-- Transforming the "grammar" of drug discovery by focusing on
molecular pathways and patient stratification
-- Redefining Research-to-Development transition through fast and
rigorous "proof-of-concept" trials
-- More than 60 new molecular entities have potential to enter
trials by end of 2008
-- Development pipeline progressing well, key data planned for
second half of 2005
CAMBRIDGE, Mass., May 3, 2005 (PRIMEZONE) -- At an investor conference to highlight progress at the Novartis Institutes for BioMedical Research (NIBR), senior Novartis scientists presented their new research strategy focused on molecular pathways that may be shared by various diseases as an organizing concept in the search for novel compounds that address unmet needs of patients.
NIBR is the global pharmaceutical research organization of Novartis that was created in May 2002 to enhance the company's long tradition of drug discovery research that has produced breakthrough therapies such as Gleevec(R)/Glivec(R) for cancer patients, Sandimmun(R)/Neoral(R) for use in transplantation and helping those with schizophrenia with Clozaril(R). More than 2,800 research scientists are now working worldwide within various NIBR institutes, including at the global headquarters in Cambridge, Massachusetts, to redefine drug discovery in the genomic era.
A key aspect of the NIBR strategy is to target key cellular pathways that may be part of the underlying mechanism causing various diseases. Traditional pharmaceutical development has relied heavily on identifying appropriate drug "targets," such as single genes or proteins. However, following the decoding of the genome, drug discovery is moving quickly toward focusing on interacting pathways of proteins, which may be at the root of several diseases and inventing compounds that target critical nodes within the signaling pathways to alter the disease-causing mechanism.
Dr. Mark Fishman, President of NIBR and a member of the Executive Committee of Novartis, and his leadership team have instituted several new fundamental discovery platforms, ranging from those focused on specific gene families to those intended to integrate key molecular pathways that cause disease and identify "drugable nodes." These platforms are already delivering targets under consideration for transition to full-scale clinical development.
"Unmet patient needs and scientific tractability, driven by an understanding of the mechanistic underpinning of a disease are the driving factors for project selection and resourcing in our research endeavors. The focus on disease pathways provides an organizational framework for studying diseases creating the foundation to discover exciting novel medicines," said Dr. Daniel Vasella, Chairman and CEO of Novartis.
"Proof-of-concept" trials to rigorously test compounds early As part of the drug discovery transformation, compounds developed at NIBR enter full-scale clinical development only after successfully completing "proof-of-concept" trials.
These trials, which are typically done with a small group of patients, are designed to rapidly assess a compound's efficacy in humans to provide a foundation for early decisions to advance or terminate projects. This approach stands in contrast to traditional, sequential Phase I and early Phase II studies, which are primarily used to assess safety in healthy volunteers and determine dosage for pivotal Phase III studies.
"All of our drug discovery efforts begin and end with the patient. By focusing early on the experience of patients alongside a commitment to understanding the mechanism of action of a particular disease, our science is geared toward improving both the patient's medical condition as well as their quality of life," said Dr. Mark Fishman. "We are harnessing the power of the genome to invent a 'new grammar' of drug discovery that will translate breakthroughs in biology and chemistry into innovative medicines for patients."
For example, Novartis scientists recently completed a successful proof-of-concept trial of a novel antibody, ACZ885, for inflammatory conditions. This trial examined patients with a rare inherited inflammatory condition called Muckle-Wells syndrome, which is manifested by rash, joint aches, fevers and migraine headaches. All of these symptoms were relieved within days by a single injection of the antibody, which was directed to an inflammatory signal known as IL-1 beta. The positive findings in Muckle-Wells patients may be indicative of efficacy in other related illnesses, such as rheumatoid arthritis.
In another positive proof-of-concept clinical trial, the success of LBM642, a dual agonist of PPAR alpha and gamma, in a dyslipidemia study suggests that the molecule has the potential for efficacy in metabolic syndrome, a disease cluster including diabetes, high cholesterol, and obesity. The results show this compound may overcome many of the disadvantages of other PPAR alpha/gamma dual agonists, in particular weight gain and edema.
In Oncology, Novartis is best known for introducing Gleevec/Glivec, which targets the Bcr-Abl kinase in certain forms of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Another novel oral compound is AMN107, which has now entered a Phase II clinical trial for patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) who are resistant or intolerant of Gleevec as well as patients with relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL), system mastocytosis or hypereosinophilic syndrome / chronic eosinophilic leukemia. The decision to proceed to Phase II was based on Phase I clinical data that showed more than 90% of patients with chronic phase Ph+ CML achieved a hematologic response, and more than 60% of patients in the advanced stages of Ph+ CML achieved similar responses.
Novartis has expanded its oncology research activities to include other mechanisms of action, particularly inhibition of cell proliferation/survival pathways and activation of apoptosis (cell death) pathways. One approach being studied is exposing cancer cells to a first-in-class SMAC mimetic, which is a small molecule that blocks the anti-apoptotic protein IAP, to induce cell death. Multiple cancer models have shown that this compound has reduced the size of tumors in animals.
Valued and open partner to the research community NIBR is developing a research strategy based on excellent cooperation with the company's Development team as well as external partners. In 2004, NIBR established approximately 150 collaborations, including 50 with major biotechnology companies, to complement internal research activities. Novartis recognizes the value of scientific advances made by partners and seeks to source the best technologies and early-stage compounds.
Novartis recognizes the importance of open exchange of information. For example, NIBR and the Broad Institute of MIT and Harvard will collaborate on a joint project to decipher the genetic causes of diabetes. This initiative establishes a research partnership of physicians, geneticists, computational scientists, pharmaceutical researchers and others to identify inherited risk factors for developing the disease and its complications. All findings will be made available to the public for free on the Internet.
NIBR is also complemented by the company's Corporate Research activities, which aim to leverage the specific scientific knowledge from the three institutes - the Novartis Institute for Tropical Disease (NITD) in Singapore, the Genomics Institute (GNF) in La Jolla, California; and the Friedrich Miescher Institute (FMI) in Basel. Corporate Research contributes basic biomedical knowledge in neuroscience, growth control and epigenetics through the FMI, new therapeutic targets and technologies through the GNF, and will contribute drugs for neglected diseases through drug discovery research at NITD.
Strong pipeline set for dynamic progress NIBR has a group of 63 new molecular entities currently in advanced pre-clinical development, of which 16 are antibodies and support the ability to deliver therapies against a broader set of novel molecular targets. These compounds are spread across eight key therapeutic areas, including a particular focus on oncology and cardiovascular/metabolism.
Novartis is consistently ranked as having one of the strongest pipelines in the industry, with 75 projects in clinical development and 55 of them in Phase II, III or registration. Some of these projects have been highlighted by industry experts for being truly innovative drugs, including SPP100 (hypertension), LAF237 (diabetes), FTY720 (multiple sclerosis) and QAB149 (asthma and COPD).
"All of our late-stage projects are progressing well in an increasingly challenging industry environment marked by an intensified focus on drug safety," said Dr. Joerg Reinhardt, Head of Development, Novartis Pharma AG. "This year will be one with strong newsflow with Phase III data and regulatory submissions expected for key products. We expect to see dynamic progress in our pipeline."
Recent developments include the submission of Exjade(R) (deferasirox), a once-daily oral iron chelator, for US and EU approval. Formerly known as ICL670, Exjade offers the potential to revolutionize the treatment of iron overload, providing a once-daily oral formulation to replace a cumbersome infusion therapy for the treatment of this potentially life-threatening condition associated with blood transfusions.
A number of additional submissions are planned for 2005, including the Phase III compound LDT600 for the treatment of hepatitis B as well as new indications for Gleevec/Glivec(R) for Philadelphia-chromosome-positive(Ph+) acute lymphoblastic leukemia and the breast cancer agent Femara(R) for use in the early adjuvant (post-surgery) setting. Phase III data for LAF237 (vildagliptin) as a monotherapy and in combination with other anti-diabetic agents is expected at the end of 2005.
This release contains certain forward-looking statements relating to the Group's business, which can be identified by the use of forward-looking terminology such as "potential", "pipeline", "search", "strategy", "may be", "intended to", "designed to", "geared toward", "suggests", "will", "aim", "expect", "potential", "planned", or similar expressions, or by express or implied discussions regarding potential new products or potential future sales of such new products, or by other discussions of strategy, plans or intentions. Such statements reflect the current views of the Group with respect to future events and are subject to certain risks, uncertainties and assumptions. There can be no guarantee that any new products will be approved for sale in any market, or that any products will reach any particular sales levels. In particular, management's expectations could be affected by, among other things, unexpected research results; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the Group's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures and other risks and factors referred to in the Group's current Form 20-F on file 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 pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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