On December 1, 2018 MaaT Pharma reported the results from its ODYSSEE (NCT02928523) Phase 1b/2a clinical trial demonstrating that the Company’s proprietary MaaT Microbiome Restoration Biotherapeutic (MMRB) therapeutic is able to restore a functional microbiome in acute myeloid leukemia (AML) patients after having undergone intensive chemotherapy and multiple courses of antibiotics (Press release, MaaT Pharma, DEC 1, 2018, View Source [SID1234531791]). The study was designed to investigate the safety and feasibility of reestablishing a functional microbiome using MaaT Pharma’s therapeutic as well as evaluating initial signs of efficacy including reduction of intestinal inflammation and the control of detrimental antibiotic-resistant bacteria. Due to the harsh treatment regimens, AML patients lose their functional microbiome and experience a variety of severe complications that dramatically impact outcomes and quality of life. MaaT Pharma’s MMRB therapeutic aims to restore microbiome function and improve clinical outcomes in these patients. The data were presented at 6:15 pm Pacific Time on December 1st, 2018 at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition held in San Diego, California.

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In total 25 AML patients were treated in the clinical trial. At the time of admission, fecal microbiota was collected from each patient, conditioned, processed and frozen according to GMP conditions. Following the first round of chemotherapy and antibiotic treatment, patients were administered two doses of the collected fecal microbiota as an enema 24 hours apart after hematopoietic recovery and before undergoing the second round of chemotherapy. Blood and fecal samples were collected on three separate days, (1) on day 0, at the time of patient inclusion in the trial, (2) on day 29, following hematopoietic recovery after the first round of intensive treatments and (3) on day 40, before the start of the consolidation chemotherapy. Microbiome profile evolution was analyzed using high-resolution metagenome sequencing and patient follow-up was scheduled for 6 months and 12 months after inclusion.

"The results from the ODYSSEE clinical trial are impressive and demonstrate proof-of-concept for the ability of our approach to restore a functional microbiome, following antibiotics and chemotherapies, in AML patients and that reestablishing the microbiome has the potential to improve survival outcomes," commented Professor Mohamad Mohty, MD, PhD, Professor of Hematology at Sorbonne University and Head of the Hematology and Cellular Therapy Department at the Saint Antoine Hospital in Paris. "Acute myeloid leukemia patients have limited treatment options and the intensive chemotherapy and antibiotic therapy regimens they have to endure significantly contribute to poor quality of life and low survival outcomes. Given these positive results, we look forward to our planned randomized trial with the off-the-shelf capsule formulation MaaT033, as the next step."

Overall, reintroduction of the patient’s own gut microbiome through MaaT Pharma’s proprietary process was well tolerated and no severe adverse events were reported. Metagenomic analysis of the patient samples collected on days 0, 29 and 40 using MaaT Pharma’s proprietary big data analysis platform, GutPrint showed that the MMRB therapeutic restored significantly greater than 90% of the microbial species diversity and structure at day 40, ten days after treatment, including a 43% reduction of the overall expression of antibiotic resistance genes. Most importantly, gut inflammation was significantly reduced to near-baseline levels following MMRB treatment as measured by fecal neopterin biomarker. These results also correlated with the significant reduction of pro-inflammatory bacterial families and restoration of beneficial species among the Lachnospiraceae and Ruminococcaceae families.

"Our commitment has always been to improve outcomes in patients with life-threatening diseases. The results and experience from this trial support our investment in developing standardized, reproducible and high diversity microbiome biotherapeutic products using our MMRB therapeutic and cGMP production facility to treat patients with blood cancers and the complications arising from its treatment," added Hervé Affagard, Co-founder and CEO of MaaT Pharma. "Our lead product, MaaT013, which is manufactured from pooled donors, was developed based on the positive data we collected from this trial and the scientific and clinical evidence showing that restoring the microbiome has therapeutic potential. MaaT013 is currently being tested in a Phase 2 clinical study to treat acute graft-versus-host-disease, a severe consequence of stem cell transplantation. We are also very pleased to have just been awarded Orphan Drug Designation by the EMA for this product after already receiving the designation by the FDA earlier this year."

The poster is available on the company website under "News" or by accessing the following link View Source

On December 1, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported positive top-line results from the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study evaluating selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue (Press release, Karyopharm, DEC 1, 2018, View Source [SID1234531776]). The data were highlighted in a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting in San Diego. For the SADAL study’s primary endpoint, single-agent selinexor achieved a 29.6% overall response rate (ORR), which included a 9.6% complete response (CR) rate in patients with heavily pretreated relapsed or refractory DLBCL. Key secondary endpoints included a median duration of response (DOR, in the responding patients) of 9.2 months and median overall survival (OS, across the entire study) of 9.1 months.

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Selinexor recently received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Karyopharm plans to submit a New Drug Application (NDA) to the FDA during the first half of 2019, with a request for accelerated approval for oral single-agent selinexor as a new treatment for patients with relapsed or refractory DLBCL.

Top-Line Phase 2b SADAL Results

Based on the modified intention-to-treat analysis from the first 115 of 127 patients (median of 2 prior treatment regimens with a range 1-6), as adjudicated by an independent central radiological committee, 34 patients responded (11 patients with a CR and 23 patients with a PR) for an ORR of 29.6%. An additional 8 patients experienced stable disease (SD) for a disease control rate of 36.5%. The median DOR across responding patients was 9.2 months and responses tended to occur rapidly. Patients with a CR had a median DOR of 23.0 months and patients with a PR had a median DOR of 7.8 months. As of the data cutoff date of November 15, 2018, 7 patients who achieved a CR remained on treatment. In addition, 12 patients remain on treatment, but as of November 15th, had not reached their first response assessment and are not included in the top-line efficacy analyses.

Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related adverse events (AEs) were gastrointestinal and constitutional symptoms, along with cytopenias; most manageable with dose modifications and/or supportive care. The most common non-hematologic AEs were nausea (50.0%), fatigue (35.9%), and anorexia (32.0%) and mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 AEs were thrombocytopenia (35.2%), neutropenia (20.3%), and anemia (10.9%) and were generally not associated with clinical sequelae. No significant major organ toxicities were observed, and bleeding and infection rates were low.

The median OS was 9.1 months for all patients in the study. As of the data cutoff date, median survival for the patients with a CR or PR was 29.7 months. The median survival for patients with best response of progressive disease or who were not evaluable for response was 3.2 months.

Selinexor showed robust, single-agent activity in patients with either GCB or non-GCB subtypes of DLBCL: of the 53 patients with the GCB-subtype, 18 responded (5 patients with a CR and 13 patients with a PR) for an ORR of 34.0%. Of the 57 patients with the non-GCB subtype, 12 responded (6 patients with a CR and 6 patients with a PR) for an ORR of 21.1%. In addition, there were 5 patients enrolled whose subtype was unclassified and 4 of these patients achieved a PR.

"The SADAL data presented at ASH (Free ASH Whitepaper) this year demonstrate that oral selinexor, when administered as a single-agent, is clinically active and capable of producing durable responses associated with prolonged overall survival," said Marie Maerevoet, MD, Institute Jules Bordet, "The 60mg twice weekly oral dose continues to be well tolerated with a low incidence of Grade 3 or greater adverse events, which were often manageable with dose modifications and supportive care. We are highly encouraged by the results of this single agent study in patients with heavily pretreated DLBCL who have limited available treatment options."

Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm, said, "In addition to the compelling efficacy and safety data observed with single agent oral selinexor, we were especially pleased to see strong response rates in patients with both the GCB and non-GCB subtypes. This is especially important because the prognosis in patients with refractory disease and the GCB-subtype is particularly poor. We believe that if selinexor is ultimately approved for use in patients with DLBCL, it will provide a meaningful therapeutic option for patients battling refractory disease regardless of DLBCL subtype. We look forward to submitting these data to the FDA during the first half of 2019 as part of a New Drug Application, with a request for accelerated approval."

Details for the Poster Presentation at ASH (Free ASH Whitepaper) 2018:

Title: Single Agent Oral Selinexor Demonstrates Deep and Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study
Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium
Abstract Number/Publication ID: 1677
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I
Date and Time:Saturday, December 1, 2018; 6:15-8:15 PM PT
Location: San Diego Convention Center, Hall GH

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,800 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On November 30, 2018 IGEM Therapeutics (IGEM or "the Company"), an immuno-oncology company developing novel immunoglobulin E (IgE) antibodies to treat cancer, reported it has secured an additional £3 million to close its Series A round at £5 million (Press release, IGEM Therapeutics, NOV 30, 2018, View Source [SID1234531742]). Two new investors, Alsa Holdings and UCL Technology Fund (co-managed by Albion Capital and UCLB, UCL’s commercialisation company) have joined initial investor Epidarex Capital who also committed further capital in this second close.

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The funding will enable IGEM to further develop its portfolio of IgE antibody candidates against a variety of cancers. The epsilon constant region of IgE has evolved to fight complex, multicellular parasitic organisms resident in tissue by recruiting powerful immune effector cells such as macrophages, basophils and monocytes. IGEM believes that potent immune responses arising from IgE are suited to the destruction of solid tumours which also reside in tissue. Pre-clinical proof of concept data repeatedly shows superior efficacy for IgE versus cognate IgG antibodies in a range of cancer models.

Alek Safarian, Chief Executive Officer of Alsa Holdings, commented: "We are excited by the promise that IGEM’s technology holds for major therapeutic advances in a host of oncology indications, and are looking forward to working with the management team to help bring new options to oncology patients in the future."

Dr Christoph Ruedig, Partner at Albion Capital commented: "The UCL Technology Fund strives to back innovative early stage companies that are seeking to translate ground-breaking research into commercial and societal impact. The pioneering work of Dr Sophia Karagiannis and her collaborators, which includes significant clinical development by clinical academics from UCL, highlight the profound potential of IgE antibody technology in cancer therapeutics. We are delighted to invest alongside Epidarex and Alsa and look forward to working with IGEM’s accomplished executive team."

Dr Peter Finan, Partner at Epidarex Capital, commented: "IGEM continues to make great progress on this disruptive platform. We look forward to working closely with Alsa and Albion to maximise IGEM’s potential"

Dr Tim Wilson, Chief Executive Officer of IGEM, commented: "This new financing will allow IGEM to continue to pioneer the development of IgE therapeutic antibodies for the treatment of cancer. We are very pleased to have attracted new investors of the calibre of Alsa Holdings and UCL Technology/Albion to IGEM as well as receiving further investment from initial investor Epidarex Capital."

On November 30, 2018 Onco360, the nation’s largest independent Oncology Pharmacy, reported that it was selected as a specialty pharmacy network partner for Astellas’ new product XOSPATA (gilteritinib) for the treatment of patients with relapsed or refractory FMS-like Tyrosine Kinase 3 (FLT3) mutation-positive acute myeloid leukemia (AML) (Press release, Onco360, NOV 30, 2018, View Source [SID1234531759]).

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"Onco360 is excited to be selected as one of only three specialty pharmacy providers for XOSPATA patients," said Paul Jardina, President and CEO, Onco360. "The recent approval of XOSPATA unlocks a new treatment option for AML patients with extremely limited treatment alternatives. As a provider of this key treatment, Onco360 can support the highly specialized needs of AML patients and their physicians across the United States."

AML is the most common form of acute leukemia in adults in the United States (U.S.). Only 27 percent of patients diagnosed with AML survive for five years following initial diagnosis. FLT3 mutations occur in about 33 percent of AML patients and is an indicator of a poor prognosis. The American Cancer Society estimates that in 2018, approximately 19,500 new patients will be diagnosed with AML in the U.S.1 Previously, there were no U.S. Food and Drug Administration (FDA)-approved products for patients with relapsed or refractory FLT3 mutation-positive AML.

XOSPATA is a manufactured by Astellas Pharma Inc. and was approved by the U.S. FDA on November 28, 2018 based on positive clinical trial results.2 Full prescribing information can be found at www.xospata.com.

XOSPATA is immediately available to order through Onco360. Referral forms and information on how to order can be found at Onco360.com/Order.

On November 30, 2018 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported presentations of clinical and scientific data related to Peripheral T-cell Lymphoma (PTCL) and EVOMELA (melphalan) at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held in San Diego, California, from December 1-4, 2018 (Press release, Spectrum Pharmaceuticals, NOV 30, 2018, View Source [SID1234531743]).

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For more information about the ASH (Free ASH Whitepaper) annual meeting and for a complete list of abstracts, please refer to the conference website at View Source

The following posters will be presented at the ASH (Free ASH Whitepaper) meeting:

Management of Mucositis with Use of Leucovorin as Adjunct to Pralatrexate in Treatment of Patients with Hematological Malignancies including of Peripheral and Cutaneous T-Cell Lymphomas-Results from a Prospective Multicenter Phase 2 Clinical Trial. Poster 2910; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH
Role of Single Agent and Combination Chemotherapy Strategies in Relapsed/Refractory Peripheral T-Cell Lymphoma: Results from the Complete Registry. Poster 2926; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH
Safety and Efficacy of Evomela in Myeloma Autotransplants; Poster 3446; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH