On November 2, 2006 XOMA Ltd. (Nasdaq:XOMA) and Takeda Pharmaceutical Company Limited (TSE4502:Takeda) reported that they have entered into an agreement for therapeutic monoclonal antibody discovery and development (Press release, Xoma, NOV 2, 2006, View Source [SID1234537390]). The collaboration is intended to capitalize on XOMA’s comprehensive antibody discovery, development and production technologies and expertise.

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The agreement calls for Takeda to make up-front and milestone payments to XOMA, fund XOMA’s R&D activities including manufacturing of the antibodies for preclinical and early clinical supplies, and pay royalties to XOMA on sales of products resulting from the collaboration. Payments to XOMA could exceed $100 million before royalties over the life of the collaboration.

Using its extensive collection of phage display libraries and antibody optimization technologies, XOMA will discover therapeutic antibodies against multiple targets selected by Takeda. Other XOMA activities will include preclinical studies to support regulatory filings, cell line and process development, and production of antibodies for initial clinical trials. Takeda will be responsible for clinical trials and commercialization of drugs after IND submission, and is granted the right to manufacture once the product enters into phase 2 clinical trials.

"XOMA’s extensive antibody discovery and development expertise and technologies fit well with Takeda’s objective of building a strategic presence and pipeline in therapeutic antibodies. We look forward to working with our new partner," said John L. Castello, chairman of the board, president, and chief executive officer of XOMA.

"We are pleased with the conclusion of the agreement with XOMA, which has state-of-the-art technology in the antibody field," said Shigenori Ohkawa, PhD, General Manager of Pharmaceutical Research Division of Takeda. "We believe that the collaboration with XOMA will accelerate our drug discovery and development activities in therapeutic antibodies, a field that continues to grow as an important source of new medicines."

On October 11, 2006 Bellicum Pharmaceuticals reported an non-exclusive, royalty-bearing licensing agreement with ARIAD Pharmaceuticals for its ARGENT cell-signaling regulation technology. ARIAD will have an equity stake in Bellicum and will receive additional payments (Press release Bellicum Pharmaceuticals, OCT 11, 2006, View Source [SID:1234500803]). Bellicum also may be granted exclusive licenses in certain product applications based on its achievement of development, regulatory and commercial milestones. The Bellicum product candidates will use ARIAD’s small molecule dimerizer drug, AP1903, which already has successfully completed a Phase 1 clinical trial.

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Bellicum Pharmaceuticals, Inc. is focused on the development of next generation therapeutic vaccines and other immunotherapeutic approaches for the treatment of cancer. Bellicum’s BP-GMAX-CD1 lead product candidate is a novel dendritic cell vaccine to treat prostate cancer. This vaccine incorporates an AP1903-activated CD40 gene, which acts as a pharmacologically regulated switch to boost the potency and enhance the durability of the anti-cancer immune response (see, Hanks, et al, Nature Medicine2005, 11:130). "We are delighted that ARIAD has selected Bellicum to advance the dimerizer technology", stated Bellicum CEO Tom Farrell. "We have assembled a compelling set of preclinical data, and completion of this license now allows us to move rapidly to clinical development of our first cancer vaccine."

In a widely reported study (Morgan, et al, Science 10.1126/science.1129003, published online 31 August 2006), researchers at the National Cancer Institute reported the cure of two advanced melanoma patients using a genetically modified autologous vaccine. According to Bellicum Founder and Baylor Prostate Center Director Kevin Slawin, M.D., "Dr. Rosenberg’s work has demonstrated proof of principle that genetically modified autologous vaccines, such as those being developed by Bellicum, can lead to the complete eradication of even advanced cancers, an achievement rarely seen with more conventional therapies, whose benefits are often more incremental".

David M. Spencer, Ph.D., Bellicum’s Co-Founder and Chief Scientific Officer, and Associate Professor of Immunology, Baylor College of Medicine, co-invented the dimerizer technology while a student in Professor Gerald R. Crabtree’s lab at Stanford University. He is also the lead author of the seminal dimerizer paper (Spencer, et al, Science 1993, 262, 1019). "It is especially gratifying to see my earlier work at Stanford come full-circle with the opportunity to apply the dimerizer technology to our work here at Bellicum," stated Spencer.

On September 4, 2006 Cancer Research Technology (CRT), the oncology-focused development and commercialisation company wholly owned by Cancer Research UK, reported that they have entered into an agreement with AstraZeneca focused on colorectal cancer (Press release, Cancer Research Technology, SEP 4, 2006, View Source [SID1234523395]).

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Within the agreement, the Cancer and Immunogenetics Laboratory led by Sir Walter Bodmer at the Weatherall Institute of Molecular Medicine will collaborate with AstraZeneca to characterise the expression of key genes involved in colorectal cancer. The Cancer and Immunogenetics laboratory will provide critical reagents and data and the programme of research will be undertaken by AstraZeneca. The findings of this collaboration will be shared by both CRT and AstraZeneca.

The data generated will be used to advance AstraZeneca’s proprietary anti-colorectal cancer programs by increasing the understanding of the link between molecular pathology of disease and efficacy of novel targeted therapeutics aimed at colorectal cancer. The results will assist in the identification of novel drug targets and in development of drugs that are effective against chemoresistant tumours.

According to Sir Walter Bodmer, "We are very excited by the opportunities offered by this collaboration between our laboratory in Oxford, CRT and AstraZeneca. The information collected will greatly enhance our ability to relate and target drug responses to the molecular pathology of colorectal cancers."

Dr. Les Hughes, Head of Cancer and Infection Research at AstraZeneca, adds, "This is a promising collaboration which builds on the strengths of both institutions. By combining our expertise I am confident that this partnership will result in findings which will ultimately benefit cancer patients."

Colorectal cancer is the fourth most common cause of death from cancer worldwide. Each year an estimated one million people are diagnosed with colorectal cancer, accounting for 8% of deaths from cancer. Current treatments for advanced disease are primarily palliative and the 5-year survival rate for patients with advanced colorectal cancer is less than 10%.

On August 31, 2006 Sareum Holdings plc (AIM: SAR), the specialist structure-based drug discovery business, reported that substantial progress has been made in its joint cancer drug discovery collaboration with The Institute of Cancer Research (The Institute), Europe’s leading cancer research centre, and Cancer Research Technology Limited (CRT), the oncology-focused development and commercialisation company (Press release, Cancer Research Technology, AUG 31, 2006, View Source [SID1234523396]). Sareum, The Institute and CRT have discovered novel compound series which show efficacy in cancer cell models.

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The collaboration, which was announced in July 2005, has discovered several novel compound series that target a specific enzyme in a key biochemical pathway, responsible for preventing the effectiveness of traditional cancer therapeutics such as chemotherapy. In the collaboration the team is now working to fully optimise a leading series of compounds to provide a validated candidate to take forward into clinical development. The new cancer therapeutics developed will potentially allow effective treatment of tumours which currently do not respond to current treatments as well as lowering the dose required of existing therapies to reduce adverse side effects.

Sareum has used its expertise in structure-based drug discovery to identify novel compounds using its innovative Template Screening technology. These compound series have been rapidly progressed utilizing Sareum’s high throughput medicinal chemistry and structure determination platforms combined with the drug screening, specialist cancer biology and medicinal chemistry expertise at The Cancer Research UK Centre for Cancer Therapeutics at The Institute.

Under the terms of the agreement CRT will commercialise the drug candidates developed by the collaboration to secure future clinical development. Payments, milestones and royalties received by CRT will be shared with Sareum and The Institute.

Commenting on the agreement, Sareum’s Chief Executive Officer, Dr Tim Mitchell, said: "The quality of the science and technology applied to this collaboration has led to outstanding progress. This demonstrates Sareum’s ongoing commitment to the discovery of new treatments to meet unmet medical needs in cancer. We are now looking forward to advancing our novel chemical series through to clinical candidate nomination next year."

Professor Paul Workman, Director of The Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, said: "The addition of Sareum’s powerful technology platform to our own in-depth expertise in the development of targeted molecular therapeutics has allowed us to move forward very rapidly on this exciting and important target. Development of a drug against this target would benefit patients who are currently resistant to current treatments."

On April 24, 2006 Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) reported that it has acquired complete ownership and control of PSMA Development Company LLC (PDC), by purchasing Cytogen Corporation’s (Nasdaq: CYTO) interest in the joint venture which is developing in vivo cancer immunotherapies based on prostate-specific membrane antigen (PSMA) (Press release, Progenics Pharmaceuticals, APR 24, 2006, View Source [SID1234523592]). PSMA is a protein primarily found on the surface of prostate cancer cells and new blood vessels associated with other solid tumors; therefore, targeting PSMA offers the potential for highly specific cancer therapy. Progenics purchased Cytogen’s 50% interest in PDC in exchange for an upfront payment of $13.2 million in cash, plus potential future milestone payments totaling up to $52 million payable upon regulatory approval and commercialization, and an undisclosed royalty on future product sales. The technologies acquired in this purchase include those originating from Memorial Sloan-Kettering Cancer Center, the institution that first discovered PSMA, as well as those developed by PDC. The purchase encompasses the PSMA antibody-drug conjugate (PSMA ADC) and two vaccine products in development by PDC.

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"We are committed to developing PSMA-based immunotherapies for prostate cancer that are potentially less toxic and more active than existing treatments," said Paul J. Maddon, M.D., Ph.D., Progenics’ Founder, Chief Executive Officer and Chief Science Officer. "Having acquired all rights to in vivo PSMA immunotherapies, we now plan to develop them fully. Prostate cancer patients with metastatic disease have the greatest unmet medical need, and we intend to initiate phase 1 clinical studies in this setting in 2007 with our PSMA ADC. Progenics has core research and development, manufacturing, clinical, and regulatory teams in place and plans to leverage them to expedite PSMA-based drug development."

PSMA antibody-drug conjugate technology

PSMA ADC is a fully human monoclonal antibody that specifically targets PSMA and is chemically linked to a cell-killing payload-auristatin, a highly potent synthetic drug. The linker is designed to be stable in the bloodstream and to release the drug payload under specific conditions once inside the targeted cancer cells, potentially sparing normal cells many of the toxic effects of traditional chemotherapy.

PSMA ADC has been tested in vitro and in animals for the ability to selectively eliminate prostate cancer cells. In laboratory studies, PSMA ADC killed PSMA-expressing prostate cancer cells at picomolar concentrations, whereas approximately 1,000-fold higher concentrations were required to kill cells that lack PSMA. PSMA ADC was similarly active against prostate cancer cells that were either sensitive to or resistant to androgen deprivation. In a recognized animal model, PSMA ADC showed activity against human prostate cancer cells and significantly prolonged overall survival.

PSMA vaccines

To prevent the recurrence of prostate cancer after initial surgery or radiation therapy, PDC is also developing two PSMA-based therapeutic vaccine candidates to stimulate the immune system to recognize prostate cancer cells as foreign and to eliminate them. The Company has begun planning human testing of a viral-vector vaccine. Phase 1 clinical studies of a recombinantsoluble PSMA vaccine have shown that certain prostate cancer patients produced anti-PSMA antibodies in response to the vaccine. Progenics’ research department is optimizing the vaccine before advancing this product candidate into phase 2 clinical testing.

Prostate Cancer

Prostate cancer is the most common form of cancer affecting men in the United States and is the second leading cause of cancer deaths among men each year. The American Cancer Society estimated that 232,090 new cases of prostate cancer were diagnosed and that 30,350 men died from the disease during 2005 in the United States.