On December 3, 2018 Amgen (NASDAQ:AMGN) reported that it will present at the Citi Global Healthcare Conference at 12:35 p.m. ET on Thursday, Dec. 6, 2018, in New York City (Press release, Amgen, DEC 3, 2018, View Source;p=RssLanding&cat=news&id=2379134 [SID1234531860]). Elliott M. Levy, M.D., senior vice president of Global Development at Amgen, will present at the conference. Live audio of the presentation can be accessed from the Events Calendar on Amgen’s website, www.amgen.com, under Investors. A replay of the webcast will also be available on Amgen’s website for at least 90 days following the event

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On December 3, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) (Press release, Xencor, DEC 3, 2018, View Source [SID1234531893]). The data were presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Farhad Ravandi, M.D., Professor of Medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.

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Key Highlights

66 patients with relapsed/refractory AML received XmAb14045. Patients were a median of 61 years old and were heavily pretreated, having had a median of three prior therapies and 30% (n=20) with a history of allogeneic stem cell transplantation. 86% of patients (n=57) were refractory to their last therapy, and 53% (n=35) were categorized as adverse risk at diagnosis by the European LeukemiaNet (ELN 2017) system.
A maximum tolerated dose (MTD) has not been reached. Cytokine release syndrome (CRS) was the most common toxicity occurring in 55% of patients (n=36). 6% of patients (n=4) experienced Grade 3 or 4 CRS. CRS was more severe on the initial dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients (n=19).
28% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels studied (1.3 and 2.3 mcg/kg weekly; n=5/18).
Two patients with responses were bridged to stem cell transplantation, and a third transplant-ineligible patient has remained in remission for 16+ weeks after discontinuation of therapy.
"We have observed multiple complete remissions in heavily pretreated, relapsed/refractory AML patients from XmAb14045 dosed weekly, and we continue to optimize dosing regimen," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor’s XmAb technology enables bispecific antibodies to retain natural antibody properties, simplifying their use and production. Our platform enables the rapid development of new bispecific antibody drug candidates addressing a breadth of targets, and throughout 2019 we anticipate several new clinical trial initiations and additional data readouts."

The data presentation is available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event tonight from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The formal remarks will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. It will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On December 3, 2018 Shenzhen Salubris Pharmaceuticals Co. Ltd. (Salubris, SZSE: 002294) and Viracta Therapeutics, Inc. reported the initial closing of a financing, with Salubris committing $10 million as the lead investor (Press release, Viracta Therapeutics, DEC 3, 2018, View Source [SID1234534657]). New investor Virtus Inspire Ventures, as well as Viracta’s existing investors, NantKwest, Inc., Latterell Venture Partners and Forward Ventures, all participated in the financing. In addition to the financing, Salubris and Viracta have entered into an exclusive Collaboration and License Agreement to bring Viracta’s novel treatment approach for virus-associated malignancies to China.

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Viracta is advancing its innovative approach for viral-associated cancers in a Phase 1b/2 clinical trial for Epstein Barr Virus (EBV)-associated lymphomas in the US and Brazil. The approach is the first targeted, orally administered therapy for EBV-associated malignancies. It incorporates Viracta’s proprietary drug candidate, nanatinostat (VRx-3996) in combination with an antiviral as a targeted treatment to eradicate a range of viral-associated cancers. Viracta plans to initiate a clinical trial for the treatment of EBV-associated solid tumors in the coming year.

EBV-associated nasopharyngeal carcinoma is endemic in Southern China. EBV is also highly associated with the incidence and progression of other solid tumors, including gastric carcinoma, as well as NK/T cell lymphomas found throughout China. Salubris CEO, Kevin Ye highlighted, "EBV-driven cancers disproportionately impact patients in China. We look forward to partnering with Viracta to develop this new treatment option in China. The approach holds the potential to provide a valuable new treatment option for these patients, who currently still face considerable morbidity and mortality."

"We are committed to bringing our treatment approach to cancer patients around the world," commented Viracta CEO, Ivor Royston, MD. "We look forward to developing nanatinostat in collaboration with Salubris to address these major healthcare needs in China."

Under the terms of the license agreement, in addition to the equity investment made by Salubris, Viracta is eligible to receive up to $58 million in pre-commercial milestones as well as significant sales level-triggered commercial milestones and tiered royalties on sales. The Companies will collaborate for clinical development of the treatment approach for viral-associated cancers with Salubris taking on responsibility for development within the Peoples Republic of China (excluding Hong Kong, Macau and Taiwan). Viracta retains development responsibility as well as commercial rights outside of China.

On December 2, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported initial clinical data from cohorts in its ongoing Phase 2 trial evaluating SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine and with daratumumab in genomically defined patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, DEC 2, 2018, View Source [SID1234531794]). These data are being presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"AML and MDS are complex diseases, and we need therapies that can be used in combination to help patients live longer and with a better quality of life," said Rachel J. Cook, M.D., M.S., Assistant Professor of Medicine and Site Director for Acute Leukemia at the Knight Cancer Institute, Oregon Health and Science University and a clinical investigator in the Phase 2 study of SY-1425. "These data provide early clinical evidence that SY-1425 may be a meaningful treatment option for defined subsets of AML and MDS patients that is generally well-tolerated in combination with other therapies. I look forward to continuing to investigate SY-1425 to fully understand its potential to benefit patients."

"These initial combination data from our ongoing Phase 2 trial of SY-1425 are promising," said David A. Roth, M.D., Syros Chief Medical Officer. "SY-1425 in combination with azacitidine showed both a high response rate and rapid onset of clinical responses in AML patients selected with our RARA or IRF8 biomarkers that we have not seen to date in the biomarker-negative cohort. The combination was generally well-tolerated with no evidence of increased toxicities beyond what would be expected with each agent alone, including myelosuppression that can sometimes be seen when combining drugs to treat leukemia. These data speak to the combination potential of SY-1425 as well as to the potential of our platform to identify patients most likely to respond to gene control medicines. We look forward to further characterizing the clinical activity of SY-1425 in combination with azacitidine as we continue to enroll and follow patients in the trial."

SY-1425 in Combination with Azacitidine
The ongoing Phase 2 trial cohort is evaluating the safety and efficacy of SY-1425 in combination with azacitidine, a standard-of-care hypomethylating agent, in RARA or IRF8 biomarker-positive patients with newly diagnosed AML who are not suitable candidates for standard chemotherapy. The trial also includes a cohort evaluating SY-1425 in combination with azacitidine in biomarker-negative newly diagnosed, unfit AML patients, with the aim of supporting the development of a commercial companion diagnostic. Patients in these cohorts were treated with azacitidine administered at standard daily doses of 75 mg/m2 intravenously or subcutaneously for seven days, followed by SY-1425 administered at 6 mg/m2 orally divided in two daily doses for the remainder of the 28-day cycle.

As of Oct. 29, 2018, 11 biomarker-positive and eight biomarker-negative patients had been enrolled in the trial. Of the biomarker-positive patients, 10 were evaluable for safety and eight were also evaluable for clinical responses. Of the biomarker-negative patients, seven were evaluable for safety and six were also evaluable for clinical responses. The median age of the biomarker-positive patients was 76 and the median age of the biomarker-negative patients was 78, with more than half the patients in both cohorts having poor risk cytogenetics. Target enrollment in both the biomarker-positive cohort and the biomarker-negative cohort is 25, and Syros continues to enroll and follow patients.

Initial Safety Data

SY-1425 in combination with azacitidine was generally well-tolerated with no evidence of increased toxicities.
Adverse events (AEs) were consistent with what has been previously seen with SY-1425 or azacitidine as single agents in AML:
Across all grades and causalities, the most commonly reported AEs were decreased appetite (41%), fatigue (35%) and hypertriglyceridemia (35%).
The most commonly reported Grade 3 or higher AEs (all causality) were febrile neutropenia (24%), thrombocytopenia (24%), neutropenia (12%) and fatigue (12%).
Initial Clinical Activity Data

The complete response (CR) and complete response with incomplete blood count recovery (CRi) rate, as defined by Revised International Working Group (IWG) criteria, was 50% in the biomarker-positive cohort.
The overall response rate (ORR), using IWG criteria, was 63%, consisting of:
Three CRs, including one molecular CR.
One CRi.
One morphologic leukemia-free state (MLFS).
Duration of these IWG responses ranged from 29 to 337 days, with four of the five responding patients remaining on treatment as of the data cutoff.
Most of the initial responses were seen at the end of the first treatment cycle.
These data compare favorably to single-agent azacitidine, which shows response rates of 18-29% in newly diagnosed unfit AML patients1 with initial responses generally occurring after four cycles of treatment in most patients who respond2.
In the cohort of biomarker-negative patients, the ORR was 17%, with one of the six response-evaluable patients achieving a cytogenetic CR. While data from this cohort are less mature, the difference in the observed ORR supports the potential predictive value of the RARA and IRF8 biomarkers for identifying patients most likely to respond to SY-1425.
SY-1425 in Combination with Daratumumab
The ongoing Phase 2 trial is characterizing CD38 induction with SY-1425 and evaluating the safety and efficacy of SY-1425 in combination with daratumumab in a pilot cohort of 12 RARA or IRF8 biomarker-positive patients with relapsed or refractory AML or higher-risk MDS. Daratumumab is an anti-CD38 targeted therapy that is approved to treat multiple myeloma. While CD38 is normally expressed at high levels on multiple myeloma cells, AML cells have low CD38 expression. In preclinical studies, SY-1425 induced CD38 expression in AML cells, sensitizing them to treatment with daratumumab. Patients in this cohort were treated with SY-1425 as a single agent administered at 6 mg/m2 orally, divided in two daily doses, for seven days, after which daratumumab was added and administered at 16 mg/kg intravenously weekly for eight doses, then biweekly for eight doses and every four weeks thereafter.

As of Oct. 29, 2018, nine patients had been enrolled in this cohort. All nine were evaluable for safety and CD38 induction, and six were also evaluable for clinical responses. The median age of these patients was 68, with more than half having poor risk cytogenetics. Syros continues to enroll patients to complete the pilot.

Initial Safety Data

SY-1425 in combination with daratumumab was generally well-tolerated with no evidence of increased toxicities.
AEs were consistent with what has been previously seen with single-agent SY-1425 in AML and MDS patients or single-agent daratumumab in multiple myeloma patients:
Across all grades and causalities, the most commonly reported AEs were febrile neutropenia (67%), anemia (44%), nausea (44%), vomiting (44%) and infusion-related reaction (44%).
The most commonly reported Grade 3 or higher AEs (all causality) were febrile neutropenia (67%) and anemia (44%).
Initial CD38 Induction and Clinical Activity Data

Eight of the nine patients had increased CD38 expression in myeloid blast cells, with a median 1.57-fold induction as measured by mean fluorescence intensity (MFI), after seven days of treatment with SY-1425.
CD38 expression increased in only two of these patients to levels exceeding those of a multiple myeloma cell line control:
One had an MLFS response.
The other progressed without a clinical response.
The initial clinical data on both combinations presented at the ASH (Free ASH Whitepaper) meeting is now available on the Publications and Abstracts section of the Syros website at www.syros.com.

Additional details about the Phase 2 trial of SY-1425 can be found using the identifier NCT02807558 at www.clinicaltrials.gov.

On December 2, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported that updated Phase 1 data evaluating indoximod plus standard-of-care chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) were presented today by Ashkan Emadi, MD, PhD, Professor of Medicine and Associate Director for Clinical Research, University of Maryland Greenebaum Comprehensive Cancer Center, in an oral session today at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA, from 9:30AM – 11:00AM PT, in Grand Hall B, Manchester Grand Hyatt (Press release, NewLink Genetics, DEC 2, 2018, View Source [SID1234531894]).

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This Phase 1 trial evaluated the initial safety and preliminary evidence of clinical activity of adding indoximod to standard 7+3 induction and high-dose cytarabine (HiDAC) consolidation chemotherapy for adult patients with newly diagnosed AML. The presentation highlighted an initial safety profile indicating that the treatment regimen was well tolerated with adverse events commensurate with chemotherapy alone. Evidence of clinical activity was observed for indoximod plus chemotherapy in newly diagnosed AML as supported by these Phase 1 data showing post-induction minimal residual disease (MRD) negativity rate of 86% and post-HiDAC1 MRD negativity of 100%.
"These data demonstrate the promising potential for indoximod in combination therapy for patients with newly diagnosed AML and the use of MRD status as a study endpoint," said Dr. Ashkan Emadi. "We remain encouraged and look forward to additional data as this study proceeds."
Fifty-seven patients were screened, and 38 patients initiated induction therapy on protocol. Five patients never received indoximod resulting in an intent-to-treat (ITT) population of 33 patients. Twenty-two patients received the pre-specified 80% of indoximod dosing required to be included in the per protocol (PP) analysis, 8 received less than 80% of the scheduled indoximod dosage, and 3 patients remained on induction treatment as of the date of data cut off. Of these 22 PP patients, 16/22 (73%) achieved complete morphological response (CR) and 6 were primary refractory. Of the patients who achieved CR, 14 had results available from MRD testing post-induction. MRD negativity was defined by a flow cytometry assay at a level of < 0.02% (Hematologics, Inc., Seattle, WA). Of those tested, 12/14 (86%) were MRD-negative. Of the 14 patients, 1 patient proceeded to transplant, and 13 began HiDAC consolidation therapy. Post-HiDAC consolidation, all 13 patients were tested for MRD status with all 13/13 (100%) reported to be MRD-negative. When benchmarked against available published studies, these initial data appear encouraging. For a more precise comparison, a contemporaneous multi-institutional dataset is being aggregated to benchmark these data against data generated from patients undergoing the same chemotherapy regimen without the addition of indoximod using the same MRD assay assessed at the same reference laboratory.
Safety data from this Phase 1 trial indicate that the combination therapy regimen was well tolerated. No RLTs were observed when combining indoximod with standard-of-care chemotherapy. Grade 3 or greater adverse hematologic events included febrile neutropenia, anemia, and thrombocytopenia while non-hematologic events included hypoxia, anemia, and pneumonia. The overall adverse event profile observed in this small sample size is consistent with that of 7+3 induction chemotherapy plus HiDAC consolidation alone.

About AML1,2
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow in which the bone marrow makes abnormal types of white blood cells, red blood cells, or platelets. AML is the most common type of acute leukemia in adults and tends to progress rapidly without treatment. In the US, approximately 19,000 patients per year are diagnosed with AML with only around 25% expected to survive longer than three years. Of those newly diagnosed patients, approximately half are categorized as young and fit for an aggressive chemotherapy treatment regimen.
1 National Cancer Institute
2 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)

About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target, suppressing immune response and allowing for immune escape by degrading tryptophan with the resultant production of kynurenine. Indoximod reverses the immunosuppressive effects of low tryptophan and high kynurenine through mechanisms that include modulation of the AhR-driven transcription of genes that control immune function. This results in increased proliferation of effector T cells, increased differentiation into helper T cells rather than regulatory T cells, and downregulation of IDO expression in dendritic cells. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications including recurrent pediatric brain tumors, DIPG, and AML.