On June 4, 2018 Kyowa Hakko Kirin Co., Ltd., (Kyowa Kirin) reported that additional analyses from the pivotal MAVORIC trial are being presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), June 1-5, Chicago (Press release, Kyowa Hakko Kirin, JUN 4, 2018, View Source [SID1234527142]). MAVORIC was the open-label randomized multi-center phase 3 trial evaluated mogamulizumab versus vorinostat for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. MF and SS are the most common subtypes of cutaneous T-cell lymphoma (CTCL).

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Presentation title at the 2018 ASCO (Free ASCO Whitepaper) Annual Congress:
Quality of life in cutaneous T-cell lymphoma subjects treated with anti-CCR4 monoclonal antibody mogamulizumab versus vorinostat: results from the Phase 3 MAVORIC trial [Abstract #7577; Poster #214; Monday, June 4, 8:00-11:30AM CDT]

Progression free survival (PFS) was the primary endpoint; the results that demonstrated mogamulizumab had a clinically relevant and statistically significant increase in progression free survival over vorinostat have already been presented. Infusion reaction and rash were the most common adverse events associated with mogamulizumab. QOL measurements were secondary endpoints and included Skindex29 (SDX-29), Functional Assessment of Cancer Therapy-General (FACT-G) and EuroQol-5D. SDX-29 and FACT-G were reported in ASCO (Free ASCO Whitepaper).

"Quality of life may be severely impacted in patients living with CTCL, and the MAVORIC study included evaluation of the effect of both treatments on a range of QOL instruments," said Jeffrey S. Humphrey, M.D., President of Kyowa Kirin Development. "We are encouraged by the QOL data and look forward to working with investigators and patient advocates to further understand how mogamulizumab might help patients with MF and SS."

The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

About Mogamulizumab
Mogamulizumab is a humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4),
which is frequently expressed on leukemic cells of certain hematologic malignancies including CTCL. Mogamulizumab
was produced using Kyowa Hakko Kirin’s proprietary POTELLIGENT platform, which is associated with enhanced
antibody-dependent cellular cytotoxicity. Mogamulizumab is an investigational product currently under review at
FDA and EMA.

About Mycosis Fungoides (MF) and Sézary Syndrome (SS)
MF and SS are the two most common subtypes of CTCL, a rare type of non-Hodgkin’s lymphoma, which is
characterized by localization of malignant T lymphocytes to the skin, and depending on the stage, the disease may
involve skin, blood, lymph nodes, and viscera.

News Release

About MAVORIC
MAVORIC is a Phase 3 open-label, multi-center, randomized study of mogamulizumab versus vorinostat in patients
with MF and SS who have failed at least one prior systemic treatment. The study was conducted in the U.S.,Europe,
Japan and Australia, and randomized 372 patients to receive either mogamulizumab or vorinostat.

On June 4, 2018 MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, reported preliminary results from its ongoing Phase I study of small activating RNA (saRNA) candidate MTL-CEBPA in advanced liver cancer (Press release, MiNA Therapeutics, JUN 4, 2018, View Source [SID1234527158]). In the study, MTL-CEBPA was generally well tolerated in patients with both healthy and impaired liver function and provided evidence of anti-tumour activity. MTL-CEBPA was also found to mediate RNAa activity in white blood cells. The data are being presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a poster titled "Preliminary results of a first-in-human, first-in-class phase I study of MTL-CEBPA, a small activating RNA (saRNA) targeting the transcription factor C/EBP-a in patients with advanced liver cancer" in the Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics poster discussion session being held on Monday June 4, 2018 from 3:00pm to 4:15pm CDT.

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"Despite recent advances in treatment options, liver cancer remains a significant unmet medical need with numerous hurdles for therapeutic intervention. New treatment options are desperately needed, in particular for those patients with impaired liver function," said Dr. Debashis Sarker, Principal Investigator at the National Institute for Health Research Clinical Research Facility at Guy’s and St Thomas’ and King’s College London, and chief investigator of the study. "These preliminary safety data and the evidence of anti-tumour activity are very promising and I look forward to evaluating MTL-CEBPA in the dose expansion part of this Phase I clinical trial."

"We are extremely pleased with the preliminary results of this first-in-human study which include safety and tolerability of MTL-CEBPA, as well as evidence of anti-tumour activity in this very advanced, heavily pre-treated cancer patient population. In particular we have seen many patients achieve stable disease or better, including a patient with advanced hepatocellular carcinoma who has achieved over 70% tumour regression and has continued on the study for over one and half years," said Robert Habib, CEO of MiNA Therapeutics. "Additionally, analysis of patient blood samples has demonstrated upregulation of target CEBPA mRNA in white blood cells, representing a significant milestone in the development of saRNA medicines and for our platform."

MTL-CEBPA was evaluated in the dose escalation part of a Phase I clinical trial in patients with advanced liver cancer. As of the data cut-off date of March 31, 2018, 23 patients had been treated once weekly at six dose levels (ranging from 28 mg/m2 to 160 mg/m2) and 5 patients had been treated twice weekly at 70 mg/m2.

MTL-CEBPA was well tolerated in patients at all doses and no Maximum Tolerated Dose was identified. The large majority of adverse events (AEs) reported by investigators were mild to moderate in severity. 12 (43%) patients experienced AEs no higher than Grade 2. AEs of Grade 3 or higher included hyperbilirubinaemia (11%), elevated GGT (11%), hypophosphataemia (11%), anaemia (7%) and hypertension (7%). Only 3 (11%) patients discontinued treatment with MTL-CEBPA due to possible drug-related toxicities including acute coronary syndrome, hyperbilirubinaemia, and elevated GGT.

Pharmacokinetic data from this study showed that Cmax (peak plasma concentration of drug) and AUC (area under the curve) were dose proportional with no evidence of drug accumulation.

CEBPA gene expression was analysed in white blood cells of 10 patients across multiple dose levels and timepoints. The level of CEBPA gene expression was significantly higher on treatment than at baseline, supporting target engagement of MTL-CEBPA. Consistent with up-regulation of CEBPA, which has a role in myeloid differentiation, significant and repeated increases in neutrophils were observed after dosing MTL-CEBPA.

Enrollment in the dose escalation part of the Phase I clinical trial has been completed. Enrollment is starting for in the dose expansion part of the Phase I clinical trial in multiple sites in the United Kingdom and Asia. For more information, please contact us at [email protected].

About MTL-CEBPA
MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES liposomal nanoparticle and is designed to activate the CEBPA gene. By restoring CEBPA expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse liver disease in a range of pre-clinical studies including models of liver cancer, liver cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). MTL-CEBPA is currently under evaluation in OUTREACH, a first-in-human Phase I clinical study in patients with severe liver cancer. The multi-centre Phase I study is assessing the safety and tolerability of MTL-CEBPA in patients with advanced liver cancer who are ineligible or resistant to standard therapies. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov

On June 4, 2018 Selecta Biosciences, Inc. (the "Company") presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business (Presentation, Selecta Biosciences, JUN 4, 2018, View Source [SID1234527193]).

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On June 4, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX), reported updated clinical data from its ongoing Phase 2 study evaluating umbralisib (TGR-1202), the Company’s PI3K delta inhibitor, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) who are intolerant to prior BTK or PI3K delta inhibitor therapy (Press release, TG Therapeutics, JUN 4, 2018, View Source [SID1234527143]). Data from this trial are being presented today during the 54th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are extremely pleased with the data presented today during the ASCO (Free ASCO Whitepaper) annual meeting. We believe there is a need for novel treatment options for patients who are intolerant to the currently approved BTK and PI3K therapies and believe the data shown today demonstrates that umbralisib can be used effectively in these patients." Mr. Weiss, continued, "We continue to be pleased with the safety and efficacy profile of umbralisib and believe umbralisib single agent, or umbralisib plus ublituximab referred to as ‘U2’, can become important treatment options across multiple b-cell malignancies. We also look forward to presenting updated umbralisib integrated safety data at the European Hematology Association (EHA) (Free EHA Whitepaper) annual congress in a couple of weeks, as well as the topline response rate data from the UNITY-CLL Phase 3 trial by the end of summer 2018."

Highlights from today’s presentation include the following:

Poster Presentation: KI Intolerance Study: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib (TGR-1202) In Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K-delta Inhibitor Therapy (Abstract Number 4314)

This poster presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent umbralisib (TGR-1202). To be eligible for the study patients had to have received prior treatment with a BTK inhibitor (ibrutinib, acalabrutinib) or a PI3K delta inhibitor (idelalisib, duvelisib) and discontinued therapy due to intolerance within 12 months of starting treatment on this study. Forty-seven patients were evaluable for safety of which 46 were evaluable for Progression Free Survival (PFS), (1 patient had a confirmed Richter’s Transformation (RT) at enrollment which did not meet eligibility criteria).

Highlights from this poster include:

●Umbralisib demonstrated a favorable safety profile in patients intolerant to prior BTK or PI3K therapy
●Only 13% discontinued due to an adverse event, of which only one patient discontinued due to a recurrent adverse event (AE) also experienced with prior KI therapy
●Nodal reductions were seen in nearly all patients evaluable for response with 3 patients achieving complete resolution of nodal disease, of which 1 patient with 17p del achieved a bone marrow confirmed Complete Response (CR)
●Median progression free survival (PFS) has not been reached with a median follow-up of 9.5 months
●In this relapsed/refractory CLL population, of which 77% required treatment within 6 months of prior KI discontinuation, 68% had a high-risk molecular / genetic marker and 6% had an ibrutinib resistance mutation, significant clinical activity has been observed

PRESENTATION DETAILS
The above referenced presentation is now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 1, 2018 Acceleron Pharma Inc. (Nasdaq:XLRN), a leading biopharmaceutical company in the discovery and development of TGF-beta therapeutics to treat serious and rare diseases, reported updated results from the Phase 2 trials of luspatercept in patients with lower-risk myelodysplastic syndromes (MDS) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting in Chicago (Press release, Acceleron Pharma, JUN 4, 2018, View Source [SID1234527159]). Luspatercept is being developed as part of a global collaboration between Acceleron and Celgene.

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"The ongoing Phase 2 trials continue to provide important insights into luspatercept’s potential to deliver long-term benefit to thousands of patients with lower-risk MDS," said Habib Dable, President and Chief Executive Officer of Acceleron. "With multiple patients on treatment for more than three years, we are increasingly confident in luspatercept’s novel mechanism as an erythroid maturation agent to address a significant unmet medical need in lower-risk MDS. We look forward to sharing top-line results from the MEDALIST Phase 3 trial over the next few months."

Patients with MDS suffer from insufficient production of red blood cells, resulting in chronic anemia that can lead to debilitating fatigue, diminished quality of life and increased mortality. Because MDS-related chronic anemia often fails to respond to unapproved therapies which include erythropoiesis-stimulating agents, many patients require frequent red blood cell transfusions.

Phase 2 Results

A total of 101 patients with lower-risk MDS have been treated with luspatercept (dose levels ≥ 0.75 mg/kg) in the Phase 2 trials.

55% (55 of 101 patients) achieved a clinically meaningful erythroid improvement (IWG HI-E criteria).
44% (30 of 68 patients) with a red blood cell (RBC) transfusion burden at baseline achieved RBC transfusion independence (RBC-TI) for at least 8 weeks.
The mean duration of treatment for RBC-TI responders was 18.3 months (n=30, ongoing).
Multiple patients continue on treatment through 40 months, and continue to sustain a clinically meaningful increase in hemoglobin and reduction in transfusion burden.
Phase 2 Safety Summary

The majority of adverse events (AEs) were Grade 1 or 2. Grade 3 non-serious AEs possibly related to study drug were ascites, blood bilirubin increase, bone pain, hypertension, mucosal inflammation, platelet count increase, and transformation to AML (previously reported as a blast cell count increase). The Grade 3 non-serious AEs occurred in one patient each, with the exception of hypertension in 2 patients.

Serious AEs (SAEs) possibly related to study drug were general physical health deterioration, muscular weakness, musculoskeletal pain, and myalgia. The four SAEs occurred in three individual patients.

The ASCO (Free ASCO Whitepaper) MDS poster presentation is available under the Science page of the Company’s website at www.acceleronpharma.com.

Luspatercept is an investigational product that is not approved for any use in any country.

About the Ongoing MDS Phase 2 Trials

Data from two Phase 2 trials were presented at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting: the base study in which patients with lower-risk MDS received treatment with luspatercept for three months and the long-term extension study in which patients who completed the base study may receive treatment with luspatercept for up to an additional five years.

About Luspatercept

Luspatercept is a first-in-class erythroid maturation agent (EMA) that regulates late-stage red blood cell maturation. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials are underway to evaluate the safety and efficacy of luspatercept in patients with MDS (the MEDALIST trial) and in patients with beta-thalassemia (the BELIEVE trial). A Phase 3 trial is being planned in first-line, lower-risk, MDS patients (the COMMANDS trial). The BEYOND Phase 2 trial in non-transfusion-dependent beta-thalassemia and a Phase 2 trial in myelofibrosis are ongoing. For more information, please visit www.clinicaltrials.gov.