On March 14, 2019 AstraZeneca will share pioneering research and development across its successful Oncology portfolio and extensive next-generation pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, USA, 29 March to 3 April 2019 (Press release, AstraZeneca, MAR 14, 2019, View Source [SID1234534328]).

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The new research will showcase AstraZeneca’s potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, taking the DNA Damage Response (DDR) pipeline beyond PARP inhibition. Additional highlights include new insights from the MYSTIC and TATTON trials for Imfinzi (durvalumab) and Tagrisso (osimertinib) in predicting response and addressing treatment resistance in lung cancer.

In total, data from 84 presentations will illustrate the progress of AstraZeneca’s Oncology pipeline, with 28 abstracts reporting new Immuno-Oncology (IO) data, 33 focused on complementary biological pathways exploring the DDR mechanism, and 20 on tumour drivers and resistance mechanisms.

José Baselga, Executive Vice President, Research & Development, Oncology, said: "AstraZeneca is continuing to strengthen its portfolio of innovative cancer medicines by exploring new indications and developing a pioneering next-generation pipeline. We will be sharing some of our latest research at the 2019 AACR (Free AACR Whitepaper) Annual Meeting, including 28 new molecular entities and six combinations, highlighting an exciting new phase of scientific discovery from our Oncology R&D."

IO pipeline explores new pathways to enhance immune response

Key data from AstraZeneca’s early-stage clinical and preclinical IO pipeline include potential new medicines targeting multiple pathways, providing insight into novel mechanisms to boost current immune response and modify the tumour microenvironment both alone and in combination with checkpoint inhibition.

Presentations will highlight AstraZeneca’s growing portfolio in small molecules and antisense oligonucleotides (ASOs) targeting immunosuppressive mechanisms in cancer, and the Company’s exploration of the adenosine pathway, which is increasingly recognised as critical to tumour suppression and represents a new frontier within IO.

Phase I and preclinical data demonstrating AZD4635, a small molecule A2AR antagonist, prevents adenosine-mediated immunosuppression. Early clinical activity has been observed with AZD4635 monotherapy or in combination with Imfinzi in patients with metastatic castration-resistant prostate cancer (Abstracts #LB-192/10, #CT026/21)
Preclinical research on the activity of ASO AZD8701 (ION-AZ7), showing that inhibiting FOXP3 may limit immunosuppressive functions and induce tumour regression (Abstract #2713)
Preclinical pharmacodynamic and mechanistic data illustrating how danvatirsen (AZD9150), a STAT3 ASO reverses immunosuppression to produce significant anti-tumour effects, both as monotherapy and in combination with anti-PDL1 (Abstract #3215/25)
Preclinical data for MEDI5083, a novel fusion protein which activates the CD40 pathway, indicating robust immune activation and anti-tumour activity (Abstract #1534/3)
Preclinical data for MEDI1191, a novel IL12-based treatment designed for injection directly into tumours, showing potential to drive anti-tumour response for patients with solid tumours both as monotherapy and in combination with anti-PDL1 (Abstract #5017/11)
Next wave of DDR targets

New research will showcase AstraZeneca’s DDR pipeline beyond PARP inhibition, including on the discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor (Abstract #DDT01-02). DNA-PK is critical in repairing DNA double strand breaks through the non-homologous end joining (NHEJ) pathway and has also been linked to the replication stress response (RSR), a type of DDR.

Additional new data will be shared on reversing PARP inhibitor resistance by targeting alternative DDR dependencies, like the RSR (Abstract #932).

Predicting response and addressing treatment resistance in lung cancer: new insights from MYSTIC and TATTON trials for Imfinzi and Tagrisso

Exploratory analyses of blood and tissue tumour mutational burden (TMB) from the Phase III MYSTIC trial assess TMB as a potential biomarker of survival in 1st-line use of Imfinzi with or without tremelimumab vs. chemotherapy in metastatic non-small cell lung cancer (NSCLC) (Abstract #CT074). The trial did not meet the primary endpoints, but Imfinzi monotherapy demonstrated clinical activity in the primary analysis. The MYSTIC trial provides the most comprehensive data set to date evaluating blood TMB and is the only Phase III randomised, controlled trial to demonstrate an association between high TMB and overall survival benefit with immunotherapy treatment. This new analysis will further evaluate the use of TMB as a potential biomarker predictive of survival benefit with IO treatment.

In addition, several abstracts will be presented from the TATTON Phase Ib trial testing the combination of Tagrisso with potential new medicines savolitinib or selumetinib in NSCLC patients who have progressed on prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment (Abstracts #CT032, #CT033, #CT034). The TATTON trial supports SAVANNAH, an ongoing Phase II clinical trial exploring the combination of Tagrisso and savolitinib to overcome MET-driven EGFR-TKI resistance following treatment with Tagrisso in EGFR-mutated (EGFRm) NSCLC. Characterisation of detection methods for identifying MET-driven EGFR-TKI resistance will be presented (Abstract #4897/20). TATTON will also inform the trial design of ORCHARD, a Phase II platform trial exploring potential new treatment options to address resistance mechanisms in patients with EGFRm NSCLC who have experienced disease progression following 1st-line treatment with Tagrisso.

Key AstraZeneca presentations at AACR (Free AACR Whitepaper) 2019

Lead author

Abstract title

Presentation details

Immuno-Oncology

Peters, S

Tumour mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a Phase 3 study of first-line durvalumab ± tremelimumab vs chemotherapy

Abstract #CT074

Session CTPL03 – Optimizing PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy: Dedicated to the Memory of Waun Ki Hong

Monday 1 April

10:30am-12:45pm

Marcus Auditorium- Bldg A-GWCC

Srinivasan, S

STAT3 ASO reverses immunosuppression and enhances cytotoxic cell function to enhance PDL1 blockade

Abstract #3215/25

Session PO.IM02.01 – Combination Immunotherapies 2

Tuesday 2 April

8:00am-12:00pm

Section 23

Barbon, CM

The A2AR antagonist AZD4635 prevents adenosine-mediated immunosuppression of CD103+ dendritic cells

Abstract #LB-192/10

Session LBPO.IM02 – Late-Breaking Research:
Immunology 2

Tuesday 2 April

8:00am-12:00pm

Section 42

Merchant, MS

Evidence of Immune Activation in the first-in-human Phase 1a dose escalation study of the Adenosine 2a Receptor Antagonist, AZD4635, in patients with advanced solid tumors

Abstract #CT026/21

Session PO.CT01 – Phase I Clinical Trials: Part 1

Sunday 31 March

1:00pm-5:00pm

Section 16

Sinclair, C

Discovery and characterization of AZD8701, a high affinity antisense oligonucleotide targeting FOXP3 to relieve immunosuppression in cancer

Abstract #2713

Session MS.IM02.01 – Rational Combinations of Immunotherapy

Monday 1 April

4:35pm-4:50pm

Room A411-Georgia World CC

Wang, Y

MEDI5083, a novel CD40L-Fc fusion protein, activates the CD40 pathway on antigen presenting cells and promotes a robust anti-tumor immune response in a B16F10 murine tumor model

Abstract #1534/3

Session PO.IM02.17 – Therapeutic Antibodies 2

Monday 1 April

8:00am-12:00pm

Section 25

Luheshi, N

MEDI1191, a novel IL-12 mRNA therapy for intratumoral injection to promote TH1 transformation of the patient tumor microenvironment

Abstract #5017/11

Session PO.IM02.10 – Tumor Immune Microenvironment

Wednesday 3 April

8:00am-12:00pm

Section 25

DNA damage response

Goldberg, FW

Discovery and first structural disclosure of AZD7648, a potent and selective DNA-PK inhibitor

Abstract #DDT01-02

Session DDT01 – New Drugs on the Horizon: Part 1

Sunday 31 March

1:24pm-1:48pm

Room A305 – Georgia World CC

Cadogan, EB

AZD7648: A potent and selective inhibitor of DNA-PK with pharmacodynamic and monotherapy anti-tumour activity

Abstract #3505/16

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

Fok, J

AZD7648, a potent and selective inhibitor of DNA-PK, potentiates the activity of ionising radiation and doxorubicin in vitro and causes tumour regression in xenograft models

Abstract #3512/23

Session PO.MCB07.03 – DNA Damage and Repair 3

Tuesday 2 April

8:00am-12:00pm

Section 35

O’Connor, M

Reversing PARP inhibitor resistance by targeting the replication stress response

Abstract #932

Session MS.ET03.01 – Drug Resistance

Sunday 31 March

4:35pm-4:50pm

Room B304 – Georgia World CC

Tumour drivers and resistance

Yu, H

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT032

Session CTPL02 – Can the Challenge of NSCLC Resistance be MET or Will We Not MEK It?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Sequist, L

TATTON Phase Ib expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)

Abstract #CT033

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Ramalingam, S

Osimertinib plus selumetinib for patients (pts) with EGFR-mutant (EGFRm) NSCLC following disease progression on an EGFR-TKI: results from the Phase Ib TATTON study

Abstract #CT034

Session Clinical Trials Plenary, Can the Challenge of NSCLC Resistance be MET or Will We Not MEK it?

Sunday 31 March

3:00pm-5:15pm

Marcus Auditorium- Bldg A-GWCC

Hartmaier, RJ

Detection of MET-mediated EGFR tyrosine kinase inhibitor (TKI) resistance in advanced non-small cell lung cancer (NSCLC): biomarker analysis of the TATTON study

Abstract #4897/20

Session PO.CL11.07 – Novel Strategies for Biomarker Identification and Use in Cancer 3

Wednesday 3 April

8:00am-12:00pm

Section 19

Liquid biopsies

Barrett, JC

Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Major Symposium: Regulatory Science and Policy

Session SYPOL07 – Regulatory Considerations for Utilizing Liquid Biopsies in Drug and Diagnostic Development

Tuesday 2 April

3:00pm-5:00pm

Room A402 – Georgia World CC

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On March 14, 2019 ESSA Pharma Inc. (TSX-V: EPI;Nasdaq: EPIX) ("ESSA" or the "Company"), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer reported that the Company will be attending the 31st Annual ROTH Conference to be held on March 17 -19 at the Ritz Carlton Laguna Niguel in Dana Point, California (Press release, ESSA, MAR 14, 2019, View Source [SID1234534324]). Dr. David R. Parkinson, President & Chief Executive Officer and Peter Virsik, Chief Operating Officer will be available for one-on-one meetings throughout the conference.

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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

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On March 14, 2019 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for selinexor (Press release, Karyopharm, MAR 14, 2019, View Source [SID1234534323]). The NDA, which is currently under Priority Review by the FDA, is seeking accelerated approval for selinexor in combination with dexamethasone for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. The previously disclosed April 6, 2019 PDUFA date has been extended by three months to July 6, 2019.

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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

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On February 26, 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) met to discuss the selinexor NDA and voted 8 to 5 recommending that the FDA wait for the results from Karyopharm’s randomized, open-label, Phase 3 BOSTON study evaluating selinexor in patients with relapsed or refractory multiple myeloma, before making a final decision regarding approval. Although the FDA considers the recommendation of this panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.

Following the ODAC meeting, at the FDA’s request, Karyopharm submitted additional, existing clinical information as an amendment to the NDA, which allowed the FDA to extend the PDUFA action date by three months. "We look forward to the continued collaboration with FDA in trying to meet the needs of patients with relapsed refractory multiple myeloma," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm.

About Selinexor

Selinexor 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. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with triple class refractory multiple myeloma. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval and was granted accelerated assessment. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Selinexor is also being evaluated in several other 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), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with 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 14, 2019 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage immunotherapeutics company, reported that Vipin K. Garg, Ph.D., President and Chief Executive Officer, and Will Brown, Acting Chief Financial Officer, will provide a corporate overview at the 31st Annual ROTH Conference (Press release, Altimmune, MAR 14, 2019, View Source [SID1234534322]). Details of the presentation are as follows:

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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

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31st Annual ROTH Conference Presentation Details
Date: Tuesday, March 19
Time: 1:30pm Pacific Time
Location: The Ritz Carlton, Laguna Niguel in Orange County, CA

On March 14, 2019 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that the United States Patent and Trademark Office ("USPTO") has issued a Notice of Allowance for an additional cancer detection technology patent (Press release, Anixa Biosciences, MAR 14, 2019, View Source [SID1234534316]). This patent provides broader coverage for the use of Anixa’s technology in a wider range of applications and protects critical new improvements developed for Anixa’s cancer detection technology. This patented technology is a key component of Cchek, Anixa’s early cancer detection platform that utilizes flow cytometry and artificial intelligence.

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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

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The patent is titled, "METHODS FOR USING ARTIFICIAL NEURAL NETWORK ANALYSIS ON FLOW CYTOMETRY DATA FOR CANCER DIAGNOSIS," and the inventors are Dr. Amit Kumar, John Roop, Anthony Campisi, and Dr. George Dominguez. This patent is assigned wholly to Anixa.

Dr. Amit Kumar, Anixa’s Chairman, President and CEO, stated, "We are pleased to receive further patent protection on our liquid biopsy technology. We plan to launch the first product utilizing this technology, a prostate cancer confirmatory test, in the third quarter of this year." Dr. Kumar continued, "Today, I will be presenting this technology including the latest data at the Molecular Medicine TriConference in San Francisco."