On April 20, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that two daratumumab abstracts have been accepted for presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, June 3 — 7 (Press release, Genmab, APR 20, 2016, View Source [SID:1234511144]). The titles of the abstracts are available on the ASCO (Free ASCO Whitepaper) website at www.asco.org via ASCO (Free ASCO Whitepaper)’s iPlanner. With the exception of the daratumumab Phase III Castor study data, which has been designated as a late breaking abstract by ASCO (Free ASCO Whitepaper), the full abstracts are scheduled to be published on the ASCO (Free ASCO Whitepaper) website on May 18 at 5:00PM EDT.

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Daratumumab Phase III Castor Study Data
Safety and efficacy data from the Phase III study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma will be presented in the Plenary Session at the ASCO (Free ASCO Whitepaper) meeting on June 5. A total of 498 patients with relapsed or refractory multiple myeloma were enrolled in the study. The study met the primary endpoint of improving progression free survival (PFS); Hazard Ratio (HR) = 0.39, p<0.0001. The median PFS for patients treated with daratumumab has not been reached, compared to median PFS of 7.2 months for patients who did not receive daratumumab.

Daratumumab showed a manageable safety profile in the study consistent with the reported safety profile of monotherapy and background bortezomib/dexamethasone therapy.

As announced on March 30, 2016 an Independent Data Monitoring Committee recommended stopping the study as the primary endpoint had been reached at the time of the pre-specified interim analysis. Patients originally assigned to the bortezomib plus dexamethasone treatment group will be offered the option of receiving daratumumab following confirmed disease progression. Patients continue to be monitored for safety and overall survival.

Abstract details: Phase 3 randomized controlled study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR study— Abstract # LBA4, Oral presentation, Sunday, June 5 at 3:10PM-3:25PM CDT

This abstract has been designated a late breaking abstract and the embargo will be lifted on Sunday, June 5 at 6:30AM CDT.
"ASCO is one of the premier medical conferences of the year and we are very pleased that highly impressive data with one of our key programs, daratumumab, will be presented again this year," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

List of Further Abstracts to Be Presented

Daratumumab
An open-label, dose-escalation Phase 1b study of subcutaneous daratumumab with recombinant human hyaluronidase in patients with relapsed or refractory multiple myeloma (PAVO) — Abstract # 333b, Trials in progress poster presentation, Monday, June 6 at 8:00AM -11.30AM CDT
The study described in this abstract is ongoing.

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) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied 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, non-Hodgkin’s lymphoma and a solid tumor indication.

On April 20, 2016 Emergent BioSolutions Inc. (NYSE:EBS) reported that it presented preclinical data on its bispecific ADAPTIRTM (modular protein technology) molecule, ES425, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, Louisiana. The ES425 molecule is being developed as a potential therapeutic for triple-negative breast cancer (TNBC) (Press release, Emergent BioSolutions, APR 20, 2016, View Source;p=RssLanding&cat=news&id=2158702 [SID:1234511142]). This product candidate was constructed using the ADAPTIR platform technology and will be further developed by Emergent’s planned spin-off company Aptevo Therapeutics.

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ES425 is a bispecific immunotherapeutic protein that redirects T-cell cytotoxicity to tumor cells expressing ROR1 (receptor tyrosine kinase-like orphan receptor 1), an oncofetal antigen expressed on TNBC and other solid tumor and hematologic malignancies.
The presentation, "Anti-ROR1 x Anti-CD3 ADAPTIRTM Molecule, ES425, Redirects T-Cell Cytotoxicity and Inhibits Tumor Growth in Preclinical Models of Triple-Negative Breast Cancer," shared results of preclinical studies examining in vitro and in vivo activity of ES425. Results showed that ES425 efficiently redirected T-cell cytotoxicity against ROR1(+) cell lines at low picomolar concentrations in vitro. T cells were activated and proliferated in response to ES425 in the presence of ROR1(+) target cells. In vivo, pharmacokinetic analysis showed inhibition of tumor growth and an improvement in overall survival in preclinical models of TNBC.

"The encouraging preclinical data demonstrate that ES425 effectively redirects T-cell cytotoxicity in preclinical TNBC models and merits investigation as a potential therapeutic in TNBC and other malignancies," said Scott C. Stromatt, M.D., chief medical officer of Emergent BioSolutions. "Effective treatment of metastatic, triple-negative breast cancer remains a highly unmet medical need and we look forward to continuing development of this molecule to enable filing an Investigational New Drug application in the next year."

About the ADAPTIR Platform

ADAPTIR bispecific proteins are modular, single chain polypeptides that are comprised of two separate binding domains, a hinge segment, and an effector domain. They have a differentiated structure from monoclonal antibodies and can generate a unique signaling response. Some ADAPTIR molecules may mediate T-cell cytotoxicity by redirecting T cells against tumor cells and some by targeted cytokine delivery. In addition, other ADAPTIR proteins may mediate complement dependent cytotoxicity and Fc dependent cytotoxicity, similar to monoclonal antibodies. ADAPTIR and any and all Emergent BioSolutions Inc. brand, product, service and feature names, logos, and slogans are trademarks or registered trademarks of Emergent BioSolutions Inc. or its subsidiaries in the United States or other countries. All rights reserved.

On April 20, 2016 Deciphera Pharmaceuticals, a clinical-stage biotechnology company focused on developing advanced kinase inhibitor treatments targeting the tumor cell and the tumor microenvironment, reported that its highly-selective small molecule CSF1R inhibitor, DCC-3014, has demonstrated highly-specific inhibition of the colony stimulating factor 1 receptor (CSFIR), a key target across many cancer indications (Press release, Deciphera Pharmaceuticals, APR 20, 2016, View Source [SID:1234511141]). In addition, DCC-3014, which was designed as a highly-specific macrophage immunomodulatory agent based on the company’s Switch Control Inhibitor platform, demonstrated significantly enhanced anti-tumor activity when used in combination with an anti-PD-1 checkpoint inhibitor in preclinical cancer models. Based on these data, which were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016, on April 20, 2016 in New Orleans, Deciphera plans to initiate a Phase 1 clinical trial with DCC-3014 in the second half of 2016.

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"DCC-3014’s robust inhibition of the CSF1R kinase, as demonstrated by these data presented at the AACR (Free AACR Whitepaper) Annual Meeting, provide encouraging evidence of its potential as a immunomodulatory agent through its action on tumor-associated macrophages (TAMs), both as a single agent and in combination with other immune checkpoint inhibitors, across a number of cancer models," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "We look forward to initiating the first-in-human Phase 1 trial with DCC-3014 later this year."

In a poster titled, "The highly specific CSF1R inhibitor DCC-3014 exhibits immunomodulatory and anti-invasive activities in cancer models," Deciphera researchers presented preclinical data demonstrating DCC-3014’s robust inhibition of CSF1R kinase, and potential utility as a macrophage immunomodulatory agent in combination with other immune checkpoint inhibitors or chemotherapeutic agents. Highlights of the data include:

DCC-3014 exhibited nanomolar potency for inhibition of CSF1R, sparing highly related kinases such as KIT, PDGFR and FLT3 by greater than 100-fold, and sparing other kinases by more than 1,000-fold.
DCC-3014 showed sustained in vivo inhibition of CSF1R, offering greater than 90% inhibition more than 24 hours after dosing, in a murine PK/PD model.
DCC-3014 demonstrated significant single agent activity and additive effects in combination with a murine anti-PD1 antibody in a murine model of colorectal cancer.
DCC-3014 blocked tumor growth, invasion and bone degradation in a prostate cancer model and exhibited optimized biopharmaceutical properties.
About DCC-3014

DCC-3014, a highly-selective small molecule colony stimulating factor 1 receptor (CSFIR), was designed as a highly-specific macrophage immunomodulatory agent based on the company’s Switch Control Inhibitor platform. In preclinical studies, DCC-3014 has demonstrated highly-specific inhibition of CSF1R, a key target across many cancer indications, as well as significantly enhanced anti-tumor activity when used in combination with an anti-PD-1 checkpoint inhibitors. Based on these data, Deciphera plans to initiate a Phase 1 clinical trial with DCC-3014 in the second half of 2016.

On April 20, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that three aldoxorubicin clinical trials have been accepted for poster presentations during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held at McCormick Place in Chicago, Illinois, from June, 3-7, 2016 (Press release, CytRx, APR 20, 2016, View Source;p=RssLanding&cat=news&id=2158694 [SID:1234511140]). The three clinical trials to be presented are:

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Title: Phase 2 study of aldoxorubicin in relapsed glioblastoma
Date/Time: June 4, 2016 1:00pm-5:00pm
Poster Session: Central Nervous System Tumors; Abstract 2027

Title: Phase 1b study of aldoxorubicin + gemcitabine in metastatic solid tumors
Date/Time: June 5, 2016 8:00am-11:30am
Poster Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics; Abstract: 2523

Title: Treatment of HIV-associated Kaposi’s sarcoma with aldoxorubicin
Date/Time: June 6, 2016 8:00am-11:30am
Poster Session: Sarcoma; Abstract: 11038

"Presenting the results from these three clinical trials at the ASCO (Free ASCO Whitepaper) Annual Meeting demonstrates the broad potential for aldoxorubicin and should raise awareness among oncologists," said Daniel Levitt, M.D., Ph.D., CytRx’s EVP and Chief Medical Officer. "Based on its unique ability to selectively bind serum albumin and preferentially release drug at the tumor site, aldoxorubicin has now shown clinical anti-cancer activity in several tumor types including our lead indication of advanced soft tissue sarcomas for which we expect top-line data in June from our pivotal Phase 3 trial."

Aldoxorubicin is CytRx’s lead anti-cancer drug candidate in clinical development utilizing its LADRTM (Linker Activated Drug Release) technology. A global, pivotal Phase 3 trial in patients with relapsed or refractory soft tissue sarcomas has fully enrolled and top-line results for the primary endpoint of progression-free survival are expected in June 2016. The trial is being conducted under a Special Protocol Assessment granted by the FDA. In addition, CytRx is conducting a randomized Phase 2b clinical trial in patients with second-line small cell lung cancer comparing aldoxorubicin topotecan. CytRx has completed enrollment of a Phase 2 trial with aldoxorubicin for patients with relapsed glioblastoma and continues to follow patients for survival. CytRx also conducted a Phase 2 trial with low doses of aldoxorubicin in patients with HIV-related Kaposi’s sarcoma. Aldoxorubicin is currently being tested in two Phase 1b trials in combination with other chemotherapies. The first trial is in combination with gemcitabine for metastatic solid tumors, and the second trial is in combination with ifosfamide as a first-line treatment for patients with soft tissue and bone sarcomas.

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.

On April 20, 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 that Curis and its collaborator, Aurigene, presented data from the following programs at the Annual Meeting of American Association of Cancer Research (AACR) (Free AACR Whitepaper) in New Orleans, LA (Press release, Curis, APR 20, 2016, View Source [SID:1234511139]).

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Curis poster presentation on CUDC-907, an oral inhibitor of histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K)

Aurigene presentation on CA-170 (previously AUPM-170), a first-in-class oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), as well as data from the PD-L1/ T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) antagonist program

Aurigene presentation on CA-4948, the lead compound from the interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor program
"Our data show significant effect of CUDC-907 on MYC levels and the compound’s antitumor activity in multiple preclinical models of MYC-altered malignancies, providing further support to the results of our Phase 1 trial where we observed objective responses in patients with DLBCL, and particularly those with MYC-altered disease," said Ali Fattaey, Ph.D., Curis’ President and CEO. "The presentations by our collaborator, Aurigene not only highlight our progress in immuno-oncology with CA-170, which we look to advance into the clinic in the first half of the year, but also Aurigene’s ability to extend the small molecule discovery capabilities to now target TIM3 in a separate program."

CUDC-907 presentation:

The Curis poster "Novel dual HDAC & PI3K inhibitor, CUDC-907, for MYC-driven malignancies" provided data on the activity of CUDC-907 in multiple MYC-altered disease models using both in vitro experiments and in vivo animal studies. Cell line and animal model studies using multiple MYC-altered DLBCL models showed that CUDC-907 had significant anti-tumor activity that correlated with the compound’s effect on downregulating MYC levels in a time and dose dependent manner. This effect was independent of disease subtypes classified using other molecular markers. CUDC-907 also showed potent anti-tumor activity in multiple cell lines of NUT midline carcinoma (NMC), a rare genetically defined tumor, which also demonstrates MYC dysregulation. CUDC-907 downregulated MYC levels in NMC cell lines and was more potent than BET inhibitors in in vitro assays of growth inhibition. The anti-tumor effects of CUDC-907 in NMC were further confirmed in a xenograft mouse model and in several MYC-amplified patient-derived xenograft models of solid tumors.

CA-170 (PD-L1/VISTA antagonist) and small molecule PD-L1/TIM-3 antagonist presentation:

The Aurigene presentation "Oral immune antagonist targeting PD-L1/VISTA or PD-L1/Tim3 for cancer therapy" provided data outlining the novel approach of identification and characterization of oral antagonists of immune checkpoint proteins. The lead IND-ready molecule, CA-170, targets PD-L1 and VISTA and has an optimized pharmacologic and safety profile required for human testing. Data from a second, independent program within the collaboration with compounds that target PD-L1 and TIM-3 immune checkpoints were also presented. In vitro studies showed that AUPM-327, a representative molecule from the PD-L1/TIM-3 program, can rescue T cell functions that are inhibited by addition of PD-L1 or TIM-3 checkpoint proteins, but does not affect other checkpoint regulators such as VISTA, CTLA4, and LAG-3, demonstrating its selectivity. Additionally, daily oral administration of the PD-L1/TIM-3 antagonist resulted in anti-tumor activity in multiple syngeneic tumor models including melanoma and colon cancer.

IRAK4 inhibitor presentation:

The Aurigene presentation "Efficacy and safety of highly selective novel IRAK4 inhibitors for treatment of ABC-DLBCL" provided a detailed profile of the pharmacologic and biologic properties of the lead molecule, CA-4948. This compound has favorable drug metabolism as well as pharmacokinetics properties and appears to have a clean in vitro toxicity profile. CA-4948 showed potent anti-tumor activity in vivo in two models of MYD88 mutant- DLBCL disease. CA-4948 also had potent anti-inflammatory effects in a rodent model of inflammation suggesting the potential use of an IRAK4 inhibitor in both cancer and inflammatory diseases.

Curis has exclusive licenses to CA-170 and CA-4948 under a collaboration agreement with Aurigene established in 2015.