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Regeneron and Sanofi Announce Positive Topline Pivotal Results for PD-1 Antibody Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma

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.

Eleven Biotherapeutics Announces Chief Scientific Officer to Chair a Session at the Antibody Engineering and Therapeutics Meeting

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.

"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.

Stemline Therapeutics Presents Detailed SL-401 Pivotal Data in BPDCN at ASH and Kicks Off its BPDCN Awareness Campaign; Updated Results From Ongoing Trials in Additional Malignancies Also Presented

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.

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)."

The Medicines Company to Host Investor Day on January 23, 2018

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]).

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.

Iovance Biotherapeutics Announces Manufacturing Decision, Provides Clinical Updates and Highlights Pipeline Expansion at Analyst Day 2017

On December 13, 2017 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that it is hosting an Analyst Day, Wednesday, December 13, 2017, beginning at 9:00am ET, in New York City (Press release, Iovance Biotherapeutics, DEC 13, 2017, View Source;p=RssLanding&cat=news&id=2322493 [SID1234522621]). During the event, the company will provide an update on its lead program in metastatic melanoma, including a presentation of updated data showing partial responses in four out of 10 patients in cohort 2 in the C-144-01 trial. The company will also review its two additional company-sponsored trials in recurrent, metastatic, or persistent cervical cancer and recurrent or metastatic squamous cell carcinoma of the head and neck as well as an expansion of the TIL pipeline into lung cancer. Additionally, the company’s proprietary Generation 2 (Gen 2) manufacturing process has now been selected for all ongoing and future TIL clinical development.

"Iovance has made substantial progress in 2017 and we are eager to showcase our work during today’s Analyst Day. We have formally selected Gen 2 as the manufacturing process to be used for registration and have switched all the ongoing study protocols over to this process," said Dr. Maria Fardis, PhD, MBA, president and chief executive officer of Iovance Biotherapeutics. "We are also enthusiastic about our expansion into lung cancer. In collaboration with two industry-leading partners, we will explore the potential of TIL therapy alone and in combination with approved systemic agents. The study at Moffitt has been initiated and the Iovance study, with MedImmune, combining TIL and durvalumab will start in the first half of 2018. We also will provide an update regarding data from cohort 2 of the C-144-01 melanoma study confirming partial responses in four out of 10 patients."

Manufacturing Update

Iovance announced today that it has selected its Gen 2 manufacturing process for all three Phase 2 trials and for all future TIL clinical development. The protocols for the company’s three existing studies have all been amended to allow for enrollment of new patients with TIL manufactured with the Gen 2 process. Cohort 1 of the C-144-01 melanoma study will be closed and new patients will be enrolled in cohort 2. The Gen 2 manufacturing process takes 22 days and the final cell product is cryopreserved for ease of scheduling and handling. The decision to use the Gen 2 manufacturing process was based on data recently presented at the SITC (Free SITC Whitepaper) 2017 Annual Meeting in November, the approximately 35 percent reduction in cost of manufacturing as well as the benefits to patients which include minimizing the time a patient has to wait to receive their TIL and flexibility of scheduling the dosing. Iovance has filed multiple provisional patent applications specific to this process, which if granted, could provide exclusive rights through 2038.

Highlights from Three Lead Clinical Programs

Phase 2 trials are ongoing with adoptive cell transfer (ACT) therapies that utilize an autologous TIL manufacturing process in metastatic melanoma, recurrent, metastatic, or persistent cervical cancer and recurrent and/or metastatic squamous cell carcinoma of the head and neck.

C-144-01 is a Phase 2 multicenter study evaluating the safety and efficacy of LN-144, Iovance’s lead product candidate for treatment of patients with metastatic melanoma. The study is currently enrolling. To date, Iovance has 11 active clinical sites in the United States and intends to start enrolling patients at clinical sites in Europe in early 2018. In November 2017, the company reported results from cohort 2 of the C-144-01 study at the SITC (Free SITC Whitepaper) Annual Meeting. The data being presented today show an objective response rate of 40 percent, with four of ten patients showing a partial response. The most common side effects were pyrexia, anemia and decreased neutrophil count. These patients had a high tumor burden despite a median of 3.6 prior therapies including anti-CTLA and PD-1 treatment.

C-145-03 is a Phase 2, multicenter study that will enroll up to 47 patients and will assess the safety and efficacy of LN-145 for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. The trial has met the efficacy threshold for the first stage of the Simon’s two stage design and will therefore continue to enroll patients to the full sample size of 47 per protocol. Iovance has amended the protocol so that newly enrolled patients can be treated using TIL produced from the Gen 2 manufacturing process. Iovance anticipates reporting early data from this study in 2018.

C-145-04 is a Phase 2, multicenter, study that will enroll up to 47 patients and will assess the safety and efficacy of LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma. The study is enrolling patients in the Unites States and is expected to start enrollment of patients in Europe in the first half of 2018. Iovance has amended the protocol so that newly enrolled patients can be treated using TIL produced from the Gen 2 manufacturing process.

TIL Pipeline Expansion into Lung Cancer

The company announced today that patient enrollment has begun in a study in collaboration with researchers at H. Lee Moffitt Cancer Center and Research Institute (Moffitt), Stand Up to Cancer, and other collaborators. Patients with advanced non-small cell lung cancer (NSCLC) will be enrolled in a study combining TIL and nivolumab in patients who have progressed on nivolumab.

The company also announced that a Phase 2 study in PD-1 and PD-L1 naïve NSCLC patients, sponsored by Iovance, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, will initiate in the first half of 2018. The study with MedImmune will allow for enrollment with LN-145 alone or in combination with durvalumab.

MD Anderson Collaboration Update

Iovance provided an update on its collaboration with the MD Anderson Cancer Center (MDA). Under the collaboration, MDA will initiate two basket studies in sarcoma and platinum resistant ovarian cancer. One study will utilize TIL manufactured by Iovance and for the second study, TIL will be manufactured by MDA. Under the agreement with MDA, Iovance also retains the rights to MDA preclinical research in expanding the understanding of TIL and certain intellectual property related to the MDA TIL manufacturing process.

Today’s Guest Speakers

Key Opinion Leaders will discuss current treatment options and the role of TIL in melanoma, head and neck, lung and cervical cancers. Invited guest speakers include:

Sylvia Lee, MD, University of Washington, Fred Hutch Cancer Research Center
Jason Chesney, MD, PhD, University of Louisville, Brown Cancer Center
Emese Zsiros, MD, PhD, Roswell Park Cancer Institute
Webcast Information
A live webcast of today’s presentation can be accessed on the investor page of Iovance Biotherapeutics’ website at View Source A replay of the webcast will be archived on Iovance Biotherapeutics’ website for 30 days following the presentation.