Physicians' Financial News November 2007

Oncology-Centered Focus Fuels Continued Pharmion Growth

Unlike some biotechnology companies, whose product lines and research and development efforts are intended to address a variety of disease states, Pharmion, headquartered in Boulder, Colorado, built its name by exclusively restricting its research and development efforts to the realms of hematology and oncology. Although, as will be demonstrated, some Pharmion products have attained broader indications, the overwhelming focus of company development efforts, as well as the continued thrust of the overall company mission, is to combat cancer.

Company Basics

Pharmion was founded in 2000, becoming a publicly traded company (PHRM on the Nasdaq exchange) in November 2003. Currently, the company is comprised of over 450 employees who are distributed throughout the world in 13 different locations. Pharmion follows a dual-tiered strategy in order to facilitate the expansion of its product line. Compounds are either developed in-house or purchased from other drug manufacturers via collaborative agreements and/or outright acquisitions. Alliances, collaborative relationships and partnerships have been forged with a range of industry players, ranging from major traditional pharmaceutical companies such as Pfizer and Schering to cutting-edge biotech concerns such as MethylGene and GPC-Biotech.

The company has two FDA-approved products, Vidaza and Innohep, as well as four product candidates (one of which is an alternative formulation of Vidaza) in various stages of clinical development (Figure). In addition, the company is developing and marketing two products outside the United States in various international venues.

Within the company, Innohep and Vidaza, Pharmion’s two flagship agents, are viewed as very important. A company spokesperson characterized the two agents as “the products that really started up this company.”

Injectable Innohep is designed to treat acute symptomatic deep vein thrombosis (DVT) with or without pulmonary embolism when administered in conjunction with warfarin sodium.

Vidaza is an injectable therapy that has been indicated to treat all myelodysplastic syndrome (MDS) subtypes including refractory anemia, refractory anemia with ringed sideroblasts if accompanied by neutropenia or thrombocytopenia or requiring transfusions, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. The DNA methyltransferase inhibitor is currently the market leader and generally acknowledged as the treatment standard for MDS.

Vidaza’s MDS treatment credentials were further bolstered with the late summer 2007 release of Phase III survival data drawn from what the company claims was the largest randomized study ever conducted of higher-risk MDS patients. A spokesperson called the results “monumental,” speculating that the 74% increase in survival over two years that was demonstrated has likely been a “key driver” in the dramatic run-up of Pharmion’s stock price over the past several months (a later section of this article covers Pharmion’s Wall Street fortunes in more detail).

Commenting on the significance of the research, Patrick J. Mahaffy, Chief Executive Officer and President, Pharmion, stated, “As the only therapy to have ever demonstrated a survival advantage in MDS, and especially to have demonstrated an improvement of this magnitude, Vidaza is unique in the treatment for this disease. We are extremely gratified with the results from the Vidaza Survival Study, which for the first time bring the hope of prolonged survival for patients with higher-risk MDS.”

Vidaza is also a significant drug because, upon obtaining FDA approval, the DNA demethylating agent became the world’s first epigenetic product. According to a company spokesperson, Epigenetic therapies represent “an emerging area of therapeutic approach,” not to mention a completely new class of anticancer compounds.

In the Pipeline

Agents in clinical trials include amrubicin, a third-generation synthetic anthracycline intended to treat small-cell lung cancer that has been on the Japanese market since 2002; MGCD0103, an oral, isotype-selective, small molecule histone deacetylase (HDAC) inhibitor being developed in partnership with MethylGene that has the potential to combat a variety of cancers including an array of solid- tumor malignancies, MDS, acute myeloid leukemia (AML), relapsed or refractory non-Hodgkin’s lymphoma, and relapsed or refractory Hodgkin’s lymphoma and is the subject of several concurrent Phase II trials, both as a monotherapy and in combination with other agents; oral azacitidine (an oral version of injectable Vidaza), an internally developed and formulated agent that has demonstrated the potential to treat MDS, AML, and malignant solid tumors; and Orplatna, a hormone-refractory prostate cancer (HRPC) therapy, which is being touted as “the only orally bioavailable platinum-based compound in advanced clinical development,” according to information published on the Pharmion website.

The Pharmion portfolio is rounded out by two agents, Refludan and Thalidomide, that are targeted at various international markets but either not available or not handled by Pharmion in the United States (i.e., the United States marketing rights for Thalidomide are held by Celgene; Refludan’s U.S. marketing rights belong to Bayer).

Refludan is a specific, direct thrombin inhibitor, indicated for anticoagulation in adult patients suffering from type-II heparin-induced thrombocytopenia and associated thromboembolic disease, that has already been approved in Europe and a number of other countries around the world. Thalidomide, orally formulated in 50-milligram hard capsules, is an immunomodulatory and antiangiogenic agent that has been approved for the treatment of relapsed and refractory multiple myeloma (MM) in Australia, New Zealand, Turkey, Israel, South Korea, and Thailand. Thalidomide, under specifically defined circumstances, is approved for limited use in Europe (i.e., on a compassionate use or named-patient basis under a comprehensive risk-management program). Pharmion has an active application pending for full European regulators approval of the drug.

Pharmion Oncology Pipeline

Drug

Cancer Type

Phase I

Oral azacitadine

Myelodysplastic syndrome and acute myeloid leukemia

Orplatna (satraplatin)

Advanced solid tumors

MGCD 0103

Solid tumors

Phase II

Vidaza (azacitadine for injection)

Acute myeloid leukemia and solid tumors

Orplatna (satraplatin)

Solid tumors

MGCD 0103

Hematologic malignancies

MGCD 0103/Vidaza (azacitadine for injection)

Myelodysplastic syndrome and acute myeloid leukemia

MGCD 01013/Vidaza (azacitadine for injection)

Lymphoma

Amrubicin

Small-cell lung cancer

Thalidomide (U.S. marketing rights belong to Celgene)

Various types of cancer

Phase III

Orplatna (satraplatin)

Hormone-refractory prostate cancer

Amrubicin

Sensitive or refractory small-cell lung cancer

Thalidomide (U.S. marketing rights belong to Celgene)

Multiple myeloma

Approved

Vidaza (azacitadine for injection)

Myelodysplastic syndrome

Innohep (tinzaparin sodium injection)

Acute symptomatic deep vein thrombosis with or without pulmonary embolism

Thalidomide (U.S. marketing rights belong to Celgene)

Multiple myeloma

Refludan (lepirudin) (U.S. Marketing rights belong to Bayer)

Heparin induced thrombocytopenia

2007 Achievements

Pharmion’s research and development efforts are ongoing. For example, as Oncology & Biotech News went to press, Pharmion announced the initiation of an international Phase III clinical trial evaluating amrubicin as a second-line treatment of small-cell lung cancer (SCLC). The randomized, controlled, multicenter study will compare amrubicin with topotecan, the only approved chemotherapy for second-line treatment of SCLC in the United States. The study enrollment process has already commenced. Researchers will select 480 patients to participate in the trial. The primary endpoint of the study will be overall survival; the secondary endpoints will include progression-free survival, overall response rate, duration of response, and quality of life.

Research and development advances have been solidly consistent throughout 2007. In addition to amrubicin’s entry into Phase III, other key recent achievements include:

• The announcement that the French drug regulatory agency has issued an expanded temporary authorization for the

use of thalidomide. The agent can now be utilized in cases where a “genuine public health need” has been

established in untreated MM. Previously, the temporary authorization has only encompassed treatment of relapsed/

refractory MM.

• The initiation of a second multidose Phase I trial of oral azacitidine. The new Phase I trial is designed as a multi-

center, openlabel, dose-escalation trial that will assess the maximum tolerated dose, dose limiting toxicities, and

safety of a seven day, multicycle dosing regimen in patients with MDS and AML. The trial will examine

pharmacokinetics and pharmacodynamic effects of orally administered azacitidine, as compared with the

FDA-approved parenteral regimen, which is marketed by Pharmion as Vidaza (azacitidine for injection).

• The release of strong interim Phase II results for HDAC inhibitor MGCD0103 in Hodgkin’s lymphoma, and the

unveiling of plans to initiate a registration program for MGCD0103 either as monotherapy or in combination with

Vidaza in a hematological malignancy.

• The announcement of plans to initiate a clinical program for Amrubicin in breast cancer.

• As this article went to press, Pharmion and MethylGene presented positive preliminary clinical data on a Phase I and

II combination trial evaluating MGC0103 (in combination with Gemzar) at the 2007 AACR-NCI-EORTC International

Conference on Molecular Targets and Cancer Therapeutics in San Francisco Francisco. Researchers demonstrated

preliminary evidence of pancreatic cancer activity and announced the initiation of the Phase II portion of the clinical

trial.

Financial Prospects

Wall Street analysts have been bullish regarding the value of Pharmion as an investment. Throughout 2007, a steadily rising level of equity sector exuberance has driven the stock to higher levels. A number of factors suggest that Pharmion’s stock price increases are well warranted, including:

• Better than expected Vidaza performances resulting from unmet medical need, a recently expanded sales force,

strong survival data, and significant upside potential for the drug to expand its marketshare at the expense of

competitors.

• Several expected upcoming European drug approvals and/or expanded indications.

• The existence of an already impressive infrastructure.

• Financial analyst predictions that Pharmion will attain profitability sometime in early 2008 (or, at the latest, according

to more conservative internal company projections, 2009).

According to updated financial guidance provided by Pharmion, the company expects to report total net sales for 2007 in a range of $250 to $260 million. This latest projection represents an increase from the previous guidance. Research and development expenses for 2007 are expected to total approximately $85 to $95 million, adjusted from the previous guidance of $90 to $100 million.

Finally, the company expects to end 2007 with approximately $225 to $235 million of cash, cash equivalents and short-term investments, an increase from previous guidance of $80 to $90 million. This increase is primarily due to the addition of the $130 million in net proceeds from the company’s equity offering completed in June 2007.

Treatment-Resistant Breast Cancer Targeted

A novel medicine is offering new hope to patients with late-stage breast cancer that has not responded to currently available treatments. Bristol-Myers Squibb (BMS) has announced its attainment of FDA approval for ixabepilone, a therapy designed to combat advanced breast cancer. The agent offers a potentially effective treatment method for patients whose breast cancer continues to spread despite treatment. Roughly 25% of patients develop resistance to existing breast cancer drugs. As a result, this population’s breast cancer becomes increasingly more severe and drawn-out, usually ending in death. Roughly 160,000 American women are diagnosed with breast cancer on an annual basis. Approximately 40,000 of these women die each year despite receiving state-of-the-art treatment.

Ixabepilone has demonstrated effectiveness in treatment-resistant breast cancer both as a stand-alone treatment and in combination with Xeloda. Clinical trials data submitted to the FDA demonstrated that in patients who underwent ixabepilone therapy, in combination with Xeloda, breast cancer tumors either decreased in size or did not grow any larger for an average period of 5.8 months. In patients taking Xeloda monotherapy, this period averaged only 4.2 months. The 1.6 month improvement average yielded by ixabepilone/ Xeloda combination therapy over Xeloda monotherapy was determined by researchers to be statistically significant.

Industry analysts have been enthusiastic about the potential of ixabepilone therapy and the future prospects of its manufacturer in the overall oncology marketplace. The new breast cancer therapy represents a potential blockbuster, possibly generating up to $500 million in annual sales by 2012. According to increasingly exuberant speculation, the approval of ixabepilone may just be the tip of the oncology iceberg for BMS. A rich pipeline, boasting a number of late-phase agents, may vault BMS back to or near the top position in oncology therapy that the company last held seven years ago.

Ixabepilone itself has future prospects for gaining expanded breast cancer treatment indications. Two ongoing clinical trials are currently evaluating whether the agent prolongs survival. Positive findings would help build a strong case for the use of ixabepilone in earlier stages of breast cancer treatment. Study results are expected to be unveiled by the end of 2008.

Ixabepilone, however, is only one of the anticancer weapons BMS’s expanding oncology arsenal. Another recent addition is Sprycel, indicated for the treatment of leukemia. Promising late-phase agents include ipilimumab, a T-cell bolstering melanoma treatment being developed in conjunction with Medarex Inc., Princeton, New Jersey, and vinflunine, a bladder cancer therapy which recently completed clinical trials and will likely begin the process of seeking FDA approval by the end of the year.

Company officials attribute the rising fortunes of BMS oncology to a marked strategic shiftin the company’s drug development paradigm. During its turn-of-the-century era Taxol-fueled glory days, BMS was known for developing drugs discovered by other concerns. Conversely, the current resurgence of the company’s oncology portfolio is largely being driven by a focus on in-house discoveries and research.

Merger-Mania Poised to Envelop BiotechSector? Biogen Among Companies on the Auction Block

The basic principles and history of the modern business world has demonstrated that industry sectors tend toward consolidation as they grow and prosper. Judging from recent Wall Street whisperings, biotechnology companies will not long be immune from the type of merger-mania that has reconfigured the landscapes of other business sectors. In what may be a sign of the biotechnology’s evolving maturation, value, scope, size and influence, much of the industry-related business news being published these days has centered around swirling innuendoes concerning potential mergers and acquisitions (M&As) between prominent biotech players and/or between large pharmaceutical companies and biotechnology concerns.

Several months ago, MedImmune was swallowed up by AstraZeneca. The general consensus among industry analysts is that the deal did not occur in a vacuum; rather, it foreshadows the beginning of a larger M&A trend. Who might be next? Prominent biotech concerns such as OSI Pharmaceuticals, Genzyme, and ImClone have been repeatedly cited as examples of acquisition targets.

Of the three companies, Imclone, with its compelling pipeline, solid research and development infrastructure, and the continuing success of flagship product Erbutix, appears the most attractive and likely partner for a union with a big pharmaceutical company. Genzyme is saddled with numerous drawbacks and uncertainties such a thinning drug pipeline, increasing competition, and its lack of prospects for near-term growth.

Perhaps the most prominent object of the M&A innuendoes being tossed about is Biogen Idec. Are Biogen’s days as a stand-alone company numbered? According to a rash of recent news reports, the answer appears to be yes. The company, through its spokespeople, has affirmed that it is entertaining the idea of a possible sale. In a conference call with analysts to discuss the third-quarter financial results, Jim Mullen, CEO, Biogen, confirmed that the company is for sale and openly seeking potential bidders. “I felt we had a need to be able to talk as directly as possible to both the shareholders as well as the employees about what was going on,” stated Mr. Mullen.

Boston Globe

Several potential buyers are expressing interest in the biotechnology concern, allegedly including, most notably, large traditional drug companies Pfizer and SanofiAventis (to date, neither company has gone on record to confirm their interest in Biogen). Other interested parties, according to a recent article, include Johnson & Johnson and Novartis.

New York City—based activist investor Carl Icahn, who, over the past few weeks, has reportedly expanded his stake in Biotech from 1% to 4%, has been among the most vocal agitators in support of a potential sale as well as one of the company’s most persistent suitors, putting together an offer valued by insiders at over $23 billion. In numerous business and biotech industry publications, Mr. Icahn has been often been quoted as strongly supporting the sensibleness, synergy and efficiency of a marriage between Biogen and a major pharmaceutical house. Earlier this year, Mr. Icahn levied a similar form of outspoken pressure to help facilitate London-based Astra Zeneca’s $15.6 billion acquisition of MedImmune, Inc.

A Biogen sale would be one of the largest in the biotechnology sector. The company, its value driven by prominent cancer drug Rituxan (which recently had positive clinical trials supporting its expanded use in lupus and multiple sclerosis) and its prominence in the multiple-sclerosis drug sector (spearheaded by Avonex, which had sales of $462 million over the last quarter), currently boasts a market capitalization of roughly $23.5 billion. According to analysts, Biogen is expected to take in $3.1 billion in 2007 revenue. The company’s own projections have forecast approximately $600 million in earnings for 2007. Biogen has stated that it expects to see a doubling of its profits by 2010.

Biogen has largely regrouped following a shocking 2005 recall of its second-generation MS drug, Tysabri, which was linked to a rare but usually lethal brain infection. The FDA has since allowed the drug back onto market and its utilization is expected to grow five-fold over the next three years. Most analysts characterize the company’s pipeline as robust, citing product candidates such as BG-12, an oral multiple sclerosis drug currently in late-stage human trials.

Despite Biogen’s generally strong outlook, some analysts have expressed skepticism about the company’s ultimate value. Especially in the context of the premium price points that Biogen is expected to command.

Many analysts are balking at the roughly 20% premium that Biogen is likely to extract from a prospective purchaser, asserting that the stock as currently priced is already valued fairly. According to Thomson First Call, twenty of twentyseven sell-side analysts that were polled by the publication have “hold” ratings on Biogen. Wall Street reticence is largely due to the fact that the vast majority of Biogen’s revenue is the result of Avonex and Rituxan, two products that have seen their sales level out.

Analyst misgivings were somewhat reinforced by the disappointing earnings that were posted by the company in the third quarter of 2007, a period during which Biogen’s net income dipped 24% to $119.4 million, or 41 cents per share, compared with $156.6 million, or 45 cents per share, for the same quarter last year.

In order to validate its value, Biogen must convince the marketplace that the strength of its future pipeline is sound and that its skyrocketing sales projections for Tysabri, its newest MS drug, will ultimately be attained. That said, Biogen’s level of biologic drug research and development expertise, especially in the area of emerging therapies such as monoclonal antibodies, is a relatively rare marketplace commodity that is highly prized by large major pharmaceutical companies.

Oncology & Biotech News

When asked by to comment on Biogen’s worth and future growth potential, top-level executives strenuously affirmed the present and future health of the company, largely basing their assertions on the potenial of their drug development pipeline. Cecil Pickett, President, Research and Development, Biogen, explained, “We at Biogen Idec continue to make strong progress on enriching and advancing our pipeline. I feel good about the strength, continued progression, and balance of our pipeline.” Mr. Mullen added, “Our goal is to continue building a robust pipeline and executing on clinical development. We are well on our way towards achieving this goal with 15 product candidates in Phase II clinical trials or beyond, and at least 10 data readouts through the end of 2008.”

Oral Therapy Option Offered for Small-Cell Lung Cancer Relapse

Patients suffering from relapsed small-cell lung cancer (SCLC) can now seek treatment for this particularly severe and rapidly proliferating cancer in the comfort of their own homes. The FDA has approved oral Hycamtin capsules, manufactured and marketed by GlaxoSmithKline. The product, indicated for the treatment of relapsed SCLC patients who had a complete or partial response to first-line chemotherapy and who are at least 45 days from the end of first-line chemotherapy treatment, will be made available in 2008.

Although a variety of Phase II and Phase III trials were submitted to the FDA to support Hycam- tin’s safety and efficacy, the data which were instrumental in securing approval were drawn from a multicenter Phase III study which compared one group of patients who underwent Hycamtin therapy in conjunction with best supportive care (BSC) with a second group who received BSC only. The Hycamtin plus BSC group demonstrated statistically significant rates of increased survival. Best supportive care is defined as any and all treatments that do not have any antitumor effects but are intended to prevent, control, and/or relieve disease complications, providing comfort and quality of life to the patient.

Journal of Clinical Oncology

The pivotal trial enrolled 141 patients with relapsed SCLC who were not considered as candidates for standard IV therapy. The randomized subjects were split into two groups; seventy of whom received BSC alone and seventy-one of whom underwent a therapeutic regimen of Hycamtin capsules (2.3 mg/m²/day, days 1 through 5, every 21 days) plus BSC. The primary objective of the research was to compare overall survival between the two treatment arms. Data reported a 36% decrease in risk of death for patients who received Hycamtin capsules plus BSC, compared with the patients who received BSC alone. Median survival with Hycamtin capsules plus BSC was 25.9 weeks, compared with a median survival rate of 13.9 weeks for the group that was treated with BSC alone. According to a recent article, this Phase III trial was the first randomized study to ever demonstrate that relapsed SCLC patients extend the length of their life when they are treated with Hycamtin and BSC when compared with patients who only undertake BSC.

Hycamtin capsules are members of the topoisomerase I inhibitor drug class. Topoisomere I is a naturally produced protein necessary for the division of both cancerous and noncancerous cells. Hycamtin capsules interact with the topoisomere I in cancer cells to disrupt cell division by causing permanent damage to cellular genetic material. The inhibition of topoisomere is fatal to dividing cancer cells.

Small-cell lung cancer is caused by aggressive cell growth that begins on the surface of the bronchi and generally spreads widely throughout the body. American Cancer Society data report that roughly 15% of patients with lung cancer have the fast-growing small cell form of the disease.

In a recent company press release, John Eckardt, MD, Director of Clinical Research for the Center for Cancer Care and Research, St. Louis, MO, asserted, “The approval of Hycamtin capsules opens up new possibilities for patients battling this disease and provides a convenient alternative to IV therapy.”

Immunomedics Wins Pancreatic Cancer Patent

Biopharmaceutical concern Immunomedics, Inc. obtained a patent for product candidate humanized PAM4 (hPAM4), a monoclonal antibody designed for potential use in the diagnosis and treatment of pancreatic cancers. The patent covers the composition of matter for the MUC1-antigen binding humanized antibody (as it pertains to use in pancreatic cancer therapy).

Monocloncal antibodies utilize certain parts of the immune system to fight cancer. According to the American Cancer Society, monoclonal antibodies are the most widely utilized form of cancer immunotherapy. The newly patented product candidate, hPAM4, works by targeting an epitope, also known as a marker, in the MUC1 antigen. The MUC1 antigen is expressed in most pancreatic cancer. An antigen is defined as any substance that causes the body to produce natural antibodies.

Immunomedics reported that a Phase I dose-escalation study with hPAM4 in patients with unresectable and metastatic pancreatic cancer has yielded encouraging initial clinical results. A second dose-escalation study, which will utilize hPAM4 in combination with gemcitabine therapy is planned to commence at some point in early 2008. Gemcitabine is the currently accepted standard first-line therapy for pancreatic cancer, either as a stand-alone treatment or in combination with other chemotherapeutics.

National Cancer Institute estimates for 2007 place the incidence of new pancreatic cancer cases in the United States at 37,170 per year. Immunomedics saw its stock rise sharply following the patent announcement.

Promising Kidney Cancer Therapy Moves Toward Phase II

ZymoGenetics presented encouraging interim research on Interleukin 21 (IL-21), its prospective kidney cancer therapy. The positive data, presented at the AACR-NCIEORTC International Conference on Molecular Targets and Cancer Therapeutics, held in San Francisco, were drawn from a dual-stage Phase I and II trial that evaluated the tolerability of IL- 21 utilized in concert with Nexavar as part of a combination regimen utilized to treat patients with renal cell cancer.

Preliminary results indicated that the use of IL-21 and Nexavar were well tolerated and demonstrated promising antitumor activity. The toxicity profile of the combined therapy was similar to the respective toxicity profiles of IL- 21 and Nexavar monotherapy.

Currently, ZymoGenetics is in the final stages of completing the Phase I part of the study evaluating the combination therapy in patients with clear-cell histology, which accounts for 85% of all renal-cell tumors. The Phase II portion of the study is expected to begin before the end of 2007 and will examine a larger patient group treated with the maximum tolerated dose of IL-21.

Evaluable patients enrolled in the Phase I portion of the study have received treatment at one of three dose levels (10, 30 and 50 μg/kg of IL-21).

Treatment consists of IL-21 administered intravenously on days 1—5 and 15–19 of a 6-week treatment course in combination with sorafenib administered at the recommended dose of 400 mg twice a day. Overall, the majority of adverse events and lab abnormalities have been mild to moderate and consistent with the known safety profiles of IL-21 and Nexavar. Dose limiting toxicities consisting of skin-related events occurred in only two patients. Over three-quarters of the study subjects experienced a decrease in tumor mass. This decrease ranged from 18% to 33%.

Since tyrosine kinase inhibitors (TKIs) such as Nexavar inhibit the growth of tumor cells, and Interleukin-21 activates the immune system to target killing of tumor cells, it is widely hypothesized that the two therapies may provide additive or synergistic effects. Treatment with a TKI may make cancer cells more sensitive to natural killer or T-cell mediated killing after activation with IL-21. Preclinical research conducted by ZymoGenetics of TKIs and IL-21 found that IL-21 had additive antitumor effects when combined with a TKI in a renal-cell cancer model.

In a recent ZymoGenetics press release, Nicole Onetto, MD, Senior Vice President and Chief Medical Officer, ZymoGenetics, was quoted as stating that IL-21’s “unique mechanism of action makes it an ideal potential candidate for combination with approved targeted agents in renalcell cancer. We were very pleased to see that the combination of Interleukin-21 and Nexavar can be safely administered for repeated courses, and that the majority of patients treated to date experience tumor shrinkage. The Phase II part of this trial should allow us to confirm these promising results.”

According to American Cancer Society statistics, an estimated 51,190 new cases of renal-cell carcinoma will occur in 2007 throughout the U.S. The annual death rate resulting from renal-cell carcinoma is estimated at roughly 19,600 Americans.