Letrah International Corporation is pleased to offer many pharmaceutical and bio-tech opportunities.
Some of the opportunities Letrah has to offer:
- We will provide the client with "state-of-the-art" turn key pharmaceutical factory
- We will provide a robust pipeline of products to produce.
- Typical return on investment time is less than 24 months.
- We offer investment opportunities to bring products to market.
Non-Viral Influenza Vaccine Development
Project Summary: Influenza represents one of the most serious and common pandemic/epidemic viral diseasesof human populations. Rapid mutations and rearrangements of the viral genome allow the virus to evade hostimmune responses, making the frequent development of vaccines to new viral variants necessary. MolecularGPS is developing a VesiVax® vaccine for influenza that incorporates the highly conserved ectodomain of thestructural M2 protein (M2e) prospectively constructed to represent a variety of influenza subtypes. The Company has previously shown that VesiVax® vaccines targeted to M2e stimulates protective responses in rodents receiving challenges with lethal doses of potential pandemic strains of influenza (published in the journal Vaccine). The Company believes that further testing of the VesiVax® influenza vaccine will demonstrate that it is a highly effective means of stimulating protective responses against the structurally conserved M2e viral protein, thereby facilitating the development of “universal” vaccines against pandemic influen za that would not be rendered ineffective by antigenic drifts and/or shifts associated with mutations or rearrangements of the influenza H and N surface proteins. An influenza vaccine based upon the VesiVax® system would also offer the opportunity to rapidly and efficiently adjust to changes in the virus, either natural or man‐made, to generate new vaccines as needed. Taken together, the attractive features of this vaccine technology are designed to provide a major improvement to the nation’s ability to respond to natural influenza infections and the potentialuse of influenza as a biological weapon.
Estimated Market: $5 billion worldwide.
Genital Herpes Vaccine Discovery
Project Summary: The primary objective of this project is to develop a safe genital herpes vaccine that is capable of providing a level of protection in male and female human populations which is better than that observed for other genital herpes vaccines. The nature of genital herpes suggests that an effective vaccine for this disease will likely have to stimulate a potent T‐cell (non‐antibody) mediated immune response in order to control both primary and recurrent infections. The company has recently demonstrated that
HSV2 VesiVax® vaccines targeted to selected fragments (epitopes) from the gD viral envelope antigen protein are capable of protecting both female and male mice from mucosal HSV2 challenge (intravaginal and intrarectal, respectively) with increased survival and markedly reduced clinical signs of infection and further, actively stimulates effective T‐cell immune responses in both sexes. More recently, it was discovered that an antigenic segment corresponding to the complete HSV2 gD ectodomain provided the most potent immune response, as judged by protection from disease in both the male and female mouse models of lethal HSV2 challenge. The
central hypothesis is that the use of the VesiVax® system to design and engineer a vaccine targeted to the gD ectodomain of HSV2 will result in sufficient protection against disease in both males and females to justify advancing this vaccine towards clinical testing. To demonstrate this, the Company is currently testing the prototype HSV2 VesiVax® vaccines in a guinea pig model of primary and recurrent disease for the ability to provide protection against mucosal infection and the manifestation of disease in vivo. The Company has
recently validated this hypothesis and expects to complete a full immunological characterization by the end of 2007. Upon completion of these studies, a lead HSV2 vaccine candidate for advancement to clinical development will be selected.
Estimated Market: $1.2 billion US
Liposomal HIV Vaccine Development
Project Summary: The search for an HIV vaccine to halt the spread of AIDS was launched nearly as soon as the virus was discovered. Over two decades later, a vaccine is still not available, nor are any candidates considered to be promising enough to be useful in the global battle against HIV. Despite the availability and success of HIV treatment drugs in the United States, the best long‐term hope for controlling the AIDS epidemic worldwide is the development and distribution of a safe, effective and affordable prophylactic HIV vaccine. Using the VesiVax® platform technology, the Companyplans to develop a vaccine against HIV based on the relatively conserved ectodomain segment of the HIV gp41 protein (HIVgp41e). It has previously been shown that three of the five known broadly protective antibodies discovered to date are targeted to the HIVgp41e region. The objective of this project is to construct a series of HIVgp41e VesiVax® vaccine candidates and test them for the ability to stimulate the production of these broadly neutralizing antibodies. The Company believes
that evaluation of the HIVgp41e VesiVax® vaccine candidates will demonstrate that one or more are highly effective at stimulating broadly neutralizing antibodies against a standardized panel of HIV subtypes. Successful demonstration of the proof of concept of the utility of one or more of the HIVgp41e VesiVax® vaccine formulations to elicit broadly neutralizing antibodies is anticipated to lead to the identification of a promising vaccine candidate for advancement to clinical development.
Estimated Market: $3 billion worldwide
Development of an Aspergillus Vaccine
Project Summary: This project focuses on Aspergillus fumigatus, a common fungus that causes disease primarily in people whose immune system has been compromised. Patients hospitalized with this condition have lengthy hospital stays and high mortality rates. Illnesses caused by Aspergillus engender a significant economic burden in the US, every other developed country, and many developing nations every year. Moreover, this burden is growing and, as documented in many epidemiologic studies, would be expected considering the increased numbers and survival of immunocompromised persons. Thus, a safe and effective vaccine against A. fumigatus
would save health care dollars (and have significant dollar value) and, most importantly, save lives. Using the VesiVax® system, the Company is constructing several vaccine candidates for testing in relevant animal models of Aspergillus infection. The Company plans on evaluating selected antigens as potential targets for vaccine development. Successful demonstration of the proof of concept of the utility of one or more of the Aspergillus VesiVax® vaccine formulations to elicit protective immune responses is anticipated to lead to the identification of a promising vaccine candidate for advancement to clinical development.
Estimated Market: $500 million
Liposomal Adjuvant for Vaccine Development
Project Summary: Advances in the development of genetically engineered vaccines to prevent outbreaks of infectious disease have prompted a re‐evaluation of vaccination strategies against a number of pathogens. The Company has been developing a new model of immunization that is based on a flexible antigen delivery platform technology designed to provide highly effective immune responses against a wide range of antigens. The Company has previously shown that this antigen delivery technology is highly effective at
stimulating active protective immune responses against viral and bacterial pathogens. However, there is a need for improved adjuvant formulations that can be conveniently modified and used as a tool in vaccine research studies. To address this need, the Company has modified the vaccine technology so that a target antigen can be easily prepared without further manipulation. Using Bacillus anthracis, the etiologic agent of anthrax, as a model disease causing pathogen, the Company has selected two critical target antigens from anthrax to establish the proof of concept for the proposed modification to our vaccine technology. Upon the successful completion of the proposed studies, the modifications to the vaccine platform technology would then be developed for general sale to the vaccine research community. This would give vaccine researchers an opportunity to take advantage of the Company’s antigen delivery system through a kit in which they would be able to prepare a vaccine in their own laboratory for use as a research tool in their vaccination studies. Further,
formulations might also be discovered through this project that could be developed into the next generation anthrax vaccine.
Estimated Market: $14.4 billion
Liposomal Disintegrin: Novel and Effective Antitumor Agent Phase II
Project Summary: Despite significant improvements in the management of breast cancer, the five year survival rate for advanced disease remains dismal, and a majority of women will eventually relapse and die from their disease. To address this situation, the Company has developed a formulation of a novel molecule isolated from the venom of the southern copperhead snake which possesses potent anticancer
activity. This molecule, derived from a class known as the disintegrins, kills cancer by shutting off the blood supply to the tumor. The immediate goal of this project is to demonstrate that this formulation can be prepared using standard commercial manufacturing methods and that material produced by such techniques is just as effective at killing breast cancer tumors as the laboratory prepared material. Successful execution of these studies will lead to the selection of a product candidate that will be advanced to the clinical stage of development.
Estimated Market: $1.5 billion
Development of a Combination Therapy for the Treatment of Prostate Cancer
Project Summary: Prostate cancer represents both the second most lethal and abundant form of cancer in American males. American Cancer Society data indicate that were 220,900 men diagnosed with and 28,900 deaths from prostate cancer in the United States in 2005. One man in six will suffer from prostate cancer during his lifetime, while one man in 34 will die of this disease. The risk of developing prostate cancer and mortality from the disease is nearly double in African‐Americans compared to whites. Current therapeutic options for
prostate cancer vary from “watchful waiting” to aggressive surgical intervention and radiation therapy, but even the radical therapeutic approach is ineffectual against aggressive metastatic disease. In addition, treatment with androgenic hormones, while palliative in the near term, almost always progresses to the androgen independent form of prostate cancer which is much more aggressive and difficult to treat, and leads to eventual death. Therefore, to limit the mortality from prostate cancer, it is imperative that new therapeutic modalities be
developed for this potentially devastating disease. To address this need, the Company has developed a formulation of a novel molecule isolated from the venom of the southern copperhead snake which possesses potent anticancer activity. This molecule, derived from a class known as the disintegrins, kills cancer by shutting off the blood supply to the tumor. The primary goal of this project is to demonstrate that thisformulation can be used in combination with other cytotoxic agents to effectively kill prostate cancer cells.
Estimated Market: $1.5 billion
Production of a Lung Surfactant SP-B Mimic
Project Summary: Surfactant Protein B (SP‐B) is crucial in the function of native lung surfactant, and is equally important for activity in clinical exogenous surfactants as well. Based on the known three‐dimensional structures of proteins in the “Saposin” class, early SP‐B models predicted that the disulfide cross‐linked, N‐ and C‐terminal domains fold as functionally essential charged amphipathic helices. For the current Phase II SBIR research, we have designed and chemically synthesized a 41 residue Super Mini‐B (S‐MB) peptide construct that emulates many of the in vitro and in vivo structural and functional properties of the 79 residue native protein. This S‐MB peptide has activity exceeding that of the promising 34 amino acid Mini‐B peptide studied in our completed Phase I SBIR and initial Phase II proposal (April, 2007). In the current application, S‐MB peptide is combined with synthetic lipids to generate two complementary fully‐synthetic exogenous lung surfactants (Minisurf™ and Minisurf‐R™) that have extremely high activity and commercial potential. Two types of synthetic lipids are
utilized to allow the production of these S‐MB surfactants: (i) a mix of synthetic lipids (L) modeled after those in native lung surfactant; and (ii) novel phospholipase‐resistant lipids (RL) synthesized to have enhanced surface properties as components in therapeutic surfactants plus reduced degradation in inflammatory lung injuries where lytic enzymes are present in increased concentrations in pulmonary tissue. In the current grant, we develop commercially viable production and quality‐control methods for S‐MB peptide and active synthetic L‐SMB
(Minisurf™) and RL‐S‐MB (Minisurf‐R™) surfactants for treating acute respiratory failure in the Neonatal Respiratory Distress Syndrome (NRDS), clinical Acute Lung Injury (ALI), and the Acute Respiratory Distress Syndrome (ARDS). Minisurf™ and Minisurf‐R™ surfactants can also potentially be used in novel pulmonary delivery systems for antibiotics, anti‐inflammatory agents, and genetic material. This Phase II SBIR proposal comprises Aims leading to the following key Milestones: 1) to define and establish process development activities required to produce commercially‐viable quantities of purified active S‐MB and; 2) to demonstrate that S‐MB peptide can be reproducibly formulated and quality‐controlled in final Minisurf™ and Minisurf‐R™ formulations that have significant potential advantages in production economy, surface activity, inhibition resistance, and physiological activity compared to current animal‐derived and synthetic surfactant drug products while exhibiting minimal toxicity.
Estimated Market: $500 million
Thermal Targeting of Drugs to Sites of Infection
Project Summary: The primary goal of this project is to conduct a series of studies aimed at establishing the proof of concept for a new approach to targeted delivery of antimicrobial agents to sites of infection. These studies will be specifically focused on demonstrating, for the first time, that novel nanoparticulate liposome formulations engineered to release their contents at well‐defined temperatures can be used to selectively deliver antimicrobial agents to sites of infection. The Company believes that the delivery of an antimicrobial agent by thermally sensitive liposomes to an infection site, where elevated temperatures have been shown to exist, will result in the immediate release of the antimicrobial compound at the infection site thus resulting in an enhanced therapeutic effect. To establish the viability of this approach, the Company has chosen Pseudomonas aeruginosa as a model pathogen because of its prevalence as one of the causes of hospital acquired infections. To test the concept, a model antibacterial drug, amikacin, will be formulated into thermally sensitive liposomes and tested in animal models of Pseudomonas infection.
Estimated Market: $1 billion