Scientific heavyweights to speak at Jan 28 Hopkins symposium

22 Jan 2005

General news and science reporters, editors, broadcasters and photographers are invited to The Johns Hopkins University School of Medicine Friday, Jan. 28, to hear six of the nation’s best-known biological scientists — including Nobel laureates David Baltimore and Sydney Brenner — at a symposium, “Toward the Third New Biology.”

The symposium, whose title refers to anticipated advances in biology in the post-double-helix, post-genome-sequencing world, will begin at 10:30 a.m. in the Wood Basic Science Auditorium at 725 N. Wolfe St., Baltimore, on the medical school campus. [The schedule of speakers is below; a short biographical note for each of the speakers is available through the contact information above.]

“The symposium is designed to celebrate interdisciplinary research, particularly in biological research and its application to human health and disease,” says Edward D. Miller, M.D., dean and CEO of Johns Hopkins Medicine.

In 1953, Watson and Crick merged evidence from chemistry, biology and structural biology to correctly describe the double-helical structure of DNA. The first “new biology” that followed saw scientists blend traditional disciplines to unravel basic genetic functions. These efforts were rewarded by the “second new biology,” ushered in by discoveries that ultimately enabled sequencing of entire genomes.

“Now the ‘third new biology,’ is beginning as researchers use genomes to help unravel fundamental biological and disease processes,” says symposium co-organizer Aravinda Chakravarti, Ph.D., director of the McKusick-Nathans Institute of Genetic Medicine at Hopkins.

“Like biology in the 1950’s and 1960’s, this new biology crosses disciplines, but the scope of questions being asked requires a new combination of approaches — particularly bioinformatics, computational biology, mathematics and chemistry,” says Stephen Desiderio, M.D., Ph.D., professor of molecular biology and genetics and director of Johns Hopkins’ Institute for Basic Biomedical Sciences. “The point is to bring people with various kinds of expertise together to address common research interests using new tools.”

The six speakers include the two Nobel Laureates with big picture views, a genetic pioneer involved in identifying victims of human rights tragedies, and a high-profile chemist who probes biological functions using “pre-drugs.” They are accompanied by a biologist studying why the wonder-drug Gleevec doesn’t work for everyone, and a scientist who knows how growing nerves meet their matches and how the connections they form determine worms’ behaviors.

At Johns Hopkins, the “third new biology” is reflected in the goals and efforts of the Institute for Basic Biomedical Sciences, the McKusick-Nathans Institute of Genetic Medicine and the Institute for Cell Engineering. The three institutes and the School of Medicine are co-sponsoring the symposium.

Symposium schedule:

10:30 – 10:45 Edward Miller, Johns Hopkins Medicine
Welcome and Opening Remarks

10:45 – 11:30 David Baltimore, California Institute of Technology
“NF-ÿB: Specificity hidden in apparent generality”

11:30 – 12:15 Stuart Schreiber, Harvard University
“Small molecules, small-molecule screens, and ChemBank”

12:15 – 1:30 Lunch break (lunch is not provided)

1:30 – 2:15 John Kuriyan, University of California, Berkeley
“Regulatory mechanisms in the Src and Abl tyrosine kinases”

2:15 – 3:00 Cornelia Bargmann, The Rockefeller University
“Oxygen sensation and the genetics of natural behavior”

3:00 – 3:30 Coffee Break

3:30 – 4:15 Mary-Claire King, University of Washington “Human genomics and human rights” 4:15 – 5:00 Sydney Brenner, Molecular Sciences Institute
“The next steps in human genetics”

A reception will follow the symposium in the lobby outside the auditoriums.

Media: To attend or to request the speakers’ short bios, contact Joanna Downer at
jdowner1@jhmi.edu or 410-614-5105.

On the Web:

hopkinsmedicine.org/geneticmedicine/Home/Index.cfm
hopkinsmedicine.org/ibbs
hopkinsmedicine.org/ice
hopkinsmedicine.org/som/index.html

Joanna Downer – jdowner1@jhmi.edu
Johns Hopkins Medical Institutions

Cancer deaths trump heart disease
Study: 5-year survival rates improve in latest figures

Advances in targeted drug therapies such as Novartis’ Gleevec used for treating some kinds of leukemia are raising hope that similar breakthroughs can be found for other cancers, Wilson said.

SAN FRANCISCO (MarketWatch) – Cancer has topped heart disease as the leading cause of death for Americans under age 85, though death rates from some cancers have dropped, according to a new study.

Death rates from both heart disease and cancer have been falling. Cancer has been known to be the bigger killer for those under 65, but the American Cancer Society (ACS) found it retained that dubious distinction when researchers raised the age threshold to 85 in the data, said Elizabeth Ward, director of surveillance research at ACS and co-author of its annual cancer statistics report.

Cancer began eclipsing heart disease among those under 85 in 1999, she said. In 2002, according to the most recent information available from the National Center for Health Statistics (NCHS), 478,089 Americans under 85 died of cancer compared with 446,774 who died of heart disease.

Heart disease is still the leading cause of death overall, and it’s especially fatal for the oldest elders. After age 85, more than 250,000 people died of it in 2002 compared with 79,182 who died of cancer, according to the NCHS.

“Heart disease deaths have been declining steadily since 1975, whereas cancer death rates had been going up between ‘75 and the early 90s and finally started showing some decline in the early 1990s,” Ward said.

The flip-flopping of cancer with heart disease in terms of fatalities was unexpected, said Dr. J. Frank Wilson, professor and chair of the radiation oncology department at the Medical College of Wisconsin in Milwaukee.

“I did find it quite surprising, and I think that’s because it’s become engrained in the thinking process of the professional element and the laity that heart disease is the No. 1 killer in Americans,” said Wilson, who was not involved in the study. “This report changes that perception quite dramatically.”

Mixed picture

Advances in early detection tools and treatments helped boost the relative five-year survival rates of people diagnosed with cancer between 1995 and 2000 to 64 percent, up from 50 percent in 1974 to 1976, according to the report, Cancer Facts & Figures 2005. A long-term decline in the prevalence of smoking also played a role.

“Probably the biggest influence on cancer death rates is the effect of tobacco control,” Ward said. “We’ve been seeing a very large decline in the lung cancer rates for men for some time, and now we’re seeing stabilization in the rates for women.”

Even so, lung cancer remains the most lethal cancer. It’s expected to kill 90,490 men this year and 73,020 women. An estimated 87 percent of lung cancer cases are attributable to smoking, a figure that includes both current and former smokers.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 211,240 new cases projected for 2005. For men, prostate cancer tops the list, with an expected 232,090 newly diagnosed cases this year.

Today, 98 percent of women diagnosed with localized breast cancer can expect to live at least five years, up from only 80 percent in the 1950s, according to the report. The five-year survival rate drops to 80 percent if it’s spread regionally.

Colon cancer, the third most common cancer in men and women, has seen mortality rates drop 1.8 percent per year over the last 15 years, the report said.

Obesity drives more cancer cases

In 2005, about a third of cancer deaths will be caused by tobacco, and another third will be traced to obesity, poor nutrition and physical inactivity, according to ACS research.

Among men, health problems arising from carrying extra weight or having a sedentary lifestyle lead to an increased risk of cancers of the liver, pancreas, stomach and esophagus, Ward said. “Men who were highly obese had 1.5 times the risk of death from cancer than those of normal body weight.”

For women, those with extra weight had a risk burden 1.7 times higher, especially for cancers of the uterus, kidney, cervix, pancreas and esophagus, she said.

While doctors aren’t quite sure why fatness results in poorer cancer outcomes, it’s a consistent factor, Wilson said. “In many studies that look at all the possible patient-based factors, obesity will sort out as an individual variable predicting poor prognosis.”

About 1.4 million Americans are expected to develop cancer this year, and 570,000 are expected to die from it.

Even so, there are about 10 million Americans living with a history of cancer, a testament to the rapidly improving treatments science is providing, Wilson said.

“Cancer is a more curable disease than most people think,” he said, calling it an “almost always a multi-disciplinary problem.”

“Expertise of different types has to be brought to bear to get the best results,” Wilson said. “We have to do the right thing at the right time and in the right way and we’re still trying to understand how best to do that for our patients.”

Research funds should continue, he added, calling the report “extremely encouraging.”

“It should energize everyone that reads it to think about what’s needed to push on to the conquest of cancer,” he said. “There are a lot of things we can do to reduce the incidence and morbidity and mortality of cancer to very low levels over the next few decades.”

The road ahead

Advances in targeted drug therapies such as Novartis’ Gleevec used for treating some kinds of leukemia are raising hope that similar breakthroughs can be found for other cancers, Wilson said.

The ACS report also highlighted the need to fight cancers linked to infectious diseases. Infections cause about 7 percent of cancers in the U.S., but they account for 17 percent of cases worldwide. Most liver cancers are caused by Hepatitis B and C, and cervical cancer is largely due to the human papilloma virus, known as HPV.

More than three out of four cancers are diagnosed in people 55 and older, according to the ACS, which based its estimates on statistics from the National Cancer Institute and the National Center for Health Statistics. Preventable cancers and those that could have been caught by earlier screening account for half of all new cases.

Colorectal cancer, the third leading cause of cancer death in men and women, is one area where Americans can improve their chances of survival by taking preventive action, Ward said. Less than half of people over 50 for whom screening is recommended are getting screened.

“Screening is so very important for that cancer because it prevents pre-malignant polyps from turning into cancer,” she said. “They can be removed and it won’t progress to cancer.”

Pancreatic and ovarian cancers are two kinds for which little is known about risk factors and how to treat them once they’re discovered, which is typically in the advanced stages, Ward said.

Distribution Source : PrimeZone Media

Date : Thursday – January 20, 2005

BASEL, Switzerland, Jan. 20, 2005 (PRIMEZONE) –Novartis (NYSE:NVS):

* 75 projects in development, including 43 new molecular entities

* Key late-stage projects progressing on track

* New data on five of ten top-priority compounds presented

* AMN107 Phase I data reveal hematological response in over 50% of Gleevec-resistant patients

* FTY720 Phase II MS data show strong efficacy as potentially first oral therapy

* QAB149 Phase IIb data underscore efficacy in asthma and COPD

* First SPP100 Phase IIb/III data confirm efficacy in high blood pressure

* ICL670 set for US/EU submission based on response in 20 mg & 30 mg doses

* New Phase III data expected on six compounds and five key submissions in 2005

At a Research & Development review today, Novartis provided an update on its industry-leading pipeline, announcing robust progress in 75 development projects that aim to address unmet medical needs.

In addition to these 75 projects in clinical development, which includes 52 in phase II, III or registration and 43 new molecular entities (NMEs), Novartis announced that it has more than 64 candidates in advanced pre-clinical testing. Key areas of development are oncology and cardiovascular diseases, with promising compounds in both primary care and specialty medicines.

“Innovation is the core of our strategy, and our strong investments of USD 3.5 billion in pharmaceutical R&D in 2004 rank among the highest in the industry. In the US alone, our investments have allowed us to bring 13 new medicines to patients over the past four years, the highest number of any pharmaceutical company,” said Dr. Daniel Vasella, Chairman and Chief Executive Officer.

“We continue to focus on novel medicines. Six of our 10 highly innovative compounds in mid-to-late-stage development are potential first-in-class medicines, and I am pleased that the expertise of our scientists, improved processes and advanced technologies have contributed to maintaining a leading position in R&D productivity,” Dr. Vasella said.

Pipeline highlights

Novartis has been consistently ranked by industry experts as having one of the best pipelines, highlighted by several innovative compounds. These include SPP100 (hypertension), QAB149 (asthma and COPD) and FTY720 (multiple sclerosis and transplantation) as well as LAF237 (type 2 diabetes) and PTK787 (cancer). Many of these projects have the potential to become a new standard of care and the first to market in their respective classes.

The priority development projects include:

Oncology & Hematology

* AMN107 is an investigational oral compound being studied in the small subset of advanced chronic myeloid leukemia (CML) patients who do not respond or stop responding to Gleevec/Glivec and have no treatment options available. The compound is a signal transduction inhibitor that selectively inhibits specific proteins called tyrosine kinases, including BCR-ABL and some mutant forms of this protein, that cause white blood cells to grow and divide uncontrollably. AMN107 has been shown in preclinical studies to be the most selective BCR-ABL inhibitor to date and more potent than Gleevec. Phase I data showed hematological responses of over 50% in Gleevec-resistant patients in advanced disease stages (accelerated or blast phases). Phase II trials are expected to start in the first half of 2005.

* PTK787 (vatalanib) is an oral angiogenesis inhibitor in Phase III development for metastatic colorectal cancer. First Phase III results for PTK787, which is being developed with Schering AG, are expected in Q2 2005 from the CONFIRM1 trial in colorectal cancer. Enrollment was completed in 2004 for both the CONFIRM1 and the CONFIRM2 trials, which aim to show that PTK787 has the potential to set a new standard of care in metastatic colorectal cancer. Novartis plans to initiate an adjuvant colon cancer trial in 2005 pending positive CONFIRM1 data. A broad Phase I/II program is underway to identify additional indications for further development, including prostate, non-small cell lung (NSCLC), breast, pancreatic and ovarian cancers as well as glioblastoma and hematological malignancies.

* ICL670 (deferasirox) offers the potential to revolutionize the treatment of iron overload, providing a once-daily oral formulation to replace the cumbersome infusion therapy Desferal. Iron overload is a cumulative, potentially life-threatening condition that may result from repeated blood transfusions required to treat certain types of anemias, including sickle cell disease, thalassemia and myelodysplastic syndromes. It is estimated that, of the more than 250,000 people worldwide who require frequent blood transfusions, and as many as 100,000 people may require an iron chelator to avoid dangerous iron overload. ICL670 is expected to increase treatment compliance of this debilitating and life-threatening condition, leading to better health outcomes. Phase III data showed efficacy in the group of patients that received 20-30 mg/kg doses. Based on the results, submission in the US and EU with Orphan Drug Status is planned for the first half of 2005.

Cardiovascular & Metabolism

* LAF237 (vildagliptin) is a first-in-class incretin enhancer for the treatment of type 2 diabetes. It has been shown in Phase II trials to be effective in lowering blood-sugar (HbA1c) levels. Phase III development as a monotherapy and in combination with other medicines remains on track. Phase III data are expected at the end of 2005. Submission is planned for early 2006.

* SPP100 (aliskiren) is the first in a new class of antihypertension agents called renin inhibitors that offers a once-daily treatment with efficacy and safety comparable to angiotensin-receptor blockers (ARBs), another class of high blood pressure treatments. In contrast to other antihypertensive agents, SPP100 lowers renin enzyme activity in the bloodstream, so it may have the potential to better protect against heart attacks (myocardial infarction) and kidney disease. Phase IIb/III data confirmed efficacy as a monotherapy and suggested benefits of combination with ARBs. Phase III trials are ongoing in the US, EU and Japan. Additional Phase III data are expected in Q3 2005. The first regulatory submission is planned for early 2006.

Neuroscience

* FTY720, an oral immunomodulator with a novel mechanism of action, has shown excellent efficacy in multiple sclerosis (MS) in a Phase II study. FTY720 has the potential to become the first efficacious oral therapy for MS, a condition estimated to affect more than one million people worldwide. Data from the Phase II study showed a significant reduction in the relapse rate and in the number of brain lesions detected by MRI scan as well as a longer time to first relapse. The vast majority of patients are continuing in the extension phase. One-year data are expected in mid-2005. Phase III studies are planned to start in mid-2005.

Transplantation

* FTY720 is also being developed for transplantation. Phase III data remain on track for completion in 2005. US and EU submissions are expected in early 2006.

Respiratory diseases

* QAB149 is a once-daily long-acting beta-2 agonist for asthma and Chronic Obstructive Pulmonary Disease (COPD) that offers a quick onset of action and true 24-hour control. New Phase IIb data showed strong efficacy in both asthma and COPD and confirmed safety at high doses. QAB149 is being developed first as a monotherapy for the bronchodilator market. Treatments like QAB149 are expected to maintain substantial market share in a rapidly growing asthma/COPD market. Phase III studies are planned to start in 2005. Regulatory submissions are planned for 2007. Several options for combination products are currently being evaluated in parallel.

* Xolair is on track for EU regulatory approval in 2005. This novel agent offers a breakthrough in treating asthma, particularly as a unique add-on therapy for adults and adolescents with severe persistent asthma who remain inadequately controlled with conventional medicines. Clinical data have shown Xolair offers substantial improvements in disease control and reduces clinically significant exacerbation rates. Xolair is being developed in collaboration with Genentech and Tanox.

Bone and joint treatment

* Aclasta(1) (zoledronic acid) has the potential to become the gold standard in treating osteoporosis. Having shown superior efficacy in Phase III studies in Paget’s disease, a condition marked by abnormal bone growth, the single once-yearly bisphosphonate infusion has the potential to provide unsurpassed compliance and excellent bone protection. Aclasta has received priority review status in the US for Paget’s disease, and a decision is expected in March 2005. EU approval is expected in the first half of 2005. Submission for postmenopausal osteoporosis is expected in 2007 following completion of ongoing Phase III trials. (1) Zoledronic acid (5 mg) is authorized to be marketed under the name Aclasta in Europe and is awaiting US approval of the name.

* AAE581 is an oral once-daily compound aiming to be the first cathepsin K inhibitor for treating osteoporosis. Well-tolerated and efficacious in Phase II trials, AAE581 has been shown to inhibit bone resorption and may have a positive effect on bone formation. Phase II trials are on schedule, and biomarker data are expected in Q4 2005. Phase III trials are planned to start in Q1 2006.

Infectious diseases

* LDT600 (telbivudine) is a once-daily tablet treatment for hepatitis B virus (HBV) infection, a disease estimated to affect about 400 million people worldwide. Phase II clinical data have shown efficacy exceeding lamivudine, the global market leader for hepatitis B therapeutics. The ongoing international Phase III GLOBE clinical trial, which includes China, is designed to evaluate telbivudine head-to-head against lamivudine. Patient enrollment was completed ahead of schedule in April 2004. Novartis holds a 57% investment in Idenix, and both companies plan to submit US, EU and international marketing applications for telbivudine beginning in Q4 2005 and extending into 2006.

Ophthalmics

* Lucentis(TM) is a recombinant antibody fragment designed as a new treatment for “wet” AMD (age-related macular degeneration), an eye condition that can cause vision loss. Developed with Genentech, which retains the right to develop and market the product in North America, Lucentis binds and inactivates VEGF (vascular endothelial growth factor), a protein that plays a role in angiogenesis (the formation of new blood vessels). Data from two Phase III trials are expected in 2005. Submission for EU approval is planned for 2006.

A total of 12 development projects were added to the portfolio, while 16 left the portfolio through approval or launch (5 projects) as well as through termination or for being put on hold (11 projects). Among the terminated projects is TCH346 in Parkinson’s disease and amyotrophic lateral sclerosis (ALS) after Phase II studies did not demonstrate efficacy.

Novartis expects the EU Mutual Recognition Procedure (MRP) for Prexige, a novel anti-inflammatory medicine being developed for osteoarthritis, to resume in mid-2005 after the European Medicines Agency (EMEA) completes a review of the COX-2 inhibitor class. Data from the landmark TARGET safety outcomes study in August 2004 demonstrated a significant 79% reduction in the incidence of upper gastrointestinal (GI) ulcer complications without compromising cardiovascular (CV) safety. The TARGET study showed that Prexige had a cardiovascular profile similar to conventional non-steroidal anti-inflammatory drugs (NSAIDs). Discussions are underway with the FDA on requirements for a new cardiovascular safety study. Additional studies are already underway to support the 100 mg dose for treating osteoarthritis. However, submission for US approval is not expected before 2007.

Promising early-stage projects

A priority of Novartis R&D efforts is to expedite “proof-of-concept” trials in humans through a “translational medicine” approach to better assess a compound’s clinical potential by collecting biomarker data as early as possible.

Novartis highlighted a group of nine early stage compounds currently in Phase I/II that offer significant potential based on the results of proof-of-concept testing. The richness of the early-stage pipeline illustrates the replacement power of the Novartis pipeline and demonstrates the continuing high performance of the research organization.

Among the priority early-stage projects is LBM642, a novel agonist of both PPAR-alpha and PPAR-gamma (peroxisome proliferator-activated receptor) for the treatment of metabolic syndrome, a group of risk factors that include obesity, insulin resistance, elevated cholesterol and high blood pressure. LBM642 was shown to be more efficacious in lipid lowering than fenofibrate in a first proof-of-concept trial. Proof-of-concept data in diabetes are expected in mid-2005.

Other early-stage projects include ACZ885, which offers a new mechanism for treating rheumatoid arthritis; AEE788, an anti-cancer agent with promise in many solid tumors; valopicitabine (also known as NM283), a novel therapy for hepatitis C infection being developed by Idenix, for which Novartis has an exclusive right to in-license; and AEB071, a first-in-class immunomodulator with potential in transplantation.

Important submissions planned for 2005

In 2005, Novartis anticipates making submissions for at least three new molecular entities for regulatory approval as well as making a series of applications for new indications of products already on the market, including the following:

* PTK787 in the US for colorectal cancer (pending Phase III results of CONFIRM1 trials)

* ICL670 in the US and EU as the first oral treatment for chronic iron overload

* LDT600 in the US for the treatment of hepatitis B

* Femara in the US and EU for a new indication for treating women with breast cancer in the early adjuvant (post-surgery) setting (pending initial data from the BIG 1-98 trial expected to be presented at the St. Gallen Breast Cancer Conference in January)

* Visudyne in the US for the occult form of age-related macular degeneration (AMD)

Seven major projects are currently in registration, including Aclasta for the treatment of Paget’s disease in the US and EU, the novel asthma medicine Xolair in the EU following approval in the US in mid-2003 and Zelnorm/Zelmac for treating irritable bowel syndrome (IBS) in the EU. Regulatory decisions are expected in 2005.

Strategic alliances complement pipeline

Novartis has more than 100 alliances with biotechnology and academic institutions looking for a major pharmaceutical company partnership. At the same time, Novartis recognizes the value of scientific advances that are made by partners and seeks to source the best technologies and early-stage compounds. Novartis has a culture designed to build fair, effective and mutually beneficial alliances.

Our alliance strategy in 2004 focused on two key components to strengthen our pipeline: development of research alliances and the in-licensing of new compounds.

A key focus of in-licensing was the acquisition of three compounds to complement internal cardiovascular/metabolism programs. D-4F, a novel apoA-I (apolipoprotein A-I) mimetic, was acquired from the US biotechnology company BruinPharma. ApoA-I is the major protein component of HDL and is considered a promising target for atherosclerosis therapy since it has been associated with beneficial effects on cardiovascular disease. Phase I development of D-4F has been initiated. An exclusive agreement was signed with Xenon Pharmaceuticals to develop and commercialize compounds from their Stearoyl-CoA Desaturase-1 (SCD1) program, which is in pre-clinical development. This program is complementary with Novartis programs targeting type 2 diabetes and the metabolic syndrome, which are conditions characterized by risk factors including obesity, insulin resistance, elevated cholesterol and high blood pressure. An agreement was also signed with Torrent Pharmaceuticals to develop its AGE (Advanced Glycosylation End-products) breaker compound in heart disease and diabetes-related vascular events, which is also in pre-clinical development.

Complementing internal discovery efforts in oncology, Novartis selected VX-322, a protein kinase inhibitor from Vertex in 2004, and also acquired from Vernalis the exclusive rights to the UK biotechnology company’s development program for Hsp90, a target implicated in a number of different cancers.

Novartis also recently acquired all rights to Triad’s pre-clinical p38map kinase program, which may deliver a promising oral therapeutic for inflammatory diseases. Novartis will be responsible for full development and commercialization of all compounds covered under Triad’s intellectual property.

New alliances included Morphosys (development of therapeutic antibodies), Cellzome (indentification of critical molecular pathways and interactions), Infinity Pharmaceuticals (expanding the chemical universe for new drug discovery), and the Broad Institute of MIT and Harvard (discovering the basic genetic causes of type 2 diabetes).

Disclaimer This release contains certain forward-looking statements relating to the Company’s business, which can be identified by the use of forward-looking terminology such as “pipeline”, “potential”, “set for”, “2005 newsflow”, “aim to”, “potential”, “expected”, “plans to”, “planned”, “being developed”, “aiming to”, “early-stage projects”, “anticipates”, “promising”, “may deliver”, or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, or regarding potential future revenues. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any of the development projects described in this release will succeed, that any new products will be brought to market, or that any new indications will be approved for any of our existing products. Similarly, there can be no guarantee that Novartis, or any present or future product, will achieve any particular level of revenue. In particular, management’s expectations could be affected by, among other things, additional analysis of clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; as well as factors discussed in the Company’s Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis AG (NYSE:NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group’s businesses achieved sales of USD 28.2 billion and net income of USD 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

Please find full media release in English attached:

http://hugin.info/134323/R/976585/143808.pdf

Further language versions are available through the following links:

German version is available through the following link: German press release: http://dominoext.novartis.com/nc/ncprre01.nsf/0/49ab0e058ce0480cc1256f8e007235dc

French version is available through the following link: French press release:

http://dominoext.novartis.com/nc/ncprre01.nsf/0/3b9af4bf62fb0fb7c1256f8e00748276

CONTACT:John Gilardi Novartis Global Media Relations +41-61-324-3018 (direct)+41-61-324-2200 (main) john.gilardi@group.novartis.com

Nehl Horton Novartis Global Media Relations+41-61-324-5749 (direct)+41-61-324-2200 (main) nehl.horton@group.novartis.com

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Knight Ridder

PHILADELPHIA – By Fawn Vrazo

“I want off,” David Wolovitz told his cancer doctor. “I want off now.”

It was the fall of 2000, and Wolovitz felt a bit stunned himself as the fateful words tumbled out of his mouth. He was sitting in a consultation room at the University of Pennsylvania, telling his oncologist, David Porter, to end the treatments that were his hope for beating a deadly blood cancer.

Wolovitz, a hard-driven electronics salesman in his early 50s, had been diagnosed with chronic myelogenous leukemia (CML) the previous March.

CML is caused by a defective gene that allows the bloodstream to become clogged with cancerous, immature white blood cells. In 2000, the only treatment options for CML were injections with interferon — a protein that stimulates the immune system — or a bone-marrow transplant. Without treatment, CML victims die within three to five years, usually from fatal infections or bleeding.

Wolovitz was deciding his own death sentence.

But he had his reasons. Interferon works well with many CML patients, but for Wolovitz the medicine was more terrible than the disease.

In its earliest stages, his CML had given him only the vaguest of symptoms. He felt fatigued and couldn’t eat more than a few bites of food — the result of his stomach being squeezed by a spleen swollen from an overproduction of white blood cells.

But the interferon was something else.

Even a few weeks after starting his daily self-injections of the drug, he felt so tired he couldn’t climb the steps at the sales conferences that were his job’s bread and butter. As the months of treatment wore on, he became so nauseous that all he could do was lie on his couch with the TV turned down low. Even reading made him woozy. One night, he vomited violently and spent hours lying on the bathroom floor of his home in Glen Mills, Pa.

But the kicker was blood tests, which showed that the interferon was not working. Even if Wolovitz found a matching bone-marrow donor, he knew that a marrow transplant would make him feel sicker, or even kill him. He ruled that option out, too.

Wolovitz had always been a take-charge, can-do type of guy. His life was his work — as an electronic-equipment salesman or manager of electronic-equipment sales forces for a variety of companies. He worked hard to provide for his wife of 30 years, Lainie, and their children, Andrea and Jeffrey. But work stole from his family life. Out at sales meetings several nights a week, he was frequently missing from the family dinner table. Business travel across the country and overseas took him away many weeks a year.

To him, life’s success was defined as “hitting target, hitting budget, hitting quotas, introducing products, growing businesses, making deals.”

Then cancer — as it does with every one of its victims, including me — did a number on his head.

First, his life became about surviving. When the treatments didn’t work, Wolovitz decided to accept his fate. He would look at his life and, in the time he had left, fix the things that needed fixing.

Wolovitz drew closer to his family and friends. He sorted out his finances. He began toning down his forceful personality; instead of being a guy who always wanted to get things done, right now, he tried to learn patience.

He made a list of the enjoyable things in life that relentless work had kept him from. He and Lainie took their first cruise, from Puerto Rico to Aruba. He went to the Netherlands with friends and planned an Alaskan cruise and a round of golf at a special resort in Canada.

Mentally, he prepared to die. But he still searched the Internet for CML clinical trials. Word was circulating about a possible CML miracle drug.

It would indeed take a miracle to save his life. But miracles do happen.

Three decades ago, the so-called war against cancer seemed so winnable. In January 1971, President Richard Nixon optimistically declared that America would “launch an intensive campaign to find a cure for cancer,” and 11 months later he signed the National Cancer Act.

Cancer was a disease. All it needed was a cure. That’s what both the public and scientists thought.

But cancer turns out to be so much more complicated. Frank Rauscher III, cancer researcher and deputy director of the Wistar Institute in Philadelphia, describes it as not just one disease but 200.

His father, Frank Rauscher Jr., headed the National Cancer Institute and the nation’s new cancer campaign in 1971 — a period his son refers to as a time of “lofty claims.”

Now, decades later, Rauscher and other scientists see cancer as many different diseases caused by many different genetic changes. Each of those minute changes — and different cancers can have several of them — allows normal cells to grow out of control, cancer’s definition.

As they spread to other parts of the body, cancer cells mutate to become stranger and more unbeatable still. Instead of the normal 46 chromosomes, they might have hundreds. They find different pathways to blood sources; they develop resistance to chemotherapy drugs and even trick the body’s immune system into ignoring their existence.

It has long been assumed that a key to successfully fighting cancer is to catch it before it spreads. And scientists increasingly believe the real task is to identify each cancer’s genetic abnormalities early and then develop drugs that will block those specific defects, stopping the cancer in its tracks.

Developed decades ago, today’s standard cancer treatments are far less specialized than that. Cancer patients refer to them, often disdainfully, as “slash, burn and poison” — cut out the cancer, radiate it, and flood it with poisonous chemotherapy that kills both good and bad cells.

The old methods have been quite successful at times. Trial-and-error combinations of chemotherapy and antibiotic drugs have brought cures to millions of childhood-leukemia victims. Surgery, chemo and radiation have cured many adults of breast, colon, prostate and other cancers.

But “targeted therapies” — specialized drugs that target cancer’s genetic abnormalities — are the big buzz now.

Researchers are optimistic that targeted therapies, either alone or in combination with standard treatments such as chemo, will be the ultimate weapon in winning the cancer war. But the road ahead is awesomely daunting.

Imagine a genetic abnormality as a defective switch that won’t shut off power — that allows cells to grow with no controls. Imagine that some cancers have not one but several defective switches, and that these switches aren’t readily visible, but hidden deep within a cell’s molecular structure. The task facing researchers is to find all the broken switches and then develop the exact drugs to turn each of them off.

Luck helps.

In 1999, a year before David Wolovitz learned he had the type of leukemia called CML, scientists were awed by the success of clinical trials testing a new targeted-therapy cancer drug. The drug brought great hope to the targeted-therapy movement and would change Wolovitz’s life in remarkable ways.

It was called Gleevec.

CML is a relatively rare cancer, with only 4,500 cases annually in the United States, and a drug for it didn’t hold much promise as a blockbuster. But the pharmaceutical company was relentlessly urged on by Brian Druker, a researcher at the Oregon Health and Science University, who had made the study of targeted therapies and CML his life.

With a modest amount of funding from Novartis but thousands more from the National Cancer Institute and the national Leukemia & Lymphoma Society, Druker began testing mice with the various compounds that Novartis provided.

Out of half a dozen compounds, one stood out.

Druker urged Novartis to test the compound on humans. CML patients using it during initial safety trials had dramatic responses. But the real eureka moment came in 1999, when every single one of 31 patients treated with the compound saw his or her white-blood-cell counts return to normal.

On May 10, 2001, Gleevec was granted the fastest-ever Food and Drug Administration approval for a cancer drug — just 2 1/2 months after its application.

David Wolovitz saw the news on CNBC.

The next day, he went to see his local oncologist, Michael Mikhail, for a prescription. Wolovitz later placed a copy of it in his scrapbook. A few days later, as soon as his pharmacy got a supply of the new drug, he was holding Gleevec pills in his hand.

All cancer patients, me included, experience the same intense moments at various stages of the disease. There is the awful moment when you learn you have cancer. There is the nervous moment — many of them, actually — when you await the results of tests showing whether treatments have worked. Before that, there are the breathless moments when your particular cancer treatments begin.

Some people pray; some just close their eyes and hope for the best.

Wolovitz was not a religious or spiritual man — “I’m a salesman,” he explains — and as he stood in his bathroom in May 2001, holding the pills, he was thinking, “Gee, I hope these work; go to work, baby.” For good measure, he threw in some visualization of the Gleevec pills attacking his leukemia.

He swallowed the four orange pills on an empty stomach — and immediately threw them up. He tossed them back down again.

Within weeks, counts of the Philadelphia chromosome — the measurement used to assess the level of cancer in CML patients — began dropping in his blood, from a high of 89 percent to 2 percent. After six months, the count was zero.

It wasn’t a cure, but the next best thing — full remission from his cancer.

Mentally, it was almost more than Wolovitz could handle. He found it all hard to believe. His cancer, the failed treatment, and then at precisely the right moment, a miracle drug.

“Why me?” he asked himself. Why was he saved, when so many others died? Survivor’s guilt gnawed at him; he wished in his heart that the “stars would line up” for all cancer patients.

On disability from his last job, he has become a fixture at the local offices of the leukemia society, where he answers phones, licks envelopes, sells cookies, whatever they need. He founded a CML support group. He has recounted his recovery story to thousands of people locally, nationally and in Ireland, raising funds for leukemia research.

“I believe now that every human being has an obligation — if you can change the life of one person in the world, then you should do that,” he says.

Meanwhile, in the world of targeted cancer medicine, newer Gleevec-type drugs are on the way to treat those resistant to the original. Gleevec has also been successful in treating a type of gastrointestinal cancer, and researchers in Philadelphia are studying whether it might help in some breast cancers.

The drug has proved a moneymaker for Novartis, with $1.1 billion in sales in 2003. A standard dose can cost $2,900 a month — mostly covered by health insurance — and patients take the drug for life.

Scientists remain hopeful that Gleevec won’t turn out to be the rare miracle cancer drug, but rather the discovery that will lead to dozens or even hundreds of successful targeted cancer therapies in the future.

Suffering few side effects, including occasional leg cramps, Wolovitz has been in remission now for nearly four years. His illness and recovery, he says, have “leaned my life closer to the good side. … I would not choose another road.”