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Novel compounds discovered in cancer drug discovery collaboration

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."

Progenics Pharmaceuticals Acquires Full Ownership of Prostate Cancer Joint Venture

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.

"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.

Pharminox signs option to in-license novel telomere signalling targeted agents from CRT

On April 19, 2006 Pharminox Limited, ("Pharminox" or "the Company") the private UK oncology R&D company, reported that it has signed a new agreement with Cancer Research Technology Limited (CRT) to secure rights to a preclinical oncology programme focused on telomere signalling targeted agents (TSTAs) (Press release, Cancer Research Technology, APR 19, 2006, View Source [SID1234523397]). The programme has come out of research by Professor Malcolm Stevens OBE, Director of the Cancer Research UK Experimental Cancer Chemotherapy group at the University of Nottingham, who is also Chief Scientific Officer of Pharminox.

Under the terms of the agreement, CRT has granted Pharminox an exclusive 12-month option to in-license exclusive worldwide development and commercialisation rights to the programme. A lead candidate, RHPS4, has already been selected and is expected to move into formal preclinical development within the next 12 months.

Commenting on today’s announcement, Peter Worrall, Chief Executive of Pharminox, said: "This agreement is our third collaboration with CRT and we welcome the opportunity to build on the strong relationship that we already have with CRT. The TSTA programme is a very valuable addition to our portfolio and represents another important step towards our goal of building a pipeline of targeted, small-molecule anti-cancer agents with novel mechanisms of action spanning research through to early-stage clinical development."

Mechanistic studies with RHPS4 suggest that it exerts its activity primarily by disrupting the function of the telomere, the single-stranded piece of DNA at the end of chromosomes. RHPS4 is also a potent inhibitor of telomerase, an enzyme whose role is to maintain telomere length in order to prevent cells entering a process known as apoptosis (programmed cell death). Telomerase is known to be highly up-regulated in 90% of all cancer cells.

RHPS4 has shown potent anti-tumour activity against a range of common human tumours in in vitro and in vivo testing. In xenograft models, it has shown tumour growth inhibition of up to 90% relative to control when given as a single agent. In a combination study with the marketed anti-cancer agent paclitaxel (Taxoltm) in a uterine tumour model, it produced complete and rapid eradication of the tumours with no observable re-growth throughout the remainder of the study. Paclitaxel given as a single agent in a separate arm of the same study achieved good tumour growth inhibition but no tumour regression.

Professor Stevens commented: "I am delighted that Pharminox has been able to secure the rights to this exciting programme. TSTAs represent a highly promising new area of cancer research and we believe RHPS4 to be one of the most advanced compounds in this class. During the option period our intention is to carry out additional in vivo studies to build on the impressive data that we have already seen and to inform the design of a clinical trial."

Dr Phil L’Huillier, CRT’s Director of Business Management, added, "We are enthusiastic about the prospects for this novel programme and we are pleased to be able to facilitate its continued development under the auspices of Pharminox and Professor Stevens."

Polaris Acquires Phoenix Pharmacologics, Inc. Intellectual Property

On March 30, 2006, Polaris reported that it has completed a series of agreements that culminates in acquiring the intellectual property of Phoenix Pharmacologics, Inc (Press release, Polaris Pharmaceuticals, MAR 30, 2006, View Source [SID1234526555]). Polaris now holds the worldwide rights, excluding Taiwan and China, to ADI‑PEG 20 and worldwide rights, excluding Taiwan, to Uricase-PEG 20. ADI‑PEG 20 is a pegylated form of the enzyme arginine deiminase, a biotherapeutic agent currently in Phase 2 clinical trials for the treatment of both hepatocellular cancer and metastatic melanoma. Uricase-PEG 20 is a pegylated form of urate oxidase, a biotherapeutic agent that has successfully completed a Phase 1 clinical study and is now being developed for the treatment of refractory gout, hyperuricemia, and tumor lysis syndrome.

With this purchase, Polaris has also acquired the rights to several early development stage biotherapeutic agents, including TNF-PEG 20 and Histidase-PEG 20, and novel potent small molecule inhibitors of casein kinase 2. These acquisitions provide Polaris with a promising pipeline, particularly in the anticancer therapeutic area.

Astex announces new drug discovery collaboration with University of Newcastle upon Tyne and CRT

On March 13, 2006 Astex Therapeutics reported a new drug discovery collaboration with the University of Newcastle upon Tyne and Cancer Research Technology (CRT) (Press release, Cancer Research Technology, MAR 13, 2006, View Source [SID1234523398]). The collaboration will aim to identify small molecule inhibitors of the Fibroblast Growth Factor Receptor (FGFr) tyrosine kinase family suitable for treatment of diseases including multiple myeloma, prostate cancer and other tumour types in which FGFr signalling is deregulated. Under the terms of the agreement, Astex will provide funding to the University to support the development of model cell systems to test novel drug compounds being developed by Astex. The University and CRT are eligible to receive milestone payments as drug compounds resulting from the collaboration are successfully developed and commercialised by Astex. Further financial details were not disclosed.

"This new collaboration builds on the experience in model cell systems and FGFr crystallography which was developed in an initial evaluation project with the University and CRT which we began in 2004. The new collaboration allows Astex to continue to access the unique expertise of the University in understanding the biology of FGFr as a novel drug target for the treatment of some of the most important cancers in humans", said Harren Jhoti, Chief Scientific Officer and Acting CEO.