On May 17, 2018 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported two data presentations supporting plans for rapid development of avapritinib, a selective KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) and systemic mastocytosis (SM) (Press release, Blueprint Medicines, MAY 17, 2018, View Source;p=RssLanding&cat=news&id=2349637 [SID1234526761]).

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Data from a retrospective natural history study of previously treated patients with advanced PDPGFRα D842V-driven GIST will be presented in a poster session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois on June 1-5, 2018. In addition, updated data from Blueprint Medicines’ Phase 1 EXPLORER trial of avapritinib in patients with advanced SM will be presented in a poster session at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden on June 14-17, 2018.

The accepted abstracts are listed below and are now available online on the ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) conference websites, respectively: View Source and View Source

2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting

Presentation Title: A retrospective natural history study of patients (pts) with PDGFRα D842V mutant advances gastrointestinal stromal tumor (GIST) previously treated with a tyrosine kinase inhibitor (TKI)
Session Title: Sarcoma
Session Date & Time: Saturday, June 2, 2018 from 8:00 a.m. – 11:30 a.m. CT (9:00 a.m. – 12:30 p.m. ET)
Abstract Number: 11533
Poster Board Number: 278
Location: Hall A, McCormick Place

23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper)

Presentation Title: Avapritinib (BLU-285), a Selective KIT Inhibitor, is Associated with High Response Rate and Tolerable Safety Profile in Advanced Systemic Mastocytosis (AdvSM): Results of a Phase 1 Study
Session Title: Myeloproliferative neoplasms – Clinical
Session Date & Time: Friday, June 15, 2018 from 17:30 – 19:00 CEST (11:30 a.m. – 1:00 p.m. ET)
Abstract Number: PF612
Location: Poster Area, Stockholmsmässan

On May 17, 2018 Obsidian Therapeutics, Inc., a biotechnology company dedicated to the development of next-generation cell and gene therapies with pharmacologic operating systems, reported that the company presented preclinical data on its regulated IL12 and IL15 programs at the Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in Chicago, IL (Press release, Obsidian Therapeutics, MAY 17, 2018, View Source [SID1234526779]).

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Obsidian is developing CAR-T therapies that incorporate Destabilizing Domains (DDs) to regulate expression of immune cytokines, thereby providing pharmacologic control over these potent but potentially toxic molecules. DDs are small, fully-human protein domains that confer conditional stability to a fused payload protein that is engineered into a cell or gene therapy product. IL12 and IL15 are two important immune cytokines that play important roles in tumor response to adoptive cell therapy but which require precise control to optimize their therapeutic benefit.

"IL12 and IL15 are critical factors that promote CAR-T cell expansion, persistence, and penetration into solid tumors," said Vipin Suri, Ph.D., Vice President of Discovery of Obsidian. "However, unregulated expression of these cytokines by CAR-T or other adoptively-transferred cells can potentially compromise safety and efficacy. Obsidian’s technology allows the treating physician to control expression of IL12 and IL15 via the use of safe, FDA-approved small-molecule drugs, and the preclinical data we present today demonstrate the elegance and effectiveness of this approach."

Highlights of the two preclinical presentations follow:

Abstract number 113: Exogenous In Vitro and In Vivo Regulation of Interleukin-12 Secretion from T Cells Using Destabilizing Domain Technology
Presenter: Dexue Sun

Session: Cancer – Immunotherapy, Cancer Vaccines I

Construction of a single-chain regulated IL12 using a DD derived from FKBP
Demonstration of small molecule-regulated expression of IL12 in a variety of cell types including primary human T cells
Use of different promoters to tune expression level of the regulated cytokine
Demonstration of in vivo regulation of IL12 in adoptively transferred T cells
Development of a CD19 CAR construct co-expressing regulated IL12, with in vitro data showing effective performance of the regulated cytokine cassette
Abstract number 133: Dose dependent exogenous regulation of membrane bound Interleukin-15-Interleukin-15 receptor alpha fusion protein for adoptive T-cell therapy
Presenter: Christopher Reardon
Session: Cancer – Targeted Gene & Cell Therapy I

Design of regulated membrane-bound IL15-IL15 Receptor Alpha (mbIL15) fusion construct incorporating DDs for pharmacologic control with small molecule ligands
Construction of mbIL15-DD construct incorporating human DDs, regulated by FDA-approved small-molecule drugs
Dose- and time-dependent regulation of mbIL15 expression in multiple cell types
Regulation of mbIL15 expression on primary human T cells in vivo
About Destabilizing Domains

Obsidian uses Destabilizing Domains (DDs) to enable pharmacologic regulation of protein activity for next-generation cell and gene therapies. Obsidian’s DDs are small, fully-human protein domains that confer conditional stability to a fused payload protein. In the absence of a specific small-molecule ligand, the fusion protein is rapidly degraded, whereas in the presence of the ligand, the fusion protein becomes stable and functional. Obsidian uses this approach to equip engineered cells with controllable functions that can be precisely tuned by the administration of non-immunosuppressive, small-molecule medicines that are readily available and dispensed by the treating physician.

On May 17, 2018 VBL Therapeutics (Nasdaq:VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported financial results for the first quarter ended March 31, 2018 and provided a corporate update (Press release, VBL Therapeutics, MAY 17, 2018, View Source [SID1234526744]).

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"We continue to advance the OVAL trial, our Phase 3 potential registration trial in platinum-resistant ovarian cancer, in collaboration with the GOG Foundation," said Yael Cohen M.D., VP Clinical Development of VBL Therapeutic. "We are in the process of amending the protocol to include an interim analysis for evidence of an early efficacy signal with a potential readout from this analysis in the fourth quarter of 2019."

"We are also advancing our MOSPD2 program for oncology and inflammatory indications and, at the recent American Academy of Cancer Research (AACR) (Free AACR Whitepaper) meeting, presented new proof-of-concept on the use of a bispecific antibody to kill MOSPD2-expressing cancer cells," said Dror Harats M.D., Chief Executive Officer of VBL Therapeutics. "VBL is well capitalized, with approximately $50 million in cash, which will enable us to continue the development of VB-111 and our deep pipeline through 2020.’

First Quarter and Recent Corporate Highlights:

Continued to treat patients in the ongoing Phase 3 OVAL trial, studying VB-111 in platinum-resistant ovarian cancer. The OVAL study has been designed to enroll up to 350 adult patients at approximately 70 clinical sites in the U.S. and Israel.

— The Company is modifying the OVAL protocol to incorporate an efficacy interim readout, which is expected to occur in the fourth quarter of 2019.

The Company is conducting an in-depth analysis of the GLOBE study, including analysis of patient subgroups, in order to better understand the outcome of the study, the major difference between the Phase II and the GLOBE trial and the potential activity of VB-111 in rGBM.

Presented late breaking research on the Company’s MOSPD2 oncology program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 annual meeting.

— The data provide proof-of-concept on the use of a bispecific antibody to kill MOSPD2-expressing cancer cells, with potential applicability to solid tumors and myeloid malignancies.

— The MOSPD2 program was also featured in a presentation at the 17th MIXiii-BIOMED 2018 Conference and Exhibition, May 15-17 in Tel Aviv, Israel.

— VBL is developing its VB-600 series of antibodies targeting MOSPD2 for oncology and inflammatory applications.

Awarded 8.9 million New Israeli Shekels (approximately US$2.5 million) non-dilutive grant by the Israel Innovation Authority (IIA).

— The funds will support the development of VB-111 as well as the Company’s Vascular Targeting System (VTS) platform for therapeutic gene therapy.

Appointed two senior pharmaceutical executives, Susan Kelley, M.D., and David Hastings, to its Board of Directors.
First Quarter Ended March 31, 2018 Financial Results:

Revenues: In 2017 the Company entered into an exclusive license agreement with NanoCarrier Co., Ltd. and received an up-front and a milestone payment of $17.0 million in aggregate, of which $0.2 million was recognized as of March 2018.

Cash Position: Cash, cash equivalents and short-term bank deposits at March 31, 2018, were $49.9 million. Working capital at March 31 was $44.3 million. The Company expects that the current cash, cash equivalents and short-term bank deposits will be sufficient to fund operating expenses and capital expenditure requirements through 2020.

R&D Expenses: Research and development expenses for the quarter ended March 31, 2018, were approximately $5.8 million, compared to approximately $4.1 million in the comparable period in 2017. R&D expenses are shown net of IIA grants.

G&A Expenses: General and administrative expenses for the quarter ended March 31, 2018 were $1.4 million, compared to $1.1 million for the comparable period in 2017.

Comprehensive Loss: The Company reported a comprehensive loss for first quarter ended March 31, 2018 of $7.2 million, or ($0.24) per share, compared to a net loss of $5.0 million, or ($0.19) per share in first quarter ended March 31, 2017.
Conference Call:

On May 17, 2018 Boston Biomedical, Inc., an industry leader in the development of novel cancer therapeutics, reported that it will feature several studies evaluating investigational compounds napabucasin and DSP-7888 at the upcoming 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held in Chicago from June 1-5 (Press release, Boston Biomedical, MAY 17, 2018, View Source [SID1234526762]).

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Napabucasin is currently being investigated in phase 3 studies – CanStem303C for metastatic colorectal cancer (NCT02753127) and CanStem111P for metastatic pancreatic cancer (NCT02993731). Included in the napabucasin studies that will be presented at ASCO (Free ASCO Whitepaper) are data from a phase 1b/2 trial in patients with metastatic pancreatic cancer (Poster, Bekaii-Saab, 6/3, 8 a.m. – 11:30 a.m.). Boston Biomedical, Inc. will also present detailed findings from the phase 3 BRIGHTER trial evaluating the efficacy and safety of napabucasin plus paclitaxel for pretreated advanced gastric and gastroesophageal junction adenocarcinoma (Poster discussion, Shah, 6/3, 4:45 p.m. – 6 p.m.). Last year, the Company announced that the study was unblinded early after the Data and Safety Monitoring Board (DSMB) determined that the study was unlikely to reach its primary endpoint. No safety concerns were identified by the DSMB. Separately, data with napabucasin in advanced thymoma and thymic carcinoma, rare tumor types, is available as an online publication.

DSP-7888 is being evaluated in several early and mid-stage studies across multiple tumor types. The Company will present the study design of a phase 2 study of DSP-7888 in combination with bevacizumab for recurrent or progressive glioblastoma, WIZARD201G (Poster, de Groot, 6/2, 1:15 p.m. – 4:45 p.m.), which recently began enrolling patients (NCT03149003).

"As our pipeline and clinical development program continues to evolve, we are looking forward to sharing our learnings with the scientific community at the ASCO (Free ASCO Whitepaper) annual meeting," said Patricia S. Andrews, Chief Executive Officer, Boston Biomedical, Inc.

Abstracts to be presented by Boston Biomedical, Inc. include the following:

Abstract Title Details Authors
A randomized, multicenter phase 2 study of DSP-7888 dosing emulsion in combination with bevacizumab (Bev) versus Bev alone in patients with recurrent or progressive glioblastoma

Abstract #TPS2071
June 2, 1:15-4:45 PM

Poster presentation

Hall A

John Frederick de Groot, University of Texas MD Anderson Cancer Center
The BRIGHTER trial: A phase 3 randomized double-blind study of napabucasin (NAPA) plus paclitaxel (PTX) versus placebo (PBO) plus PTX in patients (pts) with pretreated advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma

Abstract #4010
June 3, 8:00-11:00 AM

Poster presentation

Hall A

June 3, 4:45 – 6:00 PM

Poster Discussion Session

Hall D2

Manish A. Shah,
Weill Cornell University, New York

Phase 1b/2 trial of cancer stemness inhibitor napabucasin (NAPA) + nab-paclitaxel (nPTX) and gemcitabine (Gem) in metastatic pancreatic adenocarcinoma (mPDAC)

Abstract #4110
June 3, 8:00-11:00 AM

Poster presentation

Hall A

Tanios S. Bekaii-Saab, Mayo Clinic Cancer Center
A phase 1b study of napabucasin (NAPA) + weekly paclitaxel (PTX) in patients (pts) with advanced thymoma and thymic carcinoma

Abstract #e20578
Online publication only

Maitri Kalra, Indiana University

About Napabucasin

Napabucasin is an orally-administered investigational agent that affects multiple oncogenic cellular pathways, including inhibition of the STAT3 pathway, which has been implicated in viability of cancer cells and cancer cells with stemness phenotypes.

Napabucasin is currently being investigated in CanStem303C, a phase 3 study for metastatic colorectal cancer (NCT02753127) and CanStem111P, a phase 3 study for metastatic pancreatic cancer (NCT02993731). It is also being investigated in earlier phases in multiple solid and hematologic malignancies. In 2016, the U.S. Food and Drug Administration granted Orphan Drug Designation for napabucasin in pancreatic cancer.

About DSP-7888 (ombipepimut-S*)

DSP-7888 is an investigational cancer peptide vaccine containing peptides that induce WT1-specific cytotoxic T lymphocytes (WT1-CTL) and helper T cells to attack WT1-expressing cancerous cells found in various types of hematologic and solid tumors. Researchers have identified that by adding helper T cell inducing peptides, improved outcomes may be achieved compared to a killer peptide treatment regimen alone.

DSP-7888 is currently being investigated in three Wizard201G monotherapy studies: a phase 1/2 study in myelodysplastic syndrome (MDS) (NCT02436252), a phase 1/2 study in pediatric patients with relapsed or refractory high grade gliomas (NCT02750891) and a phase 1 study in advanced malignancies (NCT02498665). DSP-7888 is currently being investigated in combination with bevacizumab in a phase 2 study in patients with recurrent or progressive glioblastoma (NCT03149003) and in a phase 1 study in combination with nivolumab or atezolizumab in patients with advanced solid tumors (NCT03311334). In 2017, the U.S. Food and Drug Administration granted Orphan Drug Designations for DSP-7888 in MDS and brain cancer. More information on DSP-7888 and ongoing clinical studies can be found at www.BostonBiomedical.com.

On May 17, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) 20, 40, 60 mg for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinoma (aRCC) (Press release, Ipsen, MAY 17, 2018, View Source [SID1234650566]). This approval allows for the marketing of Cabometyx (cabozantinib) in this indication in all 28 member states of the European Union, Norway and Iceland.

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"Today’s EC approval is a step forward for advanced kidney cancer patients in Europe who will be able to access a new oral first-line treatment option that offers significant improvement over the standard of care", said Harout Semerjian, Executive Vice President, Chief Commercial Officer, Ipsen. "Ipsen remains committed to improving patients’ lives by continuing to develop new therapies and expanding the potential of Cabometyx across different indications."

Giuseppe Procopio, M.D., Head of the Genitourinary Unit at Fondazione Istituto Nazionale Tumori Milan, stated: "The value of treatment with Cabometyx has been corroborated by the data generated in clinical trials, and since 2016 physicians have also witnessed the potential of it when treating patients following VEGF-targeted therapy. For both of these reasons, physicians will be pleased to soon have access to this new first-line treatment option for intermediate- or poor- risk advanced RCC patients."
Today’s decision is based on the CABOSUN trial, which demonstrated that cabozantinib significantly prolongs progression-free survival (PFS) compared to sunitinib in treatment-naive aRCC patients with intermediate- or poor-risk. Cabozantinib is the first and only monotherapy to demonstrate superior clinical efficacy over sunitinib in treatment-naïve aRCC patients with intermediate- or poor-risk.
The detailed recommendations for the use of this product are described in the Summary of Product Characteristics (SmPC), available here (View Source).
About the CABOSUN study
On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with intermediate- or poor-risk aRCC per IMDC (International Metastatic RCC Carcinoma Database Consortium) criteria as determined by investigator assessment. CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These results were first presented by Dr. Toni Choueiri at the meeting of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2018).i
On June 19 2017 Exelixis announced that the analysis of the review by a blinded independent radiology review committee (IRC) has confirmed the primary efficacy endpoint results of investigator-assessed progression-free survival (PFS) from the CABOSUN randomized phase 2 trial of cabozantinib as compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Per the IRC analysis, cabozantinib demonstrated a clinically meaningful and statistically significant reduction in the rate of disease progression or death as measured by PFS. The incidence of adverse events (any grade) and the incidence of grade 3 or 4 adverse events between cabozantinib and sunitinib were comparable.
CABOSUN is a randomized, open-label, active-controlled phase II trial that enrolled 157 patients with aRCC determined to be intermediate- or poor-risk per IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, four weeks on followed by two weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate- or poor-risk per IMDC criteria (Heng, JCO, 2009).ii Prior systemic treatment for RCC was not permitted.
About advanced Renal Cell Carcinoma
With the incidence predicted to rise 22% by 2020, renal cell carcinoma (RCC) threatens to become one of the fastest growing cancers in the world.iii Targeted therapies including tyrosine kinase inhibitors (TKIs) of the VEGF receptor (VEGFR) introduced a decade ago, significantly transformed the treatment landscape of aRCC.iv
The American Cancer Society’s 2017 statistics cite kidney cancer as one of the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.v Clear cell RCC is the most common type of kidney cancer in adults.vi If detected in its early stages, the five-year survival rate for RCC is high. For patients with advanced- or late-stage metastatic RCC, however, the five-year survival rate is only 12% with no identified cure for the disease.vii Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.viii
The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL, and VEGF.ix–x These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness, and metastasis.xi, xii, xiii, xiv MET and AXL may provide escape pathways that drive resistance to VEGFR inhibitors. xii – xv
About CABOMETYX (cabozantinib)
Cabometyx is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA approved Cabometyx tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.
On December 19, 2017, Exelixis received approval from the FDA for Cabometyx for the expanded indication of treatment of advanced RCC.
On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinomain the European Union, Norway and Iceland.