On May 9, 2017 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer, reported financial results for the first quarter ended March 31, 2017 and provided a review of business and clinical highlights (Press release, Xencor, MAY 9, 2017, View Source [SID1234519088]).

"We have been focused on advancing our clinical development pipeline across the breadth of our portfolio," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "Today, we are pleased to announce data from our Phase 1 trial of subcutaneously administered XmAb5871, which support use of this formulation as a simpler, more flexible treatment option for patients and doctors. We look forward to further advancing our XmAb5871 program in the months ahead, with topline data from our ongoing Phase 2 study in IgG4-Related Disease and additional clarity on the clinical and regulatory path forward expected this year. Also in the quarter, we initiated our Phase 1 study of XmAb13676 in non-Hodgkin lymphoma and chronic lymphocytic leukemia, and continued to enroll patients in our Phase 1 study of XmAb14045 in acute myeloid leukemia."

Recent Business Highlights and Anticipated Upcoming Milestones

XmAb5871: XmAb5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain, and uses Xencor’s XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. XmAb5871 is currently in Phase 2 clinical studies for the treatment of IgG4-Related Disease (IgG4-RD) and systemic lupus erythematosus (SLE).

· Topline data from IgG4-RD Phase 2 trial expected in 2017
· Initial data from SLE Phase 2 trial expected in late 2018/early 2019

Xencor recently completed its subcutaneous (SC) administration Phase 1 study of XmAb5871. Multiple dose SC administration of XmAb5871 was safe and well tolerated at doses of 125 to 375 mg in all 40 subjects administered SC XmAb5871. Treatment emergent adverse events (TEAEs) occurring in subjects receiving any dose of SC XmAb5871 were mild in severity. The only drug-related TEAE occurring in more than two subjects who received any dose of SC XmAb5871 was injection site bruising (three subjects, 8%). No subject receiving SC XmAb5871 discontinued the study due to an adverse event and there were no serious adverse events during the study. Pharmacokinetic and bioavailability data from the study support an every other week dosing schedule. Based on these results, Xencor plans to implement SC administration in newly-initiated clinical trials.

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At the 3rd International Symposium on IgG4-Related Disease and Fibrosis in February 2017, investigators from Xencor’s ongoing Phase 2 study of XmAb5871 in IgG4-RD presented an update on IgG4-RD biomarker development, including flow cytometry methods for measuring circulating B cells, plasmablasts and CD4-positive cytotoxic T lymphocytes. The presentation also included preliminary flow cytometry data for patients enrolled in the ongoing Phase 2 study, which showed a partial reduction in B cells, consistent with previous clinical experience, and a rapid reduction of circulating plasmablasts following treatment with XmAb5871. No significant apoptosis of B cells or CD4 T cells was induced by XmAb5871 therapy.

XmAb7195: XmAb7195 is a first-in-class monoclonal antibody that targets IgE with its variable domain and uses Xencor’s XmAb Immune Inhibitor Fc domain to target FcγRIIb, resulting in three distinct mechanisms of action for reducing IgE levels. A subcutaneously administered formulation of XmAb7195 is currently in a Phase 1b study for the treatment of allergic disease.

· Topline data from subcutaneous administration Phase 1b trial expected in 2017

Bispecific Oncology Pipeline: Xencor’s initial bispecific antibody programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T cells for highly potent and targeted killing of malignant cells. Their XmAb Fc domains confer long circulating half-lives, stability and ease of manufacture. XmAb14045 is currently in a Phase 1 study for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies, and XmAb13676 is currently in a Phase 1 study for the treatment of B-cell malignancies.

· Initial data from XmAb14045 Phase 1 trial expected in 2017, pending alignment on timing with Novartis
· Initial data from XmAb13676 Phase 1 trial expected in 2018, pending alignment on timing with Novartis
· Investigational New Drug (IND) application filing for XmAb18087, a somatostatin receptor 2 (SSTR2) x CD3 bispecific antibody for the treatment of neuroendocrine tumors, expected in 2017
· IND application filing for XmAb20717, a PD-1 x CTLA-4 dual checkpoint inhibitor for the treatment of multiple oncology indications, expected in 2018

At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2017 Annual Meeting in April, Xencor presented preclinical data supporting the development of XmAb18087 for the treatment of SSTR2+ cancers, including neuroendocrine tumors and small cell lung cancer (SCLC). In in vitro and mouse models, XmAb18087 eliminated SSTR2+ tumor cells by stimulating redirected T cell-mediated cytotoxicity, and in cynomolgus monkeys, XmAb18087 stimulated SSTR2-dependent T cell activation, T cell margination and cytokine release. Xencor also presented preclinical data on additional bispecific antibodies deploying its XmAb bispecific and half-life extension technology, highlighting a bispecific antibody targeting PD-1 and an undisclosed co-stimulatory receptor (PD1 x costim) and IL15/IL15Rα heterodimeric Fc-fusions.

Partnered XmAb Programs: Nine pharmaceutical companies and the National Institutes of Health are advancing novel drug candidates either discovered at Xencor or that rely on Xencor’s proprietary XmAb technology. Seven such programs are currently undergoing clinical testing.

· In March 2017, Xencor was notified by its partner, CSL Limited, that CSL licensee Janssen Biotech Inc. advanced CSL362 (now called talacotuzumab) to the Phase 3 portion of its ongoing Phase 2/3 study for the potential treatment of patients with AML. Talacotuzumab uses Xencor’s XmAb Cytotoxic Fc Domain. The trial initiation triggered a milestone payment to Xencor from CSL Limited of $3.5 million.

Corporate:

· In April 2017, Xencor announced the appointment of Kevin Gorman, Ph.D., to its Board of Directors. In March and April 2017, respectively, Xencor also announced that Bruce Carter, Ph.D., and Robert Baltera will not stand for re-election to the Board of Directors at the 2017 Annual Meeting of Stockholders.

First Quarter Ended March 31, 2017 Financial Results

Cash, cash equivalents, and marketable securities totaled $392.7 million as of March 31, 2017, compared to $403.5 million on December 31, 2016. The decrease reflects net spending on operations in the first quarter of 2017.

Revenues for the first quarter ended March 31, 2017 were $4.3 million, compared to $7.3 million in the same period of 2016. Decreased revenue for the first quarter of 2017 over revenue for the same period in 2016 is primarily the result of revenue earned from our Amgen collaboration in the first quarter of 2016 compared to milestone revenue received from CSL in the first quarter of 2017.

Research and development expenditures for the first quarter ended March 31, 2017 were $15.0 million, compared to $10.0 million for the same period in 2016. Increased research and development spending in the first quarter of 2017 over the same period in 2016 reflects increased spending on our bispecific pipeline of candidates including our first two clinical candidates, XmAb14045 and XmAb13676 and development spending on the next two candidates, XmAb18087 and XmAb20717.

General and administrative expenses in the first quarter ended March 31, 2017 were $4.8 million, compared to $4.0 million for the same period in 2016. Increased spending on general and administration in the first quarter of 2017 over the comparable period in 2016 reflects increases in stock based compensation charges in 2017.

Non-cash, share based compensation expense for the first quarter ended March 31, 2017 was $3.2 million, compared to $2.0 million for the same period in 2016.

Net loss for the first quarter ended March 31, 2017 was $14.6 million, or $(0.31) on a fully diluted per share basis, compared to a net loss of $6.4 million, or ($0.16) on a fully diluted per share basis, for the same period in 2016. The increased loss for the first quarter ended March 31, 2017 compared to 2016 is primarily due to lower revenue of $2.9 million and increased spending of $5.9 million in the first quarter of 2017 compared to the first quarter of 2016.

The weighted-average shares outstanding used to compute net loss per share was 46,598,797 for the quarter ended March 31, 2017, compared to 40,626,729 for the quarter ended March 31, 2016.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations beyond the end of 2020. Xencor expects to end 2017 with approximately $340 million in cash, cash equivalents, and marketable securities.

On May 10, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that atezolizumab did not meet its primary endpoint of statistically meaningful improvement in overall survival (OS) compared to chemotherapy in the phase III IMvigor211 study in patients with locally advanced or metastatic urotherial carcinoma (mUC) whose disease progressed during or following a platinum-containing chemotherapy (Press release, Chugai, MAY 10, 2017, View Source [SID1234518961]). The safety profile of atezolizumab in this study was consistent with those observed in previous studies, with no new or unexpected adverse events. The results observed in people treated with atezolizumab in IMvigor 211 were generally consistent with those observed in a similar group of people in the Phase II IMvigor 210 study. However, the chemotherapy arm results were better than study design assumptions. The data of the study will be presented in the future.

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"The previous studies showed atezolizumab helped people with locally advanced or mUC. We were hopeful that we could show a similar result in this study," said Dr. Yasushi Ito, Senior Vice President and Head of the Project Life Cycle Management Unit. "We will be working together with Roche to better understand the results and determine the next steps."

About the IMvigor211 Study
The global phase III, multi-centre, open label, randomized controlled study designed to evaluate the safety and the efficacy of atezolizumab compared to chemotherapy* (vinflunine, paclitaxel or docetaxel) in patients with locally advanced or mUC whose disease progressed during or following platinum-containing regimen.
・ The primary endpoint of this study is OS.
・ Secondary endpoints include safety, overall response rate, progression free survival, and duration of response.
931 patients were randomized into groups with a one to one ratio to receive either one of the chemotherapies vinflunine (320 mg/m2) / paclitaxel (175 mg/m2) / docetaxel (75 mg/m2) or atezolizumab (1,200 mg) by intravenous injection once every three weeks. Treatment with atezolizumab was continued as long as the principal investigator determined that the patient was receiving a clinical benefit or until an unacceptable adverse event was confirmed.

* As paclitaxel and docetaxel are not approved for the indication of UC in Japan, reimbursement of the use of two drugs for the treatment of UC is officially allowed by the Ministry of Health, Labour, and Welfare. Vinflunine is not approved in Japan.

About atezolizumab
Atezolizumab is a monoclonal antibody designed to target a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 binds to PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this coupling, atezolizumab releases the suppression of T cells and promotes T cells to attack tumour cells.
Atezolizumab (overseas brand name: Tecentriq) is the anti-PD-L1 immune checkpoint inhibitor and was granted accelerated approval for the second line treatment of locally advanced or mUC by the FDA in May, 2016. The FDA also granted accelerated approval for atezolizumab as the treatment of metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy in October, 2016 and as the first line treatment of locally advanced or mUC who are ineligible for cisplatin chemotherapy in April, 2017. In Japan, the new drug application of atezolizumab for the treatment of unresectable advanced or recurrent NSCLC was filed in February, 2017.

Scynexis has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Scynexis, 2017, MAY 8, 2017, View Source [SID1234521707]).

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Novavax has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On May 8, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a highly potent pan-FLT3/BTK inhibitor, exerts compelling activity against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3 and eradicates AML tumors in a murine xenograft model (Press release, Aptose Biosciences, MAY 8, 2017, View Source;p=RssLanding&cat=news&id=2270752 [SID1234518895]). The data were presented in a poster on Sunday, May 7, 2017 at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, held May 6-9 in Boston, MA.

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The poster, entitled CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3, demonstrated the superior potency of CG’806, relative to competitive agents, against hematologic malignancy cell lines driven by various WT or mutant forms of FLT3. In addition, once daily oral dosing of CG’806 in a murine model achieved sustained micromolar plasma concentration over a 24hr period, and was accompanied by complete elimination of AML FLT3-ITD tumors in the absence of toxicity.
Results were presented by Weiguo Zhang, M.D., Ph.D., Assistant Professor of Leukemia at The University of Texas MD Anderson Cancer Center, for a research team led by Michael Andreeff, M.D., Ph.D., Professor of Leukemia.

"Given the potency of CG’806 against all of the mutant forms of FLT3 AML and the ability to eradicate AML tumors in murine xenograft models, CG’806 has demonstrated the potential to be superior to other FLT3 inhibitors and is beginning to differentiate itself as a targeted treatment for AML," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "We believe CG’806 has the potential to become the best-in-class FLT3 inhibitor, and our internal efforts now are focused on delivering CG’806 to AML patients as soon as practicable."

CG’806 and competitor FLT3 inhibitors were tested for potency to kill a series of isogenic cells, in which a specific form (WT or mutant) of FLT3 drove survival and proliferation of cells. Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with the ITD mutation, D835 mutations, the ITD plus F691I/Y842D/D835 mutations, or in FLT3 wild-type cells. The IC50s were 0.17, 0.82, 9.49, 0.30, 8.26, 9.72, and 0.43 nM for human FLT3-ITD mutated AML cells MV4-11 (FLT3-ITD) and MOLM13 (FLT3-ITD), murine leukemia Ba/F3 (FLT3-WT), Ba/F3 (FLT3-ITD), Ba/F3 (FLT3-D835Y), Ba/F3 (FLT3-ITD+D835Y), and Ba/F3 (FLT3-ITD+F691L) cells, respectively. CG’806 triggered profound apoptosis in cell lines harboring FLT3-ITD mutations and suppressed FLT3 and its downstream MAPK/AKT signaling. Moreover, CG’806 demonstrated in vivo tumor eradication without toxicity when administered orally, once daily for 14 days as a single agent in the MV4-11 AML murine xenograft model, and demonstrated sustained micromolar plasma drug levels in mice after a single oral administration.

The presentation will be published in the AACR (Free AACR Whitepaper) Hematologic Malignancies Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG’806
CG ‘806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.