Unique off-the-shelf therapeutic DC-cancer vaccine in clinical trials

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1 Unique off-the-shelf therapeutic DC-cancer vaccine in clinical trials BUSINESS DESCRIPTION Immunicum AB (publ) is a biopharmaceutical company that develops unique therapeutic cancer vaccines (INTUVAC is the most advanced and based on the COMBIG-platform). Immunicum seeks to enter partnerships with, and to out-license its products to, larger pharmaceutical companies interested in immunotherapy. The company was founded in 2002 as a spin-off from Sahlgrenska University Hospital in Gothenburg, Sweden. THE NEW SHARE ISSUE This is Immunicum ABʼs 4th tranche of new shares to be issued, bringing in 21.5 MSEK in new financing. With this new financing, Immunicum s goals throughout 2014 are to: Complete the ongoing clinical phase I/II trial in renal cell carcinoma in Sweden and an upcoming clinical phase I/II trial in a new indication. Receive orphan drug designation for INTUVAC in a new indication. 1) Allogeneic DCs are injected TECHNOLOGY DESCRIPTION 2) NK-cells are recruited to the Immunicum has developed therapeutic cancer vaccines based on the unique approach of using dendritic cells (DCs) from healthy donors, in contrast to all other DCcancer vaccine competitors that are using DCs from each patient to be treated. The technologies are based on over intratumorally. tumor where they induce an NK-cell mediated tumor cell death, thus releasing tumor antigens ready for 30 years of research within the area of transplantation uptake by antigen-presenting-cells such immunology. The US-market approval for Provenge as DCs. (Dendreon) in 2010 and recent advances in the understanding of DC-based vaccine approaches appear 3) Autologous DCs are recruited to the tumor to have stimulated increased interest in this class of where they engulf tumor antigens and migrate vaccine. In fact, the Nobel Prize in Medicine 2011 was to the draining lymph nodes. awarded the discoverer of the DC, the most efficient antigen-presenting cell known today. 4) DCs present tumor antigens to naïve T-cells who subsequently become tumor specific cytotoxic T-lymphocytes (CTLs). Figure 1: Description of INTUVACʼs meachnism of action.

2 There are four major advantages of INTUVAC 1. The vaccine targets any cancer in patients who have a solid tumor eligible for intratumoral injection. 2. INTUVAC is patient independent and possible to mass produce. 3. The concept utilizes the patients own tumor antigens, thus guaranteeing an optimal battery of tumor antigens to be used for each individual patient in the activation of a tumor-specific immune response. 4. Immunicum is not dependent on third party antigen inlicensing. tumor and two patientsʼ extracted primary tumors. The tumors in picture 2 have been stained for CTLs and show a substantial increase of infiltrating CTLs in both patientsʼ extracted primary tumors in comparison to untreated tumors after INTUVAC-RCC vaccination. Strengths and opportunities Promising clinical data on CTL infiltration response. Orphan drug designations for both RCC and melanoma. Experienced team. Cancer vaccine immunotherapy area with recent clinical and commercial success stories. Immunicum s project portfolio Immunicum s project portfolio consists of four different entities (see figure 2 on the next page). This document will however mostly focus on projects based on the prioritized vaccine INTUVAC. INTUVAC-RCC INTUVAC is currently used in a clinical phase I/II trial in renal cell carcinoma (RCC) in Sweden (see picture 1). The trial will be conducted on 12 patients and is expected to be completed by Q Thus far, patients that have been treated with INTUVAC show promising immunological response, no adverse effects, and clear signs of health improvements. Picture 1: The first INTUVAC-RCC vaccination. INTUVAC-clinical data gathered thus far are promising The patientʼs primary tumor, along with the entire kindey, is extracted, which gives Immunicum an interesting opportunity to analyze the immunological response one month after first vaccination. Picture 2 a-d below shows a comparison of the infiltration of CD8+ T-cells/CTLs (the cells that have the ability to fight cancer) in an untreated Untreated tumor! a) Treated tumor, first patient! b) Treated tumor, second patient! c) Treated kidney/healthy tissue, d) second patient! Picture 2 a-d: A comparison of the infiltrating CD8+ T-cells/CTLs (black stains) in treated and untreated tumors. Untreated tumor (a) shows an average of 15 CTLs per investigated area, to compare with an average of 42 CTLs for the first patient (b) and 300 CTLs for the second patient (c). Rightmost picture (d) shows lack of infiltrating CTLs in the healthy tissue of the treated kidney which indicates that the CTLs are tumor specific.

3 Figure 2: Immunicumʼs project pipeline. MARKET ANALYSIS In 2009, the global cancer vaccine market was estimated to be worth $1,8 billion. By year 2020, this number is expected to have risen to $8 billion, thanks to the introduction of new therapeutic cancer vaccines and an increasing number of cancer patients. The number of people living with cancer is expected to have increased by 50 % in year Thus, the total market for therapeutic cancer vaccines has multi-billion dollar potential. Approximately new cases of RCC are diagnosed worldwide each year, representing about two percent of all cancers. GlobalData estimates that the global RCC market was valued at $1.3 billion in 2009 and is forecast to grow and reach $3.8 billion by Competition The arrival of Sutent and other targeted drugs represents a major step forward compared to the previous standard treatment of RCC. Most of the new treatments target tyrosine kinase pathways and block angionesis, the formation of new blood vessels which help the tumour grow. Sutent earned $1.066 billion in worldwide sales in 2010 according to Pfizerʼs annual report. Even though Sutent and other targeted drugs on the market have been shown to prolong overall survival of metastatic RCC-patients, there is room for improvement, as these drugs are associated with adverse effects, and numerous pharma companies are looking to produce a drug which will represent this next step forward. Immunicum has also identified four (4) companies that are currently developing therapeutic RCC-vaccines (phase I/II-III), however all these vaccines have important drawbacks in comparison to INTUVAC. About 26% of identified therapeutic cancer vaccines in clinical development are antigen-based vaccines and thus ideal to combine with Immunicum s core-concept. All companies in need of effective adjuvants,in addition to all companies that are focused on using patients own (autologous) white blood cells, are considered potential partners. Increased interest in therapeutic cancer vaccines Big Pharma seek partnerships with small Biotechs as part of their strategic plan for acquisition of novel technologies and new drug candidates. Several Big Pharma, such as Pfizer and Eli Lilly, have recently also shifted strategic focus to the oncology market and more emphasis has been placed on developing cancer vaccines. In addition, there has been a renewed interest in cancer immunotherapy due to the first approval of a therapeutic cancer vaccine (Provenge) in the US in An increased interest in cancer vaccines can be exemplified by the billion dollar deal Amgen struck with BioVex in January 2011 to gain access to their late stage therapeutic cancer vaccine OncoVex.

4 ORGANIZATION Immunicum s team brings front edge competence in cancer immunology together with extensive experience from commercial drug development. Immunicum s Chairman of the Board is Agneta Edberg, current CEO of Mylan Nordic. Agneta Edberg has held leading positions within Pfizer and Pharmacia in addition to having been COO for the venture capital firm LinkMed. Bengt Furberg is an expert in clinical trials and has written several books and scientific articles within the field. He spent 10 years as Medical Director at GlaxoWellcome in Sweden and was also part of the company's management team in addition to being member of the corporate group's Medical Board and Safety Board. Per-Olof Gunnesson has over 40 years of experience from the pharmaceutical industry. He has held several management positions at the Astra Group where he also acted as VP of Finance and Licensing. Two of Immunicum s founders, Alex Karlsson-Parra (acting Chief Scientific Officer) and Bengt Andersson, are also members of the Board. They bring over 25 years of experience each from transplantation and infection immunology, in the order given. Jamal El- Mosleh is acting CEO of Immunicum since 2007 and is a graduate from Chalmers University of Technology (Industrial Engineering and Management) and Göteborg International Bioscience Business School (Innovation and Entrepreneurship). He previously worked as a management consultant and as a manager for a biotech startup. Scientific Advisory Board Immunicum has also established a Scientific Advisory Board (SAB), headed by Bengt Furberg, with a very diverse set of important competencies. Rolf Kiessling, MD, PhD, is professor in Experimental Oncology at Karolinska Institutet since 1995 and is a worldrenowned clinical immunologist, among other things known for having discovered and named the Natural Killer (NK)- cell. His group is carrying out investigator initiated clinical trials on cancer patients and also performs basic research in preclinical animal models. Roger Henriksson, one of Sweden s most prominent clinical oncologists is a professor in Experimental Oncology and Chief Physician, Medical Oncology and Radiotherapy since He currently works as Chief of the Regional Cancer Center Stockholm-Gotland. Curt Furberg is an internationally recognized cardiovascular epidemiologist with expertise in clinical trials and public health. He has served on the FDA Advisory Committee on Drug Safety and Risk Management and testified before Congress. Dr. Furberg s honors and awards include the National Institutes of Health Director s Award and the Established Investigator in Clinical Science Award. Finally Dan Magnusson holds a M.Sc. in Pharmacy and Economy and brings broad experience from pharmaceutical industry production and from acting as Qualified Person. Previous experiences include working as International Marketing Manager for Astra/Hässle for the international launch of Losec. FINANCING Total funding to date amounts to approximately 24 MSEK. This funding includes a major grant of 3.5 MSEK in 2010 from The Swedish Governmental Agency for Innovations Systems (VINNOVA s) program Innovations for future health. Among a total of 250 applicants, Immunicum was one of 13 organizations which received funding, after having been reviewed by 17 experts in different areas, based on the following motivation: The application describes an interesting and important project with possibilities of hindering growth and development of existing tumors, and a vision of hindering growth of new tumors. The concept is based on well-founded research. There is good potential that the treatment will be used as a cancer therapy, as well as for other indications. The application has a good clinical relevance, patent strategy, and commercialization plan. OWNERSHIP STRUCTURE As of today, Immunicum has a total of 16 shareholders in addition to seven owners of options with the right to buy shares in the company. The three largest shareholders are: Loggen Invest AB (27%), Holger Blomstrand Byggnads AB (21%), and Chalmers Innovation (15%). The CEO currently owns 4,4% of Immunicum.

5 INTELLECTUAL PROPERTY Immunicum s patent portfolio consists of six patent families protected by one approved Swedish patent, one approved European patent, and six pending patent applications. Former Head of the Patent and Trademark Department at Astra AB, Gerhard Miksche, made the following statement after having reviewed Immunicumʼs patent portfolio: The patent portfolio of Immunicum is varied and well adapted to the business idea. While about half of the patent term of the basic patent family A has passed, later filed patent applications protect important improvements of the basic concept, and thus secure a factual monopoly extending far beyond the term of the basic patents. The main inventor s good understanding of the patent system is a nonnegligible asset of the company. We recently met with representatives of Immunicum who presented the COMBIG concept of allo-dc vaccination. The concept that allo-vaccination with DCs triggers a cascade of immune responses including innate (NK cell activation) and subsequent adaptive, antigen specific responses is interesting and is deserving of further development. We are fully supportive of this work and believe that this allo-dc model may well result in the initiation of anti-tumoural responses where in vitro manipulated autologous DCs have limitations both in terms of GMP manufacture and in their capacity to generate consistent clinical responses. Our own clinical experience suggests that such an approach would be of benefit in melanoma and a range of other solid tumours. Professor Angus Dalgleish, principal of CVI. Dendritic cell, loaded with tumor antigens