On November 1, 2018 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported updated data from the ongoing Phase 1 dose-escalation part of its Phase 1/2 clinical trial of cusatuzumab (ARGX-110) in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) (Press release, argenx, NOV 1, 2018, View Source [SID1234530646]). As of the data cut-off on July 16, 2018, a 92% (11/12 patients) overall response rate (ORR) was observed, with 42% of patients achieving minimal residual disease (MRD) negativity. The median response duration was 6.9 months as of the data cut-off date.

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Data from this ongoing AML trial are expected to be further updated, including ORR and duration of response, during a company workshop to be held around the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"The clinical data published today are encouraging and underscore our decision to move forward into a Phase 2 clinical trial of cusatuzumab in AML, which we launched earlier this year. These data also support the deep understanding of the disease biology of CD70 as demonstrated by the preclinical work of our collaborators at the University of Bern, highlighting cusatuzumab’s potential to offer a novel mechanism of action in AML against leukemic blasts and leukemic stem cell compartments," commented Nicolas Leupin, MD, Chief Medical Officer of argenx. "We look forward to providing an update on key metrics from the Phase 1 dose-escalation of the Phase 1/2 trial, including response rate and duration of response, at our annual workshop around ASH (Free ASH Whitepaper)."

Phase 1/2 Results for Cusatuzumab in AML

In this trial, argenx evaluated the safety, tolerability and efficacy of cusatuzumab in combination with azacytidine (AZA) in an open-label, Phase 1/2 clinical trial in 12 newly diagnosed AML patients unfit for intensive chemotherapy. The data published today are from all 12 patients across four dose cohorts (1 mg/kg, 3 mg/kg, 10 mg/kg and 20 mg/kg) from the Phase 1/2 dose-escalation trial.

As of the data cut-off on July 16, 2018, the ORR across the 12 patients was 92% (11/12 patients), including 9 patients (82%) with a complete response with or without hematologic recovery (CR/CRi), 1 patient (9%) who reached morphologic leukemia-free status, and 1 (9%) partial response (PR). The median duration on study as of data cut-off was 6.9 months, ranging from 2 to 14.4 months, with 7 patients still on study. Five patients (42%) achieved MRD negativity as measured by flow cytometry. Translational data demonstrated that cusatuzumab monotherapy and in combination with AZA

significantly reduced leukemic stem cells in the bone marrow of AML patients. Cusatuzumab continued to be well-tolerated in AML patients across the different doses. More details can be found here.

Cusatuzumab in Cutaneous T-cell Lymphoma

argenx also announced today updated results from its non-randomized, open-label, multicenter Phase 1/2 trial of cusatuzumab in 27 patients with cutaneous T-cell lymphoma (CTCL). More details can be found here.

argenx announced in May 2018 that it is no longer devoting resources to the development of cusatuzumab in CTCL in order to focus on the drug candidate’s potential in AML.

About Cusatuzumab

Cusatuzumab (ARGX-110) is an investigational SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. Cusatuzumab is designed to: block CD70, kill cancer cells expressing CD70 through complement dependent cytotoxicity, enhanced antibody-dependent cell-mediated phagocytosis and enhanced antibody-dependent cell-mediated cytotoxicity, and restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). Cusatuzumab is currently being evaluated in patients with hematological malignancies, including a Phase 1/2 trial in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) and the Phase 2 part of a Phase 1/2 trial in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Preclinical work on cusatuzumab in AML was performed in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won, together with Prof. Manz at the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

On November 1, 2018 In conjunction with DURECT Corporation’s (Nasdaq: DRRX) reported third quarter 2018 financial results press release, you are invited to listen to a conference call that will be broadcast live over the internet on Wednesday, November 7, 2018 at 4:30 pm Eastern Time (1:30 pm Pacific Time) (Press release, DURECT, NOV 1, 2018, http://investors.durect.com/phoenix.zhtml?c=121590&p=irol-newsArticle&ID=2374981 [SID1234530663]).

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A live audio webcast of the presentation will be available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section.

On November 1, 2018 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that nine abstracts from its complement research and development program have been accepted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, December 1 to 4, 2018 (Press release, Alexion, NOV 1, 2018, View Source [SID1234530490]). Key data will include both new analyses and previously announced results from the two Phase 3 studies of ALXN1210, the Company’s investigational long-acting C5 complement inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH), in addition to further data on Soliris (eculizumab) for the treatment of PNH and atypical hemolytic uremic syndrome (aHUS). Collectively, the breadth of the data to be presented at ASH (Free ASH Whitepaper) demonstrates continued progress extending the company’s leadership in understanding and treating rare complement-mediated diseases.

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The accepted abstracts are listed below and are now available on the ASH (Free ASH Whitepaper) website.

ALXN1210

A Phase 3 Study of Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria Naive to Complement Inhibitors: Results of a Subgroup Analysis with Patients Stratified by Baseline Hemolysis Level, Transfusion History, and Demographics. Abstract ID#: 110623 – Oral Presentation, December 3, 2018, 11:00-11:15 a.m. PST, Grand Hall C.

Results from a Phase 3, Multicenter, Non-Inferiority Study of Ravulizumab (ALXN1210) Versus Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Currently Treated with Eculizumab. Abstract ID#: 119147 – Oral Presentation, December 3, 10:30-10:45 a.m. PST, Grand Hall C.

Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria: Pharmacokinetics and Pharmacodynamics Observed in Two Phase 3 Randomized, Multicenter Studies. Abstract ID#: 110858 – Oral Presentation, December 3, 10:45-11:00 a.m. PST, Grand Hall C.

A Prospective Analysis of Breakthrough Hemolysis in 2 Phase 3 Randomized Studies of Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria. Abstract ID#: 110874 – Poster Presentation, December 2, 6:00-8:00 p.m. PST, Hall GH.

Soliris (eculizumab)

Efficacy of Eculizumab in Pediatric Patients with Paroxysmal Nocturnal Hemoglobinuria in the International PNH Registry. Abstract ID#: 111306 – Poster Presentation, December 3, 6:00-8:00 p.m. PST, Hall GH.

Economic Benefit of Early In-hospital Diagnosis and Treatment Initiation of Eculizumab in aHUS. Abstract ID#: 112893 – Poster Presentation, December 2, 6:00-8:00 p.m. PST, Hall GH.

PNH

Prognostic Value of Clone Size in Paroxysmal Nocturnal Hemoglobinuria (PNH) for Thrombotic Events in Untreated Patients in the International PNH Registry. Abstract ID#: 111324 – Poster Presentation, December 1, 6:15-8:15 p.m. PST, Hall GH.

Baseline Characteristics of Patients with Paroxysmal Nocturnal Hemoglobinuria Identified in the Department of Defense Database. Abstract ID#: 113478 – online.

The Value of Population Based Data to Study Rare Diseases: An Example Using the Department of Defense Healthcare System. Abstract ID#: 113497 – online.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating, and potentially life-threatening ultra-rare blood disorder that can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,2,3 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.2 In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis (the destruction of red blood cells)4, which in turn can result in progressive anemia, fatigue, dark urine, and shortness of breath.5,6,7 The most devastating consequence of chronic hemolysis is thrombosis (the formation of blood clots), which can damage vital organs and cause premature death.8 Historically, it had been estimated that one in three patients with PNH did not survive more than five years from the time of diagnosis.2 PNH is more common among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).9,10,11 In certain patients with thrombosis of unknown origin, PNH may be an underlying cause.4

About ALXN1210

ALXN1210 is an innovative, investigational, long-acting C5 inhibitor discovered and developed by Alexion that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). In Phase 3 clinical studies in complement inhibitor-naïve patients with PNH, and patients with PNH who had been stable on Soliris, intravenous treatment with ALXN1210 every eight weeks demonstrated non-inferiority to intravenous treatment with Soliris every two weeks, with numeric results for all primary and key secondary endpoints favoring ALXN1210. ALXN1210 is also currently being evaluated in a Phase 3 clinical study in complement inhibitor-naïve patients with aHUS, administered intravenously every eight weeks. In addition, Alexion plans to initiate a Phase 3 clinical study of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS.

ALXN1210 has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, and Japan, and for the subcutaneous treatment of patients with aHUS in the U.S.

About Soliris (eculizumab)

Soliris is a first-in-class complement inhibitor that works by inhibiting the C5 protein in the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in severe rare and ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Soliris is approved in the U.S., EU, Japan, and other countries as the first and only treatment for patients with PNH and aHUS, in the EU as the first and only treatment of refractory generalized MG (gMG) in adults who are anti-AchR antibody-positive, in the U.S. for the treatment of adult patients with gMG who are anti-AchR antibody-positive, and in Japan for the treatment of patients with gMG who are AChR antibody-positive and whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis (PLEX). Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).

Soliris has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, Japan, and many other countries, for the treatment of patients with aHUS in the U.S., EU, and many other countries, for the treatment of patients with MG in the U.S. and EU, for the treatment of patients with refractory gMG in Japan, and for the treatment of patients with neuromyelitis optica spectrum disorder (NMOSD) in the U.S., EU, and Japan. Alexion and Soliris have received some of the pharmaceutical industry’s highest honors for the medical innovation in complement inhibition: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

For more information on Soliris, please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection, available at www.soliris.net.

Important Soliris Safety Information

The U.S. prescribing information for Soliris includes the following warnings and precautions: Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current Centers for Disease Control (CDC)’s Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with meningococcal vaccines at least two weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions.

In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis, back pain, and nausea. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia. In patients with gMG who are anti-AchR antibody-positive, the most frequently reported adverse reaction observed with Soliris treatment in the placebo-controlled clinical study (≥10%) was musculoskeletal pain.

On November 1, 2018 Clinical Genomics, a leading innovator of tests for colorectal cancer, and Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported a 5-year extension to their U.S. supply agreement for the InSure ONE fecal immunochemical test (FIT) (Press release, Clinical Genomics, NOV 1, 2018, View Source [SID1234530506]). This agreement builds upon a long standing collaboration to provide InSure FIT and the new InSure ONE FIT for colorectal cancer screening programs.

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Clinical Genomics manufactures FIT tests, including InSure ONE, which Quest provides to physicians and organized provider groups across the United States. These provider groups include specialized programs to improve screening adherence rates for Accountable Care Organizations (ACOs) and other organizations focused on improving quality metrics under value-based care models. Quest is also an investor in the company. Under the agreement, Quest will continue to offer broad access to both the Insure FIT and Insure ONE FIT products in the U.S.

"We are pleased to continue this important partnership with Quest Diagnostics ensuring that screening programs have broad access to InSure ONE, an easy to use FIT that may lead to improved patient compliance," says Betsy Hanna, Chief Commercial Officer, Clinical Genomics.

"Barriers to screening often delay or prevent early diagnosis," said Kristie Dolan, General Manager, Oncology, Quest Diagnostics. "Insure ONE FIT helps overcome several of these screening barriers to prompt earlier screening. Our collaboration with Clinical Genomics will ensure that patients and providers in the U.S. continue to have broad access to the innovative Insure FIT and the new InSure ONE FIT."

InSure ONE is an FDA 510(k) cleared FIT for detecting blood in stool as an aid in the detection of lower gastrointestinal bleeding. A number of medical conditions may be associated with lower gastrointestinal bleeding, including colorectal cancer, iron deficiency anemia, diverticulitis, ulcerative colitis, polyps, and adenomas.

Unlike other FIT’s, InSure ONE is the only test that is performed using toilet water collected from a single bowel movement. InSure ONE employs a patented brush sampling method which has been preferred by many doctors and patients for more than 15 years. A water sample is collected from the toilet bowel by simply brushing the surface of the stool to release any blood into the surrounding water, rather than having to collect a stool sample or smear feces.

Annual FIT is recommended by the American Cancer Society (ACS) for screening programs to detect the early signs of adenomatous polyps, precursors to cancer, and colorectal cancer. Recently, the ACS updated its recommendations lowering the screening age from 50 to 45 years. FIT, along with colonoscopy, is also recommended as a ‘Tier 1’ preferred test for colorectal cancer screening programs by the U.S. Multi-Society Task Force (MSTF). When considering large, organized colorectal cancer screening programs, the U.S. MSTF also recognizes that given the annual nature of FIT and the performance characteristics of this assay in identifying blood in the stool, FIT is "more effective and less costly" than the use every 3 years of FIT-fecal DNA, approved by FDA specifically for use in colorectal cancer screening.1

Colorectal cancer is the second leading cause of cancer death in the United States, with more than 140,000 people per year expected to be diagnosed with the disease and an estimated 50,000 who will die from it. According to U.S. Preventative Service Task Force recommendations, screening for colorectal cancer in adults who are 50 to 75 years old and at average risk reduces colorectal cancer mortality. Many people, however, are not screened according to guidelines, and studies show aversion to colonoscopy and other methods may factor into decisions not to screen. The disease is often highly treatable when caught in early stages.

Rex DK, et.al. U.S. MSTF Consensus Guideline, Gastroenterology 2017; 153:307-323

On November 1, 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 positive progress in the Phase 1 clinical trial of its immuno-stimulating STAT3 inhibitor, WP1066, with initial results showing bioavailability of the drug in patients (Press release, Moleculin, NOV 1, 2018, View Source [SID1234530522]).

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"Although this data is preliminary, it represents a significant milestone for the development of WP1066," commented Dr. Donald Picker, Moleculin’s Chief Science Officer. "In the first two cohorts of the Phase 1 study, we are already seeing measurable levels of the drug in the patient’s plasma resulting from oral administration. Knowing we can deliver drug this way opens the door for further development and expanded clinical activity."

Walter Klemp, Moleculin’s Chairman and CEO added, "We believe WP1066 is a first-in-class compound capable of stimulating a natural immune response in animal models while directly attacking tumors by modulating transcriptional activity and repressing what we call ‘oncogenic transcription factors.’ Chief among these is STAT3, considered a master regulator of tumor progression. While activity in animal models has been very promising, one of the goals of this trial was to determine the potential for bioavailability in humans. The initial positive indications of this clinical trial increase our confidence that WP1066 has the potential to become an important drug in the treatment of certain cancers. The initial demonstration of human bioavilability is an important milestone."