Mymetics Corporation is US registered biotechnology company with its main offices in Switzerland and the Netherlands. Focused on developing next generation preventative vaccines for infectious diseases. Mymetics core technology and expertise are in the use of virosomes, lipid-based carriers containing functional fusion viral proteins in combination with rationally designed antigens and membrane proteins.
Mymetics currently has 5 vaccines in its pipeline:
Current Share Structure:
Oustanding Shares: 303.7 million (11/2016 & no change since 2012)
Floating Shares: 91.1 million* (a/o 03/29/16)
* verified by TA (https://www.otcmarkets.com/stock/MYMX/profile)
Current Market Cap (12/7/16): $5.0 million
Enterprise Value: $54.09 million*
*Enterprise value can be thought of as the theoretical takeover price if the company were to bought. In the event of such a buyout, an acquirer would generally have to take on the company's debt, but would pocket its cash for itself. EV differs significantly from simple market capitalization in several ways, and many consider it to be a more accurate representation of a firm's value.
RECENT NEWS WITH SANOFI:
Mymetics Starts Research Project with Sanofi for Influenza Vaccines
Dec 01, 2016
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EPALINGES, Switzerland, Dec. 1, 2016
EPALINGES, Switzerland, Dec. 1, 2016 /PRNewswire/ -- Mymetics Corporation (OTCQB: MYMX), a pioneer and leader in the research and development of virosome-based vaccines to prevent transmission of human infectious diseases, announced today that its subsidiary Mymetics B.V. has agreed on a research project with Sanofi Pasteur, the vaccine division of Sanofi (NYSE: SNY). The project will investigate the immunogenicity of influenza vaccines based on Mymetics' proprietary virosome technology platform in pre-clinical settings. If this project is successful it could result in a further and more extensive collaboration between the two companies.
"We are very excited to start this initial collaboration project with Sanofi, a world leader in the vaccine industry," said Ronald Kempers, CEO of Mymetics. "We look forward to show that our proprietary virosome technology and more than 30 years of virosome vaccines expertise can make a valuable difference in improving the effectiveness and cost competitiveness of influenza vaccines."
Mymetics Corp. (OTCQB: MYMX) is a Swiss based biotechnology company, with a Research Lab in the Netherlands, focused on the development of next-generation preventative vaccines for infectious diseases. It currently has five vaccines in its pipeline: HIV-1/AIDS, intra-nasal Influenza, Malaria, Chikungunya, Herpes Simplex Virus and the RSV vaccine. HIV, malaria and intra-nasal influenza vaccines have successfully finished Phase 1 clinical trials, while the others are in the pre-clinical phase.
Mymetics' core technology and expertise are in the use of virosomes, lipid-based carriers containing functional fusion viral proteins and natural membrane proteins, in combination with rationally designed antigens. Mymetics' vaccines are designed to induce protection against early transmission and infection, focusing on the mucosal immune response as a first-line defense, in combination with humoral and cellular immune responses as a second-line defense, which can be essential for the development of an effective vaccine.
Mymetics' unique approach is being validated through partnerships with leading pharmaceutical or research organizations, including projects with PATH-MVI and the Bill and Melinda Gates Foundation.
For further information, please visit www.mymetics.com.
WO/1999/025377 (GP41 mutee) Method for obtaining vaccines for preventing the pathogenic effects related to a retroviral infection Mymetics Corp. Expiration date: November 16, 2018
WO/2005/010033 (GP41 ter) New soluble and stabilized trimeric form of GP 41 polypeptide Mymetics Corp. Expiration date: July 28, 2024
WO/2007/099446 (Virosome-P1) Virosome-like vesicles comprising gp41 - derived antigens Mymetics Corp. + INSERM + Pevion Expiration date: January 3, 2027
US/61/202 215 (GP41 4th gen) Mymetics Corp. Expiration date: February 5, 2029
US/61/202 219 (Splitting GP41) Mymetics Corp. Expiration date: February 5, 2029
WO/2004/106366 (UK39) Methods for synthetizing conformationally constrained peptides, peptidomimetics and use of such peptidomimetics as synthetic vaccines Mymetics Corp. Expiration date: June 1, 2024
WO/2004/078099 (AMA49) Compositions and methods for the generation of immune response against Malaria Mymetics Corp. Expiration date: March 2, 2023
WO/2004/045641 (APRECS) Antigen-complexes Bestewil BV Expiration date: November 19, 2023
WO/2004/110486 (Lipopeptide) Functionally reconstituted viral membranes containing adjuvant Bestewil BV Expiration date: June 17, 2024
WO/2004071492 (DCPC) Virosome-like particles Bestewil BV Expiration date: December 2, 2023
[Viruses that can be applied and used in the formation of the virosome-like-particles according to the invention can be derived from all sorts of viruses, non-limiting examples of such viruses being: Retroviridae such as Human Immunodeficiency virus (HIV); rubellavirus; paramyxoviridae such as parainfluenza viruses, measles, mumps, respiratory syncytial virus, human metapneumovirus; flaviviridae such as yellow fever virus, dengue virus, Hepatitis C Virus (HCV), Japanese Encephalitis Virus (JEV), tick-borne encephalitis, St. Louis encephalitis or West Nile virus; Herpesviridae such as Herpes Simplex virus, cytomegalovirus, Epstein-Barr virus; Bunyaviridae; Arenaviridae; Hantaviridae such as Hantaan; Coronaviridae; Papovaviridae such as human Papillomavirus; Rhabdoviridae such as rabies virus. Coronaviridae such as human coronavirus; Alphaviridae, Arteriviridae, filoviridae such as Ebolavirus, Arenaviridae, poxyiridae such as smallpox virus, and African Swine Fever virus.] http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,901,920.PN.&OS=PN/7,901,920&RS=PN/7,901,920
Virosomes: A Novel Strategy for Drug Delivery and Targeting
Virosomes are reconstituted viral envelopes that can serve as vaccines and as vehicle for cellular delivery of macromolecules. The prospect of drug delivery and targeting using virosomes is an interesting field of research and development. Because virosomes are biocompatible, biodegradable, nontoxic, and non-autoimmunogenic, attemps have been made to use them as vaccines or adjuvants as well as delivery systems for drugs, nucleic acids, or genes for therapeutic purposes. Influenza virus is the most common virus of choice. The success of virosomal drug delivery depends on the methods used to prepare the encapsulated bioactive materials and incorporate them into the virosomes, as are characterization and formulation of the finished preparation. Virosome technology could potentially be used to deliver peptides, nucleic acids or genes, and drugs like antibiotics, anticancer agents, and steroids.
Promising drugs are often discontinued during development because they cannot be suitably delivered to target cells, tissues, and organs. The new generation of therapeutics against cancer or neurodegenerative disorders require delivery systems that target drugs to specified cell types and host tissues by receptor-mediated uptake and contolled release. Virosomal technology presents a novel sophisticated delivery system to meet these challenges.
Virosomes are reconstituted viral envelopes, including membrane lipids and viral spike glycoproteins, but devoid of viral genetic material. The external surface of the virosome resembles that of a virus particle, with spike proteins protruding from the membrane, but their interior compartment is empty. Because virosomes display viral envelope glycoproteins, which, in their native conformation stimulate humoral responses, they are highly effective as vaccine antigens and adjuvants.10-12. Moreover, since the receptor-binding and membrane-fusion properties of the viral envelope glycoprotein can be preserved, virosomes can be used as transport vehicles for cellular delivery of biologically active macromolecules.
Overall, virosomes protect pharmaceutically active substances from proteolytic degradation and low pH within endosomes, allowing their contents to remain intact when they reach the cytoplasm.This is the major advantage of virosomal carrier systems over other drug-delivery vehicles, including liposomal and proteoliposomal carrier systems.
Advantages of Virosomal Drug Delivery
Virosomal technology is approved by the FDA for use in humans, and has a high safety profile
Virosomes are biodegradable, biocompatible, and non-toxic12
No disease-transmission risk
No autoimmunogenity or anaphylaxis10
Broadly applicable with almost all important drugs (anticancer drugs, proteins, peptides, nucleic acids, antibiotics, fungicides)
Enables drug delivery into the cytoplasm of target cell
Promotes fusion activity in the endolysosomal pathway
Protects drugs against degradation
Virosomal Structure and Modifications
Figure 1: Virosomes are reconstituted influenza virus envelopes devoid of inner core and genetic information
Virosomes are spherical unilamellar vesicles with a mean diameter of around 150 nm. Influenza virus is most commonly used for virosome production. Virosomes cannot replicate but are pure fusion-active vesicles. In contrast to liposomes, vorosomes contain functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase (NA) are intercalated within the phospholipid bilayer membrane (Figure 1). Further characteristics of virosomes depend on the choice of bilayer components. Virosomes can be optimized for maximal incorporation of the drug, or for the best physiological effect by modifying the content or type of membrane lipids used. It is even possible to generate carriers for antisense-oligonucleotides or other genetic molecules, depending on whether positively or negatively loaded phospholipids are incorporated into the membrane. Various ligands, such as cytokines, peptides, and monoclonal antibodies (MAbs) can be incorporated into the virosome and displayed on the virosomal surface. Even tumor-specific monoclonal antibody fragments (Fab) can be linked to virosomes to direct the carrier to selected tumor cells.1,11
Bioactive drug compounds can be entrapped in the aqueous interior of the virosome or in the lipid membrane of the virosome for facilitated entry of the compounds into the cells.19
Virosomes are particularly useful for delivering nucleic acids or genes. These compounds are delivered into the host cell cytoplasm on fusion of the virosome with the endosome or plasma membrane.20 Nucleic acids or genes encoding a naturally occuring protein can be introduced into host cells and can be expressed, provided that the expression cassette contains the proper cis-acting regulatory elements.20,21
Drugs or nucleic acids can be incorporated into the virosome at the time of virosome preparation. The bioactive compound is typically added to the lipid-HA containing solution following removal of the nucleocapsid. Alternatively, the bioactive compound is initially incorporated into a liposome, which is then fused with a virosome containing two hemagglutinins with different pH thresholds to form a virosome-liposome hybrid.22
Proteins also can be delivered to cells via virosome. For example, the gelonin subunit A of diphitheria toxin and ovalbumin have also been successfully delivered by virosome to target cells.15,22,23 Virosomes carrying peptides derived from the influenza nucleoprotein or intact ovalbumin induced strong cytotoxic T lymphocyte responses, which suggests that the encapsulated peptides and proteins gained access to the cytoplasm.24,25
Targeted Drug Delivery
Ideally one would like to be able to target drug delivery to selected tissues. One can tailor virosomes to targets by incorporating specific molecules (e.g. Fab fragments and ligands) into the virosome's composition. The feasibility of targeted delivery of anticancer drugs by means of virosomal carrier has been demonstrated recently by two independent approaches. In one, a MAb cross-linked to the surface of virosomes mediated specific targeting of the virosomal carrier containing an anticancer drug (e.g. doxorubicin) to human cancer cells. MAbs can bind specifically to cancer-related antigens, providing a means to target systemically administered virosomes to cancerous tissues. Alternatively, ligands that bind surface receptors on the target cells also can be bound to the virosomes to achieve targeted drug delivery. Tumors of mice treated with targeted drug-loaded virosomes failed to grow, and mortality of these animals was significantly reduced. These positive results will definitely open a new field of applications for virosomal technology.18,19
Administration of Virosomes
Several formulations have been reported. Generally, virosomes are suspended in buffered saline (135-150 mMNaCl), but other suitable vehicles also exist. These compositions should be sterilized by conventional liposomal sterilization techniques, such as membrane filtration. The formulation also generally contains auxillary substances as required to stimulate physiological conditions, such as buffering agents and isotonicity adjusting agents (sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride).12,17 The concentration of virosomes used in the vehicle ranges from 20-200mg/ml. These concentrations are varied to optimize treatment with different virosome components or for particular purposes.19
The virosomes are administered in a variety of parenteral routes, including intravenous, intramuscular, subcutaneous, inta-arterial, and inhalable delivery. In addition, virosomes can be administered topically, orally, or transdermally. The virosomes also can be incorporated into implantable devices for long-term release.19,21,22
Authors : Mazumder B., Bhattacharya S. References 1. Almeida JD, Brand CM, Edwards DC, Heath TD. Formation of virosomes from influenza subunits and liposomes. Lancet 1975; 2:899-901
10. Gluck R, Mschler R, Finkel B, Que JU, Scarpa B, Cryz SJ. Immunogenicity of new virosome influenza vaccine in elderly people. Lancet, 1994;344:160-3
11. Huckriede A, Bungener L, Veer W, Holtrop M, Daemen T, Palache AM, Wilschut J. Influenza virosomes: combining optimal presentation of hemagglutinin with
immunopotentiating activity. Vaccine, 2003;21:925-31
12. Huckriede A, Burgener L, Stegmann T, Daemen T, Medema J, Palache AM, Wilschut J. The virosome concept for influenza vaccines. Vaccine 2005;23(s1):S26-38
15. Bron R, Ortiz A, Wilschut J. Cellular cytoplasmic delivery of a polypeptide toxin by reconstituted influenza virus envelopes (Virosomes). Biochem, 1994;33:9110-17
17. Huckriede A, Bungener L, Stegmann T, Daemen T, Medema J, Palache AM. The virosome concept for influenza vaccines. Vaccine. 2005;23:S26-38
18. Felnerova D, Viret JF, Gluck R, Moser C. Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs. Curr Opin Biotechnol. 2004;15:518-29
19. Cusi MG. Application of influenza virosomes as a delivery system. Human Vaccines. 2006;2:1-7
20. Daemen T, de Mare A, Bungener L, de Jonge J, Huckriede A, Wilschut J. Virosomes for antigen and DNA delivery. Adv Drug Deliv. Rev.2005;57:451-63
21. Sarkar DP, Ramani K, Tyagi SK. Targeted gene delivery by virosomes. Methods Mol Biol. 2002;199:163-73
22. Schoen P, Chonn A, Cullis PR, Wilschut J, Scherrer P. Gene transfer mediated by fusion protein hemagglutinin reconstituted in cationic lipid vesicles. Gene
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