Singapore, Dec. 2, 2009 - S*BIO Pte Ltd today announced data presentations on its novel oral JAK2 inhibitor, SB1518, at The American Society of Hematology 51st Annual Meeting and Exposition in New Orleans.
Data will be presented on the clinical results from the Phase 1 dose-escalation trial of SB1518 detailing its safety, tolerability and harmacokinetic/pharmacodynamic (PK/PD) profile in dose levels ranging from 100 to 600 mg. These doses were administered once daily continuously in 28-day cycles in patients with advanced myelofibrosis (MF) and acute myelogenous leukemia (AML). More than 35 patients have been enrolled to date and treated at multiple dose levels ranging from 100-600 mg daily. SB1518 demonstrated promising activity in MF patients. The study generated a positive signal that warrants further investigation.
In an oral presentation, data will be presented from a Phase 1 dose-escalating trial of SB1518 tested in four doses, from 100 to 400 mg per day, in heavily pre-treated relapsed or refractory Hodgkins (HL) and non-Hodgkins lymphoma (NHL) patients. SB1518 was well tolerated with mostly grade 1/2 gastrointestinal side effects. The maximum tolerated dose was not reached in the study and dose escalation is continuing. 15 of 17 treated patients were assessed for tumor response at the eight-week treatment mark. Three patients demonstrated partial and minor responses at the 300 mg dose level and overall 11 patients had stable disease.
“Our clinical findings provide further evidence of SB1518’s potential as a viable treatment for myeloproliferative disorders and other hematological malignancies,” said Dr. Jan-Anders Karlsson, CEO of S*BIO. “Demonstration of safety, tolerability, and signs of activity in different disease states in our Phase 1 trials, has allowed us to advance SB1518 into Phase 2 clinical trials for further testing of the safety and efficacy of our compound.”
Validation of pharmacodynamic (PD) biomarker assays for SB1518 will be presented in a poster, demonstrating PD target efficacy of SB1518 in animal tumor models, as well as, in patients in ongoing Phase 1 clinical studies for advanced leukemias, myeloproliferative diseases and lymphoma. The fourth poster will highlight the effects of SB1518 on ex vivo expanded polycythemia vera (PV) erythroid progenitors which correlate with clinical observations.
Poster No.: 3905, Time: 6-8 p.m. CST, Monday, Dec. 7, 2009, Location: Hall E (Ernest N. Morial Convention Center)
Phase I Dose-Escalation Trial of SB1518, a Novel JAK2/FLT3 Inhibitor, in Acute and Chronic Myeloid Diseases, Including Primary or Post-Essential Thrombocythemia/ Polycythemia Vera Myelofibrosis SB1518, which is a potent ATP-competitive inhibitor of JAK2 (IC50=22nM), JAK2V617F mutant (IC50=19nM), FLT3 (IC50=22nM) and its mutant D835Y (IC50=6nM), is being tested to determine its safety, tolerability and PK/PD profile when administered orally once daily continuously in 28-day cycles. SB1518 was well tolerated at doses up to 500 mg daily in patients with advanced myelofibrosis (MF) and acute myelogenous leukemias (AML), and shows clinical activity in MF patients with splenomegaly.
Oral Presentation Abstract No.: 588, Time: 4 p.m. CST, Monday, Dec. 7, 2009, Location: Room R02-R05
Phase 1 Study of the Novel Oral JAK-2 Inhibitor SB1518 in Patients With Relapsed Lymphoma: Evidence of Clinical and Biologic Activity. A Phase 1 dose escalating study of the novel JAK2 small molecule inhibitor SB1518 is being conducted in patients with relapsed Hodgkin (HL) and non-Hodgkin lymphomas (NHL). The primary objectives are to examine the safety and efficacy of SB1518 in this patient population. Patients are treated at four dose levels (100 mg, 200 mg, 300 mg, and 400 mg) orally daily without interruption. Treatment was well tolerated. Three patients at the 300mg dose level demonstrated disease response with reductions in the tumor measurements (follicular lymphoma, small lymphocytic lymphoma and mantle cell lymphoma). Overall 11 patients (73%) had stable disease. Preliminary analysis demonstrated that SB1518 inhibited the JAK/STAT pathway as early as four hours after dosing. Collectively, these data demonstrate the safety of chronic administration of the oral JAK2 inhibitor SB1518. Ongoing clinical responses observed in a variety of lymphoma subtypes suggest that targeting the JAK2 pathway may have therapeutic value in patients with relapsed lymphoma.
Poster No.: 1888, Time: 5:30-7:30 p.m. CST, Saturday, Dec. 5, 2009, Location: Hall E (Ernest N. Morial Convention Center)
Pharmacodynamic (PD) Biomarker Assay Validation for SB1518, a Novel Oral JAK2 Inhibitor in Phase 1 Clinical Trials for Advanced Leukemias, Myeloproliferative Diseases and Lymphoma Biochemical biomarker assays have been developed to assess the pharmacodynamic (PD) efficacy of SB1518 in the Phase 1 clinical trials. Initial data obtained from analysis of whole blood and PBMCs from patients treated with SB1518 in the ongoing Phase 1 clinical trials demonstrate target inhibition even at the lowest dose level of 100 mg/day on the first day of oral dosing.
Poster No. 2913, Time: 6-8 p.m. CST, Sunday, Dec. 6, 2009, Location: Hall E (Ernest N. Morial Convention Center)
The Effects of SB1518, a Novel Oral JAK2 Inhibitor, on Ex Vivo Expanded Polycythemia Vera (PV) Erythroid Progenitors (EPs) Correlate with Clinical Observations EPs from PV patients and healthy volunteers were treated with SB1518 and other JAK2 inhibitors to determine the effects of JAK2 inhibition on downstream signalling, cell viability and JAK2V617F allele frequency. SB1518 inhibited phospho-STAT5 levels in a dose-dependent manner (IC50 < 200 nM) and reduced the viability of expanded erythroid progenitors from all sources; normal volunteers with JAK2WT (mean IC50 = 260 nM) or PV patients with JAK2V617F (mean IC50 = 230 nM). The difference in IC50 between the two groups was not statistically significant. These data are consistent with current observations in JAK2 clinical trials.
About S*BIO Pte Ltd
S*BIO is a privately-held biotech company focused on the research and clinical development of novel targeted small molecule drugs for the treatment of cancer with leading programs around histone deacetylases (HDAC) and kinases. S*BIO’s lead candidate, SB939, entered the clinic in 2007. SB1518, S*BIO’s potent and orally-active JAK2 inhibitor, entered the clinic in 2008 and has received orphan drug designation from the U.S. FDA. S*BIO has entered into a development collaboration, and option & license agreement with Onyx Pharmaceuticals, Inc. to develop and commercialize SB1518 and its other novel JAK2 inhibitor, SB1578. S*BIO’s SB1317, a novel multikinase inhibitor, is in pre-clinical development and under a worldwide exclusive license with Tragara Pharmaceuticals, Inc. for its development and commercialization.
In line with its vision to be a leading fully-integrated oncology-focused biotech company in Asia Pacific, S*BIO has established a state-of-the-art R&D infrastructure, complemented by a strong clinical development team. S*BIO has strong links with a network of medical oncologists in Asia Pacific and its investors include EDB Investments’ biomedical sciences subsidiary Bio*One Capital, Aravis Ventures, Novartis Bioventures and other international funds. In 2009, S*BIO received the BioSpectrum Editor’s Choice, Emerging BioScience Company of Singapore Award. More information about S*BIO can be found at www.sbio.com.
S*BIO Pte Ltd: Russo Partners:
Stephen Keith Rhind, Ph.D. Tony Russo, Ph.D. +1 212-845-4251
Senior Vice President, Corporate Development Tony.Russo@russopartnersllc.com
Tel: +65 6827 5000 (Singapore) Andreas Marathovouniotis +1 212-845-4253