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Patent Infringement Lawsuit Filed Against Genmab and Janssen in the United States Regarding DARZALEX®

On April 4, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that Morphosys apparently has filed a complaint at the US District Court of Delaware against Genmab and Genmab’s collaboration partner Janssen Biotech, Inc. for patent infringement under US patent no. 8,263,746 based on activities relating to manufacture, use and sale of DARZALEX (daratumumab) in the United States. The US patent relates to CD38 antibodies defined by functional features (Press release, Genmab, APR 4, 2016, View Source [SID:1234510380]).

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DARZALEX is approved in the US for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent and a marketing application has been submitted in the EU for daratumumab for use in patients with relapsed and refractory multiple myeloma by Janssen.

Janssen will in consultation with Genmab determine the appropriate action in response to the complaint.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,1,2 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,1,2 antibody-dependent cellular phagocytosis3,4 and antibody-dependent cellular cytotoxicity.1,2 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) both of which express CD38. These reductions in MDSCs and Tregs were paralleled by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.1

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma.

CytRx Global Pivotal Phase 3 Clinical Trial with Aldoxorubicin Achieves 191 Target Events Triggering Statistical Data Analysis

On April 4, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has reached the target number of progression events in its pivotal, global phase 3 clinical trial with aldoxorubicin as a treatment for patients with second-line soft tissue sarcomas (Press release, CytRx, APR 4, 2016, View Source [SID:1234510371]).

In accordance with the statistical analysis plan which is incorporated in the Special Protocol Assessment (SPA) granted by the FDA, 191 events were required to trigger the analysis of the primary endpoint of progression-free survival (PFS). The events were reviewed and verified by an independent, blinded radiology organization contracted by CytRx to analyze all of the scans for the Phase 3 pivotal clinical trial.

"Reaching the number of events is an important milestone for the aldoxorubicin Phase 3 trial," said Daniel Levitt, M.D., Ph.D., CytRx’s EVP and Chief Medical Officer. "Now we, along with our contract research organization, are in the process of collecting, verifying and analyzing all of the trial data from the 79 sites around the globe. While this is a large undertaking, we expect to have top-line results at the end of this quarter. We are continuing to actively treat and follow patients who have not progressed and are analyzing data to determine the overall survival and safety."

"Aldoxorubicin represents an important new drug for treating patients with advanced soft tissue sarcomas," commented Sant Chawla, M.D., F.R.A.C.P., Principal Investigator and the Director of the Sarcoma Oncology Center in Santa Monica, California. "The Phase 3 trial design is unique in that it is the first trial in soft tissue sarcoma to compare a single agent to five of the most commonly used treatment options. Like many in the sarcoma community, I eagerly look forward to the top-line results with aldoxorubicin."

CytRx plans to discuss with the FDA initiating a rolling New Drug Application by the end of 2016, subject to the outcome of the Phase 3 pivotal trial. Pursuant to FDA approval, CytRx expects to launch aldoxorubicin in the United States as a treatment for patients with second-line soft tissue sarcoma in the second half of 2017.

Phase 3 Trial Design

The multicenter, randomized, open-label pivotal Phase 3 clinical trial enrolled 433 late-stage patients with metastatic, locally advanced or unresectable soft tissue sarcomas who have either not responded to, or who have progressed following treatment with one or more systemic regimens of nonadjuvant chemotherapies. Trial patients were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel. The primary endpoint of the study is PFS and will be calculated after 191 events occur. Secondary endpoints include overall survival, response rates and safety. In January 2014, CytRx announced that it received approval from the FDA to amend the Phase 3 protocol to continue dosing patients with aldoxorubicin until disease progression as defined by RECIST 1.1 criteria. The ability to dose until disease progression creates the potential for substantially improved Phase 3 efficacy results.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue, and can arise anywhere in the body at any age. According to the American Cancer Society, there are approximately 50 types of soft tissue sarcomas. In 2013 more than 11,400 new cases were diagnosed in the U.S. and approximately 4,400 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.

About CytRx Corporation

Curis Announces Publication of CUDC-907 Phase 1 Clinical Trial Data in Lancet Oncology

On April 04, 2016 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported the publication of results from the dose escalation part of the Phase 1 clinical trial in the journal Lancet Oncology (Press release, Curis, APR 4, 2016, View Source [SID:1234510370]).

The publication, titled "Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial" was authored by the clinical investigators of the first-in-man Phase 1 study as well as members of Curis’ clinical and scientific teams. The publication is also accompanied by an independent commentary in the journal titled "Dual inhibition of oncogenic targets for B-cell malignancies" by Paul G. Richardson, M.D., R.J. Corman Professor of Medicine at the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute.

"The data from the Phase 1 monotherapy trial for CUDC-907, especially in heavily pretreated patients with relapsed/ refractory DLBCL are very encouraging and we look forward to data emerging from the current Phase 2 trial in patients with MYC-altered DLBCL," said Dr. Anas Younes, M.D., Chief of the Lymphoma Service of the Memorial Sloan Kettering Cancer Center in New York City, the Principal Investigator of the Phase 1 trial and the publication’s senior author.

Based on the clinical activity observed in patients with relapsed/ refractory-DLBCL, particularly those with cancers harboring MYC alterations, Curis has initiated a Phase 2 trial to evaluate CUDC-907 in patients with MYC-altered RR-DLBCL. Additional details of the Phase 2 trial can be found at www.clinicaltrials.gov (study identifier: NCT02674750)

About CUDC-907:

CUDC-907 is an oral, dual inhibitor of Class I and II HDAC, as well as Class I PI3K enzymes. Specifically, CUDC-907 is designed to inhibit HDACs 1, 2, 3, 6 and 10 and PI3K-alpha, delta and beta isoforms. CUDC-907 is being investigated in clinical studies in patients with lymphomas and advanced solid tumors. The development of CUDC-907 has been supported in part by The Leukemia & Lymphoma Society (LLS) under a funding agreement established in 2011 between Curis and LLS’s Therapy Acceleration Program.

Cancer Metabolism Company Metabomed Completes $18 Million Series A Financing

On April 4, 2016 Israeli cancer metabolism company Metabomed LTD. reported that it has completed an extension of its Series A round from current and new investors, bringing the total of its raise to $ 18 million (Press release, Metabomed, APR 4, 2016, View Source [SID:1234510367]). Existing investors include MS Ventures, Boehringer Ingelheim Venture Fund (BIVF), Pontifax Fund, and the Technion Research and Development Foundation. New investors Pfizer Inc. (NYSE: PFE) and Arkin Holdings also joined the round. The final transaction is subject to the successful completion of the approval process by the Israel Antitrust Authority.

Metabomed was co-founded by MS Ventures and three leading researchers in the field of cancer metabolism and computational biology — Prof. Eyal Gottlieb from the Beatson Institute for Cancer Research in Glasgow, UK, Prof. Eytan Ruppin from Tel Aviv University and the University of Maryland, and Prof. Tomer Shlomi from the Technion Israel Institute of Technology.

Metabomed is focusing on the discovery and development of potential small molecule drugs directed against novel targets in the field of cancer metabolism. Based on its proprietary interdisciplinary target identification platform, Metabomed utilizes a unique approach to discovery, which allows the company to potentially identify new targets that form a synthetic lethal gene pair with metabolic genes inactivated in cancer cells. By inhibiting these targets, Metabomed intends to develop more selective anti-cancer drugs that may potentially be highly targeted, and therefore sparing of normal cells.

Metabomed operates out of the state-of-the-art facilities at the MS Ventures Israel BioIncubator, which has supported the development of the new start-up with its infrastructure and a wide range of incubation services. Following the completion of this round, Simone Botti, current Head of the MS Ventures Israel BioIncubator, will leave his position in order to join Metabomed as its full-time CEO.

Simone Botti commented: "This Series A extension is a major success for Metabomed.. We believe that the vote of confidence from the existing syndicate and the addition of new top tier investors such as Pfizer and Arkin Holdings confirm the excitement around Metabomed and its technology, and I am very honored to have been chosen to lead the company as its CEO."

"We are proud to work with companies such as Metabomed that are exploring exciting and innovative technologies that may help lead to potential new treatment options in the field of oncology," said Robert Abraham, Ph.D., Senior Vice President and Head of Pfizer’s Oncology-Rinat Research & Development Group, who will also become a member of Metabomed’s scientific advisory board. "Metabomed shares in our mission to deliver safer and more effective medicines to our patients."

The Influence of Disease Severity of Preceding Clinical Cases on Pathologists’ Medical Decision Making.

Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance haematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified, but in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular circuitry that underpins the self-renewal of human HSCs will facilitate the development of targeted strategies that expand HSCs for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs, the post-transcriptional mechanisms that guide HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we show that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood HSPCs. Our study gives mechanistic insight into RNA networks controlled by RNA-binding proteins that underlie self-renewal and provides evidence that manipulating such networks ex vivo can enhance the regenerative potential of human HSCs.