TOTUM•63: for the management of prediabetes

TOTUM•63 is a unique and patented combination of 5 plant extracts, designed to target a number of pathophysiological mechanisms of type 2 diabetes. Its efficacy was clinically proven in people with prediabetes.

• 14 communications at international scientific congresses since 2016, including 11 selections by the three main global diabetes congresses: American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and the International Diabetes Federation (IDF).
• 6 scientific papers published by international journals since 2021: a first set of preclinical and clinical results on TOTUM•63 published, as part of a comprehensive publication plan for this active substance.

Prediabetes is defined by learned societies as a risk condition for developing type 2 diabetes¹. It involves a moderate rise in fasting blood glucose and/or glucose intolerance and/or a moderate increase in glycated hemoglobin levels (HbA1c). Without effective treatment, 70% to 90% of prediabetic patients will develop type 2 diabetes during their lifetime². Although type 2 diabetes is an irreversible condition in the large majority of cases, prediabetes can, for its part, be reversed: it is a warning sign and an opportunity to take action. The only treatment option available is a healthier diet and lifestyle, as no drug or healthcare product specifically indicated for prediabetic patients exists today.

Sources:
¹Standards of care in Diabetes, ADA 2017;
²Tabak AJ. et al., Lancet, 2012;
³Nathan DM. et al., Diabetes Care, 2007;
4Knowler WC et al., N Engl J Med, 2002.

900 million people worldwide are prediabetic today and at risk of developing type 2 diabetes.

Source: AEC Partners 2019.

700 million people worldwide will have contracted type 2 diabetes by 2045, according to current forecasts (463 million prediabetics in 2019).

Source: IDF 2019.

TOTUM•63, a unique patented combination of five plant extracts specifically designed to target a number of pathophysiological mechanisms of type 2 diabetes. This multi-target mode of action was identified in preclinical studies.

• Muscle: restoration of insulin signaling pathways and insulin-stimulated glucose uptake.
• White adipose tissue: restoration of insulin signaling pathways, reduction of inflammation.
• Brown adipose tissue: activation of thermogenic genes, reduction of inflammation.
• Liver: decrease in hepatic steatosis, reduction of pro-inflammatory macrophages, restoration of insulin signaling pathways.
• Intestine: improvement in the composition of the microbiota and in particular the abnormalities observed in prediabetes, reduction in glucose absorption, and decrease in lipid absorption.

TOTUM•63 is a unique patented combination of five plant extracts that target the key pathophysiological mechanisms of type 2 diabetes. The efficacy of TOTUM•63 is the subject of the first health claim related to the reduction of the risk of type 2 diabetes filed in Europe, North America and other key markets.

– Phase II clinical results on TOTUM•63

The efficacy of TOTUM•63 was evaluated in a Phase II international clinical study on prediabetics. The positive results demonstrated that TOTUM•63 significantly reduced fasting blood glucose and blood glucose at two hours, two risk factors for type 2 diabetes, compared to the placebo. TOTUM•63 also significantly reduced body weight, waist circumference and triglyceride blood levels compared to the placebo.

This was a randomized, double-blind, placebo-controlled study.

* p<0.05
*** p<0.001

– Safety and tolerance on TOTUM•63

The safety and high tolerance of TOTUM•63 were demonstrated in a Phase I/II clinical study in healthy volunteers, then confirmed by the Phase II clinical study in prediabetic patients.

– Last stage of clinical development, in partnership with Nestlé Health Science

Today, TOTUM•63 is in Phase II/III of its clinical development, the last stage before the submission of an application for a health claim recognized by the American, European and Canadian regulatory authorities.
This international randomized, placebo-controlled, double-blind study called “REVERSE-IT” was launched in mid-2020.
The study enrolls 600 patients with prediabetes or early-stage untreated type 2 diabetes. Its primary endpoint is a reduction of fasting blood glucose.

The REVERSE-IT study targets two strategic objectives:
• Confirm Phase II’s positive results on fasting blood sugar levels, a well-established risk factor for developing type 2 diabetes;
• Extend the evaluation of TOTUM•63 to patients with early-stage untreated type 2 diabetes to broaden the final target population.

The recruitment of the 600 volunteers in the study is complete, as announced on July 28, 2022.

In addition, a mode of action clinical study in humans is being implemented in 2022 by INAF, Quebec City (Canada). It will provide additional data to strengthen the scientific communication and support the commercialization of TOTUM•63.

Valbiotis has adopted a global strategy to protect its intellectual property: patent applications have been filed for TOTUM•63 in 63 countries, including key markets: Europe, USA, Canada, China, Russia, Japan, Brazil and Australia.
Patents have already been issued in 57 countries, including in the USA, Europe (39 countries), China, Russia or Japan, providing a very high level of protection.

In 2020, Valbiotis signed a global long-term strategic partnership with Nestlé Health Science for the development and worldwide commercialization of TOTUM•63. This partnership is unique in the field of health nutrition and provides for the worldwide market rollout of TOTUM•63 by Nestlé Health Science, potentially before a health claim authorization is issued, depending on the country.