Stock in YM Biosciences Inc. gained 15.8 percent Tuesday on positive results of a Phase I/II trial of its JAK1/JAK2 inhibitor in myelofibrosis.

The trial in 166 patients produced transfusion independence in more than half of the participants for at least 12 weeks with significant improvements in splenomegaly and constitutional symptoms.

YM determined that a dose of 300 mg per day was safe and effective, and plans to move forward with pivotal trials in mid-2012. The results appeared in a poster session at the 53rd Annual Meeting of the American Society of Hematology in San Diego.

The outcome of the trial is notable in that it not only produced improvement in spleen enlargement and constitutional symptoms of the disease, but also has a significant effect on anemia – an effect that was rather unexpected before the drug was tested in humans.

'The magnitude of the benefit was somewhat surprising. We expected a less myelosuppressive drug, but the magnitude of the effect in the clinic was very encouraging and unprecedented in this space,' YM CEO Nick Glover told BioWorld Today.

Glover said that the drug had a 'real shot' at changing the natural history of the disease.

YM reported that CYT387 has potential in a broad range of disorders in which JAK1 and JAK2 are implicated, including other blood disorders like myelodysplastic syndrome and leukemia, and even solid tumors.

The study was comprised of nine 28-day treatment cycles of oral CYT387 at 150 mg once daily, 300 mg once daily or 150 mg twice daily. Sixty-five percent of the 166 subjects had a diagnosis of primary myelofibrosis, 22 percent have post-polycythemia vera and 14 percent have post-essential thrombocythemia.

Sixty-one percent of the patients had a prognostic risk score (DIPSS-Plus) of intermediate-2. Eleven percent were intermediate-1, and 28 percent were scored high risk. Seventy-six percent of the group were JAK2V617 positive, 44 percent were transfusion dependent and 80 percent had palpable splenomegaly. Survival with the disease ranges from two to 15 years, depending on the stage at diagnosis and other factors.

In myelofibrosis, up-regulation of blood cells production causes fibrotic tissue to develop in the bone marrow. It is believed to arise from acquired mutations that target hematopoietic stem cells. Mutations implicated in the disease surround the JAK signal transduction family.

When blood production in the bone marrow slows down due to the fibrosis, the spleen and liver take over. The spleen becomes enlarged as it attempts to handle the load, and constitutional symptoms emerge.

An extension phase of the study is available to patients and thus far 97 percent of patients who have completed the core study chose to continue into the extension phase.

Of the group of 68 patients that started the trial dependent on transfusions, 54 percent have become independent for at least 12 weeks. The trial has not yet reached the median duration of transfusion independence.

Spleen response was evaluable in 142 patients. Thirty-one percent of those patients achieved a response, and the median duration of that response has also not been reached.

Typical constitutional symptoms of myelofibrosis include fatigue, anorexia, itching, bone pain and night sweats, among others. A majority of patients who had constitutional symptoms at baseline showed improvement or complete resolution of their symptoms.

The drug was well tolerated, and adverse events included thrombocytopenia, dizziness, peripheral neuropathy and liver or pancreatic abnormalities. There were rare reports of treatment-emergent anemia and neutropenia.

Glover said that CYT387 differentiates from Incyte's Jakafi (ruxolitinib), released in November 2011, in a very important way. Jakafi, Glover said, has a 'detrimental effect on anemia,' whereas CYT387 had a corrective effect on anemia. 'It's a great fit with clinical need and best suited to deal with the three major factors associated with myelofibrosis.'

Those factors are anemia, spleen enlargement and constitutional symptoms.

Rodman and Renshaw's Reni Benjamin commented, 'The Phase I/II ASH data adds strength to CYT387's overall clinical profile and increases the value proposition for potential partners. On the commercial front, we believe that CYT387 has solid potential to attract partnership interest that reflects the approximate $1 billion deal benchmarks set by Novartis (NVS, not rated) and Eli Lilly (LLY, not rated). Importantly, given the $1 .8 billion valuation for competitor Incyte (INCY, not rated), we believe there exists upside potential for YM BioSciences shareholders.'

Avik Roy, of Moness, Crespi, Hardt, was impressed with the anemia results. 'Anemia benefit is long and strong. The biggest concern of investors going into YM's data was: would the company be able to reproduce the anemia benefit shown at ASH last year? The answer was yes,' he noted.

Wells Fargo's Brian Abrahams wrote, 'Overall, we believe the data are very solid, suggesting the previously observed anemia benefits may be real, confirming '387's benefits in a larger number of patients and clinical trial sites, and providing some reassurance that the peripheral neuropathy should not be a significant liability.'

Roth Capital Partners analyst Joseph Pantginis got down right sentimental about YM's results. 'In short, we believe the data delivered and holiday visions of sugar plums could turn into visions of partnership, in our belief, based on these data.'

YM (NYSE:YMI) closed at $1.69 Tuesday, up 23 cents.

In other news from ASH:

• Aeterna Zentaris Inc., of Quebec City, and Keryx Biopharmaceuticals Inc., of New York, said in a Phase II trial of perifosine with Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer AG) in refractory and relapsed Hodgkin lymphoma with high phosphorylation levels of Erk and Akt, preliminary response data showed the drug combination significantly increased median progression-free survival, as compared to those with low levels of Erk and Akt.

• Alnylam Pharmaceuticals Inc., of Cambridge, Mass., reported clinical data from a number of programs. Its preclinical RNAi product, ALN-APC, for hemophilia, and preclinical RNAi product, ALN-HPN, for refractory anemia, plus preclinical programs in beta-thalassemia and erythropoiesis showed positive results. The company remains on track to nominate its fifth Alnylam 5x15 program.

• Astellas Pharma Inc., of Tokyo, and Ambit Biosciences Corp., of San Diego, shared updated results from an interim analysis of a Phase II trial of quizartinib (previously AC220) in acute myeloid leukemia, showing that quizartinib monotherapy had activity in refractory and relapsed FLT3-ITD-positive acute myeloid leukemia (AML). In 62 patients, there were composite complete response rates of 40 percent, 46 percent and 55 percent in patients refractory to prior treatment. The company also shared data relating to pharmacodynamic effects of quizartinib in a pooled analysis from Phase I and II studies, and showing that quizartinib enhances chemotherapy in an in vivo model of AML with the FLT3-ITD mutation.

• Bio-Path Holdings Inc., of Houston, presented results from Cohort 1 of its Phase I trial of BP-100-1.01 (liposomal Grb-2), a systemic liposomal antisense treatment for blood cancers, suggesting that the drug is well tolerated at a dose of 5 mg/m2 and showed some possible anti-leukemia activity. Lab parameters for six evaluable patients showed that each experienced transient reductions for blasts and bone marrow results.

• Biovest International Inc., of Tampa, Fla., said the National Cancer Institute (NCI) presented long-term (11-year) outcome data from its BiovaxID Phase II trial conducted in collaboration jointly with the NCI. The results demonstrated that vaccination with BiovaxID active immunotherapy following rituximab combination chemotherapy induced nearly universal immune responses, which strongly correlated with overall survival in treated patients. Those immune responses consisted mostly of tumor-specific T-cell immune responses, which complemented the effects of induction rituximab chemotherapy in a highly aggressive non-Hodgkin's lymphoma, mantle cell lymphoma.

• Celgene International Sarl, of Boudry, Switzerland, reported data from a subanalysis of a Phase II study of HDAC inhibitor Istodax (romidepsin) in subtypes of refractory or relapsed peripheral T-cell lymphoma (PTCL) – PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic lymphoma kinase-1-negative anaplastic large-cell lymphoma (ALK-1-negative ALCL). Overall response rates were similar across those three common subtypes: 29 percent (20 of 69) patients with PTCL-NOS, 30 percent (eight of 27) with AITL and 24 percent (five of 21) with ALK-1-negative ALCL. With a median follow-up of 21 months, the median duration of response for all responders was 17 months. In a separate presentation, Celgene reported data from an open-label Phase II study testing pomalidomide plus low-dose dexamethasone vs. pomalidomide alone in relapsed and refractory multiple myeloma patients. Of the 191 evaluable patients, partial response or better was seen in 34 percent of patients in the combination group compared to 13 percent in the pomalidomide-only group. In a third presentation, Celgene said final results from a Phase II trial of Revlimid (lenalidomide) and Vidaza (azacitidine) in myelodysplastic syndrome showed an overall response rate of 72 percent, out of 35 evaluable patients. Fifteen patients (42 percent) had a complete response, and 11 (28 percent) had hematologic improvement. Three patients had progressive disease. Median duration of complete response was 16 months, and median overall survival for those patients was 27 months. The company also reported updated Phase III data evaluating continuous treatment with Revlimid (lenalidomide) in patients with high-risk asymptomatic smoldering multiple myeloma, which demonstrated that early treatment with lenalidomide and dexamethasone followed by continuous lenalidomide delayed time to symptomatic disease and demonstrated a projected survival advantage compared with observation.

• Cell Therapeutics Inc., of Seattle, and Chroma Therapeutics Ltd., of Oxford, UK, reported final results from a Phase II (OPAL) study of tosedostat in relapsed or refractory acute myeloid leukemia. Fifty-one percent achieved disease control, and 22 percent achieved major leukemic response. Twelve percent had a complete bone marrow response. Median overall survival for patients with complete response was 323 days. For those with partial responses, it was 195 days, and those with stable disease had survival of 162 days.

• Coronado Biosciences Inc., of Burlington, Mass., gave an oral presentation on Phase I results of a clinical trial of CNDO-109, a biologic that activates natural killer (NK) cells to treat acute myeloid leukemia (AML) and solid tumors. Patients experienced a longer complete remission (CR) after receiving CNDO-109 activated NK cells than their previous CR. Analysis was based on eight AML patients of whom five were in a subsequent CR, one was in a first CR, one was in partial relapse and one was in relapsing disease.

• Cylene Pharmaceuticals Inc., of San Diego, said two preclinical leukemia candidates showed activity in models of the disease. CX-5461 triggered nongenotoxic activation of p53 in models of MLL-rearranged acute myeloid leukemia. CX-4945 showed activity in patient samples of chronic lymphocytic leukemia.

• Daiichi Sankyo Co. Ltd., of Tokyo, said in a pooled analysis edoxaban, its Factor Xa inhibitor significantly reduced the risk of venous thromboembolism after total knee or hip arthroplasty, compared to enoxaparin. There was no statistically significant difference in bleeding between groups. The analysis was from two randomized, double-blind, double-dummy, Phase III trials (STARS E-III[i] and STARS JV[ii]) in 1,326 Japanese and Taiwanese patients.

• Fate Therapeutics Inc., of San Diego, said a Phase Ib trial of ProHema (FT1050-enhanced umbilical cord blood) in adults with hematologic malignancies achieved its primary objective of demonstrating safety and tolerability based on patient engraftment by day 42. In subjects that received a ProHema unit and an untreated unit, the median time to neutrophil recovery was 17.5 days, compared to a median of 21 days for a historic control group. Adverse events were no greater than background.

• GlycoMimetics Inc., of Gaithersburg, Md., presented preclinical data showing that GMI-1257, an antagonist of E-selectin and CXCR4, plus cytarabine depleted 90 percent of CD34-positive leukemia cells from the bone marrow, reducing bone marrow burden in acute myeloid leukemia. Other data highlighted how GMI-1070, which is now in Phase II for vaso-occlusive crises associated sickle cell disease, can decrease venous thrombosis and inhibit inflammation in animal models.

• Immunomedics Inc., of Morris Plains, N.J., presented data from a Phase I/II study of anti-CD74 antibody milatuzumab combined with second-generation anti-CD20 antibody veltuzumab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma after at least one prior therapy. Results showed no dose-limiting toxicities. Overall, 14 of 18 patients had evidence of antitumor activity, with four patients (22 percent) having an objective response, including two complete responses.

• Ligand Pharmaceuticals Inc., of San Diego, reported preclinical data showing that granulocyte colony-stimulating factor receptor (GCSFR) agonist LG7455 activated STAT5 and STAT3 signal transduction in in vitro models and increased the viability of cells containing human GCSFR. The drug also promoted differentiation of human bone marrow cells into granulocytes, significantly increasing the expression of the granulocyte-specific marker CD15.

• Merrimack Pharmaceuticals Inc., of Cambridge, Mass., said the first patient has been dosed in a Phase I clinical study combining MM-121, a fully human monoclonal antibody that targets ErbB3, with Erbitux (cetuximab, Eli Lilly and Co.) and Camptosar (irinotecan, Pfizer Inc.) in patients with advanced cancers.

• Millennium, of Cambridge, Mass., a unit of Takeda Pharmaceutical Co. Ltd., presented Phase I data showing that oral proteasome inhibitor MLN9708 was given to a maximum-tolerated dose of 20 mg/m2 on a twice-weekly dosing schedule. Of the 46 patients evaluable for response, one achieved a complete response and five achieved partial responses. Data from a Phase I/II study showed that MLN9708, when given in combination with Revlimid (lenalidomide, Celgene Corp.) and dexamethasone in patients with previously untreated multiple myeloma produced at a partial response or better in 100 percent of 15 evaluable patients, including four complete responses.

• Novartis AG, of Basil, Switzerland, reported additional results from two Phase III trials of JAK inhibitor INC424 (ruxolitinib) for myelofibrosis. In COMFORT-II there was substantial improvement in health-related quality of life and myelofibrosis symptoms compared with baseline for patients that received the drug, whereas those endpoints remained the same or worsened for patients receiving the best available therapy. In COMFORT-I, patients who received INC424 had greater reductions in spleen volume and in total symptom score vs. placebo. In a separate presentation, Novartis reported Phase III data showing that adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are treated with Tasigna (nilotinib) have deeper levels of response compared to those treated with Gleevec (imatinib). The study showed that twice as many patients switched to Tasigna 400 mg twice per day achieved undetectable Bcr-Abl levels by 12 months compared to Gleevec (23 percent vs. 11 percent, p = 0.0202).

• Onyx Pharmaceuticals Inc., of South San Francisco, presented final data from its Phase II trial of carfilzomib in relapsed and/or refractory multiple myeloma patients not previously treated with Velcade (bortezomib, Millennium/Takeda Pharmaceutical Co. Ltd.). The overall response rate was 52 percent, and the clinical benefit rate was 64 percent when carfilzomib was administered at 27mg/m(2). Carfilzomib is a proteasome inhibitor currently under FDA review. (See BioWorld Today, Dec. 13, 2011.)

• Pieris AG, of Freising-Weihenstephan, Germany, said in preclinical studies of PRS-080, the drug increased serum iron levels by binding its hepcidin target with high affinity and specificity, and that its pharmacokinetic and pharmacodynamic profile was tunable. The drug is being developed for treatment of anemia, and it is projected to enter clinical trials in the first half of 2013.

• Sangamo BioSciences Inc., of Richmond, Calif., presented data showing that a disease gene in an adult mouse model of hemophilia B was permanently corrected with systemic delivery by zinc finger nucleases of clotting factor, Factor IX. The company said it circumvents the problems of uncoupling the gene from its regulatory mechanism.

• Spectrum Pharmaceuticals Inc., of Henderson, Nev., launched a repositioning campaign for Zevalin (ibrutumomab tiuxetan) for non-Hodgkin lymphoma. The goal is to reintroduce physicians to a simplified administration protocol following removal of the bioscan requirement by the FDA, as well as to familiarize patients and payers with it.

• Symphogen A/S, of Copenhagen, Denmark, reported data from an open-label Phase II trial of rozrolimupab in immune thrombocytopenia purpura, showing that it induced a rapid increase in blood platelets. The drug also had a favorable safety profile. Median response time was 59 hours, and median duration of response was 14 days.

• Telik Inc., of Palo Alto, Calif., reported that in a Phase I trial of Telintra with Revlimid (lenalidomide, Celgene Corp.) in patients with myelodysplastic syndromes, 40 percent of patients showed hematologic improvement in red blood cell levels at a dose of 2,000 mg Telintra and 10 mg Revlimid. Seven patients were transfusion dependent, and three of those achieved transfusion independence. The median duration of transfusion independence was not reached. Telik also announced the results of its gene expression analysis, carried out during the trial. A number of genes and unidentified transcripts were found that may play a role in response to Telintra.