NEWS

To whom it may concern:

Nothing is set in stone when it comes to clinical research, but occasionally we will have to reinvent the wheel. Victor Hugo ones stated: “Nothing is more powerful than an idea for which the time had come.”

OXOVASIN (Drug substance: TCDO) has been just approved by the Food and Drug Administration (FDA) of Thailand, the first shipment arrived in Bangkok on 16^th June 2023.

OXOVASIN is a clinically proven, safe, and effective topical solution for treatment of infected, inflamed, chronic and immune compromised wounds, burns, decubitus, and wound cavities, based on unique modulation of the innate immune response:
1. OXOVASIN effectively terminates cell- and tissue destruction via specific inhibition of the Myeloperoxidase (MPO)-pathway.
2. OXOVASIN creates superior tissue repair by inducing apoptosis, phagocytosis, and neo-angiogenesis. It modulates the Phosphatidyl-Inositol-Kinase (PI3K)-pathway.
3. OXOVASIN-derived efficient removal of apoptotic cells is ‘sine qua non’ for tissue development and homeostasis, as well as protection against neoplasia and chronic inflammation.
4. OXOVASIN is pharmacologically effective in treatment of wounds in patients with immune suppression and anergic wounds by reversing the effects of cortisone. (see: In Memoriam: Paul Ehrlich).

OXOVASIN is identical with the international known drug Oxoferin which is manufactured by the same factory at OXO Translational Science Inc., Wanzleben, Germany.

OXO Translational Science Inc. is the leading company in development of chlorite-based drugs.
 
In Memoriam Prof. Paul Ehrlich, Shriners Burn Institute, Boston, USA
In 1990 I had the honor to host the ‘International Symposium for Tissue Repair’ in Pattaya, Thailand.

It was organized by Prof. Nopadol Wora-Urai, Phramongkutklao Milary Hospital, Bangkok, Prof. Thong-Ueb Uttaravichien and Assoc. Prof., Vajarabhongsa Bhudhisawasdi, both from Srinagarind University Hospital, Khon Kaen, Thailand.

Among the 200 attendees from Asia, USA, Europe, including Russia (Chernobyl), were world-renowned scientist involved in pre- and clinical research of wound healing and tissue repair. The most prominent among the attendees were Prof. Thomas K. Hunt from San Francisco University Hospital (UCSF). Owing to his experiences as a physician in the Vietnam War, he dedicated his academic life to improve and teach knowledge about tissue repair. Prof. Charles Baxter from University of Texas, Dallas, who tried to save President John F. Kennedy’s life after he was shot in his open limousine, presented his scientific legacy ‘Nutrition in Burns’.
Placed for eternity was the presentation from Prof. Paul Ehrlich, great grandson of the Nobel Laureate Paul Ehrlich. He worked at Shriners Burns Hospital, Boston, USA.
 
Paul developed an experimental animal model (in 1990) to test efficacy and safety of drugs with the objective to induce apoptosis/phagocytosis, and homeostasis in impaired wound healing of immunocompromised subjects, an unmet medical need. Together with Prof. Ludwig Hatz (Ludwig’s Maximilian University (LMU) Munich, Germany) he published their findings in Springer’s ‘Phagocytic Biology’: “TCDO reversed the effect of Cortisone on wound healing. Treatment with TCDO resulting in statistically significantly accelerated wound healing of immune-compromised wounds”. Animals receiving cortisone in combination with TCDO displayed markedly enhanced wound healing, including restoration of tensile strength, collagen synthesis, and wound contraction. The results indicate that TCDO could be a potential agent of wound healing in immunosuppressed patients and anergic wounds.

Other Topics of the named conference were ‘Oxygen as an antibiotic’, and ‘Modulation of Innate Immune Response by Oxidants with anti-inflammatory properties’. Pharmacological approaches to limit Cell- and Tissue Damage were discussed, data from Pre- and Clinical studies using the chlorite-based drug TCDO were presented revealing robust clinical efficacy in treatment of epithelial dysfunction in Proctitis (Prof. Thong-Ueb Uttaraviechien) and hemorrhagic/interstitial Cystitis (Assoc. Prof. Vutisiri Veerasarn, Siriraj Hospital, Bangkok, and Assoc. Prof. Vicharn Lorvidhaya, Chiang Mai University, Chiang Mai) and Mucositis (Radio-Oncology Group of Thailand).

Prof. Erich Elstner and Prof. Schempf from Klinikum Rechts der Isar/ Technical University of Munich (TUM) Munich, Germany (the Oxygen Guru) presented molecular mechanism of the chlorite molecule with Heme-proteins, among it the specific inhibition of Myeloperoxidase (MPO), leading to effective resolution of neutrophilic inflammation by induction of apoptosis/phagocytosis. Efficient removal of apoptotic cells is necessary for tissue development and homeostasis, as well as protection against neoplasia and chronic inflammation.

Assoc. Prof. Chairat Burusapat and Sophilak Sringkarawat (Phramongkutklao Military Hospital, Bangkok),
Thirty (30 years) later (2021), in ‘Plastic and Reconstruction Surgery’ the results from a Prospective, Randomized, Controlled Trial (RCT), comparing Negative-Pressure Wound Therapy (NPWT) with NPWT and installation of TCDO (abbreviated NPWTi), were published. The results reported included a blinded analysis from an independent pathologist analyzing the quality of deep tissue after 15 days NPWTi and NPWT alone treatment. The highlights were:
1. Bacteriology: No difference in microbiome reduction in both groups
2. Healing: Statistically Significantly better wound healing in NPWTi compared to NPWT alone (p>0.01 on day 15)
3. Granulation in NPWTi was superior compared to NPWT alone
4. Tissue quality: NPWTi (TTCDO) did not leave any edematous stroma cells behind, and showed visible neoangiogenesis,
5. NPWT alone left substantial edematous stroma cells behind, and no neoangiogenesis was detected (see histology)

Unfortunately, the investigators did not enroll immune-compromised patients out of 107 patients selected for study entry, despite referencing to Paul Ehrlich’s work and results of other investigators.

I tried to contact Paul Ehrlich to debate this paper with him, only to find out that he passed away during the Corona Pandemic with only 79 years of age.

Paul as a believing Catholic lived a modest way. His legacy is still alive.
 
Burusapat and colleagues confirmed prior findings from their German colleague Prof. Ulf Thiede (Zenker, Erdmann, Thiede, University of Kiel, Germany).
1. TCDO installation statistically significantly accelerated wound healing but did not show difference in microbial reduction.
2. TCDO installation showed visible granulation on bones, tendon, and facies, statistically significantly accelerated wound healing as well as excellent deep tissue quality, compared to antiseptic solutions (Betaisodonna).

Conclusion: Pharmacological Control of Cell and Tissue Destruction, paired with induction of apoptosis and phagocytosis by OXOVASIN installation, is an ultimate approach for state-of-the-art wound healing and tissue repair.

It is also an ultimate approach for treatment of chronic inflammation.

Assoc. Prof. Narongchai Yingsakmonkol is also member of the Khon Kaen School of Surgery. He was one awarded a scholarship to Heidelberg University (Prof. Herfarth and Prof. Buechler) and for years at Srinakharinwirot University, Nakhon Nayok, Thailand. He dedicated his life to wound healing and tissue repair, in a similar fashion as T.K. Hunt from San Francisco, and he became one of the most experienced Surgeons in treatment of complicated wounds in ASEAN, including diabetic osteomyelitis. His published results were outstanding and were just confirmed by Prof. Yazid Bajuri from National University of Malaysia, Kuala Lumpur. After retirement from the academic school, he still treats complicated wounds at Private Hospitals (Ladprao Hospital and Kasemrat Hospital).

I bow my head in recognition to all of those mentioned above for their valuable contributions to pre-and clinical science.

References
Bajuri MY, Zainol Z, Sabudin RZAR, Gafor AHA, Sukor N, Flemmig J, Kuehne FW: Redox-active clearance of highly glycated RBCs: A new frontier for the treatment of diabetic vasculopathies. J Diabetes Treat 2022; 7(4):1-11.
Burusapat C, Sringkarawat S: Efficacy of Negative-Pressure Wound Therapy with Tetrachlorodecaoxygen-Anion Complex Instillation Compared with Standard Negative-Pressure Wound Therapy for Accelerated Wound Healing: A Prospective, Randomized, Controlled Trial. Plastic and Reconstructive Surgery; 148(2):339-352.
Hatz RA, Kelley SF, Ehrlich P: The Tetrachlorodecaoxygen Complex Reverses the Effect of Cortisone on Wound Healing. Plastic and Reconstructive Surgery 1989:953-959.
Hinz J, Heinz H, Stahl KW: Rationale for and results from a randomized, double-blind trial of Tetrachlorodecaoxygen anion complex in wound healing. The Lancet 1986; 825-828.
Thiede A: The value of TCDO in gas gangrene infection. International Symposium on Tissue Repair, Pattaya, Thailand 1990.
Yingsakmongkol N, Maraprygsavan P, Sukosit P: Effect of WF10 (immunokine) on diabetic foot ulcer therapy: a double-blind, randomized, placebo-controlled trial. J Foot Ankle Surg 2011; 50(6):635-640.
Yingsakmongkol N, Tanunyutthawongse C, Flemmig J, Kuehne FW: Effect of the Chlorite-Based Drug WF10 on Hemoglobin A1c, Hematological Biomarkers in Uncontrolled Diabetic Patients with Foot Ulcer. J Diabetes Treat 2021 6:1086.
Zenker W, Thiede A, Dommes M, Ullmann U: Die Wirksankeit von Tetrechlorodecaoxid (TCDO) zur Behandlung komplizierter Wundheilungsstörungen. Chiurg 1986; 57:334-339.

Kuala Lumpur, Heidelberg, Magdeburg/Wanzleben, Bangkok

OXO Translational Science GmbH (OXO TS) Germany, a pharmaceutical company engaged in drug development for treatment of inflammatory diseases and diabetic vascular complications, reports the publication of a new patent in the European Patent Bulletin entitled “Use of chlorite to treat red blood cell diseases and indications mediated thereby”. The patent application has been filed in on 22^nd August 2016 (EP16763581.2). An official communication under rule 71(3) EPC on the granting of the patent was sent on 27^th September 2022.

Red Blood Cell (RBC) dysfunctions are the reason for many currently uncurable or unstoppable diseases, e.g. Sickle Cell Anemia. Dysfunctional RBCs are also responsible for the damage of the endothelial cell wall of blood vessels (particularly in the microcapillaries) of individuals diagnosed with Diabetes Type 1 and Type 2. In these patients, RBC dysfunction is characterized by high levels of Hemoglobin A1c (HbA1c). The latter reflects glycation of hemoglobin with RBCs, which leads to metabolic, functional and structural disturbances of the cells. Highly glycated dysfunctional RBCs in Diabetic patients as well as hemolytic products from these cells lead to endothelial damage and vascular inflammation.

In October 2022 the Journal of Diabetes and Treatment published an article entitled “Redoxactive Clearance of Highly Glycated Red Blood Cells: A New Frontier in the treatment of Diabetic Vasculopathies”. This open-access article reports the results from a scientific clinical collaboration project between 1) the National University of Malaysia (Kuala Lumpur, Prof. Yazid Bajuri), 2) the University of Heidelberg, Department for Internal Medicine (Sonderforschungs-bereich SFB1118: ‘Reactive Metabolites as cause of diabetic complications’, Prof. Peter Nawroth), and 3) the OXO TS Research Group, (Wanzleben, Germany and Bangkok, Thailand)

In this controlled clinical trial, a number needed to treat (NNT) of only 20 patients (mean HbA1c > 10%) was sufficient to convincingly proof WF10, propriety drug of OXO TS, as a completely new therapeutic concept for reduction of ele-vated HbA1c levels and restoration of endothelial integrity. In the treatment group, receiving standard of care glucose lowering drugs AND the i.v. drug WF10, > 83% of patients achieved HbA1c values characteristic for NON-diabetic patient within 4 – 6 weeks, whereas in the control group, receiving ONLY standard of care medication, only 25% of
the patients achieved those values

Dr. Joerg Flemmig, Chief Scientific Officer at OXO TS and co-author of the paper, stated: “We are grateful to be able to provide a safe and meaningful drug for treatment of diabetic vascular complication. In our recent clinical studies, we were able to show that not high blood sugar levels per se but glycation-derived dysfunctional RBCs are responsible for diabetic vascular complications.”

WF10, the flagship drug of OXO TS, is approved in Thailand and the launch in ASEAN is lined up. Based on the European patent approval, the company is looking for partners to co-finance the pivotal Phase III study for EMA Approval.