bio in ve n t a n n ua l r ep o rt 2 00 6
Annual Report
2006
2006
2006
Contents
BioInvent in brief 2 Comments by the CEO 4 Our Strategy and Business 6
The Innovation Gap – Significant Need for New Drugs 8 BioInvent’s Pipeline 12
Project BI-204: 13 Project TB-402: 16 Project TB-403: 18 Research Portfolio 20
Technology Platform and Patents 22 Risks and Risk Management 26 Directors’ Report 28
Income Statements 33 Balance Sheets 34 Cash Flow Statements 36
Change in Shareholders’ Equity 37
Accounting Principles and Information in Notes 38 Audit Report 49
The BioInvent Share 50 Five-year Review 52 The Board and Auditors 54 Senior Management 54 Glossary 56
Annual Shareholders’ Meeting 58
Financial calendar
BioInvent will present the following financial reports:
Interim reports – 12 April, 12 July, 17 October 2007 Financial Statement 2007 – 14 February 2008
Investor Relations
Svein Mathisen, President and CEO,
+46 (0)46 286 85 50, mobile: +46 (0)708 97 82 13 BioInvent’s financial reports are also available at www.bioinvent.com
Legal disclaimer
This annual report contains statements about the future consisting of subjective assumptions and fore- casts for future scenarios. Predictions for the future only apply as of the date they are made and by their very nature, in the same way as research and develop- ment work in the biotech segment, are associated with risk and uncertainty. With this in mind, the actual outcome may deviate significantly from the scenarios described in this annual report.
operations
BioInvent is a research-based pharmaceutical company that discovers and develops therapeutic antibodies – a strongly growing segment in the pharmaceutical market. Through its strong technology platform and in just a short space of time, BioInvent has developed a portfolio of innova- tive projects in clinical and late preclinical development phase. Having strong development partners is a priority for the Company: one of the projects is being developed in cooperation with the leading US biotech company Genentech, and two other projects are being developed with the Belgian biotech company ThromboGenics, which specializes in vascular diseases.
BioInvent is located in the Ideon Science Park in Lund and has 96 employees. BioInvent has been listed on the Nordic Stock Exchange since June 2001.
Focus on antibody drugs
Antibodies are a vital part of the immune system and constitute one of the human body’s most important defense mechanisms against disease. Treating the patient with artificial antibodies can specifically and effectively impact many diseases.
Antibody drugs are already a powerful and established treatment alter- native for many diseases. Up to now, 18 products have been registered and approved. In 2006 they accounted for sales of almost USD 18 billion, com- pared with USD 12 billion the year before. Also, more than one hundred antibody drugs are at the clinical development stage, and this is expected to further increase the significance of antibodies as treatment options.
BioInvent has developed a powerful technology platform for discovery, development, and production of human antibodies. The n-CoDeR
®anti- body library is the source of the Company’s drug candidates.
As an important complement to the library, the Company has decided to develop its own processes and manufacturing capacity. This gives BioInvent maximum control and flexibility in the individual projects, and increases the Company’s chances of effectively advancing projects in the value chain.
Broad project portfolio increases the chance of success
BioInvent is currently involved with innovative development projects in thrombosis, atherosclerosis, and cancer. All of the drug projects focus on disease areas with significant medical need for new treatment options.
The Company’s strategy is to develop a broad portfolio of drug candidates to spread the risk and opportunities over several projects.
Value generation
BioInvent develops antibody-based drugs from the early discovery phase and proceeds to show their efficacy in humans in clinical trials. The Company has a broad product portfolio. Some projects can be sold early during development, while others can be developed all the way to sales through the Company’s own sales channels. This strategy reduces business risk and can be adapted to market and company-specific conditions. At the same time the right conditions are created to take maximum advantage of value growth in successful projects. The Company’s potential for ful- filling this strategy is supported by its ability to attract strong partners.
bioinvent
in brief
3
aDvanCes During tHe past year
BI-204: Agreement with Genentech
A collaboration was initiated in January 2007 with Genentech, Inc., for development and commercialization of the Company’s product candidate BI-204. BioInvent received the first partial payment of SEK 105.5 million for this collaboration in January. In addition BioInvent can receive milestone payments of up to about SEK 1.2 billion, as well as royalties on sales in North America. BioInvent retained the rights in the rest of the world for this product, which in preclinical studies showed promising characteris- tics for preventing and limiting the atherosclerotic process.
TB-402: Clinical trials initiated
Clinical trials of the product candidate TB-402 for preven- tion of thrombosis began in February 2007.
TB-403: EU grant accelerates development
The product candidate TB-403 received a development grant of SEK 18 million from the EU.
Significant advances in research portfolio
During the year BioInvent made considerable advances
in the research portfolio, providing good grounds for
selecting new product candidates.
candidates into clinical phase. I have high hopes that we will con- tinue to expand our clinical development activities over the year.
Equally important is the expansion of our portfolio with new drug projects. We are still analyzing target proteins, which are linked to disease processes and which are appropriate for treatment with antibodies, with undiminished strength. In the future, recruiting such target proteins from external research groups will also be an important element of our strategy. As we advance our positions in the value chain, we also deepen our knowledge in individual therapy areas, which in turn could lead to our own innovations and ideas that could serve as cornerstones for new drug projects. For example, in the field of oncology we are conducting projects in the research phase that are based on our own research findings.
Another possibility for expanding the portfolio is to acquire drug projects, which are already in clinical phase, or on the way there in the not too distant future. This strategy would move the time element in our portfolio forward, at the same time that it would generate momentum throughout our organization.
However, we must remember that attractive projects with good potential for the future are usually accompanied by a high price.
Our collaboration with ThromboGenics is an example of another method of broadening our project portfolio. Our two companies’ skills complement each other and create a good com- bination, which also drives us forward in the clinical process.
The fact that we recently initiated clinical trials in our joint thrombosis project is evidence that our partnership has been successful. I believe that the same model for collaboration could be repeated with other partners and other projects.
Obviously the addition of new projects and the resources they require must be considered in light of the needs of current projects and the investments that will be necessary down the road. BioInvent has also always considered it to be important to find an optimal balance between total investment needs for research and development on the one hand, and short- and long-term revenues on the other. We have shown through our development assignments that we can create a steady revenue flow from our technology platform. It is gratifying that reve- nues from this operation have climbed significantly in 2006 compared with the previous year. This success makes it easier for the Company to develop and strategically control im- portant technologies and resources without any financial burden to the Company.
Through the agreement with Genentech we have demon- strated our ability to create revenues and value in innovative drug projects, even though they are still in a relatively early phase of development. All of our projects represent new approaches to fill major important medical needs, which is crucial if the projects are to be able to attract potential part- ners, and to be able to price them in such a way that we can enjoy the benefits of their commercial success.
In conclusion I would like to thank our personnel for their efforts during a successful year.
Svein Mathisen
President and CEO BioInvent BioInvent’s collaboration agreement with US pharmaceutical
company Genentech was probably the most important event of the past year. Although notification that we would work together to develop an antibody-based drug for cardiovascular disease came a few days into the new year, the collaboration was the culmination of lengthy preparations.
In our 2005 annual report I stressed that one of our most important duties during the coming year was to try to initiate alliances with respect to some of our drug candidates. Our atherosclerosis drug candidate was selected as a project for which the need for a partner would become apparent even before initiating clinical trials.
That is what happened and to our great pleasure, in the end we signed a far-reaching collaboration agreement with Genentech. Genentech is an ideal partner. The company has documented experience of taking new innovative antibody projects to market. This experience will now also benefit BI-204. I am convinced that through this agreement we have provided the best possible conditions for BI-204 to develop into a commercially successful product.
Because we retained the rights for the product outside North America, we will increase our share of future value generation as the project progresses through development, creating conditions for significant revenues through new business in the future. The collaboration with Genentech for further development of BI-204 also provides the opportunity to move forward at a speed that would have been difficult without the agreement.
This agreement therefore comprises an important step in BioInvent’s development into a commercial and product- focused company. At the same time, the agreement means that we have shared the risk and that we have ensured our strong influence over continued development. Retaining the rights for a large part of the global market also gives us maximum flexibility for the future.
For BioInvent the agreement also represents a stamp of quality on the operation that we have built. It is a compliment to our technology when a company with Genentech’s accomp- lishments in antibody development chooses to invest in one of our antibody projects. It also compliments our organization and our expertise, at the same time that the agreement con- firms BioInvent’s ability to identify and initiate new innova- tive drug projects.
However, we will keep in mind the fact that partnership with Genentech only involves one of our projects, albeit an important one. Our main challenge is still to enhance our project portfolio by including new research and development projects. It is also crucial that we are able to drive the projects forward in the development chain.
We still have an early project portfolio measured in clinical terms, which makes us vulnerable because the probability of set- backs is greater in the early development phase. Unfortunately we experienced this when our HIV project ran into setbacks in clinical trials, though we are still hopeful that with a new formulation the project will finally become successful.
During the year we will therefore work hard to bring our drug
Comments by tHe Ceo
The collaboration agree-
ment with Genentech
enables BioInvent to
increase its share of future
value generation in the
development of BI-204.
bioinvent 2006 l strategi/affärs-/intäktsmodell
our strategy anD business
BioInvent develops innovative antibody-based drugs for areas in which there is significant medical need. We build value by pursuing the projects until we can demonstrate biological effects, preferably in humans. We work with partners to continue development and achieve commercialization. This strategy enables the Company to maintain a broad product port- folio, which reduces risk and allows a more constant and earlier revenue flow.
BioInvent’s place in the value chain
BioInvent focuses on discovery and development of therapeutic antibodies and documents their biological activity and effect in early clinical trials. In order to bring product candidates through late development to full commercialization, the Company collaborates with large pharmaceutical companies.
The timing for such collaboration is determined by cost, risk, competence requirements and the value that could be gained if BioInvent completes an additional step in the process. The strategic purpose of the agreements is to ensure that the projects receive the necessary expertise and resources without BioInvent tying up too many resources in any individual project.
In order to maximize the Company’s potential to benefit from total value generation, it will try to retain market rights in individual geographic markets, where the Company con- siders it feasible to establish a competitive marketing and sales organization. In those cases in which the BioInvent’s produc- tion capacity is adapted to needs it will also retain production rights for the clinical program, as well as for production of the commercial product. Ensuring active participation in the projects is the best way to protect the Company’s interests.
Broad portfolio
In just a short time BioInvent has put together an innovative and broad portfolio of drug projects. This portfolio is being broadened and expanded to give BioInvent more opportunities for successful development of new products, thereby increasing the likelihood of commercial success. In this way the Company avoids becoming too dependent on the success of any one individual project. The capacity that the established technology platform provides is a good foundation for further expansion of the portfolio.
Each project is based on a target protein that is linked to
disease progression. Four criteria are important when choosing
these target proteins: large market potential, strong patent
protection, high level of innovation, and the target protein’s
biology must be suitable for treatment with antibodies. So far
BioInvent has mainly recruited projects through alliances with
external research groups, either in academic environments or
within the industry. These research groups provide not only
target proteins, but also significant biological and medical
expertise within their indication areas. They also contribute to
a large extent with relevant in vitro and in vivo models to test
the selected product candidates. This strategy has enabled the
Company to build up a portfolio of projects spanning several
medical disciplines.
our strategy anD business
business ConCept, goal anD strategies
Complementary business in the form
of development assignments
As a partner and supplier, BioInvent has been able to build the technology platform that the Company is now using to generate value in proprietary projects. The Company’s port- folio of proprietary projects will continue to be supplemented by development assignments on behalf of partners. Such assign- ments generate revenue that counterbalances a portion of the risk associated with BioInvent’s development of proprietary drugs.
Revenue model
BioInvent’s business model generates revenues as follows:
• From a development partner who buys into the Company’s proprietary projects. These revenue flows are expected to include:
– cash payment when the agreement is signed – R&D milestone payments, which means payments
when projects pass preset milestones. The number of milestones increases the earlier in the development process that the agreement is signed and the larger the portion of the payment falls due in the late stages of the project
– payment for manufacturing the product for clinical programs and commercial products, if any
– royalties involving a percentage of sales of the end- product
– revenues from sales of the product in those markets in which the company has retained market rights.
• From customers for whom BioInvent conducts develop- ment projects.
Up until the collaboration agreement with Genentech, BioInvent’s revenues have come from development projects.
With the partnership strategy and the role in the value chain that BioInvent aspires to achieve, with time it expects proprie- tary projects to be the predominant source of revenue. Over time, BioInvent intends to achieve a balanced cash flow through cash payments, milestone payments, and production for clinical programs within the Company’s proprietary projects, combined with revenue flows from development assignments. Long-term profitability is ensured through royalties and revenues from own sales in selected markets, as well as payment for commercial production in any projects that successfully reach the market.
Our business concept BioInvent develops innovative anti- body drugs to treat diseases where there is a significant medical need.
Our goal
To generate value by building a sustainable portfolio of clinical deve- lopment projects and over time, successfully launching several innova- tive drugs.
Our strategy
l to commercialize product candidates in cooperation with partners
l to retain market rights in individual geographic markets, where the Company considers it to be feasible to establish a competitive marketing and sales organization
l to retain production rights for clinical programs and for manufacturing commercial products in cases where the Company’s production capacity meets the need
l to broaden and expand the portfolio to include projects that provide us with more opportunities to create successful products and thereby in- crease the likelihood of commercial success for the Company as a whole
l to gain access to innovative target proteins and/or projects from exter- nal research groups and to develop unique medical concepts through our technology platform.
Our business is characterized by
l revenues from cooperation agree- ments linked to our own drug projects in the form of license fees, milestone payments, ongoing com- pensation for manufactured products, and royalties on the final sale of products, as well as from our own sales. Customer projects also gene- rate revenues
l sustainable profitability, expected to be achieved the day one of our pro- jects reaches the market. Profits may be reported in certain years before this point, when significant break- throughs are made in one of our projects.
Developing new medications is a lengthy and expensive process.
Development costs for the average biotech product have been estimated at USD 1.2 billion – almost SEK 10 billion (Tufts Center for the Study of Drug Development, 2006), and it often takes over ten years to take a project from idea to product, approved for sale on the market. At the same time the risk of setbacks is substantial during the process – historical data show that only one of ten drug candidates tested in humans ever become a commercially sold product.
Pharmaceutical companies’ aggregate costs for developing drugs have also risen sharply over a long period of time (Figure 1). It is therefore not surprising that the pharmaceutical indus- try is one of the industries that dedicate the most resources to research and development, 15–20 percent of sales revenues, which is extremely high even compared with other knowledge- intensive industries. But despite this intensive investment in in-house research, pharmaceutical companies have had a hard time discovering innovations that lead to new products. The number of products launched annually has been relatively constant over the past few decades, but has actually fallen sharply over the last decade (Figure 1). At the same time patent protec- tion is expiring for several of the major drug companies’ best- sellers (“blockbusters”), which means that the companies are at risk of declining growth in the future. Analysts are discuss- ing an innovation or productivity gap in the industry – few new drugs are launched despite increased investments, at the same time that significant medical needs are waiting for a solution.
tHe innovation gap – signifiCant neeD for new Drugs
There is a shortage of new drug pro- jects in the market, as can be seen in the increasing competition even for early drug programs. At the same time the price of innovative projects is rising. BioInvent is well positioned to meet this need from large biotech and pharmaceutical companies.
0 10 20 30 40 50 60
86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04
45 40 35 30 25 20 15 10 5 0
Number of new approved medications Global cost R&D (USD billion)
Number of new approved medications per year
Innovation gap
Total cost of research and development (R&D)
Figure 1. Sharply rising development costs have not resulted in an increased number of new drug launches (Datamonitor 2006).
Market dynamics – Rising prices for early projects
Because of the lack of financially viable in-house projects capable of reaching the market, it is becoming increasingly common for large firms to look for projects to license (Figure 2). These projects have often been developed by relatively small biotech companies specializing in early drug develop- ment. The demand for external projects has therefore in- creased and companies are paying more for these projects now than in the past. Both the number of deals and their average value are rising (BioCentury, 2005; Datamonitor 2006).
Another consequence, which has become more apparent over the past one to two years, is that to a greater extent, large companies tend to look for licensing opportunities among early projects, including projects in preclinical development, prior to the required clinical trials in humans (Datamonitor 2006). Over the past five-years the average cost of an early project has increased from about USD 20 million to USD 75 million (Figure 3). However, it should be noted that such figures are difficult to compare, since the agreement structure has a major impact on the total deal value. However, the evidence indicates that deal values have increased sharply.
In recent years firms traditionally described as biotech compa- nies have also begun to reach the marketing phase of their products. US enterprises are years ahead of their European counterparts in this regard. Large biotech companies such as Amgen, Genentech, and Gilead currently market several best- sellers, and their present market capitalizations are on a par
tHe innovation gap – signifiCant neeD for new Drugs
with the biggest pharmaceutical companies. The growth of these companies is also significantly more robust, with annual increases of 20 to 40 percent, compared with 5 to 15% for pharmaceutical companies, and the companies are character- ized by a strong research profile. The major biotech companies have also been successful at licensing in products and a grow- ing percentage of these licensing agreements are between bio- tech enterprises, rather than between biotech enterprises and pharmaceutical companies (Recap 2006).
BioInvent is extremely well positioned to meet the need for new drug projects from the pharmaceutical industry
BioInvent is a biotech enterprise with a broad technology platform for developing antibody-based drugs. Combined with efficient preclinical development, years of experience of antibody production, and its own clinical development department, the company is well-positioned to develop thera- peutic antibodies, a rapidly growing category of drugs in the market. Antibody-based drugs have become successful for many reasons. They represent a large value for the firms that developed them.
Antibodies are nature’s own defense molecules
Antibodies are optimized through evolution to recognize and eliminate foreign or harmful substances as effectively as possible. Antibodies are highly selective, and in their natural
0 10 20 30 40 50 60 70 80 90 100
2000 2001 2002 2003 2004
Figure 2. Number of in-licensed products by the top 20 pharmaceutical companies (Datamonitor, 2006)
0 10 20 30 40 50 60 70 80
1991-93 1994-96 1997-99 2000-02 2003-05 Figure 3. Average payment in USD million for drug projects in preclinical phase (1991–2005)
(Recap, 2006)
10
form extremely well tolerated by the body. This means that the activity can be expected to be more predictable, with a lower risk of undesirable side effects than in conventional drugs.
Antibodies allow faster development at a lower cost
Development time for antibodies is shorter than for traditional drugs, especially in the preclinical phase. The time from concept to clinical development has been estimated at only 40 percent of the time necessary for traditional small-molecule drugs (SCRIP 2002). Costs are also significantly lower; SCRIP (2002) indicates that the preclinical development cost of a typical antibody-based drug is USD two million, while a traditional small-molecule drug costs ten times as much. The reason is that conventional drugs require expensive optimiza- tion and usually more demanding toxicological studies. It is therefore more difficult to find a drug candidate with the desired characteristics.
Antibody-based drugs Increase likelihood of success
BioInvent’s antibodies come from the body’s own defense system and are extremely specific, improving the likelihood of success in toxicological and early clinical trials, during which side effects and the medication’s metabolism in the body are investigated. Antibodies have a natural biological function and therefore the mechanisms of action are usually easier to anticipate than for traditional drugs, which may explain why the risk of unexpected setbacks also seems to be lower in later clinical development phases. Statistics of previously conducted clinical trials show that antibodies and other biologics are up to three times more likely to reach the market than chemical molecules (CMR International – R&D Factbook 2004).
Antibody-based drugs are unique
Commercial therapeutic antibodies are usually monoclonal;
in other words, all produced molecules are identical to each other and have the same properties. But since they are bio- logical products and are produced from living cells they are difficult to copy. It can therefore be expected that antibody- based drugs will have a longer life cycle, with less competition from enterprises that produce copies of medications after patent expiry.
An eventful year
The past year has been eventful in the biotech sector in general, especially for antibody companies. Many significant licensing deals have been carried out, along with several acquisitions of antibody companies with products under development and innovative technologies. According to PharmaDeal’s database, 159 agreements were signed involving antibody products in 2006, indicating that therapeutic antibodies may be the commercially most interesting category among biotech products. For example, in mid-December the Danish antibody specialist Genmab licensed out an antibody in late clinical phase for treatment of cancer to the British pharmaceutical company GlaxoSmithKline (GSK) for more than USD 450 million in up-front payment and equity, plus potential future payments totaling USD 1600 million. This product deal is the biggest ever in terms of value in the pharmaceutical industry. Genentech was also involved in a major transaction in late December, when it licensed the rights to another cancer antibody in clinical phase II from US-based Seattle Genetics, where the total amount could reach USD 800 million. Just a few days later, BioInvent and Genentech announced their agreement, concluding a hectic licensing year for the major US biotech company, which was involved in six large licensing agreements.
Several antibody companies were acquired during the year.
One category involved firms with products in or close to the market, such as Genentech’s acquisition of Tanox for over USD 900 million, and Novartis’ acquisition of British NeuTec for USD 560 million. One important deal was when AstraZeneca acquired British CAT last summer for over USD 1 billion.
CAT was one of the pioneers in phage display technology and had several products in clinical trials. Another company, Domantis, with a strong technology for detection of a special type of antibody-based drugs, but no product in clinical develop- ment, was also acquired during the year. The buyer was GSK and the price tag over USD 450 million. A third category involves antibody companies, with technologies that can im- prove characteristics of drug candidates. Merck bought two such technology companies – Abmaxis and GlycoFi.
A table of major deals in the antibody market during the
past year can be seen on the next page.
11
Major commercial deals during the past year involving antibody products, companies, or technologies (source: PharmaDeals)
Date Company Partner company Type of deal
Total value excluding royalties (USD million)
Up-front payment (USD million)
Equity (USD million)
Total milestone payments
(USD million) Product status Jan.
2007
BioInvent International AB
Genentech, Inc. Product license – North America, R&D collaboration
190 15 175 Preclinical
Jan.
2007
Seattle Genetics, Inc.
Genentech, Inc. Product license, development cooperation,
860 60 800 Clinical
phase 2
Jan.
2007
Ablynx NV Boehringer Ingelheim GmbH
Product license, R&D collaboration
265 Research
phase
Dec.
2006
Genmab AS GlaxoSmithKline plc Development cooperation, sales alliance, product license
2,100 102 357 1600 Clinical
phase 3
Dec.
2006
Domantis Ltd GlaxoSmithKline plc Corporate acquisition 454 Preclinical
Dec.
2006
AC Immune Ltd Genentech, Inc. Product license, R&D collaboration
300 Preclinical
Nov.
2006
Tanox, Inc. Genentech, Inc. Corporate acquisition 919 Marketed
product, clinical phase 2
Nov.
2006
Ablynx NV Wyeth Pharmaceuticals Product license, R&D collaboration,
212 Research
phase
Nov.
2006
XOMA Ltd Takeda
Pharmaceutical Co. Ltd
Multi-product collaboration, R&D collaboration, production
100 Research
phase
June 2006
NeuTec Pharma plc
Novartis AG Corporate acquisition 569 Registration
phase, clinical phase 3
May 2006
Cambridge Antibody Technology plc
AstraZeneca plc Corporate acquisition 1074 Marketed
product, clinical phase 2, clinical phase 1
May 2006
Immunomedics, Inc. UCB Group Product license, development cooperation
203 38 20 145 Clinical phase
3
May 2006
Abmaxis, Inc. Merck & Co., Inc. Corporate acquisition 80
May 2006
GlycoFi, Inc. Merck & Co., Inc. Corporate acquisition 400
Mar.
2006
Argos Therapeutics
Novo Nordisk AS Product license, technology collaboration
69 Research
phase
Jan.
2006
Trubion Pharma- ceuticals, Inc.
Wyeth Pharmaceuticals Development cooperation, sales alliance,
R&D collaboration,
800 40 760 Clinical phase
2
12
bioinvent pipeline – aDvanCing to CliniCal pHase witH strong partners
Clinical phase I/II Clinical phase III Registration &
launch Discovery of
target protein Preclinical
research Preclinical
development
Completed Ongoing
Development projects Thrombosis TB-402 with TromboGenics Atherosclerosis BI-204 with Genentech Cancer TB-403 with TromboGenics
Research projects Cancer Angiomotin
Cancer Tumoricidal antibodies (2 projects) Cancer Research projects with UCB Celltech Ophthalmic diseases Angiomotin
Ophthalmic diseases Research project with Immusol
Infectious diseases Tat (HIV)
In just a short time BioInvent has created an innovative and broad portfolio of drug projects. The purpose is to develop antibody-based drugs for disease areas with significant medical needs. All of the projects represent unique medical concepts with the strong support of patents and patent applications.
A broad product portfolio of mature projects reduces risk and cost-effectively increases opportunities for future success.
By entering into partnerships based on certain products the company gains access to valuable expertise at the same time that development risk can be substantially limited.
Together with partner ThromboGenics, in February 2007 BioInvent took product candidate TB-402 into clinical phase.
The results of this first study are expected in late 2007. At the
same time the Company’s other projects have successfully
advanced through the preclinical phase and clinical trials of
TB-403, with ThromboGenics, and BI-204, with Genentech,
are likely to begin in the near future. The Company is there-
fore well equipped with a broad, diversified and rapidly
maturing drug portfolio.
13
bi-204
partnersHip agreement witH leaDing antiboDy Company genenteCH allows
ContinueD strong Development of projeCt
In January 2007 BioInvent entered into a partnership agreement with the major US biotech company Genentech to jointly develop and commercialize BI-204. Under this agreement, Genentech received the North American rights to the drug, while BioInvent retained the rights for rest of the world.
BioInvent therefore has the ideal partner, with a recognized track record of developing and commercializing antibody- based drugs. Strength, expertise and experience were important criteria for choosing a partner. It was also important for BioInvent to retain the rights to the drug for the rest of the world, outside North America, and to share responsibility with a partner for continued clinical development of the drug candidate. With this strategy the company ensures continued strong involvement in the development process, while taking advantage of Genentech’s considerable experience in develop-
Indication: Prevent additional myocardial infarction in patients with acute coronary artery disease.
Target protein: Oxidized ApoB100-proteins in LDL particles.
Anticipated competitive advantages: The treatment is expected to be able to reduce plaque size and prolong survival.
Partner: Clinical development will take place in coopera- tion with Genentech, which has the US commercialization rights to the medication. The patent rights for the project are the result of research at MAS University Hospital in Malmö and Cedars-Sinai Medical Center in Los Angeles.
Status: Toxicological studies are in progress.
Next milestone: Start of clinical trials of the drug in healthy volunteers.
faCts
ing antibody-based drugs. BioInvent also retains great flexi- bility with respect to its involvement in the future development and commercialization of the project, with the potential to benefit from the considerable value growth associated with later steps in the drug development process, or to enter into future partnership agreements for other geographic areas.
BI-204 is a human antibody aimed at oxidized forms of the bad cholesterol LDL. Several animal models have shown that BI-204 can substantially reduce both plaque formation and the extension of plaque that is already present. Treatment with BI-204 affects the inflammatory processes in the athero- sclerotic plaque, thereby reducing harmful inflammation and plaque extension. The toxicological programme is in progress.
The next milestone involves clinical trials of BI-204 in
healthy volunteers.
1
BI-BI- 204
1
BioInvent’s strategy for the treatment of atherosclerosis is to eliminate the undesired effect of oxidized forms of a lipoprotein (apoB100) that is part of the LDL particle.
LDL is ”the bad cholesterol”. Research in recent years has shown strong links between these oxidized particles and harmful inflammatory processes in the vessel walls.
These inflammations can result in plaque forming, pull- ing apart and causing blood clots.
The oxidized LDL particles can be used as target pro- teins for antibody drugs. The concept of protecting the vessel against atherosclerosis with the help of antibodies against target proteins is supported by earlier research.
This protection was shown to be linked to an increased level of naturally occurring antibodies against the target proteins. The study shows that development of plaque is reduced when the amount of antibodies increases. There is therefore good reason to believe that antibodies aimed at oxidized LDL particles will have a protective effect against atherosclerosis.
Clinical need
BI-204 is expected to be able to be used in patients who recently had a myocardial infarction. These patients are at substantially increased risk of complications – 30 per- cent suffer from additional infarctions within three years.
Currently no effective medications are available for these patients, especially drugs with significant effect on the basic problem, the generally extensive atherosclerosis.
Atherosclerosis is characterized by stenosis of the blood vessels and occurs when cholesterol is deposited on the inside of the vessel walls and plaque is formed.
This plaque narrows the blood vessels, impedes the blood flow and increases the risk of serious diseases such as myocardial infarction. Over 15 million people on the five largest markets have suffered at least one myocardial infarction.
An important risk factor for the development of atherosclerosis is high cholesterol levels in the blood and the current treatment strategy is therefore to lower cholesterol levels. Statins are the most common group of drugs used for this purpose. Statins reduce the level of lipids in the blood by blocking an enzyme needed for cholesterol formation. Treatment with statins has signifi- cantly reduced the number of people developing cardio- vascular diseases associated with atherosclerosis; how- ever, many of the treated patients still suffer from heart attacks or stroke.
There is therefore a significant medical need for a new treatment for atherosclerosis that can stabilize plaque that is at risk of bursting, and hopefully also reduce its size. Since a drug of this kind would have great commercial potential, considerable research initiatives are under way in this field.
Market and competition
Lipid-lowering drugs are the largest group of drugs in the world, alongside gastric ulcer medicines. Sales in 2004 reached USD 26 billion (Datamonitor 2006). Statins, which account for the largest percentage of drugs used to treat atherosclerosis in terms of sales, are included here.
Over a dozen companies are now competing for this market. The bestseller in this class of drugs is atorvastatin, which is the drug with the highest sales of all categories.
In addition to statins, new combination drugs are expected to dominate for the foreseeable future the treatment of patients with high lipid levels, atherosclerosis and other risk factors for cardiovascular disease.
As mentioned above, these drugs do not by any means help all patients with atherosclerosis. The mortality rate remains high. Major clinical trials have shown that the effect of statins on plaque size is modest at best.
Clinical studies have shown that new drugs under development have the ability to significantly reduce plaque size in the vessels of patients. This has greatly increased interest in innovative treatment methods that affect the progress of atherosclerosis. These drugs work by increasing the positive effect of “the good cholesterol”
HDL. One way to increase HDL levels is to block a key enzyme in cholesterol metabolism, called CETP. CETP in- hibitors have generally been viewed as the most promising approach to attacking the atherosclerotic process by influencing HDL levels. However, during 2006 develop- ment of the most advanced drug candidate with this mechanism of action was stopped after an ongoing large phase III study showed that it caused serious side effects.
BioInvent’s antibody differs from these drugs because it is not only expected to reduce plaque volume in general, but will also reduce inflammation in the vascular wall, which would stabilize unstable plaque. Our hypothesis is also that the side effect profile will prove to be favorable since the target protein is a toxic substance resulting from degenerative change and not an enzyme or other mole- cule that has a specific physiologic function in the body.
Project status
During 2006 continued experiments have further clarified BI-204’s mechanism of action. Data support that the mode of action underlying BI-204 is a modulation of the inflam- matory process resulting in a reduction of pro-inflamma- tory cells in treated plaque, which in turn leads to decreased new formation of plaque and regression of existing plaque. Thus experiments in animal models have con- firmed that treatment with BI-204 has highly significant effects on extension and composition of plaque.
The toxicological programme is in progress. The next milestone involves clinical trials of BI-204 in healthy volun- teers.
Patent protection
The oxidized forms of the apolipoprotein apoB-100 that causes harmful inflammation in the vascular wall, their use in drug development and products aimed at these target proteins are patent pending in about 40 countries, including major markets such as the US, Europe, Canada, Japan, Australia, China and India.
tb-402
new antiCoagulant to inHibit tHrombosis enters CliniCal trials
Indication: Stroke prophylaxis in patients with atrial fi brillation and thrombosis prophylaxis in connection with orthopedic surgery.
Target protein: Factor VIII. The antibody only partially inhibits this coagulation factor.
Anticipated competitive advantages:
The partial inhibition of coagulation by a human antibody is anticipated to pose a low risk of side effects such as bleeding and liver toxicity. Long-acting medication eliminates the need for daily treatments and facilitates patient monitoring.
Partners: The product is being devel- oped in collaboration with Thrombo- Genics Ltd. Professor Marc Jacquemin, Flanders Interuniversity Institute of Biotechnology (VIB) and the university in Leuven, Belgium, who developed the concept and remains as a partner.
Status: A clinical trial aimed at inves- tigating whether TB-402 is safe and well tolerated was initiated in February 2007 in Denmark.
Next milestone: The clinical phase I study is expected to be concluded in late 2007.
faCts
The recently initiated clinical development of the new drug candidate TB-402 represents the achievement of an important milestone for BioInvent and its partner ThromboGenics.
However, the future success of this medication may be especially significant for the many patients who annually are at risk for life-threatening thromboses, such as in conjunction with major surgery, or as a consequence of certain arrhythmias such as atrial fibrillation.
TB-402 represents a new way of preventing thrombosis.
It is a human antibody that targets Factor VIII, which plays a pivotal role in blood coagulation. The antibody has demon- strated beneficial partial inhibition of Factor VIII, even when administered in extremely high doses. This unique concept makes it possible to prevent thrombosis long term and with minimal risk of bleeding. Research indicates that the medica- tion cannot be overdosed.
Results from the phase I trial, which has the primary pur- pose of demonstrating that TB-402 is safe, are expected to be reported in late 2007. A phase IIa-trial is being planned that will also be able to indicate whether TB-402 provides the desired antithrombotic effect in patients who have undergone orthopedic surgery.
TB-
TB-402
1
1
TB-402 is a human monoclonal anti-Factor VIII-antibody, a new anticoagulant treatment for a number of indica- tions such as atrial fibrillation and deep vein thrombosis.
The antibody has the unique ability to only partially inhibit coagulation, regardless of the concentration reached in the treatment of individual patients. This gives the treatment a favorable safety profile, which has been confirmed in preclinical testing. The treatment’s thrombosis-inhibiting effect has also been very good.
The drug candidate has demonstrated beneficial partial inhibition of Factor VIII, even when administered in extremely high doses. This indicates a well-controlled inhibition of Factor VIII activity, with a low risk of spon- taneous bleeding, which means that the risk of overdose and the need to monitor patients is avoided. Factor VIII is a factor in the blood coagulation process. Data from preclinical tests indicate that the drug can be given once for the treatment of acute indications, or once or twice a month to treat chronic indications such as atrial fibrilla- tion (all currently available anticoagulants require daily administration). This suggests that it will be possible to develop a product with an excellent safety profile, ease of administration and good compliance.
BioInvent and ThromboGenics are collaborating on this project, which is part of a larger partnership between the companies initiated in 2004. The parties will continue to conduct this development program together. The project is based on research about inhibiting the Factor VIII coagulation factor under the leadership of Professor Marc Jacquemin of Flanders Interuniversity Institute of Biotechnology (VIB) and the University in Leuven, Belgium, in cooperation with ThromboGenics.
Clinical need
Several patient groups have a significant great need for improved and safe anticoagulant therapy, perhaps most of all, patients with atrial fibrillation. They are often affected by complications such as small blood clots in the lungs (pulmonary emboli), which can lead to stroke if a blood clot is transported to the brain. Prospects are good for TB-402 to become a new, safe and effective treatment option for this patient group.
The first clinical trial began in February 2007 in Denmark and involves healthy volunteers. Clinical trials with TB-402 in patients will be conducted among indi- viduals who had orthopedic surgery. These patients are at risk for the complication pulmonary embolism. Current treatment, mainly heparin drugs, requires daily injections and can sometimes cause spontaneous bleeding without preventing deep vein thrombosis in all patients. Other more recent forms of treatment also cause side effects involving bleeding. The side effect profile of new antico- agulants is therefore very important, especially with respect to bleeding.
The mortality rate of patients affected by deep vein thrombosis or pulmonary embolism is high and the costs for society relating to the acute medical needs of these patients and their subsequent long-term care is great.
Current treatment for these patient groups needs to be improved because today’s treatments involve the risk of serious complications related to spontaneous bleeding and require daily doses of drugs. Unlike current treat- ments, it is expected that a treatment based on partial inhibition of Factor VIII by giving patients a human anti-
body could be administered only once, or up to every two to four weeks for chronic conditions. The risk of bleeding and other side effects such as liver toxicity is also expected to be low.
Market and competition
The oral anticoagulants include Warfarin, which is often given to prevent embolism when a patient has atrial fibrillation. Warfarin entails risks because it must be administered in precise doses. Warfarin is one of the ten most prescribed drugs; three million patients in the US alone receive more than 30 million prescriptions per year (BioCentury 2004). The most important injectable anti- coagulant is low molecular weight heparin, with annual sales of USD 3.5 billion (Datamonitor). Patients on heparin treatment require daily injections. Two newer injectable anticoagulants are fondaparinux and idraparinux, which are expected to achieve sales of USD 350–400 million by 2010 (Datamonitor).
BioInvent’s concept—to partially inhibit Factor VIII—
is unique. There are, however, a number of alternative strategies in development to inhibit coagulation. They can be divided into the following sub-categories (Hirsch, 2004, Blood):
• inhibitor of Factor VIIa and its the signals (such as TFPI)
• inhibitor of Factor Xa (fondaparinux and idraparinux)
• activated protein C and soluble thrombomodulin (drotregocin-alpha, ART-123)
• direct thrombin inhibitors (hirudin, bivalirudin, ximelagatran).
Several of these candidates have shown promising effect data in clinical studies. However, certain medications have been shown to have significant side effects such as spontaneous bleeding, for which there is no effective remedy, and toxicity problems such as liver toxicity.
Around 1.5 million knee and hip operations take place and a million acute cases of pulmonary embolism occur every year in the seven largest drug markets, and the number of cases is increasing relatively quickly due to factors such as an ageing population and obesity.
The value of the market for thrombosis inhibiting drugs (which includes both anticoagulants and platelet aggregation) was estimated at USD 10 billion in 2004, and is expected to grow by more than six per cent per year over the next ten years.
Project status
Clinical trials in healthy volunteers began in February 2007 for the drug candidate TB-402. Preclinical trials have shown that the antibody has a beneficial partial inhibition of Factor VIII, even when administered in extremely high doses. Extensive testing in several animal models has shown that TB-402 strongly reduces the risk of thrombosis without increasing the risk of spontaneous bleeding.
The report from the initiated phase I study is expected in late 2007, and will be followed by a phase IIa trial in patients who have undergone orthopaedic surgery.
Patent protection
Patent applications have been submitted in Europe, Japan, Canada, the United States, Australia and other countries for antibodies that partially inhibit Factor VIII, pharmaceutical preparations involving such antibodies and their use in therapeutic applications.
1
TB-403 targets the tumor’s blood supply, thus starving it.
Treated patients should experience fewer adverse effects than with rival medications.
The drug candidate is a humanized antibody that shows good specificity for the PlGF target protein. It is a growth factor that is secreted by tumors and is specifically expressed in cancer and chronic inflammatory conditions. It affects the formation of new vessels in tissue that is under stress. Unlike VEGF, which is targeted by the drug Avastin, PlGF does not seem to affect normal, physiological angiogenesis. This char- acteristic is important because it means that the inhibition of PlGF can be expected to cause fewer side effects, while still having the desired effect on various diseases.
TB-403 will initially be developed to treat oncological diseases. Examples of indications include prostate and colorectal cancer. It could potentially be used in combination therapy together with other cancer drugs such as chemotherapy and hormone therapy. In the future it is also expected that combi- nations of multiple angiogenesis inhibitors will improve treat- ment outcome. Development of resistance to an active inhibi- tor by the tumor expressing other growth factors could therefore be prevented or delayed. There is also good reason to expect that TB-403 could be used in other diseases where angiogenesis plays an important role.
The drug candidate (TB-403) has shown good inhibition of PlGF-associated angiogenesis in preclinical studies. Toxico- logical studies are in progress. The project is being developed within the framework of the alliance with ThromboGenics.
Indication: Forms of cancer that are sensitive to angiogenesis such as pancreatic, prostate, kidney, colorectal, breast and lung cancer.
Target protein: Target protein: PlGF, a growth factor that binds to the VEGFR1 receptor in the endothelial cells of newly formed vessels.
Anticipated competitive advantages:
Anti-PlGF is also expected to have an effect in patients resistant to anti-VEGF treatment. A favorable side-effect profi le is expected, since PlGF is mainly secreted in connection with pathologi- cal conditions.
Partners: BioInvent is developing this project in cooperation with
ThromboGenics Ltd. and Professor Peter Carmeliet of the university in Leuven.
Status: The toxicological program is in progress.
Next milestone: Phase I clinical trials.
faCts
tb-403
antiboDy tHat Cuts off tHe supply of blooD to tumors
TB-
TB-403
1
TB-403 is a humanized antibody that targets the PlGF growth factor secreted by tumors. It is a homologue to VEGF and binds to one of its receptors. PlGF expression is specifi cally increased in connection with conditions such as cancer and chronic infl ammatory conditions and thereby affects the formation of new vessels in tissue that is under stress. Unlike VEGF, PlGF does not seem to affect normal, physiological angiogenesis. VEGF-inhibition has been shown to cause certain adverse effects such as neuropathy and hypertension, as well as rare serious side effects in the intestinal mucous membrane. Inhibition of PlGF is therefore expected to have the advantage of causing limited adverse effects while still providing the desired effect. There is also reason to believe that TB-403 could also be effective in certain patients who do not respond to anti-VEGF treatment. This hypothesis is supported by animal data from BioInvent and ThromboGenic’s partner Professor Peter Carmeliet at the university in Leuven, Belgium.
Clinical need
Cancer is a heterogeneous group of diseases, which makes it more diffi cult to develop drugs aimed directly at killing tumor cells. A new and interesting strategy is to attack the blood supply to tumors indirectly by blocking the growth of new blood vessels.
The formation of new blood vessels is a process called angiogenesis. These vessels supply growing tissue with nutrients and transport waste away from the tissue.
Tumors over a certain size are dependent on the forma- tion of new blood vessels to grow and survive. A substance that inhibits the growth of new blood vessels could therefore reduce the tumor and increase the patient’s chances of survival.
Such treatment could be used for a number of different forms of cancer, such as pancreatic, prostate, kidney, colorectal, breast and ovarian cancer, as well as lung cancer and lymphoma. Within each of these diseases there is sales potential from a few hundred million to a few billion US dollars.
Today these forms of cancer are usually treated with combinations of chemotherapy, radiation and surgery.
Certain forms of cancer also respond to hormone therapy.
Angiogenesis inhibitors are expected to be able to work in combination with current treatments, and this theory is supported by clinical trials that have been carried out using other angiogenesis inhibitors under development and in the market. The effect of the treatment has been shown to be additive or even synergistic, both in patients that have just started treatment and others who have undergone several courses of treatment. Angiogenesis inhibitors are therefore a class of drug with a broad area of application, partly because many oncology indications are expected to respond to this treatment, but also be- cause a large percentage of patients in each indication are expected to be able to benefi t from the treatment.
Market and competition
Interest in angiogenesis inhibitors in cancer treatment has intensifi ed over the past year. One of the main reasons is that the antibody called bevacizumab (Avastin) was approved in 2004 in both the United States and Europe for treatment in combination with chemotherapy
for colorectal cancer and subsequently in 2006 in the US even for non-small cell lung cancer. The product has quickly become a great commercial success with sales in 2006 of USD 1,746 million in the US alone (Genentech Q406). This underscores the great potential of this new class of drug and shows that it meets a signifi cant medi- cal need.
Bevacizumab works by binding to and blocking the angiogenesis-promoting factor VEGF that some tumors secrete.
At present more than 30 angiogenesis inhibitors are in clinical development. A decade from now there will probably be several angiogenesis inhibitors on the market targeting different segments. Due to its unique concept and broad areas of application, the Company’s projects are expected to stand up well to this competition.
In the future it can also be expected that combina- tions of multiple angiogenesis inhibitors will improve treatment outcome. The development of resistance against an active inhibitor caused by the tumor’s up- regulation of other growth factors can thereby be prevented or delayed.
ImClone, in the US, is developing an antibody against PlGF’s receptor VEGFR1 (or Flt-1), which is in early clinical trials. Merck is developing another molecule, an “siRNA”, which inhibits the cell’s production of VEGFR1. The prod- uct is mainly being developed for ophthalmic diseases and initial tests have been conducted in humans.
Project status
The product candidate (TB-403) has shown good inhibition of PlGF-associated angiogenesis and tumor formation in preclinical studies. Toxicological studies are currently in progress.
Patent protection
Patent applications have been submitted relating to treatment with antibodies against PlGF aimed at reduc- ing or preventing pathological angiogenesis, vascular leakage, pulmonary hypertension, cancer and infl amma- tion. Applications have been submitted in several counties, including the United States and Canada. The patent is approved in Europe.
Potential to expand future treatment areas for angiogenesis inhibitors
Angiogenesis is a physiological process which it may be benefi cial to control pharmacologically in connection with indications areas other than cancer. In these diseases, new vessel formation may exacerbate an already adverse pathological condition. The vessels formed in such diseases are often of poor quality, which could result in vascular leakage and the accumulation of infl ammatory cells.
With certain conditions, such as the eye disease age- related macular degeneration of the “wet” type, this vascular leakage is believed to be a direct factor in the progress of the disease. It has also proved possible to use with antiangiogenesis drugs to attack other diseases that have a distinct infl ammatory component. Diseases that could be treated with angiogenesis inhibitors, other than cancer, include certain ophthalmic diseases, as well as infl ammatory diseases such as rheumatoid arthritis.
20
BioInvent’s research portfolio consists of several projects in the phase prior to selection of product candidates. The Company’s research portfolio focuses on cancer, ophthalmic and infectious diseases. The portfolio includes both early projects with a focus on research and more mature projects in which an array of data supporting mechanisms of action and effects have been produced. BioInvent conducts these research projects alone or in cooperation with various partners. Several of the research projects have advanced significantly over the past year and are approaching the point when a product candidate will be selected.
BioInvent aspires to continue to pursue early research projects in order to continuously fill the clinical trial pipeline, thereby ensuring continued development of the company.
researCH portfolio
BioInvent’s research portfolio, with projects in the phase before a product candidate is chosen, has taken significant steps forward the past year.
There are good opportunities for research projects to advance to the Company’s portfolio of development projects.
21 CANCER
Cancer is a disease category with significant medical needs. Researchers have developed several antibody- based drugs in recent times that have proven successful in the treat- ment of some of these patients.
Antibody drugs are successful due to their high selectivity and their ability—directly or indirectly—to effectively kill cancer cells with limited effect on normal cells.
Tumoricidal antibodies Based on a patent pending selection technology, BioInvent has identified several antibodies that directly kill cancer cells extremely effectively.
This can take place through various mechanisms of action by the anti- body binding to the cancer cell and conveying a direct death signal (apoptosis), or activating other anti- body-dependent effector functions.
Antibodies with these mechanisms of action could work without need- ing to be linked with cytotoxins or radioactivity.
A number of very specific anti- bodies and their corresponding tar- get structures have been identified.
These antibodies have been shown
Collaboration with UCB In 2002 BioInvent initiated a research and development partner- ship with Oxford GlycoSciences (OGS) for the development and commer- cialization of antibody drugs. Follow- ing company acqusitions, collabora- tion is now in progress with the Belgian pharmaceutical company UCB. This collaboration has been extended after an initial three-year period.
Currently the companies are involved in several projects within the framework of this partnership.
BioInvent has delivered a number of antibodies to all of these projects.
UCB is responsible for all animal ex- periments, continued clinical devel- opment and for commercialization of any products that result from the collaboration. If product develop- ment is successful BioInvent will re- ceive milestone payments as well as royalties on future sales. During the year BioInvent received one mile- stone payment in conjunction with initiation of animal experiments with the second developed antibody.
to have the ability to kill effectively various types of tumor cells in test tubes and to block tumor growth of human tumors implanted in animals.
BioInvent has applied for pat- ents to protect these antibodies and their use in certain types of cancer.
Within the next year the Company is expected to carry out expanded studies in relevant animal models.
Anti-angiomotin
This project is based on the discovery of a new and central receptor in angiogenesis. It is called angiomotin and is only expressed in cells in blood vessels during angiogenesis. The receptor is considered to be crucial for the formation of new vessels and by aiming antibodies at it, tumor growth can be prevented by block- ing the formation of new blood ves- sels. During the year BioInvent has produced promising data from ani- mal models in the project, showing that antibodies can block undesired angiogenesis. Currently researchers are studying the effect of antibod- ies on tumor growth. The project is based on patent rights acquired in April 2003 from a research group at Karolinska Institutet.
OPHTHALMIC DISEASES A number of clinical trials have shown that eye diseases such as age- related macular degeneration of the “wet” type, and diabetic retin- opathy are sensitive to angiogenesis inhibitors. Researchers also believe a harmful inflammatory component is involved in the course of the disease in these patients. The need for new
effective drugs to treat these ophthalmic diseases is significant, since patients without effective treatment may become blind. These diseases are the most common cause of blindness in older people.
Angiogenesis inhibitors could significantly arrest the progress of such diseases. BioInvent believes that both angiomotin and PlGF (and therefore even drug candidate
TB-403) are interesting target proteins in this context. Antibodies against angiomotin, PlGF or its re- ceptor VEGFR1 have already shown promising effects in vitro and in vivo that support the Company’s opinion.
BioInvent is working on a third project related to ophthalmic diseases in cooperation with the US-based company Immusol.
INFECTIOUS DISEASES In 2006 BioInvent reported that its earlier product candidate for HIV, BI-201, did not demonstrate the desired pharmacokinetic properties when tested in patients. Closer analysis showed that the antibody contained carbohydrate chains that probably contributed to rapid elimi- nation from circulation. Since then BioInvent has continued with pre-
clinical evaluation of back-up anti- bodies, aimed at identifying a new product candidate.
The backup antibodies differ from BI-201 with respect to carbo- hydrate content and pharmacoki- netic data from animals suggest a more favorable half-life in humans.
As with BI-201, these antibodies aim to block and neutralize the HIV- specific Tat protein, which is vital for the ability of the virus to
multiply and spread to new cells.
Supplying antibodies that block Tat represents a completely new HIV treatment strategy, and it should therefore be possible to use the treatment even in patients who develop resistance to other HIV drugs. In addition, this therapeutic concept is associated with little risk of developing new resistance.
