• A directed new share issue that raised SEK 150 million for the company before transaction costs was implemented in February.
• In March BioInvent entered into a product partnership with Human Genome Sciences to develop and commercialise therapeutic antibodies.
• A phase I study of the BI-505 product candidate for the treatment of multiple myeloma was launched at the beginning of the year.
• Net revenues for January - March 2010: SEK 15.1 million (36,8 including BioInvent's share, SEK 21.7 million, of the first milestone payment for TB-403).
• Current investments together with cash and bank as of 31 March 2010: SEK 179.1 million (192.3).
• Cash flow from current operations and investment activities for January – March 2010: SEK -49.3 million (-20.1).
• Loss after tax for January - March 2010 amounted to SEK -37.9 million (-34.7) and the profit after tax per share was SEK -0.65 (-0.62).
BioInvent is a research-based pharmaceutical company that focuses on developing antibody drugs. The Company is currently running innovative drug projects mainly within the areas of thrombosis, cancer and atherosclerosis.
Comments by the CEO
The new share issue carried out in February has put us in a stronger position to be able to further develop our project portfolio and exploit the commercial opportunities that our portfolio and our technology platform represent.
Our agreement with Human Genome Sciences demonstrates our goal of broadening our product portfolio to include new drug candidates. This partnership will initially focus on inflammatory diseases and is an example of how collaboration can pave the way for broadening our participation in a number of innovative new drug concepts. As we establish strong alliances with other companies, we are also continuing to forge ties with academic teams with projects and technology that can result in new drug projects. Within the framework for these types of partnerships we have recently started projects based on interesting mechanisms within cancer and diabetes.
Now that BI-505 has entered into the clinical development phase, we have four clinical projects. Both the product concept itself and our in-house developed screening technology that led to the discovery of the product candidate have attracted a lot of interest recently.
We ended last year by stepping up efforts to develop our own drug portfolio. This year we intend to take additional steps with a view to strengthening the portfolio and the company’s profile as a strong organisation in the development of antibody-based drugs. These ambitions combined with the fact that we expect to reach milestones in the form of reporting clinical results and starting new phase ll studies makes me optimistic about 2010.
Development projects
BioInvent is currently running four projects in the development phase. In the development phase the safety profile of the product candidate is tested in animal models, before testing safety and efficacy in clinical trials.
Thrombosis (TB-402)
TB-402 is a human antibody binding to Factor VIII. The antibody has shown a beneficial partial inhibition of Factor VIII, even when applied in excess dosage. This reduces the risk of undesirable bleedings. The objective is to initially develop a drug that prevents Deep Vein Thrombosis (DVT) following orthopaedic surgery. DVT is caused when a blood clot forms in a deep vein, most commonly in the deep veins of the lower leg. DVT is a major public health issue and it is estimated that in the US alone, more than 600,000 individuals are affected by DVT or pulmonary embolism (PE) each year. The number of patients undergoing total hip or knee replacement is estimated at around 2.4 million in 2009 and is expected to grow to approximately 3.1 million 2015 in the seven major pharmaceutical markets. Patients undergoing hip replacement or knee surgery are particularly at risk of developing DVT and all patients are therefore treated with anticoagulants prophylactically in order to reduce the risks of blood clots. The project is carried out within the alliance with ThromboGenics.
Results from the Phase I trial show that TB-402 is both safe and well-tolerated. No serious adverse events related to TB-402 were reported. The pharmacokinetic analysis undertaken as part of the Phase I trial confirm a prolonged half-life of approximately three weeks, which will allow for single dose treatment in orthopaedic surgery patients and/or a once-a-month administration for long-term stroke prevention in atrial fibrillation (AF), as opposed to daily treatment with current anticoagulants. The pharmacodynamic analysis confirms that TB-402 achieves only partial inhibition of Factor VIII activity without the undesired effect of total inactivation. A stable long-acting anticoagulant effect based on partial Factor VIII inhibition could also be shown.
Additional studies have shown that the effect of TB-402 can be reversed by giving the target protein (Factor VIII) that blocks TB-402 and also that TB-402 is safe and well tolerated in patients that are given standard treatment (enoxaparin and warfarin) for deep vein thrombosis. The results show that TB-402 has prospects to be developed into a safe and well-controlled treatment for several medical conditions in which thrombosis prevention is of great importance.
A phase II study was launched in February 2009 for the prevention of DVT in patients receiving artificial knee joints. All of the patients, 315 in all, had been treated by the end of October 2009. The results are expected to be reported in the current quarter.
The Phase II trial is an active (enoxaparin)-controlled, dose-escalating, multicenter, prospective, randomised, open label trial evaluating TB-402 for the prophylaxis of DVT after knee surgery. The study assesses three different doses of TB-402 given as a single intravenous bolus injection post knee replacement surgery. The objective of the study is to assess the safety and efficacy of the three escalating doses of TB-402.
Atherosclerosis (BI-204)
The product candidate BI-204 targets oxidized forms of the LDL cholesterol (oxLDL). Links have been shown between oxidized forms of certain lipoproteins and the inflammatory processes that lead to plaque formation in the vessel walls. BI-204 has in preclinical studies reduced inflammatory processes and reduced plaque formation significantly. The results also show a considerable reduction in the size of existing plaques in animals treated with BI-204. Results supports that the mechanism behind BI-204 is a modulation of the inflammatory process resulting in a reduction of pro-inflammatory cells in treated plaques, which in turn leads to a reduction in new plaque formation and the regression of existing plaques. It is being developed as a drug for the prevention of secondary events in patients with cardiovascular disease. In a population-based, prospective, observational study of the risk of development of coronary artery disease (JAMA. 2008; 299 (19) 2287-2293) higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of insulin resistance and hyperglycemia. These observations support the picture that oxidized LDL can be an important target structure for developing new medications to treat patients with type 2 diabetes and metabolic syndrome. BI-204 is developed in collaboration with Genentech, a wholly-owned member of the Roche Group.
The phase I programme was completed in the second quarter 2009. The study was a double-blind, within-group randomised dose-escalation trial testing both single and multiple doses of BI-204 administered either intravenously or subcutaneously. In total, 80 healthy male or female subjects with elevated levels of LDL cholesterol were included in the trial. BI-204 was well tolerated and pharmacokinetic results showed the half life was in the expected range for fully human antibodies.
Cancer (TB-403)
The product candidate TB-403, is a monoclonal antibody directed against placental growth factor, PlGF. TB-403 binds PlGF with high affinity and specificity and has been shown to inhibit tumour growth in animal models. TB-403 blocks tumour angiogenesis, the development of new blood vessels, which is required for tumour nutrient and oxygen supply supporting tumour growth. Angiogenesis is also required for disease progression and metastasis, the dissemination of the tumour to distal sites of the body.
The PlGF growth factor is secreted by tumours and is specifically over expressed in cancer and chronic inflammatory conditions. It affects the formation of new vessels in tissue that is under stress. PlGF is not required for survival of normal resting vasculature and blocking PlGF is expected to be relatively safe, because mice lacking PlGF are healthy and reproduce normally. Preclinical research has also shown that inhibition of PlGF does not induce resistance mechanisms because it does not induce “angiogenic rescue” mechanisms, whereby tumour expression of proangiogenic growth factors is upregulated, which may enable escape from therapy. This angiogenic rescue phenomenon has been demonstrated with some angiogenesis inhibitors.
Up to June 2008 the project was carried out within the alliance with ThromboGenics. In June 2008 BioInvent and partner ThromboGenics entered into a strategic license agreement with Roche for development and commercialisation of TB-403. Roche received a worldwide, exclusive license to develop and commercialise TB-403. BioInvent and ThromboGenics retained co-promotion rights for the product in the Nordic, Baltic and Benelux regions.
The first Phase l study in 16 healthy male subjects was successfully completed in June 2008 and showed that TB-403 is safe and well tolerated, with pharmacokinetic properties enabling it to be developed as a novel anti-cancer agent. A follow-up study in patients with advanced cancer was presented in November 2009 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, U.S. This dose escalation study examined tolerability, pharmacokinetics and pharmacodynamics of TB-403 in 23 patients. TB-403 was shown to be well tolerated and no dose limiting toxicity was observed with doses up to 10 mg/kg weekly and 30 mg/kg every three weeks. In this patient population with advanced solid tumours, stable disease was observed in six of 23 patients whereof two patients had stable disease in 12 months.
Cancer (BI-505)
The drug candidate BI-505 is a human antibody that targets the adhesion protein ICAM-1 (also called CD54). In tumour cells the expression of ICAM-1 is elevated and it is therefore a candidate for being a suitable target protein for a therapeutic antibody. In addition to inducing apoptosis the antibody also provides important immuno-effector functions that help to kill tumour cells. BI-505 has in different animal models proved to be very effective at killing tumours and more effective than existing drugs.
BioInvent’s intention is, in an initial stage, to treat patients with multiple myeloma. Other forms of hematologic cancer may also become relevant as indications. The possibility of treating ICAM-1 expressing solid tumours will also be examined further in additional preclinical trials. The number of newly diagnosed patients with multiple myeloma is more than 40,000 per year and the number of newly diagnosed patients with blood cancer is more than 200,000 per year.
BI-505 has been granted orphan drug designation in the United States and Europe for the indication of multiple myeloma. This status gives BI-505 possibility for market exclusivity for treatment of multiple myeloma with an antibody against ICAM-1 for up to 10 years after marketing approval is obtained.
A phase I study for the treatment of multiple myeloma was launched in the US at the beginning of the year. The study will investigate safety, pharmacokinetics and pharmacodynamics and will aim to define the optimal dose of the antibody for upcoming clinical phase II development. The study will involve 30 – 40 patients. The patients will be treated with intravenous doses of BI-505 every other week for a 28-day period with the possibility of extending the treatment until the condition deteriorates again.
Research projects
BioInvent is running a number of projects in the research phase i.e. the stage prior to selection of a Candidate Drug. The company’s research portfolio currently includes projects mainly within the areas of cancer and inflammation. The research in the cancer field is aimed at additional product candidates that will impede undesirable vessel growth and thus the blood supply to tumours, as well as at programmed cell death inducing antibodies that kill tumour cells. BioInvent has together with a leading academic group launched a project focusing on new drug concepts based on the role of cancer-associated fibroblasts in tumour development.
The company’s inflammation research is being enhanced by a partnership entered into in March with the US company Human Genome Sciences. Under this partnership the companies will work together to develop and commercialise antibody-based drugs based on target proteins from Human Genome Sciences’ research and BioInvent’s antibody technology.
BioInvent has initiated a new project in cooperation with a leading academic group for the treatment of type I diabetes.
The company is also conducting research and development on antibody-based drugs on behalf of other external partners. Such partners includes Bayer HealthCare, Daiichi Sankyo and Mitsubishi Tanabe. All in all BioInvent has entered into agreements of this kind with the possible development of up to 30 antibody-based products. As well as undisclosed license fees and research funding, BioInvent will receive milestone payments and royalties on sales of any products commercialized.
Revenues and result
Net revenues for the January – March period amounted to SEK 15.1 million (36.8). Revenues for the January – March 2010 period mainly come from partnerships where antibody-based drugs are developed using the n-CoDeR antibody library. BioInvent's share, SEK 21.7 million, of the first milestone payment for TB-403 is included in reported net revenues for 2009.
The Company’s total costs for the January – March period amounted to SEK 52.7 million (72.5). Operating costs are divided between external costs of SEK 28.0 million (48.0), personnel costs of SEK 22.2 million (21.6) and depreciation of SEK 2.5 million (2.9).
Research and development costs for January – March amounted to SEK 44.4 million (63.8). Depreciation according to plan reduced the operating result for the period by SEK 2.5 million (2.9), of which depreciation of intangible fixed assets amounts to SEK 1.3 million (1.5).
Financial position and cash flow
As of 31 March 2010, the Group’s current investments together with cash and bank amounted to SEK 179.1 million (192.3). The cash flow from current operations and investment activities for January – March amounted to SEK -49.3 million (-20.1). Cash flow was reduced by normal fluctuations in working capital.
In February BioInvent implemented a directed new share issue totalling 5,434,800 shares that raised SEK 150 million for the company before transactions costs. The subscription price was set at SEK 27.60 per share.
The shareholders’ equity amounted to SEK 162.6 million (196.8) at the end of the period. The Company’s share capital was SEK 30.5 million. The equity/assets ratio at the end of the period was 73.5 (75.6) per cent. Shareholders’ equity per share amounted to SEK 2.66 (3.54). The Group had no interest-bearing liabilities.
Investments
Investments in tangible fixed assets amounted to SEK 0.9 million (0.0). No investments were made in intangible assets during the period (-).
Upcoming financial reports
BioInvent will present the following financial reports:
Interim reports 14 July, 14 October 2010
Financial statement for 2010 10 February 2011
About BioInvent
BioInvent International AB, listed on the NASDAQ OMX Stockholm (BINV), is a research-based pharmaceutical company that focuses on developing antibody drugs. The Company is currently running innovative drug projects within the areas of thrombosis, cancer and atherosclerosis. The Company has signed various strategic alliances around these product candidates and is developing them in collaboration with partners including Genentech, Human Genome Sciences, Roche and ThromboGenics.
These projects are based around a competitive and in substance patented antibody development platform. The scope and strength of this platform is also utilised by partners, such as ALK-Abelló, Bayer HealthCare, Daiichi Sankyo, ImmunoGen, Mitsubishi Tanabe, OrbusNeich, UCB and XOMA.
More information is available at www.bioinvent.com.
