On November 28, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported an update on its late-stage clinical development program for the Company’s proprietary galinpepimut-S (GPS) in patients with acute myeloid leukemia (AML) (Press release, Sellas Life Sciences, NOV 28, 2018, View Source [SID1234531677]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Following a clinical and regulatory strategy defining Type C dialogue with the U.S. Food and Drug Administration (FDA), the Company plans to proceed with a clinical study design and biostatistical plan to support a Phase 3 registrational study for maintenance therapy for AML patients who have achieved complete remission after second line (salvage) antileukemic therapy, or CR2. This study will be used as the basis for a Biologics License Application (BLA) submission, subject to results that are both statistically significant and reflective of an effect of sufficient magnitude to be clinically meaningful.

"Following discussion with the FDA, we are embarking upon a revised Phase 3 study for GPS in the monotherapy maintenance setting for AML patients who have achieved CR2. The new design is expected to streamline sample size, time to accrual completion, primary endpoint readout and potential time to market, as well as costs. We believe this new study design provides SELLAS with a quicker path to approval, provided the study is positive," said Dr. Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "In addition to a statistical analysis plan which we believe accords a viable pathway for meeting the primary endpoint, we have built in an adaptive design, thus further enhancing the probability of a positive study."

GPS was previously given fast track and orphan drug designations in AML by the FDA.

The planned Phase 3 registrational study will be a 1:1 randomized, open-label study comparing GPS monotherapy in the maintenance setting to investigators’ choice best available treatment (BAT) in AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation.

The study is expected to enroll approximately 116 patients at around 50 clinical sites in the United States and Europe. It is powered at 90% to show a statistically significant difference in the primary endpoint of overall survival (OS) from the time of study entry. Secondary endpoints to be measured include leukemia-free survival, antigen-specific T-cell immune response dynamics, measurable residual disease by multigene array, and assessments of AML clonal evolution and inflammasome molecular signatures in the tumor microenvironment in bone marrow biopsy samples. The study will have a planned interim analysis for safety and futility after 80 events.

This streamlined CR2 study design, as compared to the previously planned study in AML patients who achieved complete remission following first-line antileukemic therapy (CR1), substantially reduces the study size (116 patients in CR2 vs. 390 patients in CR1) and time until topline data (up to 2.5 years in CR2 vs. 4.5 years in CR1) which will result in corresponding significant cost savings. A Phase 2a study of GPS in the AML CR2 setting conducted at the Moffitt Cancer Center previously demonstrated a clinically meaningful and statistically significant three-fold OS prolongation in patients receiving GPS when compared to a comparable group of contemporaneously assessed unvaccinated patients with a median OS of 16.3 months vs 5.4 months and a p-value of 0.0175, respectively, with treatment-related adverse events primarily comprised of grade 1 or 2 local injection site reactions and only one grade 3 (transient leukopenia) adverse event. A prior Phase 2 study of GPS in AML patients who achieved CR1 also met its primary endpoint with an OS rate at 3 years from first vaccination of 47%.

"We are excited to begin this late-stage Phase 3 program with GPS in AML. Earlier studies have positioned this agent to be a potentially effective approach in prolonging survival by delaying or preventing recurrence in patients in complete remission, most of whom harbor measurable residual disease and have a poor prognosis if they are unable to undergo allotransplant. We are hopeful that this new immunotherapeutic vaccine approach will improve outcomes in this patient population, which is at a very high risk of leukemic relapse," said Hagop M. Kantarjian, MD, Professor and Chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, and principal investigator of the upcoming Phase 3 AML clinical development program.

On November 28, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it launched the antitumor agent trastuzumab BS for intravenous drip infusions 60 mg and 150 mg "Daiichi Sankyo" (generic name: trastuzumab (genetical recombination)[trastuzumab biosimilar 2], hereafter, "the product") in Japan today (Press release, Daiichi Sankyo, NOV 28, 2018, View Source [SID1234531676]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The product is a pharmaceutical agent developed by Amgen Inc. (Headquarters: Thousand Oaks, CA, U.S.A; hereafter, "Amgen") as a biosimilar product to the anti-HER2 antibody, trastuzumab. The product was approved on September 21, 2018, and indicated for breast cancer with HER2 overexpression (Dosage A), and unresectable advanced or relapsed gastric cancer with HER2 overexpression (Dosage B).

Based on the exclusive agreement on the commercialization of biosimilars concluded with Amgen in July 2016, Daiichi Sankyo is responsible for the distribution and commercialization of the product in Japan, while Amgen is responsible for its manufacture.

The product is the first biosimilar product launched by Daiichi Sankyo, and the company expects that the product will provide patients and medical professionals with various options for cancer treatment, thereby further contributing to medical treatment.

Product name

Trastuzumab BS for intravenous drip infusions 60 mg and 150 mg "Daiichi Sankyo"

Generic name

Trastuzumab (Genetical Recombination)[Trastuzumab Biosimilar 2]

Indications

Breast cancer with HER2 overexpression

Unresectable advanced or recurrent gastric cancer with HER2 overexpression

Dosage and administration

・Dosage A is applied for breast cancer with HER2 overexpression.

・Dosage B in combination with other antineoplastic agents is applied for unresectable advanced or recurrent gastric cancer with HER2 overexpression.

Dosage A: In adults 4 mg/kg (body weight) trastuzumab (recombinant) [biosimilar 2 of trastuzumab] is intravenously infused once daily at the first administration, and 2 mg/kg for 90 minutes or longer at one-week intervals for the second and subsequent treatments.

Dosage B: In adults 8 mg/kg (body weight) trastuzumab (recombinant) [generic product 2 of trastuzumab] is intravenously infused once daily at the first administration, and 6 mg/kg for 90 minutes or longer at three-week intervals for the second and subsequent treatments.

If the initial dose is well tolerated, the administration time can be shortened up to 30 minutes for the second and subsequent treatments.

Date of approval for manufacturing and marketing

September 21, 2018

Date of listing in the NHI reimbursement

November 28, 2018

Day of launch

November 28, 2018

Marketing authorization holder

DAIICHI SANKYO COMPANY, LIMITED

Partner

Amgen Inc.

On November 28, 2018 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that data from an independent test in animal models confirmed, as previously believed, that its immuno-stimulating STAT3 inhibitor achieves disproportionately high accumulation in the pancreas (Press release, Moleculin, NOV 28, 2018, View Source [SID1234531674]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our own sponsored research suggested that WP1732 might be an ideal candidate for treating pancreatic cancer," commented Dr. Donald Picker, Moleculin’s Chief Science Officer. "Now, we have independent testing with radiolabeled drug confirming this in animal models. The propensity for such enhanced pancreatic distribution could be highly beneficial for a new pancreatic cancer drug."

Walter Klemp, Moleculin’s Chairman and CEO added, "Published research shows that the growth and survival of pancreatic cancer requires activated STAT3 (p-STAT3) and our own research suggests that WP1732 may be one of the most effective inhibitors of p-STAT3 that has demonstrated activity in in vivo models. Confirming the disproportionately high accumumulation of WP1732 in the pancreas puts us one step closer to introducing an entirely new approach to treating pancreatic cancer. This is very encouraging and confirms the direction that Moleculin has taken with WP1732. We are heavily engaged in preparing the data necessary for an Investigational New Drug (IND) application with the FDA which we are targeted to file in 2019."

On November 28, 2018 MabVax Therapeutics Holdings, Inc. (OTC Pink: MBVX), a clinical-stage biotechnology company focused on the development of antibody-based products to address unmet medical needs in the treatment of cancer and pancreatitis, reported that the Company had entered into an equity purchase agreement with Triton Funds LP, a Delaware limited partnership ("Triton Funds"), in which Triton Funds has agreed to purchase up to $1,000,000 of the Company’s to be designated Series P Convertible Preferred Stock, par value of $0.01 per share (the "Series P Preferred Stock"), subject to the effectiveness of an S-1 registration statement that the Company filed with the Securities and Exchange Commission (the "SEC") on November 20, 2018, that registers shares of common stock upon conversion of the Series P Preferred Stock (the "Equity Purchase Agreement") (Press release, MabVax, NOV 28, 2018, View Source [SID1234531673]). Under the terms of the Equity Purchase Agreement, Triton Funds is able to convert the Series P Preferred Stock into common stock at a rate based on the 5-day volume-weighted average price prior to the conversion date, or the stated market purchase price, times 75%. In addition, we agreed to issue 175,000 shares of common stock to Triton Funds LLC, manager of Triton, upon execution of the Equity Purchase Agreement to support the cost of the student-run fund. The summary above is subject to and qualified in its entirety to the Company’s filing of a registration statement on Form S-1 which can be found at:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

View Source

Dmitriy Slobodskiy Jr, Research Analyst of Triton Funds, stated, "Here at Triton Funds we strive to locate and invest into companies that make a meaningful impact on significant unmet medical needs. MabVax Therapeutics is one of the cases where a company is developing novel treatments for deadly and debilitating diseases of the pancreas, a small organ that plays a large role in human health."

Sam Yaffa, Founder of Triton Funds, stated, "One of the key factors we look for before we invest is how effective is the management team in advancing the company’s technology, and the team at MabVax has proved to be persistent in its efforts to provide benefits to patients in need of new therapies for unmet medical needs."

President and CEO J. David Hansen, stated, "We are pleased and honored that Triton Funds became interested in MabVax and its clinical stage human antibody development programs for the diagnosis and treatment of pancreatic cancer, and more recently for the development and testing of a clinical stage antibody for the treatment of pancreatitis. We intend to use these proceeds for developing a proof of concept clinical trial protocol for the treatment of pancreatitis using the Company’s antibody designated as MVT-5873 and for general corporate and working capital purposes."

On November 28, 2018 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that nine abstracts, including two oral presentations, relating to the company’s hematology/oncology portfolio were accepted for the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego from December 1-4 (Press release, Jazz Pharmaceuticals, NOV 28, 2018, View Source;p=RssLanding&cat=news&id=2378498 [SID1234531666]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We look forward to showcasing our commitment to the hematology/oncology community at ASH (Free ASH Whitepaper) by advancing the science and addressing the clinical needs of patients with blood cancers and with complications of stem cell transplantation," said Allen Yang, M.D., Ph.D., head of clinical development and acting chief medical officer of Jazz Pharmaceuticals. "We’ve made great progress in the last year with the initiation of new clinical trials for Vyxeos and Defitelio, the marketing authorization of Vyxeos in the European Union, and a collaboration with MD Anderson Cancer Center to evaluate potential treatment options for hematologic malignancies."

Jazz Pharmaceuticals data at the 2018 ASH (Free ASH Whitepaper) Annual Meeting will highlight the following:
Results from a post-hoc analysis from the pivotal Phase 3 randomized trial of Vyxeos (daunorubicin and cytarabine) liposome for injection, also known as the molecule name CPX-351, in a subgroup of older patients with newly diagnosed high risk (secondary) AML with myelodysplasia-related changes (AML-MRC) that evaluated the efficacy of Vyxeos compared to conventional 7+3 chemotherapy on overall survival and remission rates as well as the safety profile in older adults with AML-MRC. Additionally, data will be presented from an exploratory analysis which evaluated the impact of hematopoietic cell transplantation (HCT) on survival in patients treated with Vyxeos compared to 7+3 in the Phase 3 trial.

Vyxeos abstracts include:

Efficacy and Safety of CPX-351 versus 7+3 in a Subgroup of Older Patients with Newly Diagnosed Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Enrolled in a Phase 3 Study [Abstract #1425; Saturday, December 1, 6:15 PM – 8:15 PM PST]
Population Pharmacokinetic (PK)/Pharmacodynamic (PD) Modeling of Myelosuppression in Patients with Hematologic Malignancies for CPX-351 and Standard-of-Care 7+3 Therapy [Abstract #4037; Monday, December 3, 6:00 PM – 8:00 PM PST]
The Impact of Hematopoietic Cell Transplantation on Survival: An Exploratory Analysis of a Phase 3 Study of CPX-351 versus 7+3 in Older Patients with Newly Diagnosed, High-Risk/Secondary AML [Abstract #2706; Sunday, December 2, 6:00 PM – 8:00 PM PST]
Final Safety and Efficacy Results from the CPX-351 Early Access Program (EAP) for Older Patients with High-Risk/Secondary Acute Myeloid Leukemia (sAML) [Abstract #1434; Saturday, December 1, 6:15 PM – 8:15 PM PST]
Impact of Post–Hematopoietic Cell Transplant (HCT) Survival on Cost-effectiveness of CPX-351 versus 7+3 in the Treatment of Therapy-Related AML or AML-MRC in the United States (online only)
A Phase I/Pilot Study of CPX-351 [Daunorubicin and Cytarabine Liposome for Injection (Vyxeos)] for Children, Adolescents and Young Adults with Recurrent or Refractory Acute Leukemia [Abstract #336; Sunday, December 2, 10:45 AM PST(oral presentation)]
In addition, data from an expanded access program and post-hoc analyses of clinical trials for Defitelio (defibrotide sodium) will be presented, including an oral presentation of a pooled analysis of survival based on timing of initiation in adults with Veno-Occlusive Disease/ Sinusoidal Obstruction Syndrome (VOC/SOS) following hematopoietic stem cell transplant (HSCT).

Defitelio abstracts include:

Incidence of Post-Hematopoietic Stem Cell Transplantation (HSCT) Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Without Hyperbilirubinemia at Diagnosis and Efficacy of Defibrotide in an Expanded-Access Program [Abstract #2080; Saturday, December 1, 6:15 PM – 8:15 PM PST]
A Pooled Analysis of Survival by Defibrotide Timing of Initiation in Adults with Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Following Hematopoietic Stem Cell Transplant (HSCT) [Abstract #815; Monday, December 3, 3:45 PM PST (oral presentation)]
Cost-Effectiveness of Defibrotide for the Treatment of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with Multi-Organ Dysfunction (MOD) Post-Hematopoietic Stem Cell Transplantation (HSCT) in Canada [Abstract #4702; Monday, December 3, 6:00 PM – 8:00 PM PST]
About Vyxeos
Vyxeos (daunorubicin and cytarabine) is a liposome formulation of a fixed combination of daunorubicin and cytarabine for intravenous infusion, and is approved for the treatment of two types of secondary AML in adult patients, newly diagnosed therapy-related acute myeloid leukaemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC). Vyxeos is the first product developed with the company’s proprietary CombiPlex platform, which enables the design and rapid evaluation of various combinations of therapies. Vyxeos received U.S. FDA approval and orphan drug exclusivity in August 2017 and EU EMA marketing authorization in August 2018. Vyxeos received Orphan Drug Designation for the treatment of AML by the U.S. FDA in September 2008 and by the European Commission in January 2012 (with retention of the designation reaffirmed in July 2018). Vyxeos received Promising Innovative Medicine (PIM) designation from the Medicines and Healthcare Products Regulatory Agency in the United Kingdom.

Important Safety Information
Vyxeos has different dosage recommendations from other medications that contain daunorubicin and/or cytarabine. Do not substitute Vyxeos for other daunorubicin- and/or cytarabine- containing products.

Vyxeos should not be given to patients who have a history of serious allergic reaction to daunorubicin, cytarabine or any of its ingredients.

Vyxeos can cause a severe decrease in blood cells (red and white blood cells and cells that prevent bleeding, called platelets) which can result in serious infection or bleeding and possibly lead to death. Your doctor will monitor your blood counts during treatment with Vyxeos. Patients should tell the doctor about new onset fever or symptoms of infection or if they notice signs of bruising or bleeding.

Vyxeos can cause heart-related side effects. Tell your doctor about any history of heart disease, radiation to the chest, or previous chemotherapy. Inform your doctor if you develop symptoms of heart failure such as:

shortness of breath or trouble breathing
swelling or fluid retention, especially in the feet, ankles or legs
unusual tiredness
Vyxeos may cause allergic reactions including anaphylaxis. Seek immediate medical attention if you develop signs and symptoms of anaphylaxis such as:
trouble breathing
severe itching
skin rash or hives
swelling of the face, lips, mouth, or tongue
Vyxeos contains copper and may cause copper overload in patients with Wilson’s disease or other copper-processing disorders.

Vyxeos can damage the skin if it leaks out of the vein. Tell your doctor right away if you experience symptoms of burning, stinging, or blisters and skin sores at the injection site.

Vyxeos can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Do not breastfeed while receiving Vyxeos. Females and males of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of Vyxeos.

The most common side effects were bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.

Please see full Prescribing Information for Vyxeos including BOXED Warning, and visit www.Vyxeos.com for additional information.

About Defitelio
In the U.S., Defitelio (defibrotide sodium) injection 80mg/mL received U.S. FDA marketing approval on March 30, 2016 for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication.

In Europe, defibrotide is marketed under the name Defitelio* (defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients undergoing HSCT therapy. It is the first and only approved treatment in Europe for severe VOD. In Europe, Defitelio is indicated in patients over one month of age. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy.

*This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC. (View Source)

Important Safety Information

Defitelio should not be given to patients who are:

Currently taking anticoagulants or fibrinolytics
Allergic to Defitelio or any of its ingredients
Defitelio may increase the risk of bleeding in patients with VOD and should not be given to patients with active bleeding. During treatment with Defitelio, patients should be monitored for signs of bleeding. In the event that bleeding occurs during treatment with Defitelio, treatment should be temporarily or permanently stopped. Patients should tell the doctor right away about any signs or symptoms of hemorrhage such as unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, or altered vision.

Defitelio may cause allergic reactions including anaphylaxis. Patients who develop signs and symptoms of anaphylaxis such as trouble breathing, severe itching, skin rash or hives, or swelling of the face, lips, mouth or tongue should seek medical attention immediately.

The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.

Please see full Prescribing Information for Defitelio and visit www.Defitelio.com for additional information.