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Arcus Biosciences Announces Five Abstracts Accepted for Presentation at AACR 2018 Annual Meeting

On March 28, 2018 Arcus Biosciences (NYSE: RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported that five abstracts have been accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting to be held April 14-18, 2018 in Chicago, Illinois. The presentations at AACR (Free AACR Whitepaper) cover three of our clinical and preclinical product candidates including our dual adenosine receptor antagonist, AB928; our PD-1 antibody, AB122; and our small molecule CD73 inhibitor, AB680 (Press release, Arcus Biosciences, MAR 15, 2018, View Source [SID1234525079]).

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Data to be presented include:

AB928:
Title: Pharmacokinetic-Pharmacodynamic relationship for AB928, a dual antagonist of the A2aR and A2bR adenosine receptors – abstract #3769

Title: Combining adenosine receptor inhibition with AB928 and chemotherapy results in greater immune activation and tumor control – abstract #5556

AB122:
Title: Preclinical characterization of GLS-010 (AB122), a fully human clinical-stage anti-PD-1 antibody – abstract #4561

AB680:
Title: CD73 inhibitors (CD73i) reverse the AMP/adenosine-mediated impairment of immune effector cell activation by Immune Checkpoint Inhibitors (ICI) – abstract #710

Title: Discovery and characterization of AB680, a potent and selective small-molecule CD73 inhibitor for cancer immunotherapy – abstract #4886

Additional information – including presentation schedule and full abstracts – can be found at www.aacr.org.

New Data on Molecular Templates’ Engineered Toxin Bodies to be Presented at the American Association of Cancer Research (AACR) Annual Meeting 2018

On March 15, 2018 Molecular Templates, Inc., (Nasdaq:MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies, a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported that new data on two of its pipeline programs will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018, to be held April 14-18 at McCormick Place North/South in Chicago, Illinois (Press release, Molecular Templates, MAR 15, 2018, View Source [SID1234524813]).

Molecular Templates has utilized the ability of its Engineered Toxin Bodies (ETBs) to route to the endoplasmic reticulum and cytoplasm to deliver cytomegalovirus (CMV) foreign antigen for presentation in the context of MHC class I molecules on tumor cells. This Antigen Seeding Technology (AST) allows for the targeted delivery, intracellular processing, and surface MHC-I presentation of CMV antigen and subsequent destruction of tumors via a CMV-specific T lymphocyte response.

Preclinical data on the company’s PD-L1 targeted ETB incorporating AST will be presented at the AACR (Free AACR Whitepaper) meeting. This molecule has been engineered to both destroy PD-L1-expressing tumor cells via ribosomal destruction and to deliver the immunodominant HLA:A02 restricted cytomegalovirus (CMV) protein-pp65 for MHC-I presentation on these cells. The dual mechanisms of action against the PD-L1 target allow for a more potent and complete destruction of tumor cells. Molecular Templates expects this program to enter the clinic in the first half of 2019.

"We are excited by this wholly novel approach to immuno-oncology," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "Antigen seeding is a way to target an immense, activated T-cell repertoire to the tumor without having to overcome T-cell exhaustion or stimulate antigen presentation from APCs. We are looking forward moving to this approach into the clinic."

Date: Monday, April 16
Time: 1:00pm – 5:00pm Central Time
Session: PO.IMO2.11 – Therapeutic Antibodies, Including Engineered Antibodies 2
Location: Section 34
Poster Title: Antigen Seeding Technology by Engineered Toxin Bodies Provides a Targeted Immuno-Oncology Approach for Treatment of Cancers
Authors: Brigitte Brieschke, Sangeetha Rajagopalan, Garrett L. Robinson, Erin K. Willert, Hilario J. Ramos

Molecular Templates will also present on its HER2 engineered toxin body program. MT-5111, a HER2-targeted ETB with picomolar potency against HER2 expressing cells, was designed to overcome mechanisms of resistance to current HER2 targeting modalities such as escape from antibody dependent cell-mediated cytotoxicity (ADCC), alterations in signal transduction, epitope masking, and enhanced small molecule efflux. Additionally, MT-5111 was genetically engineered to reduce the anti-drug antibody response and signaling through innate receptors, allowing for repeat dosing.

In vitro and in vivo data will be presented at the AACR (Free AACR Whitepaper) meeting, highlighting the potential for MT-5111 as a novel agent in development for treatment of breast carcinomas and other malignancies overexpressing the HER2 receptor. Molecular Templates intends to file an IND with MT-5111 in 2018.

"Antibody, small molecule, and ADC approaches to HER2 have all shown meaningful benefit in patients with HER2+ cancers but ultimately cease to work in most patients even though HER2 expression persists," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We believe the unique mechanism of action of our HER2 ETB may circumvent mechanisms of resistance to the other HER2 modalities."

Date: Wednesday, April 18
Time: 8:00am – 12:00pm Central Time
Session: PO.ET01.02 – Antibodies, Fusion Proteins, and Related Biologics
Location: Section 35
Poster Title: Targeted Engineered Toxin Bodies Provide a Novel Mechanism of Action Against HER2 Positive Cancers
Authors: Brigitte Brieschke, Garrett L. Robinson, Sangeetha Rajagopalan, Hilario J. Ramos, Jensing Liu, Jack P. Higgins, Erin K. Willert

Adaptimmune Sees Positive Early Results in Cancer Treatment

On March 16, 2018 Shares of Adaptimmune Ltd. surged late Thursday after the company reported it saw three partial responses in three of the four myxoid/ round cell liposarcoma (MRCLS) patients the company dosed with its NY-ESO SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cells (Press release, BioSpace, MAR 15, 2018, View Source [SID1234524855]).

The news sent company stock up more than 20 percent to $12.41 per share. Since that spike, shares have fallen back some to $10.74 as of 10:51 a.m.

Those positive results are also good news for GlaxoSmithKline, which licensed the NY-ESO SPEAR T-cell therapy program last fall. The two companies initiated their collaboration in 2014 and last year the pharma giant exercised its option to exclusively license Adaptimmune’s NY-ESO SPEAR T-cell therapy program. The transition has not yet been completed.

MRCLS is a type of liposarcoma that is characterized by the proliferation of adipocyte (fat cell) precursors called lipoblasts that have undergone differentiation arrest. MRCLS represents about 30 to 35 percent of liposarcomas and 5 to 10 percent of all adult soft tissue sarcomas. It is estimated that there are approximately 2000 patients in the United States and Europe with MRCLS each year.

Rafael Amado, Adaptimmune’s chief medical officer, said the company is encouraged by the initial responses in the first patients dosed. He said the news validates the potential for its platform to treat a broad range of tumors, including those known to be unresponsive to current immunotherapy treatments.

"Although MRCLS is a soft tissue sarcoma which commonly expresses NY-ESO, there are fundamental differences in its clinical course, natural history, molecular signature, and responsiveness to standard treatments that make it distinct from synovial sarcoma. As we expect data from our other trials with our wholly owned assets throughout 2018, these results in a second solid tumor strengthen our conviction that our pipeline of unique TCRs will be capable of addressing multiple solid tumors," Amado said in a statement.

So far Adaptimmune has dosed four patients with its treatment. Of the three partial responses the company said two have been confirmed and one has yet to be confirmed. The other patient was classified as having stable disease. Adaptimmune said the doses were well-tolerated. However, the company said it did see cases of cytokine release syndrome (CRS), a systemic inflammatory response that has been a persistent concern in other CAR-T and cell therapy trials. The CRS cases Adaptimmune patients encountered were managed following standard treatment guidelines, the company said.

Two years ago the U.S. Food and Drug Administration placed a partial clinical hold on the NY-ESO SPEAR T-cell study for MRCLS. The hold was lifted after Adaptimmune revised the trial protocol.

In addition to its NY-ESO SPEAR T-cell study, Adaptimmune is using SPEAR T-cells in two clinical trials targeting MAGE-A10, one in non-small cell lung cancer (NSCLC), and a triple tumor study in bladder, melanoma, and head & neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen. In addition to the MAGE-A10 trial, Adaptimmune is also targeting MAGE-A4. The newly manufactured SPEAR T-cell at the Philadelphia site will be used in a multiple tumor study in bladder, melanoma, head & neck, ovarian, non-small cell lung, esophageal, and gastric cancers.

Deciphera Pharmaceuticals, Inc. to Report Clinical and Preclinical Data with DCC-2618 at the Upcoming 2018 American Association for Cancer Research (AACR) Annual Meeting

On March 15, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that two abstracts highlighting DCC-2618, the Company’s KIT and PDGFRα inhibitor have been selected for presentation at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 14-18, 2018 in Chicago, IL (Press release, Deciphera Pharmaceuticals, MAR 15, 2018, View Source [SID1234524792]).

Details of the presentations on DCC-2618 are as follows:

Poster Title: Pharmacokinetic (PK), Safety and Tolerability Profile of DCC-2618 in a Phase 1 Trial Supports 150mg QD Selected for a Pivotal Phase 3 Trial
Author: Filip Janku, M.D., Ph.D.
Session: Phase I Clinical Trials 1
Abstract #: CT029
Date & Time: Sunday Apr 15, 20181:00 PM – 5:00 PM CT
Location:McCormick Place South, Hall A, Poster Section 42, poster board # 22

Poster Title: Inhibition of Oncogenic and Drug-resistant PDGFRα and KIT Alterations by DCC-2618
Author:Bryan D. Smith
Session: Resistance and Biology
Abstract #: 3925
Date & Time: Tuesday, April 17, 20188:00 AM – 12:00 PM CT

"We are pleased to present these data demonstrating potent inhibition of KIT and PDGFRα alterations and mutations with DCC-2618 at the upcoming AACR (Free AACR Whitepaper) annual meeting," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "Importantly, these results support the growing body of clinical data reported with DCC-2618 in solid tumors and the selection of 150mg once daily as the dose for the recently initiated pivotal Phase 3 trial of DCC-2618 in gastrointestinal stromal tumors (GIST)."

About DCC-2618

DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, glioblastoma multiforme and systemic mastocytosis. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, known to be present in GIST patients and the D816V exon 17 mutation known to be present in ASM patients. DCC-2618 inhibits PDGFRα mutations in exon 18, including the D842V mutation that drives a subset of GIST.

Janssen Announces U.S. FDA Breakthrough Therapy Designation for Erdafitinib in the Treatment of Metastatic Urothelial Cancer

On March 15, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reportred that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for erdafitinib in the treatment of urothelial cancer (Press release, Johnson & Johnson, MAR 15, 2018, View Source [SID1234524811]). Urothelial cancer, most frequently in the bladder, is the sixth most common type of cancer in the U.S.1 A Breakthrough Therapy Designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.2 The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.

"For patients diagnosed with urothelial cancer, outcomes are unfortunately disheartening due to the aggressiveness of the disease," said Peter Lebowitz, MD, PhD, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "Through the continued development of erdafitinib, and working closely with the FDA, we look forward to bringing a potential new treatment option to patients."

The Breakthrough Therapy Designation is based on data from a multicenter, open-label Phase 2 clinical trial evaluating the efficacy and safety of erdafitinib in the treatment of adult patients with locally advanced or metastatic urothelial cancer, whose tumors have certain fibroblast growth factor receptor (FGFR) genetic alterations. The Phase 2 study BLC2001 presented at the 2018 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium showed an overall response rate of 42 percent in 59 patients with relapsed/refractory metastatic urothelial cancer whose tumors harbored actionable FGFR mutations (ASCO-GU abstract #411).3
About Urothelial Cancer
Urothelial cancer, also known as transitional cell cancer, is the sixth most common type of cancer in the U.S.1 These cancers start in the urothelial cells that line the inside of the bladder.4 In 2018, an estimated 81,190 new cases of bladder cancer are expected, resulting in 17,240 deaths.4 For patients with metastatic disease, outcomes can be dire due to the often rapid progression of the tumor and the lack of efficacious treatments, especially in relapsed or refractory disease. The relative five-year survival rate for patients with metastatic disease is five percent.

About Erdafitinib
Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being evaluated by Janssen in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer. FGFRs are a family of receptor tyrosine kinases which may be upregulated in various tumor cell types and may be involved in tumor cell differentiation and proliferation, tumor angiogenesis, and tumor cell survival.5 In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Therapeutics Ltd. to develop and commercialize erdafitinib.