The on-off saga of XOMA’s delisting continues with news that XOMA has received a letter from NASDAQ indicating that the exchange has concluded that XOMA’s previously-announced common share financing completed on September 30, 2009 did not comply with NASDAQ’s Listing Rule that requires that a company obtain shareholder approval for the issuance of common shares or securities exercisable for common shares equal to 20% or more of the common shares outstanding before the issuance for less than the greater of book or market value of the shares. XOMA says it working with NASDAQ and investors to address the issue and take any required corrective action. In the event XOMA is unable to do so, NASDAQ could issue a letter of reprimand or a determination to initiate a process to de-list XOMA’s common shares.
Monthly Archives: November 2009
On November 30 3009 Sanofi-aventis signed an exclusive licensing agreement with Intelliject Inc for a novel epinephrine injector for the emergency treatment of anaphylaxis in North America (US and Canada). Sanofi-aventis is to take responsibility for manufacturing and commercial activities in North America and Intelliject the on-going development and regulatory submission in the US. In addition Intelliject retained certain rights to co-promote the product in the US. Under the agreement Intelliject received an upfront payment and is eligible for future milestone payments and royalties on product sales.
How many partners does Sanofi-aventis have?
Like many pharmaceutical companies Sanofi-aventis does not reveal its exact number of alliances, but in 2008 the company’s Anuual Report indicated the company was stepping up the number of alliances it would like to enter. Some idea of how busy the company is in the alliance space is the fact that the company announced the signing of seven key alliances in the seven months between May and November 2009.
In its Annual Report for 2008 the company listed that its income from alliance agreements was €472 million in 2008, €323 million in 2007 and €382 million in 2006.
According to the company’s partnering brochure more than 25% of the products in Sanofi-aventis’s pipeline were developed through partnerships and more than 30% of its net sales in 2008 came from products developed through partnerships or alliances. Presently 27% of the molecules now in development at Sanofi-aventis originate from external collaborations.
Three of the company’s leading products were developed and are marketed through partnerships with other companies: Bristol-Myers Squibb, Procter & Gamble and Teva Pharmaceuticals.
Sanofi-aventis’ current assets in terms of receivables (source: SEC Form 20-F, 2008)
|From alliances and other*||781||754||947|
|% from alliances||42%||35%||49%|
* This line mainly comprises amounts due from alliance partners, advance payments to suppliers, sales commission receivable, and amounts due from employees.
How does Sanofi-aventis form alliances?
Sanofi-aventis has a team dedicated to sourcing and managing alliances. These teams are based in the following departments: R&D External Innovation and Corporate Business Development.
In November 2009 Christopher Viehbacher, the Chief Executive of Sanofi-Aventis, indicated that the company was looking to up aventure capital fund to help develop strategic partnerships with drug-developers.
Who are Sanofi-aventis’s partners?
Ajinomoto, Becton Dickinson, BioWa, Bristol-Myers Squibb, Coley, Crucell, DNDi, Dyax, Exelixis, Genfit, Human Genome Sciences, Johns Hopkins University, Novozymes, IDM, Immunogen, Innogenetics, Inserm, Institutes of Biological Sciences (Shanghai), Institute of Hematology and blood diseases Hospital in Tianjin (China ), Intercell, Kyowa Hakko Kirin, Malaria Venture, Maxigen, Merrimack, Micromet, Oxford BioMedica, Procter & Gamble, RainDance Technologies, Regeneron, Salk Institute, SSI, Taiho Pharmaceutical Co Ltd, Teva Pharmaceutical, UCB, University Louis Pasteur, University of Pennsylvania, Vactech, Wayne State University, Wellstat Therapeutics and Zealand Pharma,
Some key collaborations has Sanofi-aventis entered into over the past few years?
- In October 2009 Sanofi-aventis and Micromet signed a global collaboration and license agreement to develop a BiTE® antibody against an antigen present at the surface of carcinoma cells. BiTE antibodies are novel therapeutic antibodies that activate patients’ T cells to seek out and destroy cancer cells. Under the agreement Micromet is responsible for the discovery, research and development of the BiTE antibody through the completion of phase 1 clinical trials under the supervision of a Joint Steering Committee. Sanofi-aventis will then have the full responsibility for the further development, as well as for the worldwide commercialization of the BiTE antibody. Micromet received an upfront cash payment of 8 million euros and is eligible for development and regulatory milestone payments of up to 162 million euros, royalties on worldwide product sales and will receive additional performance-based sales milestones of up to 150 million euros.
- In October 2009 Sanofi-aventis and Wellstat Therapeutics entered a global licensing agreement on PN2034, a novel oral first-in-class, insulin sensitizer, for the treatment of Type II Diabetes, currently in Phase II clinical testing. Under this agreement, Sanofi-aventis received an exclusive worldwide license to develop, manufacture and commercialise PN2034 and related compounds. Wellstat Therapeutics received an upfront cash payment for the development, manufacturing and commercialisation rights, and is eligible for $350 million in development and regulatory milestone payments. Wellstat Therapeutics is also to receive royalties on the worldwide product sales and performance based sales milestones.
- In October 2009 Sanofi-aventis and Merrimack Pharmaceuticals entered an agreement whereby Sanofi-aventis woul receive an exclusive worldwide license to develop, manufacture and commercialise MM-121, a first-in-class, fully human monoclonal antibody in phase 1 clinical testing designed to block signaling of the ErbB3 (also known as HER3) receptor, for the management of solid malignancies. Under the agreement, Merrimack retained potential co-promotion rights in the US. Merrimack received an upfront cash payment of US$60 million for the research, development, manufacturing and commercialisation rights and is eligible for development and regulatory milestone payments up to US$410 million on MM-121, royalties on the worldwide product sales and could receive additional performance milestones of up to US$60 million on worldwide sales. Merrimack is participating in the development of MM-121.
- In May 2009 Sanofi-aventis and Exelixis entered a global license agreement for XL147 and XL765 and an exclusive collaboration for the discovery of inhibitors of phosphoinositide-3 kinase (PI3K) for the management of solid malignancies. The agreement granted Sanofi-aventis an exclusive worldwide license to both compounds which are currently in phase 1 clinical trials. Sanofi-aventis has sole responsibility for all subsequent clinical, regulatory, manufacturing and commercial activities while Exelixis is to participate in ongoing and future clinical trials. The two companies are combining their research efforts to establish several preclinical programmes related to isoform-selective inhibitors of PI3K with Sanofi-aventis taking sole responsibility for all subsequent clinical, regulatory, commercial and manufacturing activities of the products that result from the collaboration and Exelixis taking responsibility for conducting certain clinical trials. Exelixis received an upfront cash payment and is eligible for development and regulatory milestone payments that could reach over $1 billion in aggregate for existing and future programmes. In addition, Exelixis is entitled to receive royalties and commercial milestones on sales when products are commercialised.
- In May 2009 Sanofi-aventis and the non-profit Drugs for Neglected Diseases initiative (DNDi)signed an agreement for the development, manufacturing and distribution of fexinidazole, a promising new drug for the treatment of human African trypanosomiasis, also known as sleeping sickness, a fatal disease that threatens 60 million people in Sub-Saharan Africa.
- In May 2009 Sanofi-aventis and Kyowa Hakko Kirin Co Ltd signed a collaboration and licensing agreement whereby Sanofi-aventis received worldwide rights to Kyowa Hakko Kirin’s anti-LIGHT fully human monoclonal antibody. Presently in the preclinical stage the antibody is expected to be a first in class therapy for ulcerative colitis and in Crohn’s disease. Under the agreement the antibody might also be pursued for other indications such as rheumatoid arthritis. Sanofi-aventis has exclusive rights to develop the product worldwide, except in Japan and Asian countries where both parties will co-develop the product. Kyowa Hakko Kirin retained the rights to market the product in Japan and in Asia, while sanofi-aventis gained exclusive rights to market and sell the product in the rest of the world. Each party has an option to co-promote the product in the territory of the other party. Kyowa Hakko Kirin received an upfront payment and is eligible for a totla of US$315 million in development milestone payments as well as royalties on sales when the product is commercialised.
- In December 2008 Sanofi-aventis signed a global licensing and collaboration agreement with Novozymes for the development and commercialisation of a new antibiotic named plectasin NZ2114 that targets the treatment of severe infections such as pneumonia and septicemia. Sanofi-aventis gained an exclusive worldwide license for the development, registration, and commercialisation of the drug. Both companies are working jointly to develop and implement industrial-scale manufacturing of the drug using a recombinant process that builds on Novozyme’s proprietary expression technology. Milestone payments under the agreement could reach up to US$64 million.
- In February 2008, Sanofi-aventis obtained an exclusive worldwide license for the development and commercialisation of Dyax Corporation’s fully human monoclonal antibody DX-2240, as well as a worldwide non-exclusive license to Dyax’s proprietary Phage Display technology. In return Dyax is eligible to receive up to US$270 million in license fees and milestone payments if the antibody is successfully commercialised for three indications and in one indication for the first antibody candidates developed by Sanofi-aventis alone using the Phage Display technology.
- In December 2007 Ssanofi Pasteur signed an exclusive collaboration and commercialisation agreement with Crucell NV for Crucell’s rabies monoclonal antibodies. Under the terms of the agreement, Crucell
was to continue to develop and manufacture the product. The contract includes milestone payments that could reach US$53 million.
- In March 2007 Sanofi-aventis and Oxford BioMedica entered into an exclusive global license agreement to develop and commercialize TroVax® for the treatment and prevention of cancers. Under the agreement Oxford BioMedica could receive up €450 million in milestone payments and is also entitled to escalating royalties on global sales of TroVax®, and to sales milestone payments if and when net sales of TroVax® reach certain levels.
- In November 2007 Sanofi-aventis signed an agreement with Regeneron to discover, develop and commercialise fully-human therapeutic antibodies. Sanofi-aventis is to provide up to $416 million for research funding over the next five years. Sanofi-aventis has an option to extend the research agreement for an additional three years. Under the terms of the development agreement, Sanofi-aventis is to fund 100% of the development costs. Once a product begins to be marketed, Regeneron will repay out of its profits (provided they are sufficient) half of the development costs borne by Sanofi-aventis. In addition, Regeneron is entitled to receive up to a total of US$250 million of sales milestone payments when the collaboration achieves certain aggregate annual excluding US sales levels. The two companies extended the alliance in November 2009 taking the collaboration up to 2018 and increasing Sanofi-Aventis’s funding of the project to US$160 million a year.
- In September 2003, Sanofi-aventis signed a collaboration agreement with Regeneron in oncology to develop the Vascular Endothelial Growth Factor (VEGF) Trap program. Under the agreement Regeneron is entitled to development milestone payments and royalties on VEGF Trap sales that could reach US$400 million if all indications specified in the contract obtain approval in the United States, Europe and Japan. Sanofi-aventis is to pay 100% of the development costs of the VEGF Trap. Once a VEGF Trap product starts to be marketed, Regeneron will repay 50% of the development costs (originally paid by Sanofi-aventis) in accordance with a formula based on Regeneron’s share of the profits, including royalties received in Japan. In 2005, the VEGF Trap program was extended to Japan, and the treatment of ocular pathologies was excluded from the scope of the collaboration agreement.
How many partners does Eli Lilly have?
Like many pharmaceutical companies Eli Lilly does not provide the exact number of collaborations it has. Some idea of how strong alliances are within the company can be seen from its product pipeline listed in the company’s Annual Report for 2008, as shown below.
Percentage of products on market and in pipeline with alliance agreements
|Total products||Alliance||% alliance|
|Major marketed products||18||6||33%|
|New Drugs Application products submitted for FDA review||9||2||22%|
|Select drug candidates in late-Stage investigation||10||2||20%|
|Select drug candidates in mid-stage investigation||29||2||7%|
How does Eli Lillty source partners?
Eli Lilly has a number of teams across the company focused on identifying, developing, and commercialising products and technologies from external sources. The key teams involved include:
- Global External Research and Development (GER&D) group, responsible for the identification, coordination, and scientific evaluation of new opportunities.
- Corporate Business Development (CBD) group, responsible for forming alliances.
- Corporate Finance—Investment Banking (CFIB), responsible for in-licensing and corporate projects through economic and financial-implication analytical work. CFIB has a strong emphasis on investment bank relationship management, valuation, financial analysis, merger and acquisition negotiation, acquisition-transaction due diligence, integration planning and execution, and other transaction-related disciplines.
- Office of Alliance Management (OAM), responsible for implementing and building relationships with each alliance partner after an agreement is signed.
In June 2009 the company set up a new web portal to facilitate more collaboration with academic laboratories and biotechnology companies. Called the Lilly Phenotypic Drug Discovery Initiative, or PD2, the portal allows external scientists to confidentially upload compounds of interest that Lilly can then apply its proprietary algorithms and assays to in order to review their therapeutic potential. This evaluation is free and at this stage, all intellectual property remains with the scientists submitting the compound. After the next tests are completed, Lilly provides the scientists with a biological profile across four assay modules: Alzheimer’s disease, cancer, diabetes, and osteoporosis. With the submission of this information to the researcher Lilly obtains the first right to exclusively negotiate a collaboration or licensing agreement, should it choose to further explore these compounds. If no agreement is reached within a pre-defined time period, the researcher is granted “no-strings-attached ownership” of the data report and can use the information freely.
Who are Eli Lilly’s partners?
Some of Eli Lilly’s partners are: 454 Life Sciences, Almac Diagnostics, Ambrx, Amylin Pharmaceuticals, BioMS Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, China Meditech, Chugai Pharmaceutical, Corcept Therapeutics, Covance, Daiichi Sankyo, Deciphera Pharmaceuticals, GE Healthcare, Glenmark Pharmaceuticals, ICOS Corporation, Isis Pharmaceuticals, Kyowa Hakko Kirin, MacroGenics, Medtronics, Nanosphere, NeuroSearch, OSI Pharmaceuticals, Piramal Life Sciences, Quintiles Transnational, Ranbaxy, Roche NimbleGen, Shionogi, Suven Life Sciences, TPG-Axon Capital, TransPharma Medical, United Therapeutics, University of Cincinnati
What collaborations has Eli Lilly entered into over the past few years?
- In September 2009 Almac Diagnostics and Lilly UK entered into a partnership to develop a companion diagnostic for ALIMTA, with cisplatin, as a combination therapy for non-squamous non-small cell lung cancer.
- In July 2009 454 Life Science and Roche NimbleGen, both units of Roche Applied Science, began a collaboration with Eli Lilly and SeqWright, a company specialising in custom genomic and molecular biology services. The goal of the collaboration is to identify genetic variants possibly associated with various psychiatric diseases. SeqWright is to utilize NimbleGen Sequence Capture technology to selectively enrich approximately 40 megabases of the human genome, which will then be comprehensively sequenced using 454 Life Sciences’ Genome Sequencer FLX System.
- In May 2009 Eli Lilly and Medtronic started a strategic marketing collaboration to improve the delivery of diabetes education for people and caregivers affected by type 1 diabetes.
- In Feburary 2009 Eli Lilly signed an agreement with NeuroSearch to form a three-year drug discovery and development alliance to investigate a defined number of undisclosed ion channel targets for their potential in treating various central nervous system (CNS) disorders. The aim of the collaboration is to discover and develop new medicines based on novel approaches to specific ion channel modulation. The collaboration comprises intellectual property and know-how from both NeuroSearch and Lilly. NeuroSearch received US$5 million upfront and is eligible to US$13 million in research funding over the next three years. Lilly also made a US$17 million equity investment in Neurosearch. Within the collaboration NeuroSearch is responsible for the drug discovery programmes any early development of novel drug candidates. Lilly has options to exercise license rights to individual compounds covered by the agreement and related intellectual property. Upon exercise of license rights, Lilly will be responsible for all subsequent development and commercialisation activities. NeuroSearch is entitled to milestone payments of up to US$ 320 million plus royalties on the product’s global sales.
- In October 2008 Eli Lilly and Deciphera Pharmaceuticals LLC entered into a collaboration and worldwide licensing agreement related to Deciphera’s preclinical B-Raf kinase inhibitor programme for the study of potential oncology therapeutics. Under the terms of the agreement, Lilly and Deciphera are collaborating in four different project areas involving selective or multi-kinase targeted B-Raf inhibitors. Lilly is to have exclusive worldwide rights to any products developed as part of this collaboration. Deciphera received an upfront payment and and is entitled to research funding over two years from Lilly. It may also receive up to US$130 million development, regulatory and sales milestones for each of the four project areas and royalties on sales from any products commercialised from the collaboration.
- In September 2008 Eli Lilly and Corcept Therapeutics entered a partnership whereby Lilly would fund studies to test the effectiveness of Corcept’s selective GRII receptor antagonis, CORT 108297, in rat models of olanzapine induced weight gain.
- In June 2008 Eli Lilly entered into a licensing and development agreement with TransPharma Medical Ltd to acquire rights to its product and related drug delivery system for the treatment of osteoporosis that was in Phase II testing.
- In February 2008 Nicholas Piramal India Ltd’s and Eli Lilly signed a second agreement to develop a new drug. The deal could bring Nicolas Priamal up to US$110 million, plus royalties on sales.
- In December 2007 Lilly and BioMS Medical entered a global licensing and development agreement whereby Lilly acquired exclusive worldwide rights to BioMS Medical’s lead multiple sclerosis (MS) compound, MBP8298 (dirucotide), a novel late-stage molecule currently being evaluated in two pivotal Phase III clinical trials in secondary progressive MS (SPMS) and one Phase II clinical trial in relapsing-remitting MS (RRMS). The two companies are co-developing the compound and sharing the costs with Lilly responsible for future research and development manufacturing, and marketing activities and BioMS Medical overseeing the clinical trials.
- In December 2007 Eli Lilly and Ambrx Inc entered into a collaboration to discover and develop novel treatments in several therapeutic areas, including metabolic diseases, central nervous system disorders and other diseases. The collaboration is applying Ambrx’s unique protein optimization technology, ReCODETM, with Lilly’s expertise in biologics discovery, development and commercialization to pursue first-in-class or best-in-class drug candidates, including therapeutic antibodies and improved variants of native proteins. Ambrx received an initial upfront payment and is eligible for ongoing research support payments and research and development milestones, and royalties.
- In October 2007 GE Healthcare and GE Global Research, two units of General Electric Co, into a three-year collaborative research agreement with Eli Lilly to develop in vitro diagnostic assays for cancer treatment. The assays would be used to predict the response of cancer treatment to targeted therapies.
- In October 2007 Eli Lilly entered into an agreement with Glenmark Pharmaceuticals Limited India to acquire the rights to a portfolio of transient receptor potential vanilloid sub-family 1 (TRPV1) antagonist molecules, including an early clinical-phase compound in development as a potential next-generation treatment for various pain conditions, including osteoarthritic pain. Since the agreement development of this compound has been suspended.
- In October 2007 Eli Lilly entered into a global strategic alliance with MacroGenics, Inc to develop and commercialize teplizumab, a humanized anti-CD3 monoclonal antibody, as well as other potential next-
generation anti-CD3 molecules for use in the treatment of autoimmune diseases. Under the agreement Eli Lilly acquired the exclusive rights to the molecule, which was in the development stage (Phase II/III clinical trial for individuals with recent-onset type 1 diabetes).
- In January 2007, Eli Lilly entered into an agreement with OSI Pharmaceuticals Inc to acquire the rights to its compound for the treatment of type 2 diabetes, then in phase I clinical trials. .
On November 27 2009 Oxford Expression Technologies Ltd signed research collaboration agreements with ParaTechs and LifeSensors to enhance and expand OET’s flashBAC™ portfolio of baculovirus protein expression systems.
The collaboration with ParaTechs will investigate the potential impact of expressing a Vankyrin gene in tandem with a foreign gene on the quality and yield of the foreign protein and to evaluate whether any benefits are enhanced by using the flashBAC system, which is already known to increase recombinant protein yields beyond those achieved using a conventional vector. This project will also compare flashBAC vectors expressing Vankyrin gene-fusions in ParaTechs Vankyrin-Enhanced cell lines, with standard insect cell lines.
The collaboration with LifeSensors aims to incorporate a SUMO (small ubiquitin-like modifier) tag into the flashBAC system, and evaluate whether this increases the quality of protein produced. The use of SUMO as a fusion tag has been shown to dramatically increase yield and solubility of protein in more traditional systems. The two companies are hoping that SUMO will create an even more powerful flashBAC system.
On November 23 2009 Pfizer Ltd acquired for US$0.75 million certain assets related to stem cell therapies from Axordia Limited, a whole-owned subsidiary of Intercytex Group plc, and a developer of stem cell therapies for human diseases.
On November 24 2009 Biovitrum AB completed the sale of its wholly-owned subsidiary Cambridge Biotechnology Ltd and certain drug development programmes to Proximagen Neuroscience plc. The drug development programmes consist of the pre-clinical stage programmes VAP-1 and Trk A as well as two clinical stage programmes, the 5-HT2c agonist and 5-HT6 antagonist programmes. In return Biovitrum is entitled to a share of future revenues generated from the pipeline. Financial details were not disclosed by the companies.
On November 25 2009 Merck & Co and Idera announced they are extending their three year partnership for fourth year. Begun in December 2006 the collaboration aims to develop vaccines that could be used against cancer, infectious diseases, and Alzheimer’s disease. The extension will complete the contract between Idera and Merck, as the companies agreed to work together for two years with two one-year options.
As of Februrary 2010 Novartis is to terminate its research collaboration agreement begun with Idera Pharmaceuticals Inc in May 2005. The aim of the collaboration was to discover, develop, and commercialize TLR9 agonists that are based on Idera’s proprietary IMO chemistry and identified as potential treatments for asthma and allergies.
Under the agreement, Idera received a US$4 million upfront license fee and in 2007 a US$1 million payment for an extension of the research collaboration. In March 2008 the research agreement was extended to December 2008 to allow for the progress of QAX935 (IMO-2134), a novel agonist of TLR9 identified in the collaboration, into human clinical trials. Idera received a US$1 million milestone payment f as a result of the initiation of the Phase 1 clinical study.
With the termination of the research collaboration in February 2010 Idera will regain all rights to IMO-2134 without any financial obligations to Novartis and will no longer be subject to restrictions on its right to develop its TLR-targeted compounds, including its TLR antagonists and TLR antisense oligonucleotides, for respiratory diseases.
On November 26 2009 Merck & Co Inc indicated that it plans to start a clinical phase IIa trial with the biotechnology company Karo Bio’s lead investigational drug candidate, MK-6913, identified as part of their joint research collaboration. The randomized, double-blind, placebo- and active-controlled study will assess the safety, tolerability, and efficacy of MK-6913 for the treatment of moderate-to-very-severe vasomotor symptoms (hot flashes/hot flushes) in postmenopausal women. It is estimated that 300 patients will be enrolled in the study.
In the partnership Merck has the exclusive worldwide rights to all compounds identified during the collaboration and is responsible for their further preclinical and clinical development. Karo Bio has the rights to certain milestone payments from Merck based upon the further successful clinical development of the compound and final drug approval, but is not to receive a milestone payment for the initiation of the phase II trial. Karo Bio has the rights to royalties on future drug sales.
The collaboration is targeting estrogen receptors with the aim to develop novel treatments in the field of women’s health. The joint drug discovery phase of the collaboration with Merck was completed in 2002. MK-6913 is the first such estrogen receptor compound arising from the collaboration to enter Phase II.