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Peter Wulff, President and CEO of Bavarian Nordic A/S will present today an update on the company’s business and development activities at the BIO CEO & Investor Conference in New York City. The following are excerpts from his presentation:
“Bavarian Nordic has achieved a leading competitive position in the development of IMVAMUNE™ as a safe smallpox vaccine. In 1999, Bavarian Nordic started to develop IMVAMUNE™ as a safe smallpox vaccine based on market analysis from the US and Europe. In contrast to many other companies, Bavarian Nordic viewed at that time and continues to view today that the biodefense market is like any other market. While customers may be different and the reason for purchasing vaccines may be different, one thing that is similar is that if you want to be a market leader you have to invest in your future. Bavarian Nordic has invested in its IMVAMUNE™ program since 1999, and only in 2003 did we start to receive governmental support. Our belief in the market and willingness to invest in our business is the reason why today we have strong clinical data package on IMVAMUNE™ making it by far the leading program for registration as a safe smallpox vaccine.
IMVAMUNE™ Global Clinical Development Programme
We have already completed 2 clinical studies in Europe, a Phase l study in 86 healthy volunteers and a Phase ll dose-finding study in 165 healthy volunteers. In addition we have 3 ongoing studies, a Phase l trial comparing IMVAMUNE™ to DryVax®, a Phase l study in patients with atopic disorders and a Phase ll study in HIV-infected patients. In the first two studies, enrolment and vaccination of patients has almost been completed.
Later this year, Bavarian Nordic will initiate 3 more Phase ll studies in 2000 subjects, including healthy volunteers and patients suffering from atopic disorders. One of the studies will be yet another trial comparing IMVAMUNE™ to DryVax®.
IMVAMUNE™ Protects Faster than Traditional Smallpox Vaccines
The current perception in smallpox vaccine protection is that traditional replicating smallpox vaccines induce protection a few days after vaccination while MVA vaccines are thought only to be effective after 2 vaccinations administered weeks apart. With that perception in mind, it is understandable then that traditional replicating vaccines have been considered for emergency use.
However, we at Bavarian Nordic have never shared that opinion simply because the biological mechanism behind traditional replicating smallpox vaccines takes time to build up in the body to a level where an immune response can be detected. Traditional replicating smallpox vaccines induce protection over a period of 10 to 14 days after vaccination. In contrast, a non-replicating MVA vaccine given at a higher injectable dose induces an immune response very quickly, with the added benefit that it is safer than the traditional smallpox vaccines.
Based on data from a number of our animal models and clinical trials, Bavarian Nordic expects IMVAMUNE™ to be effective and to protect against smallpox infection 3 days after JUST ONE vaccination while traditional replicating vaccines only show protection after 10 to 14 days.
In addition, our completed Phase II study showed that a single vaccination with IMVAMUNE™ resulted in a detectable immune response in 94% of the people vaccinated. This result is comparable to the historical rates for immune responses after vaccination with traditional smallpox vaccines.
The only current advantage then for using a traditional replicating smallpox vaccine would be the concept that long-term protection is induced after one vaccination. While the long-term protection induced by IMVAMUNE™ is still under investigation, conceivably two vaccinations may be necessary to induce similar long-term protection beyond 6 months. However, in an emergency situation this is irrelevant and does not change the fact that IMVAMUNE™ has shown in trials to be a safer vaccine with a faster-acting onset of action, offering protection against smallpox much earlier than traditional vaccines.
IMVAMUNE™ Commercial Production
Bavarian Nordic has several years of manufacturing experience with MVA-based vaccines, both in the production of recombinant MVA vaccines and IMVAMUNE™ for clinical trials. In addition, and more importantly, Bavarian Nordic has long-term experience with manufacturing vaccines on the primary Chicken Embryo Fibroblast cell culture method. In fact Bavarian Nordic has manufactured more than 80 million doses of Elstree-BN smallpox vaccine based on this cell culture method. IMVAMUNE is also produced on this cell culture method.
In the first half of 2004 Bavarian Nordic completed the optimisation of the manufacturing process for IMVAMUNE™ to industrial scale. From November 2004 to-date we have completed 12 out of 20 test-runs on the robustness of the commercial manufacturing process. Therefore, Bavarian Nordic can state with confidence, that the industrial scale manufacturing process in terms of vaccine yield, production output and process control is ready for commercial production.
At the Kvistgård facility in Denmark we are near completion of pre-production activities. Most all process equipment has been set up in the production building and all of the technical equipment (water, steam, ventilation, etc) is in operation. Validation of manufacturing at the Danish production facility will occur in the spring with production ready to start well before the award of RFP 3, expected later this year.
In addition, Bavarian Nordic has a global agreement with GlaxoSmithKline to produce IMVAMUNE™ which includes back-up manufacturing should it be necessary. Such an arrangement offers extra security to our international governmental customers.
HIV Vaccine Programmes
Bavarian Nordic is pursuing 3 vaccine strategies in HIV. The first approach, which is also the most technologically simple, is based upon a single HIV antigen (Nef)
The second path is much more technologically advanced. This approach is based upon the fact that T-cells in the body’s immune system are responsible for controlling the suppression of chronic viral infection. Bavarian Nordic, together with US-based biotech firm, Epimmune, has developed an MVA-BN® polyepitope vector expressing a large number of Helper T-cell epitopes and Killer T-cell epitopes in one vaccine construct.
The third approach is to use MVA-BN®’s capability to express a large number of heterologous genes. Bavarian Nordic has constructed an MVA-BN® vaccine expressing 8 full-length HIV antigens from the HIV clade B virus. This vaccine is being developed as a prophylactic HIV vaccine and is expected to have the potential to protect against all HIV clades.
HIV Vaccine Programmes – Clinical Development Status
A Phase I/II study with Bavarian Nordic’s MVA nef vaccine in HIV-infected patients on HAART therapy with CD4 counts down to 400 – the borderline of being immune-compromised - has shown that the vaccine was able to control HIV replication in 7 out of 14 patients for 11 months and still controls replication in 5 out of 14 patients for 34 months. During this time period all patients have remained off HAART therapy.
In other words, for almost 3 years these 5 HIV-infected patients have not had any other treatment or therapy other than 3 vaccinations of the MVA nef vaccine. Throughout the entire trial period, MVA nef has been able to control these 5 patients’ HIV infection.
Based upon this promising data, Bavarian Nordic has started a Phase II study in 75 patients with CD4 counts down to 250 of which 50 patients will receive the MVA nef vaccine and 25 patients will receive the IMVAMUNE™smallpox vaccine as a control arm for the study.
Moving to the MVA-BN® polytope vaccine programme, 3 studies are being planned for 2005. Two studies are planned in Europe and one here in the US with Epimmune to be financed by the NIAID (National Institute of Allergy and Infectious Diseases). The two Bavarian Nordic studies are a Phase l trial in healthy volunteers and a Phase l/ll trial in HIV-infected patients.
The MVA-BN® multiantigen vaccine to prevent HIV has been cloned and transferred to Bavarian Nordic’s pilot manufacturing facility in Berlin for production of the vaccine for clinical trials.
Cancer Immunotherapy
In 2002, Bavarian Nordic decided to close its cancer vaccine programme, including the MVA tyrosinase vector project for the treatment of melanoma, to focus all of the company’s resources on the accelerated development of the safe smallpox vaccine programme.
In the meantime, we have received particularly positive data from an earlier clinical trial in Italy which has now demonstrated that Bavarian Nordic’s MVA vector technology has the potential to break tolerance against cancer self-antigens. Breaking tolerance towards self-antigens is the single most important basis for the development of cancer vaccines. If you cannot break tolerance – you cannot develop a vaccine against cancer. Moreover, the data has shown that not only could the MVA-based vaccine break tolerance, but it could also raise a long-lasting immune response of significant magnitude for more than 1 year. These results have lead to our decision to re-enter cancer immunotherapy and the reason why Bavarian Nordic has established a subsidiary in California to develop cancer vaccines.
We have a number of cancer vaccines in development but our first project will be an MVA-BN®-based vaccine against breast cancer. The vaccine has already been constructed and ready for clinical production. The next programmes will be MVA-BN®-based vaccines for the treatment of prostate and colon cancers.
News Flow – 2005
Bavarian Nordic’s 2004 results will be published on the 3rd of March and in the early summer we will carry out a public offering to generate DKK 300 million (approximately USD 50 million) in new net capital.
We expect to publish important safety data from our IMVAMUNE™ clinical trials in high risk groups, such as HIV-infected patients and people suffering from atopic disorders. In addition, we will initiate clinical trials with IMVAMUNE™ in 2000 healthy volunteers and sufferers of atopic disorders to support an early registration of IMVAMUNE™.
We expect an RFP-lll award this year and to start industrial production of IMVAMUNE™ in the summer of 2005.
Finally we also expect interim data from our Phase ll clinical study with the MVA nef vaccine as a therapeutic HIV vaccine.”
The preceding are excerpts from Peter Wulff’s presentation at the BIO CEO & Investor Conference in New York City today. Due to the amount of market information in this presentation, the company has decided to issue this stock exchange release. A copy of the presentation will be made available tomorrow on the company’s website, www.bavarian-nordic.com.
Copenhagen, 24 February 2005
Asger Aamund
Chairman of the Board
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