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YM BioSciences Reports Positive Interim Data from Phase I/II Trial of JAK1/JaK2 Inhibitor CYT387

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YM BioSciences Inc. has announced positive interim data from the first 60 patients enrolled in the Phase I/II trial for its JAK1/JAK2 inhibitor, CYT387, in myelofibrosis. The results were reported in an oral presentation at the 52nd American Society of Hematology (ASH) Annual Meeting being held in Orlando, Florida.

"Anemia is the most serious symptom associated with myelofibrosis, so I am highly encouraged by the emerging activity profile of CYT387, which uniquely continues to demonstrate a substantial ability to improve anemia while producing similar results to its peers in reducing spleen size and controlling constitutional symptoms," noted Dr. Alayew Tefferi, Chair of the Study. "I also encourage YM to evaluate CYT387 in other diseases where anemia has a significant impact."

"These unprecedented results highlight the potential safety and efficacy advantages of CYT387 compared with other JAK inhibitors. If CYT387 continues to demonstrate this unique anemia benefit in larger trials, it may ultimately serve as a drug of choice for the majority of patients with myelofibrosis who find anemia problematic," said Dr. Nick Glover, President and CEO of YM BioSciences. "We look forward to updated data from the full 140 patient trial in calendar mid-2011."

Patient Characteristics:

The presentation described interim results for the first 60 patients enrolled in the dose escalation (n=21) and dose confirmation (n=39) portions of the 140 patient Phase I/II trial, for which recruitment is ongoing. In the dose-confirmation phase, subjects were started at one of two dose levels that were deemed clinically effective: 150 mg/day (n=18) and 300 mg/day (n=21). Thirty-three subjects (55%) were red cell transfusion-dependent at study entry.

Forty-five subjects (75%) expressed the JAK2V617F mutation. Forty-eight (80%) had palpable splenomegaly greater than 10 cm. A number of the patients had discontinued treatment with other JAK inhibitors (INCB018424, n=11; TG101348, n=3) or pomalidomide (n=13). The median time to follow up since study start is currently 4.9 months, ranging from 0.9-12.5 months.

Efficacy Results:

- The Overall Response Rate (anemia, spleen) to date, as per the International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria, is 62%.

- Anemia Response: Of 42 subjects who were evaluable for anemia response (baseline Hgb less than 10 g/dL or red cell transfusion- dependent), 21 subjects (50%) had achieved Clinical Improvement (CI) as per the IWG-MRT criteria. A 57% response rate was observed in transfusion dependent patients. For the 150 mg/day dosing group, the anemia response rate was 41% (43% for transfusion dependent patients). For the 300 mg/day dosing group, the anemia response rate was 58% (69% for transfusion dependent patients). Responses were observed in five of nine (55%) patients who had discontinued treatment with other JAK inhibitors (INCB018424, TG101348) and 5 of 12 (42%) who had discontinued pomalidomide.

- Spleen Size Reduction: Twenty-five (47%) of the 53 evaluable subjects who had splenomegaly at baseline achieved a minimum 50% decrease in palpable spleen size, thus qualifying them for CI per IWG-MRT criteria. For the 150 mg/day dosing group, 53% qualified for CI. For the 300 mg/day dosing group, 46% qualified for CI.

- Constitutional Symptoms: CYT387 controlled constitutional symptoms in a significant percentage of patients (night sweats: 88%, bone pain: 80%, pruritus: 92%, fever: 100%).

Safety Results:

In the dose escalation portion of the study, at the highest dose level (400 mg/day), two of six subjects experienced dose limiting toxicity (DLT) (one each of reversible asymptomatic Grade 3 hyperlipasemia and Grade 3 headache); consequently, the maximum tolerated dose (MTD) was declared at 300 mg/day.

CYT387 was well tolerated. The overall discontinuation rate was 5% and there were no patient withdrawals for drug-related adverse events. No Grade 4 non-hematological toxicities were observed. Grade 3 non-hematologic adverse events were infrequent and included increased transaminases (n=2), headache/head pressure (n=2), and increased lipase (n=3), No QTc prolongations greater than Grade 1 were observed.

Some patients experienced a "first-dose effect" characterized by Grade 1 lightheadedness (26 subjects, 43%) and hypotension (31 subjects, 52%). The phenomenon was self-limiting, generally resolved within 3-4 hours and did not recur after the first dose.

Grade 3/4 thrombocytopenia was seen in 16 (27%) subjects. It should be noted that the minimum platelet count specified in the inclusion criteria for the study is 50,000/mcl. The majority of Grade 3/4 thrombocytopenia were observed in subjects where baseline platelet counts were less than 100,000/mcl.

Treatment-emergent Grade 3 anemia was seen in four subjects (7%). None of the subjects developed new red cell transfusion requirements. Treatment-emergent Grade 3/4 neutropenia was seen in three subjects (5%).