On March 19, 2018 SELLAS Life Sciences Group, Inc. (NASDAQ:SLS) ("SELLAS" or "the Company") reported the presentation of open label Phase 2 clinical and immunological data for its lead cancer immunotherapeutic candidate, galinpepimut-S (GPS), in the treatment of high-risk multiple myeloma at the 44th Annual European Society for Blood and Marrow Transplantation (EBMT) Meeting (Press release, Sellas Life Sciences, MAR 19, 2018, View Source [SID1234525471]). Safety results from the study were also presented. The EBMT presentation is being delivered by Guenther Koehne, M.D., Ph.D., Chief of Bone Marrow Transplantation and Hematologic Oncology at Miami Cancer Institute, Baptist Health South Florida.

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Median progression-free survival (PFS) of 23.6 months was reported in the high-risk disease setting, compared to historically inferior outcomes while on an immunomodulatory drug (IMID) or proteasome inhibitor post-ASCT maintenance. Median overall survival has not been reached to date. The open-label Phase 2 study consisted of 19 patients with multiple myeloma who had high-risk cytogenetics at diagnosis and remained at least minimal residual disease (MRD)-positive after a successful autologous stem cell transplant ("ASCT").

"These results are encouraging particularly given the patients’ poor prognosis due to their high-risk cytogenetic profile at disease presentation and their still harboring minimal residual disease prior to GPS treatment", said Angelos M. Stergiou, M.D., Sc.D. h.c., President and CEO of Sellas. "The improved PFS at 23.6 months in this setting instills further confidence in our advancing GPS development as an important immuno-therapeutic treatment option for aggressive multiple myeloma."

GPS was administered to patients in the study who achieved a stable disease or better status following ASCT, but still exhibited at least measurable minimal residual disease. GPS, a novel WT1-targeting direct immunizer, was evaluated as consolidation therapy to potentially stimulate a highly-specific immune response against WT1 to prevent or delay myeloma progression.

In the study, key data findings were:

Clinical activity was linked to antigen-specific immune responses.

GPS stimulated time-dependent and robust CD4+ T cell or CD8+ T cell immune responses (IRs) specific for all four WT1 peptides within GPS, two of which are heteroclitic (mutated, by design). In addition, GPS stimulated similar IRs against the two counterpart native peptides. The IRs were confirmed in up to 91% of patients across HLA allele types, with multivalent IRs emerging in up to 64% of patients.

Multifunctional cross-epitope T cell reactivity was observed in 75% of patients to antigenic epitopes against which hosts were not specifically immunized, in a pattern akin to epitope spreading.

The GPS data suggest a distinctive link between clinical and immune responses, which has not been previously described for a peptide vaccine in multiple myeloma. The results offer mechanistic underpinnings for immune activation against WT1 in patients with aggressive multiple myeloma and are supportive of further testing of the putative anti-myeloma activity of GPS in more extensive clinical studies.
Dr. Koehne’s complete EBMT presentation covering the GPS results can be accessed at: www.sellaslifesciences.com/publications/galinpepimut-s-gps/default.aspx.

"High-risk multiple myeloma is a disease subset with high potential of short-term disease progression following autologous stem cell transplants, providing opportunities to improve on this limited clinical outcome. We are seeing an encouraging signal from GPS in our Phase 2 study with progression-free survival (PFS) exceeding historical outcomes with standard therapies," stated Guenther Koehne, M.D., Ph.D. Dr. Koehne added that "Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12-14 months". Dr. Koehne was the Principal Investigator for this study while at MSKCC.

About galinpepimut-S (GPS):
GPS is a heteroclitic multivalent, multi-peptide cancer immunotherapeutic agent composed of four peptides, addressing over 20 epitopes, and derived from the WT1 protein, which has been ranked by the National Cancer Institute as a top priority among cancer antigens for immunotherapy. Importantly, because the WT1 antigen is overexpressed in many malignancies, and is not found in most normal tissues, GPS has the potential to be a broad immunotherapy, effective across a multitude of diverse cancer types and patient populations.

On March 19, 2018 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported that Dr. Angie You, Chief Business & Strategy Officer, Head of Commercial, will present an overview of the company at the Future Leaders in the Biotech Industry Conference being held in New York. The presentation is scheduled for 3:00 p.m. ET on Friday, March 23 (Press release, Sierra Oncology, MAR 19, 2018, View Source [SID1234525461]). A live audio webcast and archive of the presentation will be accessible through the Sierra Oncology website at www.sierraoncology.com.

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On March 19, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that eight posters will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting taking place April 14-18, 2018 in Chicago (Press release, Karyopharm, MAR 19, 2018, View Source [SID1234525409]).The eight poster presentations will feature preclinical data for the Company’s lead, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor, its second-generation oral SINE compound eltanexor, and its pipeline asset KPT-9274, an oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT).

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Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm commented, "Collectively, the data being presented at AACR (Free AACR Whitepaper) this year continue to provide important insights that will help guide the future clinical development of selinexor, eltanexor and KPT-9274 across a wide range of malignancies, both as single agents and in combination."

Details of each of the presentations are provided below:
Selinexor
Galinski et al. show that the combination of selinexor with bortezomib (SV) is synergistic and reduces the activity of nuclear factor kappa-B (NFkB) in aggressive neuroblastoma cell lines. These results further support observed synergies driving Karyopharm’s ongoing Phase 3 "BOSTON" study of SV plus low dose dexamethasone (SVd) versus Vd, which is being studied in patients with relapsed myeloma. Furthermore, these results may lead to additional applications of the SV and/or SVd combination regimens.

Title:Combination Treatment with Selinexor and Bortezomib for Management of Highly Aggressive Neuroblastoma
Presenter: Basia Galinski, Albert Einstein College of Medicine
Poster Board #: 3193/25
Session: PO.TB08.02 – Pediatrics 2: Preclinical Therapies, Resistance, and Stem Cells
Location: Section 7
Date and Time:Tuesday, April 17, 2018; 8:00 AM – 12:00 PM CT

Chang et al. show that the combination of selinexor with the PARP inhibitor Zejula (niraparib) provide enhanced efficacy over either agent alone in preclinical models of ovarian cancer. These results support the previously reported activity of single agent selinexor in patients with ovarian and endometrial cancers in the SIGN study (ESMO, 2017), as well as the ongoing combination of selinexor with the PARP inhibitor Lynparza (olaparib) in an investigator-sponsored study at the MD Anderson Cancer Center in Houston, Texas. Furthermore, based on these data, selinexor combinations with additional PARP inhibitors are being considered.

Title:Enhanced Anti-Tumor Effects of Selinexor and Niraparib in Preclinical Models of Ovarian Cancer
Presenter: Hua Chang, Karyopharm Therapeutics, Inc.
Poster Board #: 5826/22
Session: PO.ET01.04 – Combination Chemotherapy 2
Location: Section 37
Date and Time:Wednesday, April 18, 2018; 8:00 AM – 12:00 PM CT

Wahbe et al. show that selinexor has activity against glioblastoma multiforme (GBM) cells in vitro and in vivo, supporting the previously reported and ongoing study of single agent selinexor in recurrent GBM in clinical study KING. These data also support planned investigator-sponsored studies of selinexor in combination with radiation and/or other DNA-damaging agents in this indication.

Title:The XPO1 Inhibitor Selinexor Attenuates Global Translation and Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and In Vivo
Presenter:Amy Wahba, National Cancer Institute
Poster Board #: 4444/11
Session: PO.MCB04.04 – Post-transcriptional and Translational Control of Cell Fate
Location: Section 21
Date and Time:Tuesday, April 17, 2018; 1:00 PM – 5:00 PM CT

Additional preclinical studies with selinexor support the potential for the agent in hormone receptor positive breast cancer as well as in gastric cancer.

Title:Combined Targeting of Estrogen Receptor Alpha and Nuclear Transport Pathways Remodel Metabolic Pathways to Induce Autophagy and Overcome Endocrine Resistance
Presenter:Zeynep Madak Erdogan, University of Illinois at Urbana-Champaign
Poster Board #: 3733/3
Session: PO.EN01.02 – Steroid Receptors and Preclinical Studies of Endocrine-Related Cancers
Location: Section 31
Date and Time:Tuesday, April 17, 2018; 8:00 AM – 12:00 PM CT

Title:Nuclear Exporter Protein XPO1 a Novel Prognostic and Therapeutic Target in Gastric Cancer
Presenter: Irfana Muqbil, University of Detroit Mercy
Poster Board #: 2491/12
Session: PO.MCB03.03 – Nuclear Oncoproteins and Tumor Suppressor Genes
Location: Section 21
Date and Time:Monday, April 16, 2018; 1:00 PM – 5:00 PM CT
Eltanexor
Preclinical studies with eltanexor support the rationale for Karyopharm’s ongoing single-agent study of eltanexor in multiple indications including castration-resistant prostate cancer (CRPC) and myelodysplastic syndromes (MDS), as well as in potential future combinations of eltanexor in CRPC, MDS or acute myeloid leukemias (AML).

Title:Selective Inhibitor of Nuclear Export (SINE) Compound, Eltanexor (KPT-8602), Synergizes with Venetoclax (ABT-199) to Eliminate Leukemia Cells and Extend Survival in an In Vivo Model of Acute Myeloid Leukemia
Presenter:Melissa A. Fischer, Vanderbilt University School of Medicine
Poster Board #: 1877/8
Session: PO.ET06.04 – Experimental Agents and Combinations for Hematologic Malignancies 2
Location: Section 38
Date and Time:Monday, April 16, 2018; 8:00 AM – 12:00 PM CT

Title:Down-Regulation of AR Splice Variants Through XPO1 Suppression Contributes to the Inhibition of Prostate Cancer Progression
Presenter: Irfana Muqbil, University of Detroit Mercy
Poster Board #: 2492/13
Session: PO.MCB03.03 – Nuclear Oncoproteins and Tumor Suppressor Genes
Location: Section 21
Date and Time:Monday, April 16, 2018; 1:00 PM – 5:00 PM CT
KPT-9274
Mpilla et al. demonstrate that PAK4-NAMPT dual inhibition with KPT-9274 has activity in preclinical models of resistant pancreatic neuroendocrine tumors.

Title:PAK4-NAMPT Dual Inhibition as a Feasible Strategy for Treatment of Resistant Pancreatic Neuroendocrine Tumors
Presenter: Gabriel Mpilla, Wayne State University School of Medicine
Poster Board #: 4368/10
Session: PO.MCB01.01 – GTPases and Their Regulators and Effectors
Location: Section 17
Date and Time:Tuesday, April 17, 2018; 1:00 PM – 5:00 PM CT

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 2,200 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 Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On March 19, 2018 Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") reported that a supplemental New Drug Application (sNDA) for XTANDI (enzalutamide) has been accepted for filing and granted Priority Review designation by the U.S. Food and Drug Administration (FDA) (Press release, Astellas Pharma US, MAR 19, 2018, View Source [SID1234525408]). If approved, the sNDA would expand the indication of XTANDI to include men with non-metastatic Castration-Resistant Prostate Cancer (CRPC), based on data from the Phase 3 PROSPER trial. XTANDI is currently indicated for the treatment of patients with metastatic CRPC.

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The FDA grants Priority Review designation to applications for drugs that, if approved, may offer significant improvements in the safety and effectiveness of the treatment of serious conditions when compared to standard applications. Under Priority Review, the FDA aims to take action on an application within six months of receipt, as compared to ten months under standard review. The Prescription Drug User Fee Act (PDUFA) goal date assigned by the FDA is July 2018. In addition, the European Medicines Agency (EMA) has validated the Type II Variation submitted for XTANDI seeking to expand the current indication to the same patient population and started the review process on March 5.
"Once cancer spreads and metastasizes, men with castration-resistant prostate cancer face a daunting prognosis and challenging odds," said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. "We’re pleased to see the FDA’s Priority Review designation as we work to potentially bring XTANDI to men living with non-metastatic CRPC."
"Treatment options have been limited for men with non-metastatic CRPC, in whom the only evidence of progressive disease is a rapidly rising PSA," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "XTANDI is already established as a standard of care for men with metastatic CRPC. This milestone marks an important step toward our ability to bring XTANDI to CRPC patients in an earlier setting."
The PROSPER trial evaluated XTANDI plus androgen deprivation therapy (ADT) versus ADT alone in 1,401 patients with non-metastatic CRPC. The study met its primary endpoint, demonstrating that the use of XTANDI plus ADT significantly reduced the risk of developing metastasis or death compared to ADT alone. Adverse events in the PROSPER trial were higher in the enzalutamide plus ADT arm compared to ADT alone (87% vs. 77%), and were generally consistent with those reported in prior enzalutamide clinical trials in patients with metastatic CRPC. Results from the PROSPER trial were presented at the 2018 Genitourinary Cancers Symposium (ASCO GU) in February.1 For more information on the PROSPER trial, go to www.clinicaltrials.gov.

The FDA approved XTANDI in 2012 for the treatment of patients with metastatic CRPC who had previously received docetaxel. In 2014, the FDA approved XTANDI to treat patients with metastatic CRPC.

About Prostate Cancer
Prostate cancer is the second most common cancer in men worldwide.2 More than 164,000 men in the United States are estimated to be newly diagnosed with prostate cancer in 2018.3 In the European Union, the estimated number of new prostate cancer cases in 2015 was 365,000.4
Castration-resistant prostate cancer (CRPC) refers to the subset of men whose prostate cancer progresses despite castration levels of testosterone.5 Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising prostate-specific antigen (PSA) level.6 Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.7

About XTANDI (enzalutamide) capsules
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
Important Safety Information for XTANDI
Contraindications
XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions
Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors, seizures were reported in 2.2% of patients. See section 5.1 of the Prescribing Information for the list of predisposing factors. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions
The most common adverse reactions (≥10%) that occurred more commonly (≥2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy-naïve patients, the most common adverse reactions (≥10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.
In the placebo-controlled study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.
Lab Abnormalities: In the two placebo-controlled trials, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In the study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.
Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.
Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in <1% of patients in each arm.
Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.
Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information for additional safety information.
About the Enzalutamide Development Program
Pfizer and Astellas are collaborating on a comprehensive development program that includes studies of enzalutamide across the full spectrum of advanced prostate cancer. Ongoing studies of enzalutamide in prostate cancer include the ARCHES trial in metastatic hormone-sensitive prostate cancer and the EMBARK trial in non-metastatic hormone-sensitive prostate cancer

On March 19, 2018 Synlogic, Inc., (Nasdaq: SYBX) a clinical-stage drug discovery and development company applying synthetic biology to probiotics to develop novel living medicines, reported that preclinical data from its immuno-oncology (IO) program will be presented at the upcoming annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held April 14 to 16, 2018, in Chicago (Press release, Synlogic, MAR 19, 2018, View Source [SID1234524892]).

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The two poster presentations featured at AACR (Free AACR Whitepaper) highlight the application of Synthetic Biotic medicines for the potential treatment of a variety of solid tumors. Abstracts can be found at www.aacr.org

Activation of Innate and Adaptive Immunity via Combinatorial Immunotherapy using Synthetic Biotic Medicines
Abstract Number: LB-131
Session Title:Late-Breaking Research: Immunology 1
Date/Time:Monday, April 16, 2018; 8:00 a.m. – 12:00 p.m. Central Time

Metabolic Modulation of the Tumor Microenvironment using Synthetic Biotic Medicines
Abstract Number: 2920
Session Category: Experimental and Molecular Therapeutics
Session Title: New Targets 2
Date/Time:Monday, April 16, 2018; 1:00 p.m. – 5:00 p.m. Central Time
Session Location:McCormick Place South, Exhibit Hall A, Poster Section 40