First-in-Class Candidate – Transketolase Inhibitor Benfo-Oxythiamine
Targeting Transketolase:
A Novel Approach
Benfovir uses a unique and unprecedented approach to inhibit newly formed transketolase, the key enzyme of the pentose phosphate pathway (PPP). This pathway utilizes transketolase activity in order to provide precursors for DNA and RNA synthesis, a process essential for cell growth, division and repair. This opens up the possibility to impact the course of the following diseases:
Viral Diseases
Inhibition of virus replication by controlling host cell metabolism. This therapeutic strategy is independent of the sequence of the virus and allows the inhibition of all known virus types as well as new virus types that will emerge in the future, since ribose is the essential building block of RNA and DNA.
Inflammation
Modulating metabolic pathways to restore immune balance and reduce harmful inflammation.
Cancer
Inhibiting the growth of cancer cells by disrupting their access to essential resources.
Benfo-Oxythiamine (B-OT): A Thiamine Analogue
B-OT acts as a prodrug, releasing oxythiamine (OT) to inhibit transketolases formed in the presence of thiamine. Thiamine binds newly formed transketolase quasi-irreversibly, preventing the natural cofactor from being displaced by inhibitors. Therefore, only newly formed transketolases will be inhibited by the thiamine antagonist B-OT.
What is a prodrug?
A prodrug is an inactive compound that, once administered, is metabolized by the body into its active form. This approach can improve drug delivery and efficacy.
How does B-OT work?
B-OT is designed to release oxythiamine (OT) within the body. OT is a known inhibitor of transketolase, interfering with metabolic processes involved in diseases.
How B-OT inhibits Cell Division to Treat Diseases
All life depends on cell division, and ribose is one of the fundamental building blocks of DNA. Without it, cell division is not possible.
We use B-OT to suppress the new synthesis of transketolase and thus limit the availability of ribose. By influencing this process, we also influence cell division – a key factor in many diseases – and are able to prevent it.
The targeted use of B-OT creates a new pathway for treatment, such as the containment of viral diseases. By depriving the virus of ribose, we deprive it of the opportunity to replicate.
The Impact of Newly Formed Transketolase Inhibition
How it affects …
… Viral Replication
Inhibition of Viral Replication
Limiting the capacity of a virus to efficiently replicate its genetic material also affects its ability to spread and infect new cells.
Reduced Nucleotide Synthesis
By limiting the availabilty of ribose, B-OT affects the production of nucleotides, which are essential for replication and spread of a virus.
Transketolase Inhibition
The ability to control the formation of new transketolases enables us to influence the availability of ribose.
… Immune Modulation
Lactate Accumulation
High lactate levels, often seen in viral infections, can suppress immune responses.
Transketolase Inhibition
Targeting transketolase can help regulate lactate production, reducing its immunosuppressive effects.
Enhanced Immune Response
By modulating lactate, transketolase inhibition supports a more effective immune response against viral invaders.
… Sepsis and Inflammation
Sepsis
A serious condition marked by a dysregulated immune response to infection.
Metabolic Dysregulation
Sepsis involves metabolic abnormalities, including lactate accumulation, that contribute to its severity.
Transketolase Inhibition
Targeting transketolase offers a potential strategy to modulate these metabolic pathways and restore immune balance.
Transketolase Inhibition:
A New Frontier in Oncology
Targeting transketolase and TKTL1 presents a novel approach to cancer treatment by targeting the metabolic demands of cancer cells.
How does transketolase inhibition affect cancer cells?
Cancer cells, with their rapid growth and division, rely heavily on the PPP and transketolase activity for nucleotide synthesis. Inhibiting transketolase disrupts this process, limiting the resources available for newly formed cancer cell proliferation.
What is the role of TKTL1 in cancer?
TKTL1, often overexpressed in cancer cells, forms a heterodimer with transketolase, further enhancing ribose production and fueling cancer cell growth. Inhibiting this interaction is a key target in cancer therapy.
We partner with Oxy5 Oncomedical AG for the clinical development of B-OT in oncology.
Phase 1 Clinical Trial: Evaluating B-OT
The exceptionally good safety profile of the inhibitory thiamine derivative B-OT was confirmed in a clinical phase 1 study with healthy volunteers (BV-01-101 / EudraCT number: 2021-005616-60). B-OT is a novel thiamine analog that acts as a prodrug and releases oxythiamine (OT), the actual inhibitor of thiamine pyrophosphate-dependent enzymes like transketolases.
Phase 1 Trial
The initial phase of clinical testing in humans, focusing on safety, dosage, and how the drug is processed by the body.
Healthy Volunteers
Phase 1 trials typically involve a small group of healthy volunteers to evaluate the drug’s safety profile.
Safety and Tolerability
By inhibiting transketolase, we aim to limit the resources necessary for rapid cell proliferation, which is characteristic of many diseases.
Phase 1 Trial
The initial phase of clinical testing in humans, focusing on safety, dosage, and how the drug is processed by the body.
Healthy Volunteers
Phase 1 trials typically involve a small group of healthy volunteers to evaluate the drug’s safety profile.
Safety and Tolerability
The primary goal of Phase 1 is to determine the drug’s safety and identify any side effects at various doses.
Positive Safety and Tolerability Profile
The results of our phase 1 trial indicate that B-OT is well-tolerated. No serious adverse effects were reported.
Well-Tolerated
The drug was well-tolerated by the participants, indicating a favorable safety profile.
No Serious Side Effects
No serious adverse events were reported during the trial, suggesting a positive safety profile for B-OT.