On June 6, 2016 Peloton Therapeutics, Inc., a drug discovery and development company focused on advancing first-in-class, small molecule cancer therapies targeting unexploited molecular vulnerabilities, reported first-in-human Phase 1 clinical data on its lead investigational candidate, PT2385, at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL (Press release, Peloton Therapeutics, JUN 6, 2016, View Source [SID:1234513120]). PT2385 is the first clinical stage antagonist of hypoxia inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney and other cancers.

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In an oral presentation titled "A Phase 1 Dose-Escalation Trial of PT2385, a first-in-class oral HIF-2α Inhibitor, in Patients with Advanced Clear Cell Renal Cell Carcinoma," it was shown that PT2385 was well tolerated with no dose-limiting toxicities and had pharmacologic activity with encouraging clinical efficacy.

Patients with advanced clear cell renal cell carcinoma (ccRCC) and at least one prior therapy with a VEGF inhibitor were treated with PT2385 to determine the recommended Phase 2 dose and evaluate safety, pharmacokinetics and pharmacodynamics.
Twenty-six patients were enrolled in dose escalation and received PT2385 from 100 to 1800 mg twice per day. Patients were heavily pretreated prior to study entry, with greater than 50 percent having four or more prior therapies. Exposure increased with doses up to the 800 mg cohort without a further increase from 800 to 1800 mg. No dose limiting toxicities were observed at any dose level. Circulating plasma levels of the HIF-2α transcriptional target erythropoietin (EPO) rapidly decreased with treatment with PT2385 and remained suppressed. Based on safety, pharmacokinetic and EPO pharmacodynamic data, 800 mg twice per day was selected as the recommended Phase 2 dose. An additional 25 patients were enrolled in an expansion cohort at the recommended Phase 2 dose.

Among the 51 patients in total, the most common all-grade adverse events (AEs) were anemia, peripheral edema and fatigue. No cardiovascular AEs were noted. To date, one patient had a complete response, three patients had a partial response, and 16 patients had stable disease for 16 or more weeks. Ten percent of patients remain in this ongoing clinical trial for at least one year.
"Research at our institution has shown than HIF-2α is strongly implicated in renal cell carcinoma. PT2385 is the first agent to target this transcription factor and is very well tolerated. Its efficacy in patients with advanced clear cell renal cell carcinoma is promising," said Toni Choueiri, M.D., from the Dana-Farber Cancer Institute and Harvard Medical School, the senior author of the study.
"We are encouraged by the initial efficacy results in this heavily pretreated population and the fact that PT2385 does not have the cardiovascular toxicities of most other kidney cancer treatments, most notably VEGFR tyrosine kinase inhibitors. In light of this favorable safety profile and preclinical evidence of synergistic activity of our HIF-2α antagonists in combination with immune checkpoint inhibitors shown at the recent AACR (Free AACR Whitepaper) conference, we have opened a clinical trial of PT2385 in combination with nivolumab (Opdivo). Additionally, we are planning clinical studies of PT2385 as monotherapy and with other combination regimens," said John Josey, Ph.D., Peloton’s Chief Executive Officer.

About PT2385
PT2385 is a first-in-class small molecule inhibitor of hypoxia-inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney cancer. It is currently being investigated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC). Loss of the von Hippel-Lindau tumor suppressor (VHL) is the key oncogenic event in up to 95% of patients with ccRCC. With the loss of the VHL protein (pVHL), the transcription factor HIF-2α accumulates and drives the unbalanced expression of numerous gene products. Preclinical data indicate that orally bioavailable PT2385 disrupts HIF-2α activity in ccRCC and thereby blocks the expression of multiple tumorigenic factors responsible for unrestrained cancer cell growth and proliferation, tumor angiogenesis, and suppression of anti-tumor immune responses characteristic of ccRCC.

About Renal Cell Cancer
The American Cancer Society estimates that more than 62,000 new cases of kidney cancer will be diagnosed and more than 14,000 people will die from this disease this year. The National Cancer Institute reports that the prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage.
About Peloton Therapeutics

On June 6, 2016 Aeterna Zentaris Inc. (NASDAQ: AEZS; TSX: AEZ) (the "Company") reported its commitment to LHRH-receptor targeted therapy and its expectation that the pivotal, phase 3 trial for Zoptrex (zoptarelin doxorubicin) in women with advanced, recurrent endometrial cancer, is expected to be completed in the third quarter of 2016 (Press release, AEterna Zentaris, JUN 6, 2016, View Source [SID:1234513119]). During the 2016 Annual Meeting of the American Society of Clinical Oncologists ("ASCO"), the Company also discussed its plans to develop Zoptrex for additional indications, based upon achieving a positive outcome in the current clinical program.

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Zoptrex (zoptarelin doxorubicin), a novel synthetic peptide carrier linked to doxorubicin as a New Chemical Entity (NCE), is the Company’s lead oncology compound. Zoptrex is currently in a fully-enrolled Phase 3 clinical trial in endometrial cancer. The Company expects to complete the Phase 3 clinical trial in the third quarter of 2016 and, if the results of the trial warrant doing so, to file a new drug application for Zoptrex in the first half of 2017.

Commenting on the significance of Zoptrex to oncologists and their patients, Dr. Richard Sachse, the Company’s Chief Scientific Officer, explained, "Zoptrex is the first targeted oncological therapy using a peptide as the targeting agent and, therefore, it represents potentially a new tool in the treatment of tumors that overexpress the LHRH receptor. The design of the compound allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH receptor-positive tumors, typically found in gynecological cancers, prostate cancer and some forms of breast cancer. Potential benefits of this targeted approach may include enhanced efficacy and a more favorable safety profile with lower incidence and severity of adverse events, as compared to doxorubicin. If Zoptrex is approved as a therapy for endometrial cancer, we intend to develop it for these additional indications. In addition, based on the results of Phase 2 studies, we believe that Zoptrex holds promise to prove its efficacy for the treatment of ovarian and prostate cancer."

During the ASCO (Free ASCO Whitepaper) Annual Meeting, the Company provided an update regarding its progress with Zoptrex during one-on-one meetings with oncological key opinion leaders. Dr. Sachse described his interactions with ASCO (Free ASCO Whitepaper) attendees as promising, stating as follows: "I’m pleased and gratified by the continuing expressions of support for our work on Zoptrex. The oncologists with whom we met were pleased to learn of our progress toward the completion of our Phase 3 clinical trial and seemed to be as excited as we are about the contribution that our new targeted oncology therapy could make to the treatment of one of the most severe forms of cancer."

On June 6, 2016 Aprea AB, a privately held, clinical-stage biopharmaceutical company developing novel anticancer therapies targeting the tumor suppressor protein p53, reported clinical data from the Phase Ib part of the ongoing PiSARRO Phase Ib/II trial in collaboration with the European Network for Translational Research in Ovarian Cancer (EUTROC) (Press release, Aprea, JUN 6, 2016, View Source [SID:1234513118]). Aprea’s PiSARRO trial is investigating the safety and efficacy of APR-246 in combination with carboplatin and pegylated liposomal doxorubicin (PLD) in patients with relapsed high-grade serous ovarian cancer. Results presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) showed:

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APR-246 can be combined with standard chemotherapy at relevant doses, allowing the highest tested dose to be selected for continuing the study in a randomized Phase II trial.
All 21 patients treated in the study that are evaluable according to RECIST criteria have stable disease or better. In addition, 15 out of 18 evaluable patients had a GCIG CA-125 (tumor antigen biomarker) response after three treatment cycles. Overall response rate (GCIG or RECIST) was 18/24 (75%).
APR-246 showed linear pharmacokinetics with no accumulation and low intra patient variability and no indication of interaction between APR-246 and chemotherapy, supporting the combination of APR-246 with carboplatin and doxorubicin at relevant doses.
The main related treatment-emergent Grade 3-4 adverse events have been neutropenia, anemia and vomiting. The most frequent treatment-emergent adverse events have been low-grade gastrointestinal (nausea/vomiting), central nervous system (dizziness) and hematological (neutropenia and thrombocytopenia) events. The hematological side effects can be attributed to the chemotherapy, although a contribution from the addition of APR-246 cannot be ruled out at this time. No new safety concerns have emerged in the study.
Prof. Charlie Gourley, Chair of Medical Oncology and Honorary Consultant in Medical Oncology at the University of Edinburgh, said of the results: "APR-246 is an extremely exciting new agent because it targets tumors with mutant forms of the p53 gene, which is the gene most frequently altered in human cancer. This study shows that APR-246 can be successfully combined with standard chemotherapy for ovarian cancer with minimal additional toxicity. The percentage of patients whose cancer responded to this treatment regime was encouraging and we look forward to validating these findings in a larger clinical trial."

Dr. Mikael von Euler, Chief Medical Officer of Aprea, said: "We are very pleased with the results of the Phase Ib trial and to be able to move this exciting drug forward into a randomized Phase II trial in the third quarter of this year. It is especially important that the patients who have more difficult-to-treat disease seem to get as much benefit as those with less aggressive disease. The current safety profile combined with the evidence of clinical activity suggests that APR-246 might become a very important drug for patients with ovarian cancer. Furthermore, the mechanism suggests that APR-246 might have relevance in other tumor types and we look forward to pursing those opportunities."

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anticancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 has been shown to reactivate mutant p53 protein – by reconverting mutant p53 into wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. APR-246 has demonstrated compelling pre-clinical antitumor activity in a wide variety of solid and hematological (blood) tumors, including ovarian cancer, small cell lung cancer, esophageal cancer and AML (acute myeloid leukemia), among others. Additionally, strong synergy has been seen with both traditional anticancer agents, such as chemotherapy, as well as newer mechanism-based anticancer drugs. In addition to pre-clinical testing, a Phase I clinical study has been completed, demonstrating a favorable safety profile and both biological and clinical responses in hematological tumors with mutations in the p53 gene. APR-246 is currently in a Phase Ib/II clinical trial in patients with high-grade serous ovarian cancer. The Phase Ib part has completed. In the Phase II clinical study, Aprea will enroll up to 400 ovarian cancer patients in Europe and the US. Patients will be randomized between carboplatin and pegylated liposomal doxorubicin with or without APR-246; the primary endpoint for the study is progression-free survival (PFS). The company is also expecting to begin additional clinical studies of APR-246 in other cancer indications.

On June 6, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) and Roivant Sciences Ltd. reported the formation of Myovant Sciences Ltd. ("Myovant"), a biopharmaceutical company focused on delivering innovative women’s health and prostate cancer solutions by efficiently advancing new medicines to market that have the potential to improve the lives of millions of patients (Press release, Takeda, JUN 6, 2016, View Source [SID:1234513109]). In addition, Lynn Seely, MD, an endocrinologist who led the development of XTANDI (enzalutamide) for the treatment of prostate cancer as the Chief Medical Officer of Medivation from 2005 to 2015, was named the President & Chief Executive Officer of Myovant Sciences, Inc.

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Myovant Partnership Summary
Takeda has granted Myovant an exclusive, worldwide license (excluding Japan and certain other Asian countries) to relugolix (TAK-385), a phase 3 drug candidate that has been evaluated in over 1,300 patients to date. Relugolix has successfully demonstrated significant clinical benefit and was generally well-tolerated across multiple, large, randomized phase 2 clinical trials in three different indications. Relugolix is being developed as an oral, once-daily, potential best-in-class gonadotropin-releasing hormone (GnRH) receptor antagonist for uterine fibroids, endometriosis and prostate cancer. Takeda will retain commercial rights for relugolix in Asian countries, including Japan, where Takeda is actively conducting two phase 3 registration studies for the treatment of uterine fibroids. Takeda has also granted Myovant an exclusive, worldwide license to RVT-602 (TAK-448), a novel, oligopeptide kisspeptin receptor agonist as a product candidate for the treatment of infertility in females. Financial terms of the partnership were not disclosed.

"With Takeda strengthening its focus around the core therapeutic areas of oncology, gastroenterology and central nervous system diseases, as well as establishing a strategy that embraces innovative partnerships, it is important that we seek alternatives to further develop and create value around promising assets that are either outside these areas of focus or where strategic partnership makes more sense for our business," said Andrew Plump, M.D., Ph.D., Chief Medical and Scientific Officer of Takeda. "The formation of Myovant Sciences represents such an innovative partnership arrangement to further advance relugolix by relying on Roivant’s and Myovant’s in-house development capabilities in the major markets where they are building deep expertise, while leveraging Takeda’s commercial presence in certain Asian territories."

"We are very pleased to partner with Takeda to meet the needs of patients suffering from hormone-driven diseases and disorders," said Vivek Ramaswamy, CEO of Roivant Sciences, Inc. "The creation of Myovant enables a ‘win-win’ outcome for both our partner and for patients by launching a company to address major unmet medical needs in women’s health, prostate cancer and beyond."

Appointment of Dr. Lynn Seely as President & Chief Executive Officer
Lynn Seely, MD, brings over 20 years of drug development and biopharmaceutical company leadership to her role as the President & Chief Executive Officer of Myovant Sciences, Inc. Most recently, Dr. Seely served as Chief Medical Officer of Medivation, Inc. from its early stages in March 2005 through October 2015. She served on the Executive Committee and led the development of XTANDI for the treatment of metastatic castration-resistant prostate cancer from IND-enabling studies through to NDA approval and post-approval clinical studies. Dr. Seely was responsible for building the clinical organization at Medivation, as well as the regulatory, quality, project management, medical affairs and biologics manufacturing functions. Dr. Seely currently serves on the board of directors of Blueprint Medicines Corporation, and she previously served as Vice President of Clinical Development at Anesiva, Inc. (formerly Corgentech) and at Cytyc Health Corporation. Dr. Seely received a medical degree from the University of Oklahoma College of Medicine and completed her residency in internal medicine at Yale-New Haven Hospital. After serving as Chief Resident in Internal Medicine at Yale University School of Medicine, she completed her basic science and clinical fellowship in endocrinology and metabolism at the University of California, San Diego.
"I look forward to delivering on Myovant’s mission to bring innovative new treatments to women suffering from diseases such as uterine fibroids and endometriosis and to men with prostate cancer," stated Dr. Lynn Seely, President & CEO of Myovant Sciences, Inc. "Relugolix and our partnership with Takeda represent an exceptional foundation on which to build this exciting new company."

About Relugolix
Relugolix is a once-daily, orally administered, potential best-in-class gonadotropin-releasing hormone (GnRH) receptor antagonist for the treatment of uterine fibroids and endometriosis, and a potential best- and first-in-class treatment for hormone-sensitive prostate cancer (HSPC). Relugolix has been evaluated in over 1,300 patients to date, and has successfully demonstrated significant clinical benefit and was generally well-tolerated across multiple, large, randomized phase 2 clinical trials in three different indications. Takeda is currently enrolling two phase 3 clinical trials of relugolix for registration in Japan for the treatment of uterine fibroids.

By inhibiting GnRH receptors in the pituitary gland, relugolix rapidly reduces circulating sex hormone levels leading to suppression of estrogen and testosterone. Suppression of these sex hormones improves the symptoms of women with uterine fibroids and endometriosis, and decreases prostate-specific antigen (PSA) levels in men with HSPC.

In a 216-patient phase 2 study for the treatment of uterine fibroids, women who received relugolix had a significant reduction in menorrhagia, or abnormally heavy bleeding during menstruation. In a 487-patient phase 2 study for the treatment of endometriosis, women who received relugolix had a significant reduction in both non-menstrual and menstrual pelvic pain. Based on these results, two phase 3 registration studies in women with uterine fibroids are underway in Japan (NCT02655237, NCT02655224). In two phase 2 studies in approximately 225 men with HSPC, which included control arms of either an injectable GnRH agonist (leuprolide acetate) or a GnRH antagonist (degarelix), respectively, oral once-daily relugolix suppressed serum testosterone to castrate levels and decreased PSA. The safety of relugolix across all phase 2 studies was generally well-tolerated, consistent with the mechanism of action.

The clinical experience to date, supported by an extensive preclinical development program, suggests that oral relugolix, administered once-daily, could be an important advancement in the treatment options available for women suffering from endometriosis and uterine fibroids. In addition, relugolix could provide men with HSPC an important new treatment option as the first oral GnRH receptor antagonist that offers an alternative to injectable therapies.

About RVT-602
RVT-602 (TAK-448) is a kisspeptin analog that acts to stimulate the physiologic release of GnRH and downstream hormones important in fertility such as luteinizing hormone. Recent evidence from trials performed in women undergoing In-vitro Fertilization (IVF) revealed that the native kisspeptin peptide has the potential to act as an alternative to human chorionic gonadotropin (hCG) or GnRH agonists in triggering egg maturation, an essential step in every IVF cycle.

About Myovant Sciences
Myovant Sciences is focused on innovative treatments for women’s health conditions and prostate cancer. The company’s lead program is relugolix, a phase 3 drug candidate for multiple indications, including uterine fibroids, endometriosis and prostate cancer. Myovant was formed through a strategic partnership between Roivant Sciences and Takeda. Additional information about Myovant Sciences is available through its website, www.myovant.com

OnJune 7, 2016 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA:CTIC) reported long-term safety and efficacy results from the pivotal Phase 3 PERSIST-1 trial evaluating pacritinib versus best available therapy, excluding treatment with JAK2 inhibitors (BAT), in patients with myelofibrosis (Press release, CTI BioPharma, JUN 6, 2016, View Source;p=RssLanding&cat=news&id=2175567 [SID:1234513106]). As previously reported, the PERSIST-1 trial met its primary endpoint in the intent-to-treat population with statistically significant reduction in spleen volume when compared to patients receiving BAT. The results represent an update on the efficacy and safety for all patients regardless of their initial platelet count, including patients with very low platelet counts at study entry, a condition known as severe or life-threatening thrombocytopenia. The most frequently occurring adverse events with pacritinib were gastrointestinal events and incidence decreased over time. For patients crossing over to receive pacritinib treatment (84 percent of BAT patients), less than 5 percent of patients had diarrhea with only one patient experiencing grade 3. Patients in the BAT arm that crossed over to receive pacritinib treatment had a similar rate of events as patients initially randomized to BAT or pacritinib. A planned analysis of the study up to 72 weeks demonstrated treatment with pacritinib led to durable reductions in spleen volume and symptom burden, two key measures of disease control, in patients with myelofibrosis, including patients with low platelets at baseline (less than 50,000 per microliter and less than 100,000 per microliter). Patients who crossed over to pacritinib from BAT experienced similar reductions in spleen volume and symptom burden as patients initially randomized to pacritinib, including patients with low platelets. Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, which are kinases found to be involved in the growth and spread of myelofibrosis and other blood-related cancers.

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"From the time a patient is diagnosed with myelofibrosis, the incidence of disease-related thrombocytopenia increases with time," stated Claire Harrison, M.D., Consultant Hematologist, Guy’s and St. Thomas’ NHS Foundation Trust, Guy’s Hospital, London, United Kingdom and one of the principal investigators for PERSIST-1. "Patients with thrombocytopenia have significantly greater symptom burden, distinct clinical characteristics and shorter overall survival. There is currently a significant unmet need for patients with myelofibrosis who are unable to tolerate or control their disease on other treatments due to low platelet counts.

Dr. Harrison added, "It is encouraging to see that patients with baseline thrombocytopenia who were treated with pacritinib, had stable mean platelet counts and hemoglobin levels through the end of treatment, and that some patients with very low platelets increased their platelet counts while receiving pacritinib treatment. In this intermediate- to high-risk patient group, pacritinib was generally well tolerated."

Myelofibrosis is a rare, but serious and life-threatening chronic leukemia that disrupts the normal production of blood cells and results in scarring of the bone marrow, limiting the ability to produce new blood cells and prompting the spleen and other organs to take over this function. The disease often leads to an enlarged spleen and lower than normal counts of blood cells – including red blood cells and platelets, which are essential for blood clotting. Frequent causes of death among patients with myelofibrosis include leukemic transformation (31 percent), disease progression (18 percent), and thrombosis and cardiovascular complications (13 percent) 1.

Below are highlights presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) being held June 3–June 7, 2016 in Chicago, Ill. The poster presentations are available at www.ctibiopharma.com.

Highlights of Data Presented

Mesa, R, et al. Pacritinib (PAC) vs. best available therapy (BAT) in myelofibrosis (MF): 72 week follow-up of the phase III PERSIST-1 trial. Abstract #7065
In this poster, an update on efficacy and safety of the PERSIST-1 clinical trial up to Week 72 is provided for all patients in the study (pacritinib n=220; BAT n=107), regardless of platelet count. Ninety patients (84 percent) randomized to BAT crossed over to receive pacritinib at a median of 27.2 weeks.

Responses to pacritinib were durable and rates of 35 percent or greater spleen volume reduction (SVR) were maintained from Weeks 24 to 72 (25 percent vs. 24 percent). Patients who crossed over to receive pacritinib achieved similar responses to those receiving initial treatment with pacritinib. Overall survival, although not a primary or secondary endpoint of the trial, did not show a statistically significant difference between the pacritinib and BAT arms. This was primarily due to an imbalance between the two arms, with higher risk patients in the pacritinib arm vs. BAT. The result was potentially confounded by a high percentage of patients who crossed over at Week 24 to receive pacritinib therapy. Pacritinib-treated patients who achieved SVR greater or equal to 20 percent had statistically significant longer overall survival vs. patients who did not achieve SVR at this level.

The most frequently occurring adverse events with pacritinib were gastrointestinal events and the incidence decreased over time. Incidence of grade 3/4 treatment-emergent diarrhea with initial pacritinib treatment was highest in Weeks 1-8 (3 percent) and decreased in Weeks 8-16 (1.4 percent), Weeks 16-24 (1.5 percent) and in the final period analyzed, Weeks 64-72 (0.9 percent). Up to 24 weeks, prior to the majority of patients in the BAT arm crossing over, there was no statistically significant difference in the incidence of cardiac and bleeding adverse events between the pacritinib and BAT arms; following crossover to pacritinib, BAT patients had a similar rate of all grades of adverse events. The incidence of all grade cardiac AEs was similar between pacritinib and BAT arms between Weeks 1 and 24; incidence of cardiac AEs was greater for pacritinib between Weeks 24 and 72 vs. BAT, but was low overall (5 percent or less at any time). Among all patients, incidence of grade 3/4 bleeding events was 3 percent or less during any 8-week time interval.

Harrison, C, et al. Pacritinib (PAC) vs. best available therapy (BAT) in myelofibrosis (MF): Outcomes in patients (pts) with baseline (BL) thrombocytopenia. Abstract #7011
This analysis examines outcomes up to 72 weeks among patients in the PERSIST-1 trial with baseline platelets less than 100,000 per microliter treated with pacritinib vs. BAT (pacritinib, n=72; BAT, n=34). For patients receiving pacritinib, a median duration of spleen volume reduction (SVR) of 35 percent or greater was 48 weeks for patients with baseline platelets less than 50,000 per microliter and 57 weeks for patients with baseline platelets less than 100,000 per microliter. For BAT-treated patients who crossed over to receive pacritinib before or after Week 24, duration of SVR was 73 weeks for patients with baseline platelets less than 50,000 per microliter and 46 weeks for patients with baseline platelets less than 100,000 per microliter. At Week 36, 46 percent (6/13) of evaluable pacritinib-treated patients with baseline platelets less than 50,000 per microliter and 48 percent (12/28) of evaluable pacritinib-treated patients with baseline platelets less than 100,000 per microliter achieved 50 percent or greater reduction in Total Symptom Score (TSS). This is an increase from 32 percent and 42 percent, respectively, at Week 24.

Patients treated with pacritinib had stable mean platelet counts and hemoglobin levels through Week 72 and increased platelet counts in patients with platelets less than 50,000 per microliter. At 24 weeks, bleeding events occurred at a similar rate in pacritinib-and BAT-treated patients; following crossover to pacritinib, BAT patients had a similar rate of events. Among patients with baseline thrombocytopenia treated with pacritinib, mean hemoglobin levels remained stable through Week 72. Due to BAT crossover to pacritinib at Week 24, there were no evaluable patients with baseline thrombocytopenia in the BAT arm beyond Week 36. These data suggest pacritinib treatment led to durable reductions in spleen volume and symptom burden.

Harrison, C, et al. Outcomes in patients with myelofibrosis and RBC-transfusion dependence in the phase III PERSIST-1 study of pacritinib vs. best available therapy. Abstract #7066
In this poster, pacritinib-treated patients demonstrated clinically meaningful reductions in spleen volume independent of RBC-transfusion independence (RBC-TI). Among pacritinib-treated patients, 16 percent (36/220) were RBC-transfusion dependent (RBC-TD) at baseline. Eighteen (18) patients were RBC-TD at the time of crossover.

Twenty-two percent (12/54) of RBC-TD patients treated with pacritinib either from study start or after crossover achieved RBC-TI during the course of the study. During the course of the study, 25 percent (9/36) of RBC-TD patients treated with pacritinib at the start of the study achieved RBC-TI vs. 0 percent (0/16) patients treated with BAT (p=0.043). Seventeen percent (3/18 patients) of RBC-TD patients at the time of crossover achieved RBC-TI during the crossover period. Pacritinib treatment was associated with improved patient outcomes for those with baseline RBC-TD.

Mesa, R, et al. Pacritinib (PAC) vs. best available therapy (BAT) in myelofibrosis (MF): Long-term follow-up of patient-reported outcomes (PROs) in the phase III PERSIST-1 trial. Abstract #7067
Patient Reported Outcomes (PRO) data at 24 weeks was previously reported and the poster presented today provided an update at Week 48. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a PRO assessment tool designed to measure myelofibrosis-related symptom burden resulting in a TSS based on how the patient feels or functions in relation to six common symptoms. The proportion of patients achieving a TSS reduction of 50 percent or greater improved from Weeks 24 to 48 and was greater than observed with BAT showing that reduction in symptoms continued to increase over time. In patients who crossed over from BAT to pacritinib, reductions in TSS improved from Week 24 to Week 36. Mean percentage reductions in common symptoms measured in both MPN-SAF versions at Week 48 were greater than those observed at Week 24 among patients treated with pacritinib.

About PERSIST-1

PERSIST-1 is a randomized (2:1), controlled Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT – which included a broad range of currently utilized treatments – in 327 patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. As previously reported, the trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan) in the intent-to-treat population (ITT). These results included patients with severe or life-threatening thrombocytopenia. At study entry, 62 percent of patients had primary myelofibrosis; 46 percent of patients were thrombocytopenic; 32 percent of patients had baseline platelet counts less than 100,000 per microliter; and 16 percent of patients had platelet counts less than 50,000 per microliter; normal platelet counts range from 150,000 to 450,000 per microliter. The design of PERSIST-1 allowed for patients on the BAT arm to crossover and receive treatment with pacritinib if their disease progresses or after they achieve the 24-week measurement endpoint. Although crossover design of clinical trials may confound evaluation of survival, which is a tertiary endpoint of PERSIST-1, such designs are frequently used in cancer studies. The median duration of treatment was 16.2 months in patients treated with pacritinib, compared to 5.9 months in patients treated with BAT. The majority of patients (84 percent) on the BAT arm eventually crossed over to receive pacritinib therapy.

About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy; or patients who are intolerant of, or whose symptoms are not well controlled (sub-optimally managed) on other JAK2 therapy. Clinical studies for pacritinib are currently subject to a full clinical hold issued by the U.S. Food and Drug Administration in February 2016. A second Phase 3 study, known as PERSIST-2, is evaluating pacritinib in a subset of patients with myelofibrosis whose platelet counts are 100,000 per microliter or less. Although not all patients enrolled reached the 24-week endpoint prior to the full clinical hold on pacritinib, approximately two thirds of the enrolled patients reached or exceeded the 24-week endpoint evaluation. Therefore, these patients will contribute to the evaluation of the study endpoints. Based on the assumptions of the design, CTI BioPharma believes there is sufficient power to reach statistical significance of the primary objectives. Top-line results from the PERSIST-2 Phase 3 trial of pacritinib are expected in the third quarter of 2016.

CTI BioPharma and Baxalta Incorporated (now part of Shire plc) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

About Myelofibrosis and Myeloproliferative Neoplasms

Myelofibrosis is one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera and essential thrombocythemia.2

Myelofibrosis is a serious and life-threatening bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue, and pain.

The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S., of which myelofibrosis accounts for approximately 18,000 patients.3 In Europe, there is a wide variation of prevalence observed across data sources. Myelofibrosis has a median age of 64 at the time of diagnosis3 and is a progressive disease with approximately 20 percent of patients eventually developing AML.4 The median survival for high-risk myelofibrosis patients is less than one and a half years, while the median survival for patients with myelofibrosis overall is approximately six years.5