MacroGenics Announces Termination of Duvortuxizumab Collaboration and License Agreement with Janssen

On August 31, 2017 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported that it had been notified by its partner, Janssen Biotech, Inc., that Janssen is terminating the collaboration and license agreement with MacroGenics relating to duvortuxizumab, a CD19 x CD3 DART molecule. Enrollment of the Phase 1 dose-escalation study of this molecule is being discontinued.

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Janssen reaffirmed its commitment to MGD015, also known as JNJ-9383, a second DART molecule licensed from MacroGenics. MGD015 is a preclinical program that targets CD3 and a non-disclosed cancer antigen expressed in hematological malignancies and lung cancer. Janssen has indicated that it anticipates initiating a first-in-human study with this molecule in 2018.

In the Phase 1 dose-escalation study of duvortuxizumab, multiple objective responses were observed in patients treated at various dosing levels tested. However, a number of patients experienced treatment-related neurotoxicity similar to that seen in patients treated with other CD19-targeted T-cell therapies. Given the recent advances in the highly competitive field for the treatment of B cell malignancies, the opportunity for development and commercialization has become less attractive.

"While this decision is disappointing, MacroGenics and its strategic partner, Janssen, continue to be fully committed to the DART platform and our ongoing collaboration on MGD015. Duvortuxizumab’s neurotoxicity profile is a CD19-targeting issue and has not been observed in our other DART clinical programs," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "Given our large portfolio of product candidates currently being pursued, it is unlikely that we will continue development of this molecule at this time."

Curis Announces CA-170 Poster Presentation at ESMO 2017 Congress

On August 31, 2017 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer, reported the presentation of a trial-in-progress poster describing preliminary clinical data from the dose escalation stage of CA-170 Phase 1 clinical trial at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress (Press release, Curis, AUG 31, 2017, View Source [SID1234520345]). The conference will take place September 8-12 in Madrid. CA-170, an oral small molecule targeting the immune checkpoints PDL1 and VISTA, is in development for the treatment of patients with advanced solid tumors or lymphomas.

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Additional information on the presentation can be found below and can be accessed at www.esmo.org.

CA-170 Poster Presentation:

Date/Time: Monday, Sept. 11, 9:15 AM — 10:45 AM CEST
Abstract Number: 1141PD
CA-170, a first in class oral small molecule dual inhibitor of immune checkpoints PD-L1 and VISTA, demonstrates tumor growth inhibition in
Presentation Title: pre-clinical models and promotes T cell activation in Phase 1 study

Immune Design Announces New CMB305 + Checkpoint Inhibitor Topline Data from an Upcoming Presentation at the ESMO 2017 Congress

On August 30, 2017 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported positive topline data from its interim analysis of the ongoing, randomized Phase 2 trial evaluating CMB305 in combination with atezolizumab (TECENTRIQ) or atezolizumab alone in 88 soft tissue sarcoma patients (Press release, Immune Design, AUG 30, 2017, View Source [SID1234520357]). The data will be presented in a poster discussion session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress, September 8-12, 2017 in Madrid, Spain.

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"The two main goals of this study are (1) to determine whether combining a next-generation vaccine like CMB305 with a checkpoint inhibitor (such as an anti-PD-L1 antibody) provides improved clinical benefit compared to that of the checkpoint inhibitor alone, particularly in a PD-L1-low or -negative tumor, and (2) in a randomized setting, to determine the biological activity of CMB305," said Carlos Paya, M.D., Ph.D., President and Chief Executive Officer of Immune Design. "We believe these interim data constitute the first steps towards answering both questions in a favorable manner."

Data to be presented at ESMO (Free ESMO Whitepaper) build upon those data on the first 36 patients summarized in the abstract, and include a greater number of patients enrolled.

Clinical Benefit: Data from the larger patient population show that patients receiving CMB305 and atezolizumab experienced greater clinical benefit in the form of Disease Control Rate (including objective responses), Progression Free Survival and Time to Next Treatment than those receiving atezolizumab alone.
Immune Response: Patients who received the combination of CMB305 and atezolizumab demonstrated an increased frequency of induced immune responses to NY-ESO-1, including NY-ESO-1-specific T cells, NY-ESO-1 antibodies, and antigen spreading, in comparison to patients who received atezolizumab alone
Biomarkers: In an exploratory analysis, a trend towards improved overall survival was observed in patients in the CMB305 and atezolizumab combination arm who had pre-existing and treatment-induced anti-NY-ESO-1 immunity, compared to the atezolizumab alone arm. Pre-treatment tumor biopsy analysis showed negligible levels of PD-L1 expression.
Safety: No new safety signals have been observed in either arm.
The fully enrolled trial is evaluating the safety, immunogenicity and efficacy of CMB305 in combination with atezolizumab, or atezolizumab alone, in a total of 88 patients with locally advanced, relapsed, or metastatic NY-ESO-1+ synovial sarcoma or myxoid/round-cell liposarcoma. Atezolizumab is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1) and is being developed by Genentech, a member of the Roche Group. The trial is being conducted pursuant to a clinical collaboration with Genentech. Immune Design intends to present survival data in 2018 once all patients have at least one year of follow up (current data are preliminary: median duration of observation

The ESMO (Free ESMO Whitepaper) Poster Discussion session presentation details are as follows:

A Phase 2 Study of CMB305 and Atezolizumab in NY-ESO-1+ Soft Tissue Sarcoma: Interim Analysis of Immunogenicity, Tumor Control and Survival
Abstract # 1480PD
Session Title: Sarcoma Poster Discussion Session
Date: Monday, Sept. 11, 2017
Time: 11 a.m. — 12:30 p.m.
Location: Bilbao Auditorium
Poster Presenter: Dr. Sant Chawla
Poster Discussant: Dr. Robert Maki

About CMB305

CMB305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors, designed to generate an integrated, anti-NY-ESO-1 immune response in vivo via a targeted, specific interaction with dendritic cells, a mechanism of action Immune Design believes differs from traditional cancer vaccines. CMB305 is being evaluated in soft tissue sarcoma patients in ongoing Phase 1 monotherapy and 2 combination studies. Immune Design has received Orphan Drug Designation for CMB305 from the U.S. Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma, as well as from the FDA and European Medicines Agency for each of the components of CMB305 for the treatment of soft tissue sarcoma.

Stemline Therapeutics to Present SL-801 Phase 1 Data at Upcoming ESMO Congress

On August 30, 2017 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel therapeutics for difficult to treat cancers, reported that data from SL-801’s ongoing Phase 1 trial in patients with advanced solid tumors has been selected by the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) for poster presentation at their Annual Congress 2017, to be held September 8-12, 2017 in Madrid, Spain (Press release, Stemline Therapeutics, AUG 30, 2017, View Source [SID1234520358]). SL-801 is a novel, potent and reversible Exportin-1 (XPO1) inhibitor.

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Details on the presentation are as follows:

Title: Ongoing Phase 1 Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors; Interim Results
First Author: Judy Wang, MD; Florida Cancer Specialists & Research Institute
Abstract: 406P

Date/Time: Monday, September 11, 2017 – 1:15-2:15 PM CET
Location: Hall 8

Karyopharm Announces the Presentation of Selinexor and KPT-9274 Clinical Data at the European Society of Medical Oncology 2017 Annual Meeting

On August 30, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported two upcoming poster presentations at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Annual Meeting, taking place September 8-12, 2017 in Madrid, Spain (Press release, Karyopharm, AUG 30, 2017, View Source [SID1234520355]). One poster will describe Phase 1 data from an ongoing investigator-sponsored trial (IST) evaluating the safety and tolerability of the Company’s lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE compound, in combination with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers. The other poster will describe Phase 1 clinical data from an ongoing study evaluating the safety and tolerability of KPT-9274, Karyopharm’s oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) in patients with advanced solid malignancies or non-Hodgkin’s lymphoma (NHL).

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"We look forward to the presentations of the findings from both of these early-stage clinical trials at ESMO (Free ESMO Whitepaper) this year, the results of which will continue to inform and guide our ongoing clinical programs," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm.

Details for the Poster Presentations at ESMO (Free ESMO Whitepaper) 2017:

Title: A Phase 1 Study of Selinexor (S) in Combination with Paclitaxel (P) and Carboplatin (C) in Patients (pts) with Advanced Ovarian (OC) or Endometrial Cancers (EC)
Presenter: Vicky Makker, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Abstract code: 970P
Session: Poster Display Session
Location: Hall 8
Date and Time: Saturday, September 9, 2017 from 13:15 – 14:15 CET

Title: A First in Human Phase 1 Study of KPT-9274, a First in Class Dual Inhibitor of PAK4 and NAMPT, in Patients with Advanced Solid Malignancies or NHL
Presenter: Aung Niang, MD Anderson Cancer Center, Houston, Texas, USA
Abstract code: 374PD
Session: Poster Discussion Session — Developmental Therapeutics
Location: Alicante Auditorium
Date and Time: Saturday, September 9, 2017 from 16:30 – 18:00 CET

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,100 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

About KPT-9274

KPT-9274 is a first-in-class, orally bioavailable, small molecule immunometabolic modulator that works through non-competitive dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). Co-inhibition of these targets is believed to lead to synergistic anti-tumor effects through suppression of ß-catenin by blocking PAK4, leading to both immune cell activation and inhibition of tumor growth, energy depletion through NAMPT inhibition, blockade of DNA repair, cell cycle arrest and ultimately apoptosis. KPT-9274 may therefore have both immune-activating and direct antitumor effects. In contrast, normal cells are less sensitive to inhibition by KPT-9274 due in part to their relative genomic stability and lower metabolic demands.