COMPANY OVERVIEW

Nutrivercell®, founded in 2009, is dedicated to the formulation and development of innovative food supplements.

Nutrivercell® draws the resources for its scientific development amongst the 5,000 polyphenols of the botanical kingdom. After identifying active ingredients with a strong health potential, Nutrivercell® characterises their mechanisms of action on human physiology, associating them where there is a proven synergistic effect and then assessing the impact of these new associations.

The food supplements coming out of the R&D programmes are currently marketed directly by Nutrivercell®.
The Nutrivercell® economic model is built upon access to the pharmacy market through a partnership for the direct sale of products in pharmacies with, in parallel, promotion to general practitioners and specialists.
The sales activities of Nutrivercell®, begun in France at the end of 2010, should expand in 2014 to international markets.


DUAB®

PRODUCT

The first focus of development for Nutrivercell® regards the field of Urinary Tract Infections. DUAB®, the first product marketed by Nutrivercell® was commercialized in France at the end of 2010. Today, DUAB® is available for direct sale in nearly 5,000 pharmacies. Since mid-2013, DUAB® has become one of the market leaders in the French food supplement genitourinary sector.

Nutrivercell® products are also available to all pharmacies in France through wholesale distribution.

Market dynamics for the genitourinary food supplements sector (French market)

At present in France, it is estimated that approximately 10% of women suffer from one bout of cystitis each year and that 15% may suffer several times in the same year (more than four episodes annually). The French genitourinary food supplement sector represents a market of approximately 30 M€.
This market sector has been highly dynamic since 2003-2004, and is still growing significantly with a progress of 11 %, against 4% for the food supplement market overall. This trend reflects a context where the bacteria responsible for urinary infections are becoming more and more resistant to antibiotics (source Antimicrobial resistance: global report on surveillance 2014 ; WHO April 2014).

DUAB® is manufactured in France by a pharmaceutical laboratory compliant to GMP standards.

INNOVATION

DUAB® is a synergistic combination of propolis and cranberry making it the only product available on the market today that acts against virulence and resistance of the main bacteria involved in urinary tract infection (Escherichia Coli).
Cranberry, thanks to proanthocyanidins (PAC type A2), have a noticeable anti-adherence activity on the bacteria E. coli: the mechanical effect, by adhesion of the PAC to the pili of the bacteria, significantly reduces their virulence; the bacteria are prevented from attaching to the epithelial cells of the urinary tract lining (“flush effect”).

However, even with this effect, cranberry can only perform part of the work needed to effectively counteract urinary infections, especially persistent infections.
PACs have shown promise concerning virulence by preventing bacteria from attaching onto the lining of the bladder, but they do not guarantee a comprehensive elimination, in particular with regard to those bacteria embedded in a biofilm in the bladder lining. These are the bacteria that are most often at the origin of recurrent infections. As shown in experiments carried out jointly with French Research Institutes, the PACs have no effect on the resistance of E. coli.

Propolis, a substance made by bees, counteracts resistance by its effective bacteriostatic action on E. coli. Furthermore, it’s important to note that bladder bioavailability of propolis is very good after oral absorption, strongly contributing to the implementation of the bacteriostatic effect.
The article “Propolis can potentialise the anti-adhesion activity of proanthocyanidins on uropathogenic Escherichia coli in the prevention of recurrent urinary tract infections” (Jean-Philippe Lavigne, Xavier Vitrac, Louis Bernard, Franck Bruyère and Albert Sotto) was published in 2011 in the BMC Research Note Review presenting the work which substantiates part of the claims developed below.

Scientific investigations showed that DUAB® properties are as follows:

  1. DUAB® is bacteriostatic regardless of the degree of resistance of E. coli (ex vitro data).
  2. DUAB® amplifies the bactericidal effects of antibiotics (ex vitro data).
  3. DUAB® prolongs the anti-adhesive effect of the cranberry: DUAB® remains active over a period of 12 hours, compared with 6 hours for cranberries alone. Nutrivercell® has demonstrated that the synergetic effect of propolis on PAC is still seen 12 hours after oral absorption, as compared with a 6-hour efficacy in the only presence of PAC (ex vivo data).

NEOGIL a nutraceutical with a potent anti inflammatory activity

DUAB® CLINICAL STUDY

Nutrivercell® has been conducting a clinical study since July 013 in partnership with the French Urology Association, A.F.U., to assess the effectiveness and tolerance of DUAB® in preventing the relapse of recurrent urinary infections in women.
The purpose of this study was to compare, over a period of six months, the frequency of acute cystitis due to E. coli in women taking DUAB® against those taking a placebo.


RESULTS OF SCIENTIFIC STUDIES IN 2014,
IN COLLABORATION WITH THE INSERM UNIT 1047, NÎMES, FRANCE.

In 2014, Nutrivercell and the INSERM unit 1047, Nîmes, France, signed a 3-year contract to support a young PhD student pursuing and developing the study of DUAB® antibacterial activity, a study which began nearly 6 years ago.

The first series of results concern :

  1. Confirmation of the bacteriostatic effect of DUAB® propolis.
  2. Confirmation of the synergetic effect of DUAB® propolis with different antibiotics.

COLLABORATION WITH THE INSERM UNIT 1047, NÎMES, FRANCE : IN VITRO TESTS

Goals

  • Determine the bactericidal curve of DUAB® propolis.
  • Verify and measure whether DUAB® can improve the performance of antibiotics.
  • Strains studied: 1 strain of E.coli reference CFT073, 6 strains of E.coli from different origins (cystitis, acute pyelonephritis) comprising 2 strains sensitive to ATB, 2 strains resistant to quinolones and 2 ESBL-secreting multi-resistant strains.

duabEtude1

Bactericidal curve of propolis with OFLOXACINE (OFX).

 

Bactericidal curve of propolis with CEFTRIAXONE (CRO).

 

Bactericidal curve of propolis with ERTAPENEM (ETP).

 

CONCLUSION : IN VITRO TEST RESULTS.

Propolis at a high concentration (>125 mg/l) has a bacteriostatic effect.
This activity is time-dependent.

DUAB® has a synergetic effect which is :

Significant with ceftriaxone and ertapenem whatever the resistance to these antibiotics.
Important with ofloxacine depending on sensitivity to this antibiotic.

CIFRE Grant : Inserm (Unit 1047) – Nutrivercell


NEOGIL®

PRODUCT

The second focus of Nutrivercell®, in partnership with the University of Bordeaux, France, regards the field of inflammation. NEOGIL® is an original formula, patented and developed in co-ownership with the Study Group for Biologically Active Substances (Groupe d’Etude des Substances à Activité Biologique, G.E.S.V.A.B) and the Faculty of Pharmaceutical Sciences of Segalen University. NEOGIL® associates two active nutritional ingredients, an extract of red grapes (Vitis vinifera) and an extract of propolis for which the strong synergetic effect on the inflammatory process has been demonstrated in vivo on arthritic rat models. The commercial launch of NEOGIL® took place in France in September 2013.

INNOVATION

Nutrivercell® has a sustained commitment to R&D and preclinical testing in which the results of the actions and effects of these various nutraceuticals are presented, notably in recognized scientific publications:

  • 1st article: “Malvidin-3-O-glucoside, major grape anthocyanin, inhibits human macrophage-derived inflammatory mediators and decreases clinical scores in arthritic rats”. Biochem Pharmacology, 2013.
  • 2nd article: “Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis”. Phytomedicine, 2013.

NEOGIL® a nutraceutical with a potent anti-inflammatory activity : mode of action


this grape polyphenols and propolis synergistic association inhibits inflammatory mediator releases from human leukocytes and reduces clinical scores in exprimental arthritis ( in vivo and in vitro models ).


Reduction of arthritis severity scores of adjuvant induced arthritis in rats following oral treatment with a mixture of grape extract GPE and propolis PR

reduction-arthritis

  • « HC » five injection of 30 mg/kg HC every 2 days
  • « GPE/PR X 5 »: hige doses, 250mg/Kg of GPE/PR X 5 every 2 days (arrows)
  • « GPR/PR con » : lower doses continuously, 50 mg/Kg of GPE/PR every 2 days until end of incubation

INTELLECTUAL PROPERTY

Nutrivercell® pursues an active protection policy for its innovations and brands. The invention patents for DUAB® and NEOGIL® were granted for France under the references No.09 55738 awarded 03/08/12 and No.11 57995 awarded 27/12/13, respectively.
These patents are currently under examination for worldwide extensions.

SCIENTIFIC COLLABORATIONS

Nutrivercell® carries out its scientific investigations in collaboration with well-known French Research Institutes such as INSERM de Nîmes and Bordeaux University.

INTERNATIONAL DEVELOPMENT STRATEGY

The establishment of DUAB® in France is sufficiently strong now for the company to envision an international expansion.
Nutrivercell® has begun to register regulatory files for the European market.
Nutrivercell® is willing to establish a long term partnership with well-established medium size companies specialized in OTC products and/or nutraceuticals which have their own commercial network and/or have secured an access to a commercial network through a partnership.
DUAB® and NEOGIL® should fit into strategic priorities of our prospective partner: our partner should already own a portfolio in women’s health and/or inflammation and/or envision to invest in these fields.
Nutrivercell® favours a distribution/supply agreement.

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