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alphaHGA - A Completely Novel anti-HIV Mechanism
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alphaHGA, formally known as MetaboliteX (MetX), is a candidate drug against HIV. alphaHGA's anti-HIV mechanism is completely novel, as it inhibits the spread of the virus from the infected cell. Crystallisation of the virus's protective capsid structure is also prevented. The substance itself is also unique - in preclinical trials, it demonstrated numerous advantages in areas where other extant HIV drugs often have serious drawbacks.
alphaHGA's key advantages are, so far, that it is demonstrably effective against all strains of HIV tested, including those that have developed resistance to other HIV drugs. It has also proved impossible to provoke resistance to alphaHGA, which has been developed from GPG during four years of ongoing in-vitro tests, and typically, inducing resistance to all approved HIV drugs is relatively easy. Previous studies of GPG on laboratory animals indicate that alphaHGA is also tolerated extremely well.
New ways of attacking the HIV virus are essential, since currently available HIV and AIDS drugs appear to be fighting a losing battle. HIV has an outstanding ability to develop resistance, and hence, to circumvent the inhibitors that stand in its way, as indeed, has happened to every known HIV drug so far. Almost half the people infected in Tripep's primary markets North America and Europe already have multiresistant viruses. Potential medicines currently being developed, and in clinical trial phases, are relatively susceptible to resistance development.
An analytical method for alphaHGA is now being developed, and provided that positive results are achieved in the complementary preclinical trials and uptake studies on healthy volunteers (phase I), plans to start clinical phase II trials are in place. These trials will be conducted in-house or in collaboration with a partner, and have a simpler objective and a more readily analysed patient group than the CTN002 study previously performed. The phase II patients will not have been previously treated for HIV. The aim is to determine whether alphaHGA affects the replication of HIV in humans as has been demonstrated in in vitro trials, rather than determining the optimal administration/dosage. If this is attained, Tripep will have excellent chances of entering a strategic development agreement for onward development.
Tripep: Microdosing study shows that alphaHGA is complete...
2004-07-21 08:03:36
Tripep Microdosing study shows that alphaHGA is completely bioavailable by the oral route
Tripep AB, the Swedish biotechnology company focusing on HIV therapy, is pleased to report that, following a microdosing study performed by Pharmaceutical Profiles Ltd in Nottingham, UK, alphaHGA is orally bioavailable in humans. Moreover, the study also showed that alphaHGA has good kinetic properties.
Tripep previously announced the discovery of alphaHGA, a new candidate drug against HIV, which has a totally new mode of action as it is the first substance in an entirely new class of compounds against HIV.
In collaboration with Pharmaceutical Profiles Ltd (a Clinical Research
Organisation based in Nottingham, UK), Tripep has tested the oral
bioavailability and plasma pharmacokinetics on human volunteers using 14C labelled alphaHGA. The results showed that alphaHGA was quickly and completely absorbed into the blood after oral administration. The terminal half-life in plasma was approximately 10 hours. The main route of elimination was by urine.
Professor Anders Vahlne, acting CEO and Head of Research at Tripep,
commented:
These results are very encouraging for the future drug development work on alphaHGA. Phase I/II studies in HIV infected individuals are expected to start later this year or early next year, following successful
completion of safety studies in animals.
As previously indicated to the market, Tripep intends to evaluate the
feasibility of an AIM listing ahead of phase I/II trials and has
appointed NCB Stockbrokers, an official AIM sponsor, in this regard.
Tripep starts first clinical placebo controlled phase I/II study of alphaHGA in HIV-positive patients
Tripep today confirmed that it has received all necessary approvals from the Thai authorities in order to commence the company's first phase I/II study of alphaHGA.
alphaHGA has a novel, unique mode of action against HIV and has in the preclinical setting displayed effect on both regular HIV-strains as well as HIV-strains multiresistant to other HIV drugs.
The study is planned to commence within the next two weeks and will be conducted at the Ramathibodi Hospital, which is associated with Mahidol University in Bangkok. The study will be monitored by a well renowned international CRO company, and will be conducted according to international standards, i.e. GCP (Good Clinical Practice). The purpose of the study is to compare the tolerability and safety of alphaHGA at different dose levels. In the study each group of patients is treated (12 with active substance and 4 with placebo) for four weeks and is then followed for another four weeks. The study is designed as a double blind study which means that neither the physician nor the patient knows if the patient receives the active substance or placebo. The screening of patients for the first treatment group has been done and this group of patients will start their treatment within the next two weeks. After the first group of patients have been treated a safety evaluation will be performed, and then the other groups of patients will be initiated. Importantly, the trial will be performed on HIV-positive patients providing efficacy data for alphaHGA in HIV.
Tripep estimates that the result of the study will be available during the second quarter of 2006.
"Starting this study means that we now for the first time will get information on the effect of alphaHGA, which has a unique mode of action in comparison with existing HIV drugs, in HIV-positive individuals. If we get a positive result it will be a very important step towards commercialisation of alphaHGA" says Tripep's CEO Jan Nilsson.
For more information, please contact:
Rolf Nordström, Chairman, Tripep AB
Tel: +44 20 7839 8686, mobile phone: +44 7776 137 400
E-mail: rolf.l.nordstrom@btinternet.com
Anders Vahlne, CEO and Head of Research, Tripep AB
Tel: +46 35 31755, mobile phone: +46 709-28 05 28
E-mail: anders.vahlne@labmed.ki.se
Conor McCarthy, NCB, Dublin, Ireland
Tel: +353 1 611 5989, mobile phone: +353 87 290 0409
E-mail: conor.mccarthy@ncb.ie
Lisa Baderoon, Buchanan Communications
Tel: + 44 20 7466 5000, mobile phone: +44 7721 413 496
E-mail: lisab@buchanan.uk.com
Notes to Editors:
Tripep AB is a Swedish biotechnology research company that develops and commercialises candidate drugs based on patented technologies. Its main focuses are:
- research and development of an HIV-inhibiting drug,
- preclinical research focusing on the development of therapeutic and
prophylactic vaccines against HIV and Hepatitis C, and
- the RAS technology platform.
For more details of the company´s technologies, please refer to the
company´s web site at http://www.tripep.se
29 Jun 2005
New drug candidate against HIV developed
As a part of a research collaboration, scientists at the Sahlgrenska Academy at Göteborg University, Sweden, have developed a new drug candidate against HIV-infection. The new substance, named alphaHGA, will be tested on patients this year. In a thesis from the Sahlgrenska Academy, parts of the research essential for the performance of the clinical trial are presented.
At the end of 2004, approximately 40 million people were living with HIV-infection, most of them in southern Africa. Annually, approximately three million people die from the infection, many of them young. Despite huge efforts, there has been no success in developing a vaccine against HIV. However, a number of drugs are used for treatment of HIV-infected individuals. The drugs cannot cure an infected person, but can slow down the disease progression. There are about 20 drugs commercially available, but since the virus can develop resistance and since the drugs are associated with side effects, there is a need for new, safer drugs.
Elin Andersson, M.Sc, presents in her thesis studies showing that the compound GPG-NH2 inhibits HIV in culture.
"GPG-NH2 inhibited the virus by a new mechanism of action. The molecule prevented the virus from forming the correct structure, and was therefore active against HIV resistant to currently available drugs" says Elin Andersson.
She also showed that in culture, HIV developed resistance to drugs used on patients today, but not to GPG-NH2. GPG-NH2 was tested on HIV-infected patients in 2001. The effect on HIV showed in culture could however not be reproduced in patients. Elin Andersson and the other scientists have now shown that GPG-NH2 in itself did not inhibit the virus. Instead, it needed to be degraded and one of the products from degradation, a so-called metabolite, was the actual active compound. The metabolite was produced by enzymatic degradation in the viral cultures. This degradation of GPG-NH2 to the active metabolite, named alphaHGA, occurs in two steps by two different enzymes present in the medium used in the viral cultures.
In her thesis, Elin Andersson has identified the first of the two enzymes, which is present in human blood. The reason for the failure of GPG-NH2 to inhibit HIV in patients was that the second enzyme needed for activation of the compound to alphaHGA is not present in human blood.
Besides the Sahlgrenska Academy, Karolinska Institutet and Uppsala University in Sweden and the Rega Institute in Belgium are part of the research collaboration. As previously reported by the biotech-company Tripep AB, the new compound alphaHGA will be tested on HIV-infected patients this year.
Pharmaceutical Profiles Completes Human Microdosing Study
29 Jul 2004
Phase 0 / I / IIa clinical development specialist Pharmaceutical Profiles reports the completion of a microdosing study and believes it is the start of a new era in drug development in which human ADME (absorption, distribution, metabolism and excretion) data plays an increasing role in candidate selection or deselection.
The study was carried out for Tripep AB (Huddinge, Sweden), a biotech research company that develops and commercializes candidate drugs based on patented and patent-pending technologies. Tripep is active in several areas, including the research and development of alphaHGA, an HIV-inhibiting drug and it is in this field of research that the microdosing study was utilized.
The sophisticated human microdosing study took less than six months from inception to completion and examined the pharmacokinetics (PK) of the HIV inhibiting molecule in healthy subjects, following dosing with sub-pharmacological, microgram quantities of drug candidate. The microdosing approach has provided Tripep with pivotal early human PK data on the performance of their candidate drug much more quickly and accurately than would have been possible using conventional development strategies. Encouragingly for the development of alphaHGA, the microdose study has shown 100% oral bioavailability for the candidate allowing fast-tracking of the molecule into 'proof-of-concept' studies with an enhanced chance of success and significantly reduced risk.
Tripep's Dr Anders Vahlne, acting CEO and Head of Research, is in no doubt of the benefits of a microdosing study at this stage of development of the peptide, explaining: "The results were very encouraging for the future development work on alphaHGA and helps us design the clinical study on HIV infected individuals expected to start by the end of this year or early next year."
Through its 'cutting-edge' human microdosing service, Pharmaceutical Profiles is combining its own early clinical development capabilities and expertise with ultra-sensitive accelerator mass spectrometry (AMS). "Microdosing studies provide a 'smarter' way to develop drugs by providing very early human data," explained Dr Ian Wilding, Executive Chairman of Pharmaceutical Profiles.
"Tripep utilized the microdosing study approach and now they have early human data they can clearly see the benefits of undertaking a microdosing study early in the development of their alphaHGA product. Many other biotechs and major pharmaceutical companies are actively discussing human microdosing studies with Pharmaceutical Profiles. We believe these studies will create a much greater understanding and awareness of the importance of PK and ADME issues in early phase drug development. Up to 40% of new drugs currently 'fail' during Phase I trials and human microdosing offers the promise of selecting the best drug candidates before advancing into full development, thereby increasing the chance of success."
AMS is one of the most precise bioanalytical approaches currently available - up to 100,000 times more sensitive than LC-MS/MS and 1,000,000 times more sensitive than liquid scintillation counting (LSC). A key biomedical application of AMS technology is in the area of human microdosing (also known as 'human Phase 0') studies. In these studies, one or more drug candidates is administered to humans in single, sub-pharmacological (microgram) levels to obtain early PK and ADME data in order to select the candidate with the optimal PK characteristics. Microdosing studies have been endorsed by the EMEA, who have determined that a microdose is 100 times below the level calculated to yield a pharmacological effect or 100 micrograms, whichever is the lower. Human microdosing studies provide the opportunity to terminate drug development programmes early, thus allowing improved compound selection and reduced attrition rates in early clinical development.
For further information, please contact:
Richard Gee
+44 (0)115 950 8399
enquiries@gbcspr.com
Paul Clewlow
+44 (0)115 974 9000
paul.clewlow@pharmprofiles.co.uk
Hepatitis C Vaccine Research
Today Tripep has acquired a patent related to the therapeutic vaccine ChronVac-C . The patent covers the ChronVac-C gene and its use in vaccines together with ribavirine. Furthermore, Tripep has acquired the commercial rights for a transgenic mouse model developed in collaboration with scientists at the Karolinska Institute. The mouse model, which is a spin off to the ChronVac-C -project, can be used for the development of new drugs, as well as, therapeutic vaccines against hepatitis C. The liver of the mouse produces the ChronVac-C gene product which corresponds to the Hepatitis C virus-enzyme protease. "Our new patent validates the ChronVac-C project. We are also happy to have acquired the animal model, which will be used in the further development of this project. In addition, Tripep will approach pharmaceutical companies for commercialisation of this unique animal model. This might well be the first product to be commercialised by Tripep. This, in it's own right, would be an important step for Tripep" says Tripep's CEO Jan Nilsson. Last year, Tripep announced the identification of two active analogues (chemical variants) of alphaHGA. The Company now can report on yet another active analogue to alphaHGA. "This third alphaHGA analogue further strengthens our patent position regarding alphaHGA and shows that we are able to broaden the family of substances belonging to this entirely new class of anti HIV drugs" adds Tripep's CEO Jan Nilsson. For more information, please contact: Jan Nilsson, CEO, Tripep AB Tel: +46 8 449 84 80, mobile phone: +46 70 466 31 63 E-mail: jan.nilsson@tripep.se Anders Vahlne, Head of Research, Tripep AB Tel: +46 8 5858 1313, mobile phone: +46 709 28 05 28 E-mail: anders.vahlne@labmed.ki.se
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