Novartis International AG: Novartis JAK inhibitor provides marked and durable clinical benefits in patients with myelofibrosis, a rare, life-threatening blood cancer

Novartis International AG / Novartis JAK inhibitor provides marked and durable clinical
benefits in patients with myelofibrosis, a rare, life-threatening blood cancer processed
and transmitted by Hugin AS. The issuer is solely responsible for the content of this
announcement.

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Myelofibrosis is a blood cancer characterized by bone marrow failure, enlarged spleen,
poor quality of life and shortened survival[1]

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Phase I/II data published in NEJM demonstrate clinical benefits of JAK1 and JAK2
inhibitor INC424, including reduction of spleen size and alleviation of debilitating
symptoms[2]

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Novartis licensed INC424 outside US from Incyte, complementing broad oncology portfolio
of potential treatments for rare diseases; Phase III trials are fully enrolled

Basel, September 15, 2010 - Results from a Phase I/II study of the Novartis Janus kinase
(JAK) inhibitor with the investigational name INC424 (also known as INCB018424 and
INCB18424) were published today in The New England Journal of Medicine, demonstrating
marked and durable clinical benefits in patients with myelofibrosis[2]. Novartis has
licensed INC424 from Incyte for development and potential commercialization outside the
US. Incyte has retained rights for the development and potential commercialization of
INC424 in the US.

Myelofibrosis is a rare, life-threatening blood cancer characterized by bone marrow
failure, enlarged spleen (splenomegaly), debilitating symptoms, poor quality of life,
weight loss and shortened survival[1]. Both the US Food and Drug Administration and the
European Medicines Agency have granted INC424 orphan drug status for myelofibrosis.

The Phase I/II study of 153 patients showed that approximately 75% of myelofibrosis
patients receiving INC424 twice-daily experienced rapid reduction in spleen size, which
was durable for more than one year of follow-up. After only one month of therapy,
patients with debilitating symptoms including fatigue, night sweats and pruritus
(itching) also achieved more than 50% improvement in symptom scores, as measured by the
Myelofibrosis Symptom Assessment Form. Patients, particularly those with weight loss,
experienced a clinically meaningful gain in total body weight following treatment.
Additional clinical benefits observed in the study included improved functional status
and increased exercise capacity. These clinical benefits were accompanied by reductions
in circulating cytokines, inflammation-causing proteins in the blood that are markedly
elevated in patients with myelofibrosis[2].

Two Phase III clinical trials, COMFORT-I in the US, Canada and Australia, and COMFORT-II
in Europe, have completed enrollment and are evaluating the benefits of treatment with
INC424 compared to either placebo or best available care[3],[4].

"Effective therapies are desperately needed for patients with myelofibrosis, which has a
poor prognosis, especially when advanced," said lead investigator Srdan Verstovsek, MD,
PhD, of MD Anderson Cancer Center, Houston, Texas. "We currently have no therapeutic
options for these patients in the US, and the rapid and durable clinical benefits
observed in this study show a real potential to provide a way to alleviate suffering."

A strong association exists between abnormal JAK signaling and the development of
myelofibrosis, polycythemia vera and essential thrombocythemia, a related group of
conditions referred to as myeloproliferative neoplasms[5]-[8]. Patients with these
diseases can progress to secondary acute myelogenous leukemia, which is virtually
untreatable and is associated with a dismal prognosis[9],[10]. The discovery of JAK
mutations common to myelofibrosis, polycythemia vera and essential thrombocythemia has
linked them on a molecular level and has led to the development of INC424, a potent,
selective inhibitor of the JAK1 and JAK2 tyrosine kinases[11].

"Complementing our rich hematology-oncology pipeline in rare diseases, this promising
JAK inhibitor exemplifies the Novartis commitment to developing new therapies for
patients with unmet medical needs," said Alessandro Riva, MD, Global Head, Oncology
Development & Medical Affairs, Novartis Oncology. "We are pleased to contribute our
expertise to the global development of INC424, complementing and leveraging Incyte's
work for myelofibrosis patients in the US."

Study details
The open-label, non-randomized, dose-escalation Phase I/II study, conducted by Incyte,
included 153 patients with myelofibrosis, and was undertaken at MD Anderson Cancer
Center and Mayo Clinic. Primary outcome measures were safety and tolerability. The
secondary outcome measure was preliminary effectiveness[2].

In this study, a starting dose of 15 mg twice-daily with individualized dose titration
was found to be the most effective and safest dose of INC424. Median duration of therapy
exceeded one year. Notably, improvements occurred in patients regardless of JAK
mutational status. Investigators observed that treatment with INC424 reduced levels of
inflammatory cytokines in the blood, which they believe could provide a rational
biological explanation for the mutation-independent response to therapy[2].

INC424 provided rapid and sustained reduction in splenomegaly, resolution of
constitutional symptoms, improvement of performance status and exercise capacity and
weight gain. At the starting dose of 15 mg twice-daily, 48% of patients achieved at
least a 35% reduction in spleen volume. Symptoms of myelofibrosis not directly related
to splenomegaly, including night sweats, fevers, fatigue, weight loss and pruritus, also
improved in response to INC424. Other clinical benefits included normalization of
elevated platelet and white cell counts. Reduction in cytokine levels while on therapy,
presumably through JAK1 inhibition, paralleled improvements in patients' systemic
symptoms[2].

At the time of the data analysis, the median duration of therapy for 153 patients
enrolled in the study was 14.7 months and 115 (75%) were still receiving INC424.
Non-hematologic side effects related to therapy were infrequent (<10%) and of low grade.
Hematologic side effects included anemia and thrombocytopenia (reduced platelet counts).
Thrombocytopenia was the dose-limiting toxicity of the drug. Mean hemoglobin levels
decreased during the first three to four cycles of therapy and then stabilized or
improved with continued treatment. Serious adverse events occurred in 59 patients, of
whom 12 experienced serious adverse events that were considered at least possibly
related to treatment[2].

About myelofibrosis
Myelofibrosis is a Philadelphia chromosome-negative myeloproliferative neoplasm
associated with bone marrow failure, splenomegaly, debilitating symptoms and shortened
survival. Of the JAK-associated myeloproliferative neoplasms, myelofibrosis carries the
greatest risk of a poor prognosis, including transformation to fatal acute myelogenous
leukemia. For myelofibrosis patients in general, clinical findings such as splenomegaly,
anemia and constitutional symptoms may significantly reduce quality of
life[1],[12],[13].

The disease has a high unmet medical need. Although allogeneic stem cell transplantation
may cure myelofibrosis, the procedure is associated with significant morbidity and
mortality and is usually appropriate only in younger patients[1]. The five-year survival
rate after transplantation is about 50%[14].

Disclaimer
The foregoing release contains forward-looking statements that can be identified by
terminology such as "potential," "pipeline," "promising," "commitment," or similar
expressions, or by express or implied discussions regarding the potential future
submission or approval for marketing of INC424, or regarding potential future revenues
from INC424. You should not place undue reliance on these statements. Such
forward-looking statements reflect the current views of management regarding future
events, and involve known and unknown risks, uncertainties and other factors that may
cause actual results with INC424 to be materially different from any future results,
performance or achievements expressed or implied by such statements. There can be no
guarantee that INC424 will be submitted or approved for sale in any market. Nor can
there be any guarantee that INC424 will achieve any particular levels of revenue in the
future. In particular, management's expectations regarding INC424 could be affected by,
among other things, unexpected clinical trial results, including unexpected new clinical
data and unexpected additional analysis of existing clinical data; 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; the impact that the
foregoing factors could have on the values attributed to the Novartis Group's assets and
liabilities as recorded in the Group's consolidated balance sheet, and other risks and
factors referred to in Novartis AG'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 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 provides healthcare solutions that address the evolving needs of patients and
societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best
meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive
vaccines, diagnostic tools and consumer health products. Novartis is the only company
with leading positions in these areas. In 2009, the Group's continuing operations
achieved net sales of USD 44.3 billion, while approximately USD 7.5 billion was invested
in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis
Group companies employ approximately 102,000 full-time-equivalent associates and operate
in more than 140 countries around the world. For more information, please visit
http://www.novartis.com http://www.novartis.com .

References
1. The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. Available at
http://www.leukemia-lymphoma.org/attachments/National/br_1190656475.pdf
http://www.leukemia-lymphoma.org/attachments/National/br_1190656475.pdf . Accessed
September 2010.
2. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2
Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September 16;363:1117-1127.

3. Controlled MyeloFibrosis Study With Oral JAK Inhibitor Treatment: The COMFORT-I
Trial. Available at
http://clinicaltrials.gov/ct2/show/NCT00952289?term=comfort+myelofibrosis&rank=1
http://clinicaltrials.gov/ct2/show/NCT00952289?term=comfort+myelofibrosis&rank=1 .
Accessed September 2010.
4. Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor
Treatment-II: The COMFORT-II Trial. Available at
http://www.clinicaltrials.gov/ct2/show/NCT00934544
http://www.clinicaltrials.gov/ct2/show/NCT00934544 . Accessed September 2010.
5. Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis
and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7:673-683.
6. Kralovics R. Genetic complexity of myeloproliferative neoplasms. Leukemia.
2008;22:1841-1848.
7. Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol
Educ Program. 2009:636-642.
8. Fourouclas N, Li J, Gilby DC, et al. Methylation of the suppressor of cytokine
signaling 3 gene (SOCS3) in myeloproliferative disorders. Haematologica.
2008;93:1635-1644.
9. Beer PA, Green AR. Pathogenesis and management of essential thrombocythemia.
Hematology Am Soc Hematol Educ Program. 2009;621-628.
10. Abdel-Wahab OI, Levine RL. Primary myelofibrosis: update on definition,
pathogenesis, and treatment. Annu Rev Med. 2009;60:233-245.
11. Plo I, Vainchenker W. Molecular and genetic basis of myeloproliferative disorders:
questions and perspectives. Clin Lymphoma Myeloma. 2009;9(Suppl 3):S329-S339.
12. Thiele J, Kvasnicka HM. The 2008 WHO diagnostic criteria for polcythemia vera,
essential thrombocythemia, and primary myelofibrosis. Current Hematol Malig Reports.
2009;4:33-40.
13. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative
neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic
algorithms. Leukemia. 2008;22(1):14-22.
14. Tefferi A. Allogeneic hematopoietic cell transplantation versus drugs in
myelofibrosis: the risk-benefit balancing act. Bone Marrow Transplant.
2010;45(3):419-421.

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