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Apexian Pharmaceuticals to Present Two Poster Sessions at AACR Meeting in Chicago – April 14-18, 2018

On April 16, 2018 Apexian Pharmaceuticals, a leading clinical-stage biotechnology company focused on developing safe and effective therapy for patients with high unmet medical needs, reported that it will present two key poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting which will be held at McCormick Place in Chicago, Illinois from April 14 – 18, 2018 (Press release, Apexian Pharmaceuticals, APR 16, 2018, View Source [SID1234525416]). Dr. Mark Kelley, Apexian’s Chief Scientific Officer, along with the research team will available at the posters session. The company will present two posters on combination therapy of APX3330 in pancreatic cancer and APE1 signaling pathway.

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"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"

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The titles and locations for these sessions are:

"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"

Session Date and Time: Tuesday, April 17, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 37

"APE1/Ref-1 Redox Signaling Regulates HIF1a-mediated CA9 Expression in Hypoxic Pancreatic Cancer Cells: Combination Treatment in Patient-derived Pancreatic Tumor Models"

Session Date and Time: Monday, April 16, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 41

The poster sessions will add significant new information gathered on the effectiveness of Apexian’s lead clinical candidate, APX3330, and the ongoing research on the APE1/Ref-1 target.

Harpoon Therapeutics Launches Immuno-Oncology Pipeline With Compelling Data From Lead Programs at the 2018 American Association for Cancer Research (AACR) Annual Meeting

On April 16, 2018 Harpoon Therapeutics, a biotechnology company pioneering a new class of T cell engaging therapeutics based on its proprietary TriTAC platform, reported that preclinical data supporting the ongoing development of the platform and its two lead molecules, HPN424 and HPN536 (Press release, Harpoon Therapeutics, APR 16, 2018, View Source [SID1234525414]). These programs are the first of four programs using TriTAC technology, which has been designed for superior tumor penetration and efficacy in combating solid tumors. The company, which announced a series B financing and a partnership with AbbVie in 2017, anticipates filing investigational new drug (IND) applications and entering the clinic with these two compounds in the next 12 months. Data were presented at the 2018 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, held April 14-18, 2018.

"Harpoon created TriTAC as a best-in-class T cell engager platform optimized for the treatment of solid tumors," said Jerry McMahon, PhD, President and CEO, Harpoon Therapeutics. "The platform allows us to bring the success of T cell engagers targeting hematologic malignancies, like Blincyto, to solid tumor treatment. At Harpoon, we have optimized serum half-life, maximized tumor penetration, and engineered superior stability and manufacturability. These features have been the foundation for our discovery and development of a robust pipeline of drug candidates targeting PSMA, mesothelin, BCMA and DLL3."

Harpoon presented preclinical data which highlighted the novel aspects of its proprietary TriTAC platform to potentially overcome the limitations of existing bispecific antibody-based and CAR-T therapies. The TriTAC platform uses a single flexible polypeptide comprised of three binding domains, and is designed to be the smallest, half-life extended T cell engaging format without the potential liabilities associated with conventional bispecific antibodies.

"We are excited to share these preclinical data for HPN424 and HPN536, which are designed to elicit targeted tumor cell destruction for both metastatic castration-resistant prostate cancer (mCRPC) and mesothelin-expressing tumors, respectively, such as lung, ovarian and pancreatic cancers," said Holger Wesche, PhD, Senior Vice President, Research. "We believe our new data underscore the significant impact our approach could make in advancing the field of immuno-oncology, and look forward to evaluating our compounds in clinical testing."

HPN424 Data Showed Potent T Cell Killing of Prostate Cancer Cells and Serum Half-Life Extension

HPN424 is a 50-kD single polypeptide containing three binding domains — for human PSMA, human serum albumin (HSA) and human CD3. In preclinical studies, HPN424 demonstrated single-digit picomolar potency for PSMA-dependent T cell killing in a panel of human prostate cancer cell lines, which translated to in vivo efficacy with efficacious doses in the low µg/kg range. HPN424 was well tolerated in a multi-dose safety study in non-human primates and showed a serum half-life of 80 hours supporting once-weekly administration for a Phase 1 dose-escalation study in mCRPC patients planned to begin this year.

HPN536 Data Showed Potent Destruction of Mesothelin-Positive Cancer Cells and Evidence of Mechanism in a Primate Study

HPN536 is a 50-kD single polypeptide containing three binding domains — for human mesothelin (MSLN), HSA and human CD3. In preclinical studies, HPN536 demonstrated single-digit picomolar potency for MSLN-dependent T cell killing in a panel of human cancer cell lines derived from mesothelioma, pancreatic, non-small cell lung and ovarian tumors, and in vivo efficacy with efficacious doses in the low µg/kg range. An exploratory safety study in non-human primates showed that HPN536 was well tolerated and supported weekly dosing in humans. The compound was also shown to elicit T cell activation resulting in mesothelial hypertrophy and lymphocyte infiltration, which strongly supports tissue penetration, the mechanism of action of the TriTAC platform, and the planned Phase 1 study.

ABSTRACT INFORMATION

Abstract #1773
Title: "HPN424, a half-life extended, PSMA/CD3-specific TriTAC for the treatment of metastatic prostate cancer"
Date and Time: April 16, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 1

Abstract #1781
Title: "HPN536, a T cell-engaging, Mesothelin/CD3-specific TriTAC for the treatment of solid tumors"
Date and Time: April 16, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 1

Abstract #3814
Title: "TriTACs are novel T cell-engaging therapeutic proteins optimized for the treatment of solid tumors and for long serum half-life"
Date and Time: April 17, 2018, 8:00 AM – 12:00 PM CT
Session: Therapeutic Antibodies, Including Engineered Antibodies 3

Biological Dynamics Announces Data Presentations at AACR Annual Meeting 2018

On April 16, 2018 Biological Dynamics, a molecular diagnostics company dedicated to improving global health outcomes by empowering global communities with low-cost, accessible cancer diagnostics, reported that new data on the company’s novel technology (ACE) will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting, at McCormick Place Convention Center on April 13 – 18 in Chicago (Press release, Biological Dynamics, APR 16, 2018, View Source [SID1234525413]).

Abstracts from two studies examining the application of the company’s technology as an isolation platform for a novel class of biomarkers, such as extracellular vesicles (EVs), and as a cell-free DNA (cfDNA)-based diagnostic assay, will be presented:

Novel AC Electrokinetic Platform for Rapid Isolation and Characterization of Extracellular Vesicles from NSCLC Patients
Presented by Raj Krishnan, Ph.D., CEO of Biological Dynamics, on April 16 at 1:00 p.m. CT in Section 44. (Late-breaking abstract # LB-174)
Diagnostic Application of Novel ACE Technology: Treatment Response Monitoring via Quantification of Cell-Free DNA (cfDNA) in Plasma from Late-Stage Cancer Patients
Presented by Robert Kovelman, Ph.D., Biological Dynamics’ Sr. Director of Assay Development and Clinical Affairs, on April 17 at 8:00 a.m. CT in Section 27. (Abstract # 3666)
Biological Dynamics announced on Friday, April 13, the addition of two new members to its Board of Directors. Irwin Jacobs, founding Chairman and CEO Emeritus of Qualcomm and Chairman Emeritus of the Salk Institute for Biological Studies, and Martin J. Wygod, founder of Medco Containment Services Inc. and former Chairman of WebMD Health Corp., have joined Biological Dynamics’ Board of Directors. (Read more here.)

X4 Pharmaceuticals Presents Clinical Data Demonstrating Single Agent X4P-001-IO Enhances Tumor Immunity

On April 16, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking to treat cancer and rare diseases, reported data from a presentation at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, X4 Pharmaceuticals, APR 16, 2018, View Source [SID1234525412]) The data, generated from serial tumor biopsies and blood draws taken from melanoma patients, demonstrated dramatic infiltration and activation of cytotoxic CD8+ T cells and increased inflammatory status in the tumor microenvironment (TME) following once-daily oral administration of X4P-001-IO. X4P-001-IO is an investigational CXCR4 allosteric antagonist. Findings highlight single agent X4P-001-IO has the ability to help restore immunity within the TME and has the potential to enhance the anti-tumor activity of agents such as checkpoint inhibitors.

Results from the tumor biopsies taken from melanoma patients before and after receiving single agent X4P-001-IO treatment for 3 weeks, were analyzed and presented. Single agent X4P-001-IO showed evidence of enhanced immune cell infiltration and activation in the tumor microenvironment, including:

Increases in proliferating CD8+ cells, indicative of cytotoxic T cell activation,
Increases in Granzyme B, a marker of immune-mediated cell killing,
Decreases in distance between CD8+ T cells and the nearest tumor cells, indicative of increased CD8+ T cell infiltration,
Increases in antigen presentation/processing gene expression, suggesting enhanced antigen priming and activation, and
Increases in the Tumor Inflammation Signature (TIS), indicative of increased inflammation status in the TME.
After single agent X4P-001-IO treatment, patients received X4P-001-IO in combination with Keytruda (pembrolizumab) for an additional 6 weeks. Continued signs of positive immune cell changes in the tumor microenvironment were seen. The combination of X4P-001-IO alone and in combination with Keytruda was well tolerated.

"These results demonstrate that CXCR4 inhibition substantially alters the tumor microenvironment in a way that is consistent with the emerging understanding of tumor immunity and inflammatory response," said Robert Andtbacka, MD, CM, a surgeon and investigator with the Huntsman Cancer Institute of the University of Utah, Associate Professor in the Division of Surgical Oncology at the University of Utah School of Medicine, and Principle Investigator of the X4P-001-IO study in melanoma.

In a separate poster presentation, preclinical findings showed that CXCR4 inhibition increases CD8+ T cells in the tumor microenvironment and has potent anti-tumor activity in the syngenic B16-OVA murine melanoma model. The anti-tumor activities were associated with the increase in immunostimulatory CD8+/Perforin+ cells and the reduction of immunosuppressive myeloid derived suppressor cells (MDSCs) and Treg populations in the tumor microenvironment.

"Results from these posters demonstrate the unique mechanism of X4P-001-IO, as it impacts critical aspects of immune cell trafficking, infiltration and activation – playing a positive role in tumor immunity," said Sudha Parasuraman, MD, X4’s Chief Medical Officer. "These data, together with X4P-001-IO’s favorable safety and tolerability profile, support the potential for X4P-001-IO to improve outcomes for patients with tumors that are less responsive to checkpoint inhibitors."

The posters were presented in the Immune Response to Therapy Session at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 14-18, 2018 in Chicago, IL.

About X4P-001-IO in Cancer

X4P-001-IO is an investigational selective, oral, small molecule inhibitor of CXCR4 (C-X-C receptor type 4) that regulates the tumor microenvironment thereby enhancing endogenous anti-tumor responses. CXCR4 is a chemokine receptor that modulates immune function and angiogenesis through the trafficking of key immune cells such as T- cells, dendritic cells, and myeloid derived suppressor cells. CXCR4 signaling is disrupted in a broad range of cancers, facilitating tumor growth by allowing cancer cells to evade immune detection and creating a pro-tumor microenvironment. X4P-001-IO is being investigated in three separate clinical studies in solid tumors.

Shire Announces Sale of Oncology Business to Servier for $2.4 Billion

On April 16, 2018 Shire plc (LSE: SHP, NASDAQ: SHPG) the leading global biotechnology company focused on rare diseases reported that it has entered into a definitive agreement with Servier S.A.S. ("Servier") to sell its Oncology business for $2.4 billion. Shire’s Oncology business includes in-market products ONCASPAR (pegaspargase), a component of multi-agent treatment for acute lymphoblastic leukemia (ALL) and ex-U.S. rights to ONIVYDE (irinotecan pegylated liposomal formulation), a component of multi-agent treatment for metastatic pancreatic cancer post gemcitabine-based therapy (Press release, Shire, APR 16, 2018, View Source [SID1234525319]). The portfolio also includes Calaspargase Pegol (Cal-PEG), which is under FDA review for the treatment of ALL and early stage immuno-oncology pipeline collaborations.

Flemming Ornskov, M.D., M.P.H., Shire Chief Executive Officer, commented:

"This transaction is a key milestone for Shire, demonstrating the clear value embedded in our portfolio. While the Oncology business has delivered high growth and profitability, we have concluded that it is not core to Shire’s longer-term strategy. We will continue to evaluate our portfolio for opportunities to unlock further value and sharpen our focus on rare disease leadership with selective disposals of non-strategic assets.

"We are confident that Servier will continue to invest in this business and our colleagues who are expected to transfer as part of the transaction in order to meet the needs of cancer patients globally.

"The proceeds from the transaction increase optionality and Shire’s Board will consider returning the proceeds of the sale to shareholders through a shareholder-approved share buyback after the current offer period regarding Takeda’s possible offer for Shire concludes."

Olivier Laureau, Servier Group President, commented:

"The acquisition of Shire’s oncology franchise enables Servier to meet its strategic ambitions to become a global key player in oncology. As an essential step in the evolution of the Group, this acquisition allows us to establish a direct commercial presence in the United States, the world’s leading pharmaceuticals market, and to strengthen our portfolio of marketed products in the territories where Servier is already present. Our goal is to bring these treatments to greater numbers of cancer patients around the world. We thoroughly look forward to welcoming Shire’s oncology teams who will join Servier after the closing."

Transaction details

Under the terms of the agreement, Servier has agreed to acquire Shire’s Oncology business for a total consideration of $2.4 billion, in cash, upon completion. In 2017, the Oncology business generated revenues of $262 million. The total consideration represents a revenue multiple of 9.2 times 2017 revenues. The transaction covers the transfer of Shire’s Oncology business including in-market products ONCASPAR (pegaspargase), a component of multi-agent treatment for acute lymphoblastic leukemia (ALL) and ex-U.S. rights to ONIVYDE (irinotecan pegylated liposomal formulation), a component of multi-agent treatment for metastatic pancreatic cancer post gemcitabine-based therapy. The portfolio also includes Calaspargase Pegol (Cal-PEG), which is under FDA review for the treatment of ALL, and early stage immuno-oncology pipeline collaborations.

The gross assets that are the subject of the transaction are approximately $1.6 billion and the profits attributable to the assets being transferred are approximately $140 million, excluding depreciation, amortization and other direct and indirect costs.

Transaction closing

This transaction constitutes a Class 2 transaction for the purposes of the U.K. listing rules and, as such, Shire shareholder approval is not required. The transaction has been approved by the Board of Directors and is expected to close in the second or third quarter of 2018.

Transaction background

Shire’s Board of Directors initiated the potential divestment of the Oncology business in December 2017. The process, which commenced in January 2018, identified multiple potential strategic buyers across the U.S., Europe and Japan.