On October 8, 2018 Adaptimmune Therapeutics plc ("Adaptimmune") (Nasdaq: ADAP), a leader in T-cell therapy to treat cancer, reported further details about two poster presentations at the upcoming ESMO (Free ESMO Whitepaper) congress, as follows (Press release, Adaptimmune, OCT 8, 2018, View Source;p=RssLanding&cat=news&id=2370701 [SID1234530171]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

MAGE-A10 poster for discussion presentation details:

A late-breaking abstract with data from the two ongoing MAGE-A10 studies ("triple tumor" and lung) was accepted for poster discussion, with the full abstract and data to be made available at the time of presentation.
Title: Safety and Anti-Tumor Effects of MAGE-A10c796TCR T-cells in Two Clinical Trials (Poster #LBA38)
Poster discussion session: Immuno 1 in ICM room 14b
Time: Saturday, October 20 from 16:45 to 17:45 CEST (10:45 to 11:45 EDT)
MAGE-A4 poster presentation details:

The full abstract for the MAGE-A4 poster is now available online (https://bit.ly/2NMBC3d) and is summarized below
Title: Initial Safety Assessment of MAGE-A4 SPEAR T-cells (Poster #1156P)
Poster display session (ID 259): Immunotherapy of cancer in Hall A3 poster networking Hub
Time: Saturday, October 20 from 12:30 to 13:30 CEST (06:30 to 07:30 EDT)
Brief summary of abstract (data cut-off 25 April 2018):
Background:

Ongoing study (NCT03132922) to evaluate safety and tolerability of SPEAR T-cells directed towards a MAGE-A4 peptide expressed on tumors in the context of HLA-A*02
Methods:

Modified 3+3 design
Patients have inoperable or metastatic (advanced) non-small cell lung cancer (NSCLC), urothelial ("bladder"), melanoma, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), head & neck, ovarian, gastric, or esophageal cancers expressing MAGE-A4
Lymphodepletion regimen:
Cohorts 1, 2: [fludarabine (Flu) 30 mg/m2/day and cyclophosphamide (Cy) 600 mg/m2/day] x 3 days
Cohort 3: [Flu 30 mg/m2/day] x 4 days + [Cy 600 mg/m2/day] x 3 days
Expansion Cohort: [Flu 30 mg/m2/day] x 4 days + [Cy 600 mg/m2/day] x 3 days
Dose:
Cohort 1: target 100 million (M) transduced cells; range 80 to 120 M transduced cells
Cohort 2: target 1 billion (B) transduced cells; range 0.5 to 1.2 B transduced cells
Cohort 3: target 5 B transduced cells; range 1.2 to 6.2 B transduced cells
Expansion Cohort: target 5 B transduced cells; range 1.2 to 10 B transduced cells
Results:

Three patients were treated with 100 M MAGE-A4 SPEAR T-cells, and transduced cells were detectable in peripheral blood
Adverse events (AEs) for the first 2 patients reported at grade (G) ≥3 included anemia, hypoglycemia, hyponatremia, lymphopenia, neutropenia, and thrombocytopenia
Serious AEs included G4 hyponatremia, G3 atrial fibrillation, G3 syncope (unrelated to T-cell therapy), G1 CRS and G2 encephalopathy syndrome (both related), and G2 generalized muscle weakness (possibly related)
None of the events were considered dose limiting toxicities (DLTs) by the Safety Review Committee
Conclusions:

MAGE-A4 SPEAR T-cells at the 100 M transduced cell dose appear to show no evidence of on‑target or off-target toxicity
Preliminary data support continued investigation of the T-cell receptor (TCR), and this trial is ongoing

On October 8, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the successful animal testing of DNA-encoded monoclonal antibodies targeting the immune checkpoint molecule CTLA-4 as published in Cancer Research (Press release, Inovio, OCT 8, 2018, View Source;Monoclonal-Antibody-dMAb-Checkpoint-Inhibitor–and-Demonstrates-Tumor-Shrinkage-in-Preclinical-Studies/default.aspx [SID1234530270]). The breakthrough preclinical study demonstrated that highly optimized dMAbs targeting mouse CTLA-4 protein can be robustly expressed in vivo, and shrank tumors in mice. More importantly, Inovio’s dMAb constructs for anti-human CTLA-4 antibodies ipilimumab (YERVOY) and tremelimumab, achieved high expression levels in mice (approximately 85µg/ml and 58µg/ml, respectively). These dMAbs exhibited long-term expression with maintenance of serum levels >15µg/ml for over a year.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This research publication is significant because it is the first to report on the use of Inovio dMAb technology to develop novel monoclonal antibody-based therapies targeting checkpoint inhibitors. Inovio is developing additional dMAbs targeting other checkpoint molecules including PD-1. When delivered directly into the body, the genetic instructions provided from the dMAb construct enable the patient’s own cells to become the factory which manufactures the therapeutic monoclonal antibody products. Inovio has previously published several papers demonstrating its dMAb product candidate’s ability to treat multiple virus targets such as flu, dengue, chikungunya, and HIV.

Laurent Humeau, Ph.D., Inovio’s Senior Vice President, Research & Development, said, "Even though conventional monoclonal antibodies represent one of the most successful segments of the biotechnology market, accounting for over $50 billion in sales today, manufacturing complexity and repeated dosing may limit a broader use of this technology. Inovio’s dMAb products may improve upon this class using our synthetic design and in vivo production. This newly published study further support that Inovio’s potent dMAb platform can be expanded to target cancer. We plan on advancing the first clinical dMAb candidate into the first-in-human study in 2019. Moreover, we expect to form partnerships to advance several dMAb products targeting cancers and infectious diseases."

David B. Weiner, Ph.D., the paper’s senior author and the W.W. Smith Charitable Trust Professor in Cancer Research at The Wistar Institute, said, "Our work provides the first demonstration that we can use synthetic DNA technology to produce checkpoint inhibitor molecules in vivo to impact tumor growth in a preclinical setting. We showed that dMAbs may represent a valuable addition to the cancer immunotherapy toolbox: In our preclinical studies, dMAbs achieved antitumor activity comparable to that of traditional monoclonal antibodies, while being delivered through a simpler formulation that may provide a bridge to expand target populations for checkpoint inhibitors."

The study highlights that delivery of a synthetic, sequence-optimized DNA plasmid designed to encode anti-mouse CTLA-4 monoclonal antibodies, with the aid of an electroporation device to enhance uptake, resulted in significant and prolonged antibody expression with even a single dose. Importantly, this approach stimulated robust CD8+ T cell infiltration, achieving tumor clearance across multiple mouse tumor models. The researchers then went on to develop human checkpoint inhibitor molecules and demonstrated their production in mice and their ability to stimulate human T cell responses associated with antitumor activity. The study clearly demonstrates how optimized dMAbs encoding the human CPI’s ipilimumab and tremelimumab are potently expressed in vivo and enhance the activation of human effector T cells with the potential to destroy tumors. This strategy provides a novel approach to immune checkpoint therapy, with the potential to expand patient access to this breakthrough immunotherapy to treat cancer.

Funded with over $60 million in R&D support from top agencies like DARPA, NIH, and the Gates Foundation, Inovio dMAb products could extend the medical benefits that marketed monoclonal antibodies have already achieved, and even potentially address diseases that conventional monoclonal antibodies cannot.

About Inovio’s DNA-based Monoclonal Antibody Platform

Traditional monoclonal antibodies are manufactured outside the body in bioreactors, typically requiring costly large-scale manufacturing facility development and laborious production. Inovio’s disruptive dMAb technology has the potential to overcome these limitations by virtue of their simplified design, rapidity of development, product stability, ease of manufacturing and deplorability, and cost effectiveness, thereby providing potential new avenues for treating a range of diseases. Another significant advancement seen in Inovio dMAb technologies is that the optimized genes for a desired monoclonal antibody is encoded in a DNA plasmid, which is produced using very cost effective and highly scalable fermentation techniques. These plasmids are delivered directly into cells of the body using electroporation and the encoded monoclonal antibody is then directly produced by these cells. Previously published studies show that a single administration of a highly optimized DNA-based monoclonal antibody targeting HIV virus produced a high level of expression of the antibody in the bloodstream of mice; Inovio similarly reported data showing that dMAb products against flu, Ebola, chikungunya and dengue protected animals against lethal challenge. Inovio Ebola dMAb product is being developed under a grant from the Defense Advanced Research Projects Agency (DARPA).

On October 8, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported it will present data on its investigational BTK inhibitor zanubrutinib and its investigational PARP inhibitor pamiparib at two upcoming medical meetings (Press release, BeiGene, OCT 8, 2018, View Source;p=irol-newsArticle&ID=2370698 [SID1234529823]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Zanubrutinib clinical data will be included in an oral presentation at the 10th International Workshop on Waldenström’s Macroglobulinemia (IWWM). The IWWM meeting is taking place in New York City from October 11th to 13th, 2018.

Pamiparib clinical data will be included in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, which will take place October 19th to 23rd in Munich, Germany.

IWWM Oral Presentation:

Title: Improved Depth of Response With Increased Follow-up in Phase 1 Trial of Patients with Waldenström Macroglobulinemia (WM) Treated With Oral Bruton Tyrosine Kinase (BTK) Inhibitor Zanubrutinib (BGB-3111)
Session ID: Session X
Location: Main Area
Date: October 12, 2018
Time: 12:45 pm ET
Presenter: Constantine Tam, M.D., Director of Hematology, St. Vincent’s Hospital and Consultant Hematologist, Peter MacCallum Cancer Center

ESMO Poster Presentation:

Title: Preliminary Results of Pamiparib (BGB-290), a PARP1/2 Inhibitor, in Combination with Temozolomide (TMZ) in Patients With Locally Advanced or Metastatic Solid Tumors
Presentation #: 421P
Session ID: Poster display session (ID 258)
Location: Hall A3 – Poster Area Networking Hub
Date: October 22, 2018
Time: 13:15 to 14:15 CEST
Presenter: Melissa Johnson, M.D., Associate Director, Lung Cancer Research Program, Sarah Cannon Research Institute
About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various lymphomas.

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by BeiGene scientists in Beijing, pamiparib is currently in global clinical development as a monotherapy and in combination with other agents for a variety of solid tumor malignancies.

On October 8, 2018 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported that its Chief Executive Officer, Jed Latkin, will present a corporate overview of the Company at the 2018 BIO Investor Forum, being held October 17-18, 2018 in San Francisco, California (Press release, Navidea Biopharmaceuticals, OCT 8, 2018, View Source [SID1234530337]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Conference Presentation Details:

Where: The Westin St. Francis Hotel, San Francisco, California
When: Thursday, October 18, 2018 at 11:15AM PDT
Room: Elizabethan C
Conference Website:
View Source

To schedule a meeting, investors can submit meeting requests through the conference one-on-one partnering system.

On October 8, 2018 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company plans to release its third-quarter 2018 financial results after the close of the U.S. financial markets on Oct. 30, 2018 (Press release, Exact Sciences, OCT 8, 2018, View Source [SID1234529880]). Following the release, company management will host a webcast and conference call at 5 p.m. ET to discuss financial results and business progress.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Third-Quarter 2018 Webcast & Conference Call Details

Date: Tuesday, Oct. 30, 2018

Time: 5 p.m. ET, 4 p.m. CT

Webcast: The live webcast can be accessed at www.exactsciences.com

Telephone: Domestic callers, dial 877-201-0168

International callers, dial +1 647-788-4901

Access code for both domestic and international callers: 6870368

An archive of the webcast will be available at www.exactsciences.com. A replay of the conference call will be available by calling 800-585-8367 domestically or 416-621-4642 internationally. The access code for the replay of the call is 6870368. The webcast, conference call and replay are open to all interested parties.