The Industry Insider: May 2007

OBTN, May 2007, Volume 1, Issue 4

News and information from the pharmaceutical industry. In this issue: 1) Multiple Deals for Affitech 2) Pfizer's Sutent Wins European Association of Urology Support 3) Aurora Breast MRI Will Meet Surge in Screening Demand 4) Two New Products for VioQuest 5) Cytyc and Quest Sign Multi-Year Agreement 6) Calando's Lead RNAi Candidate Shows Anti-Cancer Effect

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â–º THE INDUSTRY INSIDER

Multiple Deals for Affitech

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ffitech AS, a privately held human recombinant antibody developer in Oslo, Norway, has made a string of announcements regarding agreements and contracts. The first three product candidates in the Affitech pipeline are fully human antibodies for cancer, and the company expects at least one of these to enter the clinical phase of development by 2008.

On March 28, Affitech announced that it has signed an agreement with Micromet AG, a developer of antibody-based products

for cancer based in Munich, Germany, for a non-exclusive worldwide sublicensable research license for Micromet and Enzon

Pharmaceutical, Inc’s complementary patent estates in the field of single-chain antibodies (SCA). The agreement terms give Affitech the rights to conduct research involving SCA technology as well as sublicense rights to third parties for conducting

research, or to develop or use an SCA product that Affitech creates.

Affitech followed with another license agreement announcement on April 3, this time with Pharmexa, a Danish immunotherapeutic and vaccine company. Through the agreement, the companies plan to promote a bi-specific single chain antibody (diabody) technology to third parties for further product development. Pharmexa and Affitech will share all proceeds from such third-party agreements. In addition, Pharmexa has granted Affitech a worldwide exclusive license for certain intellectual property rights to diabodies, and Affitech will utilize the technology for its own research. “Because of the built-in dual specificity, diabodies are extremely interesting in the field of cancer research,” said Martin Welschof, Affitech’s chief executive officer. “Therefore, we see them as having great potential in our chosen field of oncology therapeutics.”

Soon after the Affitech-Pharmexa agreement, Affitech and ProBioGen AG, a biotechnology company headquartered in Berlin,

Germany, made a joint announcement on April 11 stating that they have entered an agreement for a producer cell line to be developed by ProBioGen. The cell line would be used for high-level production of one of the lead antibody candidates in Affitech’s oncology antibody pipeline. ProBioGen will combine its cell generation process for biopharmaceutical cell lines with an automated cloning process to identify and develop a high producer line. The companies did not disclose the financial details of the agreement.

Pfizer's Sutent Wins European Association of Urology Support

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he European Association of Urology (EAU) has recommended Pfizer’s Sutent (sunitinib malate) as first-line treatment

in patients with metastatic renal cell carcinoma of intermediate risk. The EAU recommendation and guidelines make Sutent the

first multi-targeted tyrosine kinase inhibitor to be approved for first-line use in the EU. The recommendation closely follows

EU marketing authorization for Sutent—in January 2007, the European Commission had granted full marketing authorization

for Sutent as a first-line therapy in patients suffering from advanced and/or metastatic renal cell carcinoma (mRCC).

The US Food and Drug Administration had approved Sutent in January 2006 for the treatment of advanced mRCC as well as gastrointestinal stromal tumor, a type of stomach cancer. According to Pfizer, Sutent’s approval was the first time that the FDA had approved a new cancer medicine for two indications at the same time.

The oral therapy drug sunitinib malate attacks cancer by starving tumors of blood and nutrients needed for growth and killing

cancer cells in tumors. Phase II clinical studies have shown that patients with resistant renal cell tumors who received the

drug have high response rates and delayed tumor progression.

The full marketing authorization for Sutent that came two months ago in the EU was based on the results of a large, nternational phase III trial, results of which were published in the January 11 issue of The New England Journal of Medicine. In

this study, 750 patients received sunitinib malate or the current standard care therapy, interferon alfa. Sunitinib malate more

than doubled prolonged progression-free survival as first-line treatment in patients with mRCC—11 months as opposed to 5

months for interferon alfa. In addition, sunitinib malate led to a five times higher objective response rate and was better tolerated with fewer discontinuations.

“Achieving EAU guideline recognition for Sutent so soon after the EU marketing authorization for the first-line treatment of

mRCC demonstrates what an important treatment option sunitinib malate has already become for physicians managing

metastatic renal cell carcinoma” said Robin Wiltshire, the medical director of Oncology Europe.

Aurora Breast MRI Will Meet Surge in Screening Demand

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he American Cancer Society’s newly established breast cancer screening guidelines may spell good news for Aurora Imaging Technology, Inc., manufacturer of the only magnetic resonance imaging (MRI) system specifically designed for

breast imaging that has been cleared by the US Food and Drug Administration. Aurora is a private company based in North

Andover, MA.

The new ACS guidelines state that women designated as being at high risk for breast cancer should have an annual breast MRI for screening in addition to their annual mammogram. Experts are expecting a surge in demand for breast cancer MRI screening, and Aurora said in a press release on March 29 that it is well-prepared to meet the increase in demand. The system is already installed in more than 23 breast care centers in the US, Europe and Asia.

Aurora users are dedicated breast radiologists, said Olivia Ho Cheng, Aurora’s president and chief executive officer. “The vast

majority have been experiencing an ongoing increase in patient volumes and many are considering a second Aurora System just to keep up with patient demand,” she said.

Aurora’s 1.5T Dedicated Breast MRI System gives physicians multiple advantages in breast cancer screening. Physicians often

have to use a whole-body MRI system that is shared by multiple hospital sections. With a dedicated breast MRI system, physicians could more quickly screen women at high risk for developing breast cancer. The system has an average patient scan time of less than 20 minutes, and it can easily handle 15-20 patients a day. The Aurora Breast MRI system delivers ultra-thin 1-millimeter slices, which offer superior resolution and clarity. Plus, it provides a three-dimensional composite model of the breast, enabling physicians to diagnose cancer earlier and more accurately, and also more accurately determine the absence of cancer.

Two New Products for VioQuest

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ioQuest Pharmaceuticals, a biopharmaceutical company based in Basking Ridge, New Jersey, made announcements on two new products on March 29. The company said that it has obtained an exclusive license to develop and commercialize Xyfid, a topical treatment for a common but serious side effect of chemotherapy, from Asymmetric Therapeutics, LLC. VioQuest also announced that it has identified and added to its pre-clinical pipeline a new orally bioavailable product candidate of its drug VQD-002 (triciribine phosphate), which is currently in phase I/IIa trials in patients with refractory leukemias and solid tumors.

In preliminary clinical studies, Xyfid has shown promise in preventing and treating Hand-Foot Syndrome (HFS), a potentially

fatal complication that arises due to multiple drug regimens that are commonly used to treat breast, colon and other cancers. The syndrome affects the palms and soles, causing burning or redness in mild cases and ulcerated breakdown of the skin when severe. It is especially common in patients receiving higher doses of capecitabine, with incidence rates as high as 50 percent. The risk of developing the syndrome becomes more likely with each subsequent treatment. Currently, there are no approved drugs for preventing HFS.

Scientists do not fully understand the action of Xyfid yet, but they suspect that uracil, an active component, may alter the response of skin to chemotherapy drugs. “Xyfid holds out the promise to make several current chemotherapy regimens safer

and easier for patients to tolerate, and may allow patients to maintain the original dose and duration of treatment planned,” said

Edward Bradley, VioQuest’s chief scientific officer. Bradley emphasized the need for phase II and phase III clinical testing to

prove Xyfid’s advantages.

VioQuest’s VQD-002 in currently in phase 1/IIa clinical trials. It inhibits the phosphorylation of Akt, a protein kinase that is

abnormally high in breast, ovarian, colorectal, hematologic, and pancreatic tumors.

Cytyc and Quest Sign Multi-Year Agreement

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ytyc Corporation, a Marlborough, MA-based provider of surgical and diagnostic products for women’s health and cancer diagnostics announced a new multi-year agreement with Quest Diagnostics for Quest’s ThinPrep Pap Test on March 28. The agreement is valid through the end of 2010, and the companies did not disclose additional terms and conditions.

Cytyc has also announced a multi-year contract extension with Laboratory Corporation of America Holdings (LabCorp) for Cytyc’s ThinPrep Imaging System and the ThinPrep Pap test. The ThinPrep Imaging System is an interactive computer system

that assists cytotechnologists and pathologists in the primary screening and diagnosis of ThinPrep Pap Test slides. LabCorp,

a S&P 500 company which specializes in commercializing new diagnostic technologies, introduced the ThinPrep Imaging System in October 2004.

Quest Diagnostics, headquartered in Lyndhurst, NJ, first introduced the Thin-Prep Pap Test in 1997 and the company has been instrumental in driving the acceptance of liquid-based Pap testing for cervical cancer among physicians. In addition to the new ThinPrep Pap Test contract, Quest Diagnostics has also agreed to evaluate the ThinPrep Imaging System at selected laboratory sites.

Calando's Lead RNAi Candidate Shows Anti-Cancer Effect

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alando Pharmaceuticals, a small interfering RNA (siRNA) therapeutics company and a majority-owned subsidiary of Arrowhead Research Corporation has published a study showing the anti-proliferative effect of the siRNA sequence that the company has selected as the therapeutic component of its leading anti-cancer compound. The findings spell good news for Calando, confirming that their compound is a promising candidate for therapeutic development. The study was published in the April 1 edition of Clinical Cancer Research.

Treatment with siRNA takes advantage of RNA interference, a naturally occurring mechanism in cells to selectively silence and regulate specific genes. RNA interference is naturally induced by double-stranded RNA molecules. These RNA molecules can be artificially induced to use chemically synthesized double-stranded siRNAs that target specific genes associated with

diseases.

In the study, Calando researchers and their collaborators determined the sequence of siRNA included in Calando’s lead

siRNA-containing nanoparticle compound. The researchers screened several siRNA duplexes and further tested those with the

most anti-ribonucleotide reductase activity. The inhibition of the enzyme ribonucleotide reductase blocks the formation of the building blocks of DNA and thus interferes with the growth of tumor cells.

The best candidate siRNA duplex showed a significant reduction of ribonucleotide reductase enzyme levels in cultured cells.

These candidates also achieved a concomitant anti-proliferative effect in a variety of different cancer cells, both in vitro and in

vivo, and in cells of various species, including human, mouse, rat, and monkey. The new study “demonstrate[s] the potential

for this siRNA duplex to have a strong anti-tumor effect,” said John Petrovich, Calando’s chief executive officer.

Calando has already filed for patent protection on several siRNA duplexes against ribonucleotide reductase—the patent application was published in November 2006. The company has also licensed patents from Alnylam Pharmaceuticals to enable it to develop and commercialize an RNAi therapeutic against ribonucleotide reductase.