based on a Phase 1 clinical trial. Further studies are required to confirm safety and efficacy in broader populations.
At a Glance
Targeted Enhancement
Targeted Inhibition of transketolase enables suppression of ribose production as essential building block for DNA / RNA synthesis and DNA repair. This approach effectively sensitizes cancer cells towards chemotherapy and radiotherapy.
Proven Safety Profile
Successfully completed Phase 1 clinical study has demonstrated no serious adverse side effects, confirming transketolase as a promising target for future cancer therapies.
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Enabling successful treatment for better patient outcomes
Building on extensive preclinical research with oxythiamine in cell cultures and animal models, our approach stands out as the first viable option to translate transketolase inhibition into patient treatment.
Advancing to Phase 2
Following the successful completion of Phase 1 trial, we are actively preparing Phase 2 studies to investigate the efficacy and safety of this innovative treatment in larger patient cohorts in various indications.
Key Advances in Cancer Therapy through Targeted Metabolic Disruption:
- Increased Efficacy: Inhibiting transketolase metabolism, weakens the cancer cells’ ability to repair the treatment related damages, making them more susceptible to existing therapies, potentially leading to better patient outcomes, and higher survival rates.
- Reduced Drug Resistance: It helps address the common issue of treatment resistance, providing a novel approach to targeting cancer cells and enabling treatment of therapy-resistant tumors.
- Improved Patient Tolerance: The tightly bound thiamine prevents inhibition of already existing transketolase enzymes thereby protecting their activity in the body. This improves overall treatment tolerability for patients and lead to a de facto specificity for newly synthesized transketolase.
Almost too good to be true –
One treatment for almost any kind of cancer?
Cancer cells, regardless of their origin or type, are dependent on DNA synthesis and DNA repair1. By inhibiting newly synthesized transketolase enzymes in cancer cells, proliferation and DNA repair are inhibited2, 3, 4. In addition to ribose production transketolases are also mandatory for the building block acetyl-CoA, and lactic acid production in the presence of oxygen (so called Warburg effect)5. Acetyl-CoA and lactic acid play a crucial role for malignancy, since acetylation and lactylation of histones activate tumour promoting genes as well as induce immunosuppression 6, 7, 8, 9, 10, 11. Recently it has been proposed that lactic acid secreted by a cancer cell is able to activate tumour promoting genes and immunosuppression in neighbouring cells thereby creating cancer cells in a mutation independent and epigenetically driven mechanism 12, 13, 14.
TKTL1 is the biochemical basis of the “Warburg effect”, an anaerobic glucose fermentation to lactic acid even in the presence of oxygen (aerobic glycolysis). In addition to the above-described epigenetic role in malignant transformation, lactic acid permits an acid-based matrix degradation of the surrounding tissue leading to invasive growth, metastasis, and immunosuppression of tumours 15, 9. The metabolic role of TKTL1 is in line with the fact that activation of the anaerobic glucose fermentation in the presence of oxygen („Warburg effect“/aerobic glycolysis), is one of the earliest events in the activation of oncogenes in somatic cells 5, 16.
Conclusion
The ability to inhibit transketolase in cancer cell has the potential to significantly augment existing cancer treatment strategies. As a co-therapy, this approach offers a promising addition that could improve overall treatment outcomes and address resistance issues. Our compound, which has successfully completed a Phase 1 clinical trial, demonstrates the safety properties. However, the full therapeutic benefits, including its specific role and advantages as a co-therapy, require further clinical investigations to confirm and optimize its use in oncology.
Management and Advisors
Dr. Johannes Coy
CEO
Prof. Dr. phil. nat. Heinz Hänel
CDO
Maik Käbisch
Chairman of the Supervisory Board
Prof. Dr. med. Dietrich Grönemeyer
Advisor
Prof. Dr. Rupert Handgretinger
Advisor
About Us
Oxy5 OncoMedical AG, based in Darmstadt, Germany, is an innovative pharmaceutical company focused on cancer treatment research, development, and manufacturing. The company was founded on the discovery of TKTL1 and its metabolic role by Dr. Johannes Coy. The aim of the company is the translation of transketolase research into cancer therapies. Transketolase inhibition offers a new option as a co-therapy for chemo- and radiotherapy as well as immune therapies. Our compound benfo-oxythiamine is the first and only transketolase inhibitor which has been successfully evaluated in a phase 1 trial.
Partner
Oxy5 OncoMedical AG is partnering with benfovir AG for the clinical development of benfo-oxythiamine in oncology.
Contact
Do you need information or do you have any questions? You can contact us directly using our form and we will get back to you as soon as possible.
Oxy5 OncoMedical AG
Gräfenhäuser Str. 26
64293 Darmstadt
Germany
Tel +49 (0) 173 3518074
info@oxy5.com
References
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