On April 17, 2018 Seres Therapeutics, Inc. (NASDAQ:MCRB) reported that new preclinical data supporting the development of microbiome therapeutics for immuno-oncology (leveraging gut microbiota to impact tumor immunotherapy)1 will be presented today by Sceneay et al in the late breaking poster session at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper) in Chicago (Press release, Seres Therapeutics, APR 17, 2018, View Source [SID1234530893]). The data presented provide new insights on the potential mechanism by which Seres’ microbiome therapies could improve the outcomes of cancer patients treated with immune checkpoint inhibitors.

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"The data presented at AACR (Free AACR Whitepaper) provide important new models and mechanistic insights that inform our planned development efforts to evaluate the ability of microbiome therapy to augment immune checkpoint inhibitors," said David Cook, Ph.D., Chief Scientific Officer and Executive Vice President of Research at Seres. "The insights described in this presentation will guide the continued development of SER-401, which we expect to enter clinical development later this year. Our objective is to use our microbiome therapeutic approach to improve the efficacy of immunotherapy in patients with life-threatening cancers."

Seres presented results from preclinical studies designed to evaluate the impact of various consortia of bacterial species on the anti-tumor immune response in murine models following treatment with an anti-PD-1 checkpoint inhibitor. Results demonstrated that both germ-free mice lacking a microbiome and antibiotics-treated mice with a dysbiotic microbiome, failed to mount an effective anti-tumor response following treatment with an anti-PD-1 checkpoint inhibitor. The response to anti-PD-1 was restored in germ-free as well as antibiotics-treated mice by introducing a diverse microbiome, and was driven by increased entry of tumor-infiltrating lymphocytes into the tumor; specifically, CD8+ T effector cells. Current pre-clinical efforts are focused on optimizing specific microbiome compositions based on functional and phylogenetic information to inform the development of therapeutic candidates.

Seres is developing SER-401, a preclinical stage oral microbiome therapy comprising a consortium of live bacteria to improve the efficacy and safety of immunotherapy. Through a collaboration with The University of Texas MD Anderson Cancer Center and the Parker Institute for Cancer Immunotherapy, Seres plans to initiate a clinical study in patients with advanced metastatic melanoma later this year. In a 2017 study published in Science, the MD Anderson research team, led by Dr. Jennifer Wargo, described a microbiome signature associated with response to checkpoint inhibitor therapy. A planned clinical trial will evaluate the impact of an anti-PD-1 checkpoint inhibitor with adjunctive microbiome therapy on patient outcomes.

On April 17, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported that it will present data today from its Phase 1 trial for AB928, its dual adenosine receptor antagonist, in healthy volunteers in a poster presentation titled "Clinical Pharmacokinetic-Pharmacodynamic Relationship for AB928, a Dual Antagonist of the A2aR and A2bR Adenosine Receptors," at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Arcus Biosciences, APR 17, 2018, View Source [SID1234525418]).

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"We are extremely encouraged by the results from our ongoing Phase 1 trial of AB928. The compound has been shown to be safe and well tolerated at all doses evaluated and achieves near complete inhibition of A2aR adenosine receptor activation in blood samples from healthy volunteers," said Terry Rosen, Ph.D., Chief Executive Officer at Arcus. "Importantly, we achieved this level of inhibition under conditions that we believe are representative of the large concentrations of adenosine found in the tumor microenvironment. These results have informed the selection of the starting dose for our clinical trials of AB928 in combination with other anti-cancer agents, and we look forward to starting these trials shortly."

Design of the Phase 1 Trial for AB928 in Healthy Volunteers
The Phase 1 double-blinded, placebo-controlled trial has enrolled 85 healthy volunteers. The trial includes a single-ascending-dose (SAD) portion as well as a multiple-ascending-dose (MAD) portion. In the SAD portion, single doses of 10, 25, 75 and 150 mg and a twice-daily dose of 100 mg have been evaluated. In the MAD portion, doses of 10, 25, 75 and 150 mg QD and 200 mg QD (with food) have been administered to subjects for four consecutive days. In each dosing cohort, 6 subjects received AB928 and 2 subjects received placebo, and dosing in the trial has been completed. Investigators remain blinded regarding subject assignment to the AB928 or placebo arms.
The objective of this trial is to assess the safety, tolerability, pharmacokinetics and pharmacodynamic profile of AB928 and to inform our selection of the starting dose of AB928 for our combination trials in cancer patients.

Summary of the Results Presented
All doses have been safe and well tolerated, and no safety events prevented escalation to higher doses. To assess the pharmacodynamic effects of AB928, blood samples were taken from subjects at different time points following the administration of AB928 or placebo. As of the cut-off date (COD) of March 30, 2018 for the poster presentation, samples from all dosing cohorts, with the exception of the 200 mg QD (with food) MAD cohort, have been evaluated to assess the pharmacodynamic effects of AB928. These samples were treated with NECA (a synthetic analogue of adenosine), which activates A2aR receptors on T cells. The ability of AB928 to block A2aR receptors on T cells was quantified by measuring the levels of pCREB, which is a marker for activation of the A2aR receptor.
When blood samples from the 150 mg MAD cohort were incubated with 5 µM NECA, AB928 achieved complete inhibition of pCREB activation at two hours post-dosing and approximately 90% mean inhibition of pCREB activation at 24 hours post-dosing on day 4. As experiments conducted in vitro by Arcus have demonstrated that NECA is at least 20 times more potent than adenosine at inducing pCREB activation in blood T cells, stimulation with 5 µM NECA should be comparable to stimulation with adenosine concentrations in excess of 100 µM.
The pharmacokinetic profile of AB928 supports once-daily dosing, with a plasma half-life that exceeds 20 hours.
Complete results from this trial, including pharmacodynamic data for the 200 mg BID (with food) dosing cohort, will be released following the unblinding of data in mid-2018.

AB928 Clinical Development Plans
The results from this healthy volunteer trial demonstrate that a safe and well tolerated dose of AB928 can provide near complete inhibition of A2aR receptor activation. Based on these results, Arcus is preparing to initiate clinical trials to evaluate AB928 in combination with three different chemotherapy regimens and in combination with AB122, its PD-1 antibody, in cancer patients. Regulatory submissions to start these trials are underway.
These trials will include a dose-escalation portion to identify the recommended dose of AB928 for each combination regimen. Based on the safety profile of AB928, the initial dose of AB928 for the dose-escalation portion should achieve close to complete inhibition of A2aR receptor activation. Once the recommended dose has been selected, AB928 will be evaluated in 11 expansion cohorts. Each expansion cohort will evaluate the AB928 + chemotherapy combination and/or the AB928 + AB122 combination in one of the following tumor types: non-small cell lung cancer, renal cell carcinoma, gastroesophageal cancer, colorectal cancer, ovarian cancer and triple negative breast cancer. In both the dose escalation portion and expansion cohorts, Arcus will conduct significant biomarker analysis, which will inform patient selection in future trials. Arcus plans to report data from the dose-escalation portion of these trials in the first half of 2019

On April 17, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company presented a positive update on its two ongoing clinical trials of VAL-083, a first-in-class small molecule chemotherapeutic, for the treatment of MGMT-unmethylated Glioblastoma Multiforme ("GBM") at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting (Press release, DelMar Pharmaceuticals, APR 17, 2018, View Source [SID1234525438]).

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"We are pleased with the continued progress of our ongoing clinical trials with VAL-083 as a potential treatment for MGMT-unmethylated GBM," said Saiid Zarrabian, interim president and chief executive officer. "These trials are important elements of our clinical development strategy to advance VAL-083 as a potential treatment for GBM patients who have little or no viable alternatives."
DelMar presented the following updates in two poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting.
1. A biomarker-driven, Phase 2 clinical trial of VAL-083 in patients with MGMT-unmethylated bevacizumab (Avastin)-naïve recurrent glioblastoma, currently being conducted in collaboration with the University of Texas MD Anderson Cancer Center.

Up to 48 patients with MGMT-unmethylated, bevacizumab-naïve, recurrent GBM, will be enrolled to determine if treatment with VAL-083 improves overall survival compared to historical reference control.
22 of a planned 48 patients have been enrolled as of March 31, 2018, compared to 15 patients enrolled as of October 31, 2017.

7 of the 22 enrolled patients (32%) have exhibited stable disease as best response.
Similar to prior clinical experience, myelosuppression has been the most common adverse event observed.
2. A Phase 1-2 clinical trial of VAL-083 in combination with radiotherapy in patients with newly diagnosed MGMT-unmethylated GBM, currently being conducted in collaboration with Sun Yat-sen University Cancer Center.
Up to 30 patients with newly diagnosed MGMT-unmethylated GBM will be treated with VAL-083 combined with radiotherapy by 24 weeks of VAL-083 maintenance therapy. The study is being conducted in two parts: (1) Dose-confirmation: VAL-083 in cohorts (20, 30 and 40 mg/m2/day IV) to assess safety and activity when administered concurrently with x-ray telescope ("XRT") to confirm the maximum tolerated dose ("MTD"), and (2) Expansion: VAL-083 will be studied in up to 20 additional patients at the target dose of 40mg/m2 VAL-083 administered concurrently with XRT.

Dose-confirmation studying 20 and 30 mg/m2/day cycles has been completed (4 patients enrolled).
No dose-limiting toxicities have been reported following treatment with multiple cycles of VAL-083.
The next patient enrolled will receive the study target dose of 40 mg/m2/day VAL-083 combined with radiation.
DelMar’s poster presentations can be viewed on the company’s website at:
View Source

About VAL-083
VAL-083 (dianhydrogalactitol) is a "first-in-class," DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute ("NCI"). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at:
View Source.
VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On April 17, 2018 ArQule, Inc. (NASDAQ:ARQL) reported that it has entered into an exclusive license agreement with Basilea Pharmaceutica International Limited(Basilea, SIX: BSLN) to develop and commercialize derazantinib, a pan-FGFR (fibroblast growth factor receptor) inhibitor in the US, EU, Japan and rest of the world excluding the People’s Republic of China, Hong Kong, Macau and Taiwan, where Sinovant Sciences Ltd., a Roivant Sciences Ltd. subsidiary, has rights to develop and exclusively commercialize the drug (Press release, ArQule, APR 17, 2018, View Source [SID1234525419]).

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Under the terms of the agreement, ArQule will receive an upfront payment of $10 million and is eligible for up to $326 million in regulatory and commercial milestones. ArQule is also entitled to receive staggered single-digit to double-digit royalties on net sales upon commercialization. Basilea will be responsible for all costs and expenses of development, manufacture and commercialization in its territory. Under certain circumstances, ArQule may have the opportunity to promote derazantinib in the US directly.
ArQule is currently conducting a registrational trial for derazantinib in the United States, Canada and Europe as a potential treatment for intrahepatic cholangiocarcinoma (iCCA), a form of biliary tract cancer. As part of the exclusive license agreement, Basilea intends to continue this trial and the further development of derazantinib in iCCA and other tumor types with FGFR dysregulation.

Ronald Scott, Chief Executive Officer of Basilea, said: "We are very excited about this partnership with ArQule. Derazantinib is an ideal match for our existing clinical oncology portfolio. It is a targeted therapy building on a solid biomarker approach in an area where patients currently have limited treatment options. This transaction underscores our continued commitment to expand our R&D portfolio with novel compounds focused on overcoming the clinical problem of resistance in oncology and infectious diseases. Our clinical oncology portfolio now includes three drug candidates in different stages of development. We continue to focus on further broadening our R&D portfolio through internal and external innovation."

"Partnering with Basilea, a company with global drug development experience and expertise, will propel the advancement of derazantinib in ways we could not have achieved independently," said Paolo Pucci, Chief Executive Officer of ArQule. "Basilea will bring a wealth of skills to the expansion of the derazantinib development plan at a time when it will benefit most from these resources, allowing it to reach its full potential in iCCA and beyond."
ArQule will hold a conference call to discuss this agreement tomorrow, April 18, beginning at 9 a.m. EDT. Paolo Pucci, Chief Executive Officer of ArQule, will lead the call. As a result of entering into the exclusive license agreement, ArQule will be updating its financial guidance on the call.

The details of the call are as follows:
Wednesday, April 18, 2018 at 9:00 AM EDT
Audio connection numbers:
US: 1 877-868-1831
Outside US: 1 914-495-8595 PIN: 4089669
A replay of the call will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations." The ArQule investor conference call will be archived and can be accessed in the "Investors and Media" section of ArQule’s website, www.arqule.com, under "Events and Presentations."
About Derazantinib
Derazantinib is a potent, orally administered inhibitor of the fibroblast growth factor receptor (FGFR) family, a key driver of cell proliferation, differentiation, and migration. In a Phase 1/2 study in patients with iCCA harboring FGFR2 gene fusions, treatment with derazantinib resulted in an objective response rate of 21%, nearly 3 times higher than standard-of-care chemotherapy. ArQule is currently conducting a registrational study with derazantinib in patients with FGFR2 fusion-positive second-line iCCA. The open-label single-arm trial is recruiting in the United States, Canada and Europe with objective response rate as the primary endpoint. More information on that program is available here.
About Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC).1 Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. iCCA is an aggressive cancer, with a median 5-year survival rate of 15% for patients diagnosed with early-stage disease.2 In China, the incidence of cholangiocarcinoma is more than 7 cases per 100,000 people, and the majority of cases are intrahepatic.3

On April 17, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that worldwide net sales of DARZALEX (daratumumab) as reported by Johnson & Johnson were USD 432 million in the first quarter of 2018 (Press release, Genmab, APR 17, 2018, View Source [SID1234525439]). Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

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About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a 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. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. 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. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL and selected solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.. Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a 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. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. 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. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL and selected solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.