LEL Lilly(Eli)

 
TIDMLEL 
 
Abstract #2814 
 
Embargoed for Release: December 12, 2011 
 
Contact: Amy Sousa, Lilly Neil Hochman, TogoRun 
 
317-276-8478 (office) 212-453-2067 (office) 
 
317-997-1481 (mobile) 516-784-9089 (mobile) 
 
Email: sousa_amy_e@lilly.com Email: n.hochman@togorun.net 
 
LILLY ONCOLOGY REVEALS FINDINGS FROM STUDY OF JAK2 INHIBITOR FOR BLOOD CANCERS 
                                AT ASH MEETING 
 
SAN DIEGO, December 12, 2011 - Eli Lilly and Company (NYSE: LLY) announced data 
from an oncology pipeline molecule today at the 53rd Annual Meeting of the 
American Society of Hematology (ASH). At the meeting, Lilly Oncology presented 
Phase I data from the investigational therapy LY2784544, a small-molecule Janus 
kinase 2 (JAK2) inhibitor, in development for the treatment of certain types of 
myeloproliferative neoplasms (MPNs), a group of blood cancers characterized by 
abnormal production of red blood cells or myeloid cells (non-lymphocyte white 
blood cells). 
 
"Research into myeloproliferative neoplasms demonstrated the importance of the 
JAK2 genetic mutation as a target for potential treatment options," said 
Richard Gaynor, M.D., vice president of product development and medical affairs 
at Lilly Oncology. "These data show that our compound has the potential to 
inhibit the JAK2 mutation and should be studied further. We hope that this 
study is the first in Lilly's ongoing research and development of LY2784544 and 
that our findings signal a potential new treatment for patients fighting 
myeloproliferative neoplasms." 
 
The Role of JAK2 in MPN 
 
In 2005, researchers reported that a point mutation in the JAK2 gene occurs in 
more than 95 percent of patients with the MPN subtype polycythemia vera (PV) 
and the majority of patients with the subtypes myelofibrosis (MF) and essential 
thrombocythemia (ET).2, The JAK2 point mutation observed in MPNs substitutes 
the amino acid phenylalanine for valine (at position 617 [V617F]) of the JAK2 
protein.2 The mutation makes JAK2 constantly active, triggering several 
signaling pathways that cause blood-forming cells to proliferate and resist 
apoptosis (programmed cell death). 
 
Phase I Study Sought to Ascertain Safety, Tolerability 
 
In pre-clinical study, LY2784544 selectively targeted JAK2 V617F while 
minimally inhibiting wild-type JAK2 so that normal marrow function wasn't 
impeded. 
 
The primary objectives of this ongoing study were to determine the safety and 
tolerability of LY2784544 and to define a recommended oral daily dose for 
further study in patients with JAK2 V617F-positive MF, ET or PV. At the time of 
the interim analysis, 19 patients (1 PV, 1 post-ET MF and 17 MF) were 
evaluated. 
 
Secondary objectives of the trial included determining pharmacokinetics, 
evaluating patient response to therapy using criteria developed by the 
International Working Group for Myelofibrosis Research and Treatment (IWG-MRT), 
and evaluating symptoms using the Myeloproliferative Neoplasm Symptom 
Assessment Form (MPN-SAF). 
 
An effective MPN treatment will ideally reverse splenomegaly (spleen 
enlargement)-a painful complication caused by an overabundance of blood cells 
infiltrating the organ. In this study, a palpable reduction in spleen length of 
at least 35 percent was seen in 13 of 17 evaluable patients (76%, including 16 
MF and 1 PV). After five cycles of therapy, a reduction in severity of 
bone-marrow fibrosis was observed in three of five MF patients for whom 
follow-up biopsies are available. 
 
When laboratory results were analyzed, one case of laboratory tumor lysis 
syndrome (LTLS) and three cases of grade 2 clinical tumor lysis syndrome (CTLS) 
were detected. TLS is a consequence of cancer treatment that encompasses 
metabolic complications caused when dying cancer cells release breakdown 
products. Specifically, the TLS occurrences involved one case of hyperuricemia 
at the 240 mg dose and three cases of creatinine increase at the 200 mg dose, 
resulting in 200 mg and 240 mg doses of LY2784544 being reported as 
dose-limiting toxicities. 
 
Based on analysis of pharmacokinetics, doses of LY2784544 associated with TLS 
appear to overlap the lower boundary of the biologically efficacious dose (BED) 
range predicted from pre-clinical evaluations. To permit testing of doses 
within the BED, the dosing regimen has been amended to include a lower-dose 
lead-in period for the purpose of reducing tumor burden, and the likelihood of 
TLS, prior to further testing of dose escalation. 
 
Assessing symptoms using the MPN-SAF questionnaire showed that most patients 
reported alleviation of symptoms within the first two therapy cycles. 
Fifty-nine percent of patients reported symptom improvement of = 50% in key 
MPN-SAF symptoms, and 47 percent reported a = 50% improvement in 
fatigue-associated parameters. At the doses tested, no reduction has been 
observed in the mutant allele burden (i.e., the percentage of blood cells 
carrying the JAK2 V617F mutation). 
 
Four patients discontinued therapy, one for each of the following reasons: 
adverse event, progressive disease, investigator decision and subject's 
decision. Serious drug-related adverse effects were seen in four patients (4 
saw grade 2 creatinine increase, 2 saw grade 4 hyperuricemia and 1 saw grade 1 
hyperkalemia). Temporarily interrupting treatment allowed all adverse events to 
resolve within 14 days. The most frequently reported drug-related adverse 
events were diarrhea (3 patients with grade 2, 5 with grade 1); nausea (2 
patients with grade 2, 4 with grade 1); transient increased creatinine (4 
patients with grade 2); anemia (3 patients with grade 2, 1 with grade 1); and 
hyperuricemia (2 patients with grade 4). 
 
About Myeloproliferative Neoplasia 
 
Over 200,000 people in the U.S. have some form of myeloproliferative neoplasm 
(MPN), a category of diseases in which genetic mutations in bone marrow stem 
cells cause the bone marrow to have abnormal production of red blood cells, 
white blood cells or platelets. Symptoms for patients can be many or few and 
not all patients will experience symptoms. Treatment of MPNs depends on the 
presence and type of symptoms, and typically aims to correct the abnormal blood 
counts.7 
 
About Lilly Oncology 
 
For more than four decades, Lilly Oncology, a division of Eli Lilly and 
Company, has been dedicated to delivering innovative solutions that improve the 
care of people living with cancer.  Because no two cancer patients are alike, 
Lilly Oncology is committed to developing novel treatment approaches.  To learn 
more about Lilly's commitment to cancer, please visit www.LillyOncology.com. 
 
About Eli Lilly and Company 
 
Lilly, a leading innovation-driven corporation, is developing a growing 
portfolio of pharmaceutical products by applying the latest research from its 
own worldwide laboratories and from collaborations with eminent scientific 
organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - 
through medicines and information - for some of the world's most urgent medical 
needs. 
 
P-LLY 
 
                                     # # # 
 
This press release contains forward-looking statements about the potential of 
LY2784544 for the treatment of myeloproliferative neoplasms and reflects 
Lilly's current beliefs. However, as with any pharmaceutical compound, there 
are substantial risks and uncertainties in the process of development and 
commercialization. There is no guarantee that this compound will be approved by 
the relevant regulatory authorities or prove to be commercially successful. For 
further discussion of these and other risks and uncertainties, see Lilly's 
filings with the United States Securities and Exchange Commission. Lilly 
undertakes no duty to update forward-looking statements. 
 
 
 
Eli Lilly and Company 
 
Lilly Corporate Center 
 
Indianapolis, Indiana 46285 
 
U.S.A. 
 
 
 
National Cancer Institute. What Are Myeloproliferative Disorders?, 
www.cancer.gov/cancertopics/types/what-are-myeloproliferative-disorders 
(Accessed: November 8, 2011). 
 
Garber, Ken. JAK2 Inhibitors: Not the Next Imatainib But Researchers See Other 
Possibilities." J of the National Cancer Institute, vol. 101, pgs. 980-982 
(Issue 14, July 15, 2009). 
 
A. Tefferi and A. Pardanani. JAK inhibitors in myeloproliferative neoplasms: 
Rationale, current data and perspective. Blood Reviews vol. 25, pgs. 229-237 
(2011). 
 
F.P.S. Santos and S. Verstovsek. JAK2 inhibitors: What's the true therapeutic 
potential? Blood Reviews vol. 25, pgs. 53-63 (2011). 
 
Passamonti and E. Rumi. Clinical relevance of JAK2 (V617F) mutant allele 
burden. Haematologica. Vol. 94, No. 1, pgs. 7-10 (2009). 
 
The National Cancer Institute, "General Information About Chronic 
Myeloproliferative Disorders," Updated: September 27, 2011. 
http://www.cancer.gov/cancertopics/pdq/treatment/myeloproliferative/Patient#Keypoint1 , 
(Accessed: November 7, 2011). 
 
The University of California San Francisco Medical Center, "Myeloproliferative 
Disorders," Updated: September 15, 2011. 
http://www.ucsfhealth.org/conditions/myeloproliferative_disorders/ , 
(Accessed: November 7, 2011). 
 
University of Maryland Medical Center, "Myeloproliferative Disorders." 
http://www.umm.edu/altmed/articles/myeloproliferative-disorders-000114.htm , 
(Accessed:November 7, 2011). 
 
 
 
 
END 
 

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