On Aug 7, 2007 Integra LifeSciences Holdings Corporation (Nasdaq:IART) ("Integra") and IsoTis, Inc. (Nasdaq:ISOT) ("IsoTis") reported a definitive agreement whereby Integra would acquire IsoTis in an all cash transaction (Press release, Integra LifeSciences, AUG 7, 2007, View Source [SID:1234510753]). This strategic combination, unanimously approved by the Board of Directors of IsoTis, will create a global leader in regenerative medicine. The transaction is expected to be completed in the fourth calendar quarter of 2007. The transaction offers a number of potential strategic benefits to Integra:

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* Combination creates comprehensive orthobiologics portfolio
* Combined company to have one of the largest sales organizations
focused on orthobiologics in the United States
* Extensive channel coverage in neurosurgery, spine and extremity
reconstruction markets expected to drive cross-selling opportunities
and enhanced revenue growth

Upon closing, IsoTis, Inc. will become a wholly-owned subsidiary of Integra. Integra will be one of the largest companies in the world focused on advanced technology in orthobiologics and will have a product portfolio that encompasses some of the largest and most trusted orthobiologic brands, such as INTEGRA(R) Dermal Regeneration Template, DuraGen(R) Dural Graft Matrix, Integra Mozaik(TM) Osteoconductive Scaffold, NeuraGen(R) Nerve Guide and the Accell family of demineralized bone matrix products, DynaGraft(R)II and OrthoBlast(R) II. The combined company will have operations in North America and Europe with more than 2,000 employees, including approximately 300 sales and service professionals and over 500 employees in Europe.

Under the terms of the merger agreement, IsoTis shareholders will receive $7.25 in cash for each share of IsoTis common stock they own, which represents total consideration of approximately $51 million, plus debt to be repaid at closing.

"This combination brings together two well-respected industry leaders in the regenerative medicine marketplace," said Stuart Essig, Integra’s Chief Executive Officer. "Both Integra and IsoTis provide some of the most advanced technology addressing surgeons’ needs. By combining our companies’ complementary, best-in-class products and technologies, we expect to drive enhanced revenue growth and value creation. Integra has a track record of successfully executing on and integrating strategic transactions and we expect to realize the benefits of this combination in both our top line growth and earnings per share over the long term."

Pieter Wolters, IsoTis’ President and Chief Executive Officer, said, " We believe this transaction enables both IsoTis and Integra to reach our shared goal of improving patient outcomes in an innovative, cost-effective manner. We are very excited about the benefits this combination of industry leaders will provide to shareholders, employees, business partners, physicians and patients."

Benefits of the Combination

Comprehensive orthobiologic product portfolio using best-in-class technology. Both Integra’s and IsoTis’ products are recognized as best-in-class. The combined company will be uniquely positioned to offer a comprehensive orthobiologic product portfolio.

Extensive channel coverage. The merged company will have one of the largest sales and service organizations focused on orthobiologics in the United States. IsoTis distributes its products through a network of independent distributor agents in the United States, which Integra intends to build upon, a network of international stocking distributors, and private label partners. Integra has direct sales organizations focused on neurosurgery, extremity reconstruction, spinal surgery and general surgery, with over 250 direct sales reps in the United States and over 50 sales professionals in Europe. Integra intends to integrate IsoTis’ domestic and international sales and marketing organization and its global network of independent orthopedics distributors into its own sales efforts and leverage this expanded distribution.

Cross-selling opportunities. By leveraging the combined company’s product offering and broader channel coverage, Integra and IsoTis expect to drive cross-selling opportunities across the organization, increasing penetration of key customer segments such as neurosurgery, spine, extremity, trauma and reconstructive surgery. These initiatives are expected to enhance revenue growth over the long term.

Expanded international presence. The merged company will benefit from a broader global platform with direct selling organizations in North America and Europe. Today, approximately 25 percent of Integra’s and IsoTis’ combined revenues are generated internationally. The companies expect to increase growth in international revenues by capitalizing on the increased scope and scale created by this transaction, which will include an international direct sales and service team of over 75 associates and 200 distribution partners selling in over 100 countries.

Cost savings. Excluding transaction related costs and charges, the combined organization is expected to generate recurring cost savings from enhanced efficiency in manufacturing, purchasing, administrative, research and sales and marketing efforts.

Integra Guidance for 2008

The companies expect to initiate programs that are expected to enhance revenue growth in the long term. Concurrent with the signing of the merger agreement, the companies have announced a strategic alliance whereby Integra will sell on a private label basis IsoTis’ DynaGraft(R) II and OrthoBlast(R) II demineralized bone matrix products through its Integra NeuroSciences and Integra Extremity Reconstruction direct sales organizations in the United States.

IsoTis has recently announced its intention to wind down its European operations. This process has begun and IsoTis expects to achieve pre-tax savings of approximately $3-$5 million per year from these actions. After elimination of its European entities and facilities, IsoTis will maintain research and manufacturing operations at a single site in Irvine, California.

"While the transaction will be dilutive to reported earnings for several quarters as we restructure the business, we expect the restructuring activities surrounding the IsoTis acquisition to generate projected pre-tax cost savings of approximately $9 to $11 million per year for 2008 and beyond, as compared to IsoTis’ historical 2006 results," said Stuart M. Essig, Integra’s President and Chief Executive Officer. "Substantial savings will come from the reduction of public company costs, duplicative board and executive management costs, redundant insurance costs, and reduced advisory, legal and accounting fees. Additionally, by the end of 2008, Integra expects to complete the integration of IsoTis’ marketing, product development, administrative and logistics functions into Integra’s existing infrastructure and generate additional cost savings."

Integra expects to incur pre-tax charges related to these activities of approximately $3 to $5 million. These charges are expected to be incurred during the fourth quarter of 2007 and the first half of 2008, depending upon the actual closing date of the transaction.

Upon the closing of the transaction, Integra will provide more detailed guidance regarding the financial aspects of the transaction and its expected impact on Integra’s future financial results.

Timing and Approvals

The transaction is subject to approval of IsoTis’ shareholders, as well as other closing conditions and approvals. The transaction is expected to close in the fourth calendar quarter of 2007.

Advisors

In connection with the transaction, Thomas Weisel Partners is acting as exclusive financial advisor to IsoTis, and provided a fairness opinion to the IsoTis Board of Directors. Latham & Watkins LLP is legal counsel for IsoTis. Willkie Farr & Gallagher LLP is legal counsel for Integra.

On July 31, 2007 Cancer Research Technology Limited (CRT), the oncology-focused development and commercialisation company, reported that it has agreed a non-exclusive licence with ArcticDx Inc. for the development of a Colo Risk test to help health professionals determine an individual’s predisposition to developing colorectal cancer (Press release, Cancer Research Technology, JUL 31, 2007, View Source [SID1234523387]).

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The agreement allows for some results from Cancer Research UK funded genome-wide association studies* to be integrated into the risk assessment technology. It is hoped this Colo Risk technology – which is currently in development – will prove effective in assessing people who may be at higher risk of developing bowel cancer so they can receive tailor-made screening and lifestyle advice.

The technology will be based on recent genome-wide association studies which were the first to identify a number of common ‘genetic variants’ that increase bowel cancer risk. These are known as single-nucleotide polymorphisms (SNPs). SNPs appear more frequently in the DNA of people who have developed bowel cancer than of those free from, or at low risk, of developing the disease.

Greg Hines, chief executive officer of ArcticDx Inc. said: "With eight years expertise in the field of in vitro diagnostics development, we’re well placed to take forward these findings and combine them with work we have already done to process information on other risk factors such as age and body mass index which we know also contribute to increased risk of developing the disease. This saliva-based test will be commercially available by the end of this year."

As part of this licensing deal, CRT will receive an upfront payment as well as royalties on any sales.

Dr Phil L’Huillier, CRT’s director of business management, said: "We are committed to ensuring that the most promising findings in the field of cancer research are developed into technology that can be used to fight cancer. This licence agreement with ArcticDx Inc. incorporates important genetic findings into potentially workable technology which could help identify and manage people at higher risk of bowel cancer – it’s an exciting development."

On June 20, 2007 Innate Pharma S.A., a biopharmaceutical company developing new drug classes targeting innate immunity, reported it has entered into a in-licensing agreement with Cancer Research Technology Limited (CRT), the oncology-focused development and commercialisation company, on novel Toll like receptor (TLR) agents (Press release, Cancer Research Technology, JUN 20, 2007, View Source [SID1234523388]).

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The agreement grants Innate Pharma exclusive and worldwide development and commercialisation rights to a panel of discovery stage toll-like receptor 7 (TLR7) modulators to which CRT has exclusive intellectual property rights. At Innate Pharma, the new project will be known as IPH 32XX.

Agents that modulate TLR7 have significant potential for anti-tumour therapy and for the treatment of autoimmune and infectious diseases. Toll-like receptors are found on cells of the immune system and usually play a role in recognising invading pathogens. In cancer therapy, TLR modulators can be used to stimulate the immune system to attack tumours by generating an influx of cancer-killing NK and T cells and the release of inflammatory mediators.

The TLR7 modulators were originally developed by Cancer Research UK-funded studies led by Dr Caetano Reis e Sousa and Dr Sandra Diebold at Cancer Research UK’s London Research Institute. Innate Pharma will support a further programme of pre-clinical research into the agents in Dr Diebold’s laboratory at King’s College London.

CRT will receive an upfront payment, as well as development-based milestones and royalty payments on sales. Financial terms of the transaction were not disclosed.

Commenting on today’s announcement, Dr Phil L’Huillier, CRT’s Director of Business Management said: "TLR7-targeting agents have great potential as cancer therapeutics. We’re delighted that Innate Pharma will be supporting the next steps towards hopefully realising that potential."

François Romagné, Innate Pharma’s EVP and CSO, said: "We now have two active TLR programs (IPH 31XX, a TLR3 agonist, and IPH 32XX, a TLR7 agonist) that have similar chemistry and that will use the same pharmacological/development platform. In addition, we have a new active collaboration with two leading research institutes that will help us to develop new TLR tools and expertise. Our ambition to become a significant player in the field of TLR pharmacology is materializing."

Hervé Brailly, Innate Pharma’s CEO and Chairman of the Executive Board, added: "Consolidating our existing platforms of products by adding new programs from acquisition or in-licensing is part of our business strategy." He added: "This new acquisition is not going to dramatically change our cash horizon, which was 3 to 4 years of cash on hand at the end of 2006."

On June 8, 2007 eXegenics, Inc. (OTC BB: EXEG) reported that it has completed its name change to Opko Health Inc (Press release, Opko Health, JUN 8, 2007, View Source [SID:1234510719]). The company also announced its common stock has been approved for listing on the American Stock Exchange (AMEX). Opko’s stock is expected to begin trading on the AMEX exchange under the ticker symbol OPK on Monday, June 11, 2007.

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"Now that we are officially Opko Health, it is fitting that our shares have been approved for listing on the American Stock Exchange," said Dr. Philip Frost, chairman and CEO of Opko Health, Inc. "The improved visibility and liquidity available to us as an AMEX-listed company should contribute to our efforts to advance our ophthalmic businesses and build shareholder value."

This approval is contingent upon Opko being in compliance with all applicable listing standards on the date it begins trading on the Exchange, and may be rescinded if the company is not in compliance with such standards.

On May 2, 2007 Cancer Research Technology Limited (CRT), the oncology-focused development and commercialisation company, reported it has licensed rights to a panel of cancer therapeutic antibodies to Peptech Limited (ASX:PTD) (Press release, Cancer Research Technology, MAY 2, 2007, View Source [SID1234523389]).

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CRT has granted Peptech an exclusive worldwide licence to a panel of cancer therapeutic antibodies for therapeutic, vaccine and in vitro diagnostic use. The antibodies were originally licensed by CRT to UK biotechnology company Scancell Limited (Scancell), who selected two preclinical lead antibodies, SC101 and SC104 for development in colorectal cancer. Peptech has acquired the entire panel of cancer therapeutic antibodies and the intellectual property relating to these programmes from both Scancell and CRT. Scancell is now using the revenue to progress its novel cancer vaccine platform that it co-developed with CRT.

The panel of antibodies was originally developed by Cancer Research UK-funded studies led by Professor Lindy Durrant at the University of Nottingham and targets antigens that are over-expressed on a variety of tumours. SC101 is a mouse monoclonal antibody recognising Lewis y/b. Unlike other known Lewis y/b antibodies, SC101 binds to both haptens on a range of solid tumours and, unusually, does not bind to normal gastrointestinal tract. The antibody has been shown to induce death in tumour cells that over-express Lewis y/b without the need of immune effector cells in vitro. The same cell model has also been used to demonstrate that SC101 inhibits the growth of human colon tumour xenografts and enhances 5-Fluorouracil (5-FU)/leucovorin killing.

SC104 is a novel mouse monoclonal antibody that recognises a cell surface antigen expressed by 90% of colorectal tumours at all clinical stages. It was generated against 4 different colorectal tumour cell lines and antigen characterisation has shown that the antibody recognises an as yet unknown sialyltetraosylceramide. SC104 directly induces tumour-specific cell death without the need for immune effector cells by induction of caspase-mediated apoptosis. The SC104 antibody also kills synergistically with 5FU/leucovorin both in vitro and in vivo.

Financial details of CRT’s agreement with Peptech were not disclosed, but CRT will receive development-based milestones and royalty payments on sales.