On Decmber 13, 2017 Stemline Therapeutics presented 2017 ASH (Free ASH Whitepaper) Conference Presentation (Presentation, Stemline Therapeutics, DEC 13, 2017, View Source [SID1234522636]).

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On December 13, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported positive topline results from a pivotal Phase 2 clinical study of cemiplimab in 82 patients with advanced cutaneous squamous cell carcinoma (CSCC), the second deadliest skin cancer after melanoma (Press release, Regeneron, DEC 13, 2017, View Source [SID1234522608]). Cemiplimab, an investigational human antibody targeting PD-1 (programmed cell death protein 1), demonstrated an overall response rate (ORR) of 46.3%, as determined by independent review. The median duration of response (DOR) had not yet been reached at the data cut-off point (32 of 38 responses are ongoing). At the time of this analysis, all patients had a minimum follow up of 6 months. The safety profile in the study was generally consistent with approved anti-PD-1 agents.

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These pivotal data will form the basis of a rolling Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA), which has been initiated and is expected to be completed in the first quarter of 2018. A rolling BLA submission allows for portions of the regulatory application to be submitted to the FDA as they are completed. A submission to the European Medicines Agency (EMA) is also expected to be completed in the first quarter of 2018. These data confirm the positive Phase 1 clinical trial expansion cohort results reported at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which led to a Breakthrough Therapy Designation for cemiplimab in advanced CSCC in September 2017.

"For patients with CSCC that cannot be cured by surgery or radiation, there are no FDA-approved treatment options, and advanced CSCC is responsible for 3,900 to 8,800 deaths per year in the U.S.," said Israel Lowy, MD, PhD, Vice President of Global Clinical Development and Head of Translational Science and Clinical Oncology, Regeneron. "This is the largest prospective study ever conducted in this disease, and we are pleased that many patients were able to achieve deep and durable responses with cemiplimab monotherapy. The high and durable response rates seen in this study are particularly notable given that the study enrolled patients regardless of biomarker status."

The efficacy data reported today include results from 82 patients in the Phase 2 EMPOWER-CSCC 1 study. Approximately two-thirds of patients had progressed after prior systemic chemotherapy or radiation.

"EMPOWER-CSCC 1 was initiated in 2016 and has enrolled rapidly, underscoring the serious unmet need in advanced CSCC," said Elias Zerhouni, MD, President, Global R&D, Sanofi. "We look forward to working with regulatory agencies globally to bring this important therapy to advanced CSCC patients as quickly as possible. We continue to rapidly advance a broad development program to evaluate cemiplimab both as monotherapy and combination across a number of solid tumor and blood cancers."

EMPOWER-CSCC 1 is a single-arm, open-label clinical trial and remains active. Enrollment is complete in the study arm of patients with metastatic CSCC receiving a 3 mg/kg dose of cemiplimab every two weeks. Enrollment continues in the remaining two study arms of patients with metastatic CSCC receiving a 350 mg flat dose of cemiplimab every three weeks and patients with locally advanced and unresectable CSCC receiving a 3 mg/kg dose of cemiplimab every two weeks.

Updated results from both the EMPOWER-CSCC 1 and the Phase 1 clinical trial will be submitted for presentation at a 2018 medical congress.

Cemiplimab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, and was invented by Regeneron using the company’s proprietary VelocImmune technology that yields optimized fully-human antibodies. Cemiplimab is currently under clinical development, and its safety and efficacy has not been fully evaluated by any regulatory authority.

About Cutaneous Squamous Cell Carcinoma (CSCC)
CSCC is the second most common type of skin cancer in the United States. Although CSCC has a good prognosis when caught early, it can prove especially difficult to treat when it progresses to advanced stages. Patients at this stage can be disfigured due to multiple surgeries to remove CSCC tumors on the head, neck and other parts of the body. CSCC is the second deadliest skin cancer after melanoma and is responsible for the most deaths among non-melanoma skin cancer patients.

On December 13, 2017 Eleven Biotherapeutics, Inc. (NASDAQ:EBIO), a late-stage clinical oncology company advancing novel product candidates based on its Targeted Protein Therapeutics (TPTs) platform, reported that Dr. Gregory Adams, Chief Scientific Officer, will chair a session focused on antibody drug conjugates and fusion proteins at the Antibody Engineering and Therapeutics Meeting in San Diego, CA (Press release, Eleven Biotherapeutics, DEC 13, 2017, View Source [SID1234522620]). As part of the session, Dr. Adams will give a talk on the potential for tumor-targeted payloads to prime the immune system to facilitate more effective therapy in combination with immuno-oncology agents, including checkpoint inhibitors.

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"Checkpoint inhibitors are a significant step forward in the quest to engage the patient’s immune system in the fight against cancer. Checkpoint inhibitors function by blocking the signals that cancers use to inhibit the immune system. However, for checkpoint inhibitors to be effective, they require the presence of an active immune response against the cancer. There is broad recognition of the potential for tumor-targeted payloads, such as Eleven’s Targeted Protein Therapeutics (TPTs), to provide this spark to the immune system and act synergistically with checkpoint inhibitors," said Dr. Gregory Adams, Chief Scientific Officer of Eleven Biotherapeutics. "Earlier this year at the American Association of Cancer Research Conference, we presented data which supports this potential, demonstrating that TPTs induce immunogenic cell death as evidenced by the presence of damage-associated molecular patterns. Our collaboration with the National Cancer Institute and AstraZeneca aims to build on this evidence."

Session Details

Title: Antibody-Drug Conjugates & Fusion Proteins
Date: Wednesday, December 13, 2017
Time: 8:10 am – 12:00 pm PT
Location: Manchester Grand Hyatt; San Diego, CA

About Vicinium

Vicinium is manufactured as a single protein anti-epithelial cell adhesion molecule (anti-EpCAM) fusion protein fused with Pseudomonas Exotoxin A (ETA) designed to specifically target and deliver a potent anti-cancer payload directly into tumor cells. It is constructed with a stable, genetically-engineered linker to ensure its potent protein payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues thereby improving the compound’s safety. Vicinium’s one-step manufacturing process offers significant cost advantages and results in the production of a homogenous product, with less batch-to-batch variability than most antibody drug conjugates. Vicinium is currently in a Phase 3 registration clinical trial for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC) in patients who have previously received two courses of Bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Eleven Biotherapeutics intends to enroll 134 subjects in the trial, including 77 subjects with carcinoma in situ (CIS), at over 70 centers in the United States and Canada. Primary and secondary endpoints include complete response (CR) in CIS subjects, time to disease recurrence and event free survival. The Company expects to complete patient enrollment in the first quarter of 2018 and to report topline three-month data in mid-2018.

On December 13, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel therapeutics for difficult to treat cancers, reported detailed data from its SL-401 pivotal trial in BPDCN, as well as results from other ongoing trials in additional indications, at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held in Atlanta, GA (Press release, Stemline Therapeutics, DEC 13, 2017, View Source [SID1234522625]). Presentations are available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.

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SL-401: Pivotal Trial in BPDCN – Primary endpoint met; Median overall survival (OS) not reached in first-line patients; BLA submission preparation underway

We believe the SL-401 pivotal trial in BPDCN is the largest multicenter prospective study ever conducted in this indication. The trial enrolled 45 BPDCN patients (32 first-line, 13 relapsed/refractory) and consisted of 3 Stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion), and Stage 3 (pivotal, confirmatory)

Key outcomes in Stages 1, 2, and 3 (ASH ’17 data)
– Across all 3 stages, 42 patients received SL-401 at 12 ug/kg/day
– In first-line BPDCN, SL-401 (12 ug/kg/day)
– 90% (26/29) overall response rate (ORR)
– 72% (21/29) rate of CR + CRc + CRi (complete response + clinical CR [CR with residual skin abnormality] + CR with incomplete bone marrow recovery)
– 45% (13/29) of patients were bridged to stem cell transplant (SCT)
– In relapsed/refractory BPDCN, SL-401 (12 ug/kg/day)
– 69% (9/13) ORR
– 38% (5/13) CR + CRc + CRi rate; 1 patient bridged to SCT
– Median overall survival (OS) not reached in first-line BPDCN (Stages 1-2, and 3), SL-401 (12 ug/kg/day)
– 71% 12-month OS in Stages 1 and 2; follow-up ongoing for 12-month OS in Stage 3
– Most common treatment-related adverse events (TRAEs) were: alanine aminotransferase increase (52%), aspartate aminotransferase increase (50%), hypoalbuminemia (50%), and thrombocytopenia (38%). TRAEs included capillary leak syndrome (19%), which was grade 5 in 2.4% (1/42) of BPDCN patients at 12 ug/kg/day, 2.6% (4/153) of all patients across all trials at all doses, and 1.7% (2/119) of patients across all trials at 12 ug/kg/day

Stage 3 pivotal cohort (first-line, 12 ug/kg/day)
– Met its primary endpoint with a 54% (7/13) CR + CRc rate (95% CI: 25.1, 80.8)
– The lower bound of the 95% confidence interval (CI) exceeded the pre-specified rate of 10%
– 77% (10/13) ORR
– 46% (6/13) of patients bridged to SCT

Next steps for BPDCN
– A BLA submission is in preparation
SL-401: Phase 1/2 Trial in myeloproliferative neoplasms (MPN): chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF)

Key outcomes (ASH ’17 data)
– SL-401 Phase 1/2 trial consists of a Stage 1 (lead-in, dose escalation) and Stage 2 (expansion); has enrolled 24 patients
– No dose limiting toxicities (DLT) were identified and a maximum tolerated dose (MTD) was not reached. Most common TRAEs include hypoalbuminemia (33%), thrombocytopenia (33%), and fatigue (29%). Most common TRAEs (grade 3 or higher), include thrombocytopenia (24%) and anemia (19%)
– Durable CR (14+ months) in CMML patient
– 65% (11/17 evaluable) of CMML and MF patients had spleen reductions >25% (range 29% to 100%)
– Durable SD in 4 patients (2 CMML, 2 MF) for 5+ to 8+ months. Three ongoing SD patients enrolled with baseline platelet counts <100,000, including 1 patient platelet count <50,000 are on treatment

Next Steps in MPN
– Continue enrollment and patient follow-up
– Favorable tolerability and preliminary signs of activity support both single agent and combination development strategies, including JAK-inhibitors and hypomethylating agents
SL-401: Phase 1/2 Trial in Acute Myeloid Leukemia (AML) in CR with Minimal Residual Disease (MRD)

Key outcomes (ASH ’17 data)
– SL-401 Phase 1/2 trial consists of Stage 1 (lead-in, dose escalation) and Stage 2 (expansion); has enrolled 16 patients
– No DLTs or MTD identified in Stage 1; Most common TRAEs (Stage 1 and 2) include hypoalbuminemia (44%), ALT increase (38%), AST increase (38%), and thrombocytopenia (38%). Most common TRAEs, grade 3+, include ALT increase (31%), AST increase (25%), and thrombocytopenia (19%). 2 cases (13%) of grade 3 CLS were noted
– Five patients, including one who went to SCT at 3+ months, were relapse-free for at least 5+ months (range 5+ to 14+), including 2 ongoing (8+ months [on SL-401] and 14+ months [SCT])

Next Steps for AML/MRD
– Patients enrolling and being followed for MRD alterations and response duration
– Given preclinical data indicating potential synergies between SL-401 and azacitidine in AML and high-risk MDS, and that a clinical trial is underway assessing that combination in AML, a transition to combination therapy in this indication is under active consideration
Ivan Bergstein, M.D., CEO of Stemline, commented "The remarkable data presented at ASH (Free ASH Whitepaper) from our pivotal trial with SL-401 in BPDCN sets the stage for our upcoming BLA submission and a successful 2018. In conjunction with these efforts, we kicked off our BPDCN disease awareness campaign at ASH (Free ASH Whitepaper), which includes outreach to hematologist-oncologists, dermatologists, and pathologists, including highlighting the BPDCN diagnostic signature triad of CD123, CD4 and CD56 (an easy to remember: 1, 2, 3, 4, 5, 6). We believe this endeavor is critical for the proper and timely diagnosis of BPDCN, a historically underappreciated and underdiagnosed malignancy. Additionally, we and our investigators believe SL-401 is beginning to demonstrate encouraging signs of clinical activity in indications beyond BPDCN, including CMML and MPN, as presented at ASH (Free ASH Whitepaper)."

On December 13, 2017 The Medicines Company (NASDAQ:MDCO) reported that it will host an Investor Day on Tuesday, January 23, 2018, from 10:00 a.m. to 12:30 p.m., Eastern Time, in New York City (Press release, Medicines Company, DEC 13, 2017, View Source [SID1234522626]).

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The event will be led by Fred Eshelman, Pharm.D., Executive Chairman of The Medicines Company, and Clive Meanwell, M.D., Ph.D., Chief Executive Officer of the Company, who will be joined by members of the Company’s management team and outside experts and key members of the ORION coalition, including:

Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and founding Chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group;
John J.P. Kastelein, M.D., Ph.D., Professor of Medicine and Chairman of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam; and
Marc S. Sabatine M.D., M.P.H., Lewis Dexter, M.D., Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, Professor of Medicine at Harvard Medical School and Chairman of the TIMI Study Group.
Presentations and panel discussions will focus on inclisiran, its highly-differentiated value proposition and clinical and non-clinical development, manufacturing, regulatory and pre-commercial projects, as well as on the continuing, unmet medical and market needs in atherosclerotic cardiovascular disease.

The event will be broadcast live via webcast. To access the live webcast and view the accompanying slide presentation, visit the "Investors – Events/Presentations" section of The Medicines Company website at least 15 minutes before the event is scheduled to begin to register and download or install any necessary software. In addition to the webcast, the event can be accessed, in listen-only mode, as follows:

U.S./Canada: (877) 359-9508
International: (224) 357-2393
Conference ID: 60380330
A replay of the webcast will be archived and available after the event for a limited period of time.

The in-person event is reserved for financial analysts and institutional investors and is by invitation only.