On March 28, 2019 Imbrium Therapeutics L.P., a clinical-stage biopharmaceutical company and operating subsidiary of Purdue Pharma L.P., in conjunction with Mundipharma EDO GmbH, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to its investigational drug tinostamustine, a potentially first-in-class alkylating deacetylase inhibiting molecule being studied in early phase clinical trials, for the treatment of T-cell prolymphocytic leukemia (T-PLL) (Press release, Imbrium Therapeutics, MAR 28, 2019, View Source [SID1234534719]).

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T-PLL is an extremely rare and aggressive T-cell leukemia that is characterized by out of control growth of mature T-cells. There are very limited effective treatment options for T-PLL. The disease typically progresses rapidly and does not respond well to standard multi-agent chemotherapy.

"This orphan drug designation represents an important step not just for Imbrium and the development of tinostamustine, but also for the patients suffering from T-PLL who do not currently have sufficient treatment options," said Richard Fanelli, PhD, head of Regulatory Affairs, Imbrium Therapeutics.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug designation is intended to facilitate drug development for rare diseases and may provide certain incentives to drug developers.1,2 T-PLL is an extremely rare and typically aggressive blood cancer. It is so rare that healthcare professionals may only see one case of T-PLL every five to 10 years.3 Due to its rarity, T-PLL can be misdiagnosed, resulting in poor patient outcomes with a median survival of around one year. 3,4 There is no guarantee that tinostamustine, an investigational agent, will successfully complete clinical development or gain FDA approval.

Craig Landau, MD, president and CEO, Purdue Pharma L.P. added, "This marks the second orphan drug designation we have received from the U.S. FDA in just the last two months and demonstrates our commitment to rapidly advancing our pipeline of oncology chemotherapeutics for rare and difficult to treat cancers."

In addition to T-PLL, Imbrium Therapeutics has initiated the early phase clinical development of tinostamustine in a range of rare and difficult-to-treat blood cancers and advanced solid tumors.

About T-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia (T-PLL) affects approximately 2 percent of all patients with mature lymphocytic leukemias.5 It is characterized by the out of control growth of mature T-cells (T-lymphocytes). T-cells are a type of white blood cell that protects the body from infections.6 The majority of patients present with hepatosplenomegaly and generalized lymphadenopathy, with skin infiltration, anemia and thrombocytopenia often seen.5 T-PLL affects older adults with a median age at diagnosis of 61 years, and it is more common in men than in women.6

T-PLL typically has rapid progression and does not respond well to standard multi-agent chemotherapy.

About tinostamustine
Tinostamustine (EDO-S101), is a novel multi-action therapy in Phase 2 clinical development for a range of rare and difficult-to-treat blood cancers and advanced solid tumors.

Preclinical studies have shown that tinostamustine has the potential to improve access to the DNA strands within cancer cells, break them, and counteract damage repair.7,8,9,10 The preclinical data also suggest that these complementary and simultaneous modes of action have the potential to overcome resistance toward some other cancer treatments.7,8,9,10

Tinostamustine is currently being studied in multiple myeloma, Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, T-cell prolymphocytic leukemia, soft tissue sarcoma, small cell lung cancer, triple-negative breast cancer, ovarian cancer, endometrial cancer and MGMT-unmethylated glioblastoma.

On March 28, 2019 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported the initiation of CONTESSA TRIO, a multi-cohort, multicenter, Phase 2 study of tesetaxel, Odonate’s investigational, orally administered taxane (Press release, Odonate Therapeutics, MAR 28, 2019, View Source [SID1234534718]).

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In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic TNBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel plus either: (1) nivolumab; (2) pembrolizumab; or (3) atezolizumab. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are IO agents approved for the treatment of multiple types of cancer. One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with metastatic TNBC. The dual primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the three PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays.
In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with HER2 negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS.
"Taxane-IO combinations hold great promise for patients living with TNBC," said Sara Tolaney, M.D., M.P.H., Associate Director, Susan F. Smith Center for Women’s Cancers, Director, Clinical Trials, Breast Oncology at Dana-Farber Cancer Institute and Principal Investigator of CONTESSA TRIO. "This study will investigate the safety and antitumor activity of tesetaxel, an orally administered taxane with a distinct tolerability and pharmacokinetic profile, in combination with three approved PD-(L)1 inhibitors. CONTESSA TRIO also will investigate tesetaxel monotherapy in elderly patients with MBC, a patient population in need of easier-to-take and better tolerated therapies."

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

About CONTESSA TRIO

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (MBC). In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus either: (1) nivolumab at 360 mg by intravenous infusion on the first day of each 21-day cycle; (2) pembrolizumab at 200 mg by intravenous infusion on the first day of each 21-day cycle; or (3) atezolizumab at 1,200 mg by intravenous infusion on the first day of each 21-day cycle. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with metastatic TNBC. The dual primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the three PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays. In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with human epidermal growth factor receptor 2 (HER2) negative MBC will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Patients with central nervous system metastases are eligible for both cohorts

On March 28, 2019 Adaptive Biotechnologies and its collaborators reported that it will present 11 studies, including an oral presentation and 10 poster presentations, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, GA, March 29 – April 3 (Press release, Adaptive Biotechnologies, MAR 28, 2019, View Source [SID1234534717]).

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New data will demonstrate how immunosequencing at scale and with precision using Adaptive’s immunoSEQ Assay may be used in clinical trials to predict overall survival and response to novel immunotherapies, such as checkpoint inhibitors and cancer vaccines, in solid tumors. Other data will examine the ability of immunoSEQ to quantify and characterize the individual T cell receptors (TCR) of tumor infiltrating lymphocytes (TILs), a type of white blood cell that attacks cancer cells and controls tumor proliferation, to assist in identifying subtypes of colorectal cancer. This information may be used to help determine response to immunotherapy and patient outcomes among subtypes. Collectively the studies also demonstrate a growing use of immunoSEQ by academia and the pharmaceutical industry to help guide clinical research.

"Adaptive’s immune medicine platform is essential to helping our academic and pharmaceutical industry partners decode the information stored in our immune systems to answer translational research questions and discover new prognostic and diagnostic signals in oncology clinical trials," said Chad Robins, CEO and co-founder of Adaptive Biotechnologies. "Making this tool widely available to research partners helps us drive toward our goal of transforming medicine to improve patient lives."

Abstracts are available on AACR (Free AACR Whitepaper) website: View Source!/6812. immunoSEQ presentations of interest include:

Exploratory analysis of T cell repertoire dynamics upon systemic treatment with the oncolytic virus pelareorep in combination with pembrolizumab and chemotherapy in patients with advanced pancreatic adenocarcinoma (abstract #2272/1), poster presentation, April 1, 1:00 – 5:00 pm ET, Exhibit Hall B, Section 20
Tumor infiltrating lymphocytes, immunoSEQ, and CMS classification in the molecular epidemiology of colorectal cancer study, (abstract #2332/1), poster presentation, April 1, 1:00 – 5:00 pm ET, Exhibit Hall B, Section 23
Detection of tumor T-cell clones in mediastinal lymph nodes is associated with lower risk of tumor progression (abstract #3175/28), poster presentation, April 2, 8:00 am – 12:00 pm ET, Exhibit Hall B, Section 21
Spatially resolved immunogenomic analyses reveal diverse sub tumoral microenvironments in the context of melanoma immunotherapy (abstract #3776/9), April 2, 1:00 – 5:00 pm ET, Exhibit Hall B, Section 7
About immunoSEQ Assays

Adaptive’s immunoSEQ Assay helps researchers make discoveries in areas such as oncology, autoimmune disorders, infectious diseases and basic immunology. The immunoSEQ Assay can identify millions of T- and B-cell receptors from a single sample in exquisite detail. Offered as a Service or Kit, the immunoSEQ Assay is used to ask and answer translational research questions and discover new prognostic and diagnostic signals in clinical trials. immunoSEQ Assay provides quantitative, reproducible sequencing results along with access to powerful, easy-to-use analysis tools. The immunoSEQ Assay is for research use only and is not for use in diagnostic procedures

On March 28, 2019 Xcovery Holdings, Inc., an oncology-focused biopharmaceutical company, reported the appointment of Li Mao, M.D., as Chief Executive Officer (CEO) and Giovanni Selvaggi, M.D., as Chief Medical Officer (CMO) (Press release, Xcovery, MAR 28, 2019, View Source [SID1234534716]). With more than 50 years of clinical experience in oncology between them, Dr. Mao and Dr. Selvaggi will oversee the clinical development of ensartinib and vorolanib, Xcovery’s two leading drug candidates currently in a global Phase 3 trial for ALK positive non-small cell lung cancer (NSCLC) and in a Phase 1/2 trial in combination with immune-oncology (IO) agents for thoracic cancer, respectively.

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"Following a thorough and rigorous process, the Board has unanimously elected Li as the CEO of Xcovery," said Lieming Ding, M.D., Chairman of Xcovery’s Board of Directors. "He will bring deep expertise in oncology, unwavering commitment to patients, and strong track record of building high performing organizations to his new role. I am confident that under Li’s leadership, Xcovery will continue to expand its impact in oncology."

"I am humbled and privileged to be the CEO of Xcovery," said Dr. Mao. "This is an extraordinary company of talented people with incomparable passion and dedication to helping patients. I look forward to working with our talented team to build on what we’ve accomplished, to deliver on the promise of our innovative programs and to make a real difference for our patients."

Prior to joining Xcovery, Dr. Mao was Vice President and Head of the Johnson & Johnson China Lung Cancer Center. Before that, he acted as a Professor and Chair of Department of Oncology and Diagnostic Sciences, and Associate Dean for Research at University of Maryland, Baltimore. Dr. Mao has also served as Leader, Experimental Therapeutics Program in the Marlene and Stewart Greenebaum Cancer Center. Previously, he was a Professor in the Department of Thoracic and Head & Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, where he is currently an Adjunct Professor. Dr. Mao has played a critical role in a number of landmark multi-institution research programs, and has authored and co-authored more than 200 peer-reviewed articles cited more than 24,000 times.

"We are also pleased to welcome Giovanni to the Xcovery team as he brings broad oncology drug development expertise and strong leadership skills," Dr. Ding added. "His recent experience in spearheading the clinical development of ceritinib (Zykadia) at Novartis and leading the immunotherapy program at Bristol-Myers Squibb in thoracic malignancies will be invaluable to us as we work to not only bring ensartinib over the finish line, but also explore synergies in the ever-changing scenario of combination therapies for vorolanib."

"It is a very exciting time to be joining Xcovery as Chief Medical Officer," stated Dr. Selvaggi. "I am very encouraged by the clinical progress to date and look forward to building on this work in the ongoing and future clinical trials. Xcovery is uniquely positioned to make meaningful impact on oncology with ensartinib having the potential to be the best in class in first line therapy for ALK positive NSCLC patients, and vorolanib being tested in various combination trials with anti PD-1 agents. I look forward to working with my colleagues to advance our programs and to help cancer patients to live longer and better lives."

Dr. Selvaggi held positions of increasing responsibility at various global pharmaceutical companies prior to joining Xcovery. He joined the pharmaceutical industry in 2010 as a medical director at GlaxoSmithKline in the MAGE-A3 cancer vaccine lung program. He then played an instrumental role in the successful development and registration of ceritinib (Zykadia) at Novartis in ALK translocated NSCLC. Most recently, Dr. Selvaggi was a part of the immunotherapy team at Bristol-Myers Squibb as Program Lead in different thoracic malignancies with a focus on SCLC. Dr. Selvaggi received his medical degree at the University of Torino Medical School in 1992 and served as staff physician of Thoracic Oncology at the University Hospital in Torino, Italy, participating in several clinical trials in lung cancer and mesothelioma over a span of 16 years.

On March 28, 2019 Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage pharmaceutical company, reported that the European Medicines Agency (EMA) has granted a meeting with the Company’s European subsidiary, IPIX Pharma Ltd., to discuss a briefing package submitted for Scientific Advice regarding the clinical development program of Brilacidin oral rinse to decrease the incidence of Severe Oral Mucositis (SOM) in Head and Neck Cancer (HNC) patients receiving chemoradiation (Press release, Innovation Pharmaceuticals, MAR 28, 2019, View Source [SID1234534715]).

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The purpose of such meetings is for the EMA to provide guidance on the appropriate tests and studies in the development program for a medicine. Receiving formal scientific advice helps ensure health authority alignment regarding appropriate testing to support an eventual marketing-authorization application in Europe.

The meeting with IPIX Pharma has been scheduled by EMA for mid-April 2019 and will serve to complement the regulatory feedback and advice obtained by the Company from the already completed End-of-Phase 2 Meeting held with the U.S. Food and Drug Administration (FDA). At this meeting, an acceptable Phase 3 development pathway was agreed upon by the FDA and the Company to advance Brilacidin for the prevention of SOM in HNC.

"We are extremely pleased to have been granted this scientific meeting with the EMA, particularly in such rapid fashion," commented Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "New and effective treatments that not only help mitigate, but actually prevent the occurrence of oral mucositis, have been long sought-after. Currently there is no approved drug to decrease the incidence of Severe Oral Mucositis in Head and Neck Cancer. We look forward to advancing Brilacidin toward potential regulatory approval, both in Europe and the United States, as we refine key aspects of our planned Phase 3 program in oral mucositis."

About Brilacidin Phase 2 Results in Treating Severe Oral Mucositis

The Company’s Brilacidin oral rinse demonstrated a strong therapeutic benefit in patients receiving an aggressive chemotherapy regimen (cisplatin administered 80-100 mg/m2, every 21 days), which currently is the standard of care. In this patient population, the incidence of SOM was reduced to 25.0% in the modified Intent-to-Treat (mITT) population, versus 71.4% of patients on placebo. In the Per Protocol (PP) patient group, incidence of SOM dropped to 14.3% for patients receiving Brilacidin-OM, compared to 72.7% among those receiving placebo.

The completed Phase 2 study met its primary endpoint, showing a reduction of SOM incidence versus placebo, as well as beneficial treatment effects in reducing the duration of SOM and in delaying the onset of SOM.

Linked below is information, published in a blog on the Company’s website, elaborating on how Brilacidin is positioned compared to other investigational Oral Mucositis drugs currently in clinical development.

View Source
About Brilacidin and Severe Oral Mucositis

There currently are no FDA-approved drugs to decrease the incidence of Severe OM (SOM) (WHO Grade ≥ 3) in Head and Neck Cancer (HNC) patients receiving chemoradiation. The additional expenses incurred by patients suffering from SOM are estimated to be as high as $18,000 to $25,000 per case in the U.S. when hospitalization is required. These factors contribute to SOM qualifying as an area of significant unmet medical need. According to published statistics, the number of new annual HNC cases in the U.S. is estimated to be 65,000, and on a worldwide basis, ~750,000 cases. Between 60 and 70 percent of these HNC patients typically will develop SOM, with the overall incidence of HNC patients developing some grade of OM (WHO Grades 1 to 4) approaching 100 percent. Because it cannot be predicted which patients will develop SOM, a preventative treatment, such as Brilacidin oral rinse, would begin in all patients as soon as starting chemoradiation and continue until its completion (typically a seven-week course). Given Brilacidin is administered as a convenient oral rinse, with plans to package it in an easily transportable sachet form, the Company believes it would be attractive both to doctors and patients—likely translating to widespread and rapid market adoption should Brilacidin oral rinse gain regulatory approval.