On April 14th, 2016 PharmaMar (MSE:PHM) reported that it will present the latest data obtained on its compounds of marine origin, lurbinectedin, plitidepsin and PM184 at the Annual Congress of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), that will be held in New Orleans from the 16th to the 20th of April (Press release, PharmaMar, APR 14, 2016, View Source [SID:1234510765]). Under the heading "Delivering Cures Through Cancer Science", oncologists and investigators from around the world will interchange knowhow and reinforce the links between research and the advancements in patient care.

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Through the studies that will be presented, PharmaMar will reveal the new results of its three molecules that are presently under clinical investigation in different types of solid and hematological tumors. Each one of these compounds has a very different mechanism of action. Apart from its direct activity on tumor cells, lurbinectedin (PM1183) also attacks the microenvironment, rendering tumor growth unfeasible. Plitidepsin (Aplidin), targets the eEF1A2 protein, and finally PM184 disrupts the tumor’s blood vessels, causing a reduction in the supply of both nutrients and oxygen to the tumor cells.
"In PharmaMar we have a commitment to the identification of new and novel mechanisms of action from marine compounds that can provide a step forward in the treatment of patients with cancer," explains Carmen Cuevas, Ph.D., R&D Director from the Oncology Business Unit at PharmaMar. "The results that we will present at scientific congresses such as the AACR (Free AACR Whitepaper) show that we are on right road and, that we can count on a robust pipeline that, without any doubt, will provide 2 new methods for attacking tumor cells."

Studies that will be presented at the 2016 AACR (Free AACR Whitepaper)
PM1183 (lurbinectedin) PM1183 is compound under clinical investigation, inhibitor of the RNA polymerase II enzyme. It is essential for the transcription process, inhibiting tumor growth, and resulting in tumor death. The antitumor efficacy of PM1183 is being investigated in various types of solid tumors.

Lurbinectedin reduces tumor-associated macrophages and the production of inflammatory cytokines, chemokines and angiogenic factors in preclinical models (abstract No 1284). Paola Allavena et al. Poster presentation, section 18, Monday April 18th, 8:00 am – 12:00 am.

This proves that part of lurbinectedin’s antitumor activity is due to its antiproliferative activity in monocytes and tumor associated macrophages, cells that are essential in the inflammatory microenvironment. Lurbinectedin inhibits transcription, therefore, the production of cytokines and angiogenic factors by these cells. Tumor growth is unfeasible, even when the tumor cells are resistant to the compound.

Lurbinectedin specifically targets transcription in cancer cells, triggering DNA breaks and degradation of phosphorylated Pol II (Abstract No 3039). Gema Santamaría-Nuñez et al. Poster presentation, section 17, Tuesday April 19th , 8:00 am-12:00 am.
Lurbinectedin (PM1183) binds to the DNA in the CG rich regions surrounding the promoter of genes, inhibiting transcription activity. The mechanism involves the ubiquitination and degradation by proteasome of the RNA polymerase II (pol II). The degradation of pol II is directly related to the appearance of DNA damage and the induction of cell death through apoptosis.
Plitidepsin (Aplidin) Plitidepsin is an antitumor drug of marine origin, at the investigational phase for hematological tumors, including a phase Ib study in relapsed and refractory Multiple Myeloma, in triple combination with bortezomib and dexamethasone, along with a phase II study in Relapsed and Refractory Angioimmunoblastic T-cell 3 Lymphoma. Recently, positive results have been seen in pivotal study in combination with dexamethasone in patients with Multiple Myeloma.

Plitidepsin targets the GTP-bound form of eEF1A2 in cancer cells (Abstract No 3015). Alejandro Losada et al. Poster presentation, section 17, Tuesday April 19th, 8:00am-12:00am.

This confirms that the protein eEF1A2 is Aplidin’s pharmacological target. This protein has numerous functions within the tumor cell, some of which have a marked oncogenic character. This assay delves into the peculiarities of the direct interaction of Aplidin with purified GTP bound eEF1A2.

PM184
PM184 is an inhibitor of tubulin polymerization. It is at the clinical development stage for solid tumors, including a Phase II trial in hormone-receptor positive, HER2-negative, locally advanced and/or metastatic breast cancer.

Anti-angiogenic properties of PM184 (Abstract No 3066). Carlos M. Galmarini et al. Poster presentation, section 25, Tuesday April 19th, 8:00am-12:00am.

The tumor cells rapidly growth, needing the supply of a large quantity of nutrients. One of the paths for the treatment of cancer at the moment is to disrupt the blood cells within the tumor, or to stop the development of new cells, cutting the supply of nutrients and oxygen to the tumor cells. Adding to its capacity to specifically eliminate tumor cells, PM184 has shown itself to have a strong intratumor vascular disrupting activity, inhibiting in this extraordinarily effective way, human transplanted tumors in mice.

On April 14, 2016 AstraZeneca and its global biologics research and development arm, MedImmune, will present 57 abstracts,
deliver five oral presentations and two lectures as well as participating in a round-table session on PD-L1 diagnostic harmonisation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans this week (Press release, AstraZeneca, APR 14, 2016, View Source [SID:1234510764]).

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DNA Damage Response: an industry-leading portfolio

Three oral presentations will provide insight into AstraZeneca’s industry-leading DNA Damage Response (DDR) pipeline of potential medicines as both monotherapy and in combination:

Phase I data evaluating the combination of first-in-class PARP inhibitor Lynparza (olaparib) and AKT inhibitor AZD5363 in germline BRCA and non-BRCA mutant advanced cancer patients (Abstract #CT1010)

Early safety and efficacy data from a Phase Ib study of novel potential medicine AZD1775, a small molecule designed to inhibit the Wee1 kinase, which plays a critical role in the DNA damage repair that enables cell division (Abstract #CT013)

Pre-clinical pharmacology of AZD0156, an ATM kinase inhibitor that detects DNA double strand breaks to enable downstream DNA repair and cell survival (Sunday 17 Apr – 14:15-16:15)

Andrew Mortlock, Vice President, Global Projects and Alliances, Oncology iMed at AstraZeneca said: "The data we will present at AACR (Free AACR Whitepaper) underscore the scientific promise shown by our industry-leading DDR portfolio as well as the clinical potential of this pioneering approach to targeting tumour cells. With three new molecules now in the clinic and one on the market, we are following the science and exploring their potential in both monotherapy and in combination with other therapies."

Immuno-Oncology: biomarkers, next-generation Immunotherapies, and combinations

AstraZeneca’s Immuno-Oncology research will feature prominently at AACR (Free AACR Whitepaper), including with new data from a comparative study of commonly used PD-L1 diagnostic tests in approximately 500 tumour biopsies (Abstract #LB-094; also included in the AACR (Free AACR Whitepaper) media programme). AstraZeneca will also take part in a roundtable discussing the value of PD-L1 diagnostic testing – "The Blueprint Project: Harmonizing Companion Diagnostics across a Class of Targeted Therapies", scheduled for Tuesday 19 April, 13.00 – 15.00 EST (Room 283, Morial Convention Center).

AstraZeneca will also provide updates on its exploration of biological targets beyond PD-L1 and CTLA-4, including MEDI1873, an agonist of the GITR receptor (Abstract #561) and MEDI9197, a TLR7/8 agonist (Abstract #1475), as well as the combination strategy of PD-L1/PD1 axis inhibition with several complementary mechanisms of action targeting NKG2A, OX40 and immTACs.

In addition, researchers at the congress will present the latest results from a Phase I/II trial of tremelimumab plus tumour ablation in patients with advanced hepatocellular carcinoma (HCC) (Abstract #2653).

David Berman, Senior Vice President, Head of Oncology Innovative Medicines, at MedImmune, said: "At AACR (Free AACR Whitepaper), we will present pre-clinical data and mechanistic characterisation that support our ongoing clinical trials exploring next-generation immuno-oncology targets and their combination with durvalumab. We will present a comparison of the different PD-L1 diagnostic assays to help advance the science for the field of PD1/L1 blockade. In addition, the activity of tremelimumab, a CTLA4 inhibitor, will be further evidenced."

Tumour drivers and resistance: A key area of expertise

AstraZeneca will also present data on Tagrisso (osimertinib), exploring the utilisation of non-small cell lung cancer (NSCLC) xenograft models from patients on Tagrisso to refine therapeutic strategies (Abstract #5192). Tagrisso recently received accelerated approval as the first indicated treatment for patients with EGFR T790M mutation-positive metastatic NSCLC in the US, EU and Japan.

The company will also showcase its continued progress in therapies targeting the genetic drivers of cancer with breaking data on an early-stage mTOR inhibitor that has shown pre-clinical activity in prostate cancer. Specific posters include:

Anti-tumour activity of mTOR inhibitor AZD2014 in a prostate cancer mouse model (Abstract #2147)

Overcoming mTOR resistance mutations with a next-generation mTOR inhibitor (Abstract #389)

NOTES TO EDITORS

AstraZeneca/MedImmune key presentations at AACR (Free AACR Whitepaper)

DNA Damage Response

Thomason AG
Discovery and pre-clinical pharmacology of AZD0156: A
first-in-class potent and selective inhibitor of Ataxia telangiectasia mutated (ATM) kinase
Oral
New Drugs on the Horizon
Sunday 17 Apr 14:15-16:15
New Orleans Theater C, Morial Convention Center
Webcast Available

Bauer TM
A Phase Ib, open-label, multi-center study to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD1775 monotherapy in patients with advanced solid tumors: Initial findings
Oral
Clinical Trials Plenary Session 2
Early Clinical Trials of Agents Targeting DNA or the Epigenome
Sunday 17 Apr 16:15-18:15
Room 291, Morial Convention Center
Abstract #CT013

Michalarea V
Phase I trial combining the PARP inhibitor Olaparib (Ola) and AKT inhibitor AZD5363 (AZD) in germline (g)BRCA and non-BRCA mutant (m) advanced cancer patients (pts) incorporating non-invasive monitoring of cancer mutations
Oral
Clinical Trials Plenary Session 2
Early Clinical Trials of Agents Targeting DNA or the Epigenome
Sunday 17 Apr 16:15-18:15
Room 291, Morial Convention Center
Abstract #CT010

Laing N
Genetic analysis of tumors from a Phase II trial evaluating AZD1775, carboplatin and paclitaxel in patients with TP53-mutant ovarian cancer
Poster
Experimental and Molecular Therapeutics
Novel Antitumor Agents
Sunday 17 Apr 13:00–17:00
Convention Center, Halls G-J, Poster Section 14
Poster Board #18, Abstract #337

Durant S
Blood-brain barrier penetrating ATM inhibitor (AZ32) radiosensitises intracranial gliomas in mice
Poster
Experimental and Molecular Therapeutics
Preclinical Radiotherapeutics
Tuesday 19 Apr 08:00–12:00
Convention Center, Halls G-J, Poster Section 18
Poster Board #1, Abstract #3041

Oplustil O’Connor L
A camptothecin-containing nanoparticle-drug conjugate combination with DDR agents provides a novel approach to increasing therapeutic index
Poster
Experimental and Molecular Therapeutics
Cell Death Pathways and DNA Repair
Tuesday 19 Apr 13:00–17:00
Convention Center, Halls G-J, Poster Section 14
Poster Board #19, Abstract #3721

Perez-Lopez R
Diffusion-weighted imaging of bone metastases as treatment response biomarker in prostate cancer
Poster
Clinical Research
Novel Molecular Diagnostics and Imaging
Tuesday 19 Apr 13:00–17:00
Convention Center, Halls G-J, Poster Section 24
Poster Board #3, Abstract #3973

Williams L
Continuous, low intensity systemic dosing maximizes the therapeutic margin of Eg5/KSP inhibition in a model of urothelial cell carcinoma
Poster
Experimental and Molecular Therapeutics
Novel Antitumour DNA-Reactive Agents
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 15
Poster Board #16, Abstract #3769

Cidado J
AZ5576, a novel potent and selective CDK9 inhibitor, induces rapid cell death and achieves efficacy in multiple preclinical hematological models
Poster
Molecular and Cellular Biology/Genetics
Cell Death 3
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 4
Poster Board #22, Abstract #3572

Pike K
Identifying high quality, potent and selective inhibitors of ATM kinase: Discovery of AZD0156
Poster
Cancer Chemistry
Drug Design
Wednesday 20 Apr 08:00–12:00
Convention Center, Halls G-J, Poster Section 21
Poster Board #24, Abstract #4859

Cuneo KC
A dose escalation trial of the Wee1 inhibitor AZD1775, gemcitabine and concurrent radiation in locally advanced pancreatic cancer
Poster
Phase I Clinical Trials in Progress
Monday 18 Apr 08:00–12:00
Convention Center, Halls G-J, Poster Section 13
Poster Board #16, Abstract #CT035

Min A
Androgen receptor inhibitor enhances the anti-tumor effect of PARP inhibitor in breast cancer cells via modulation of DNA damage response
Poster
Late-Breaking Research: Experimental and Molecular Therapeutics 1
Monday 18 Apr 8:00 AM – 12:00
Convention Center, Halls G-J, Poster Section 11
Abstract #LB-107

Immuno-Oncology

Uppala A
Tremelimumab plus tumor ablation for patients with hepatocellular carcinoma: Clinical results, Immunomonitoring analysis of peripheral T cells and tumor biopsies
Oral
Immunology
Session Title TBD
Monday 18 Apr 15:00-17:00
New Orleans Theater B, Morial Convention Center
Abstract #2653
Press Programme

Messenheimer DJ
Timing of PD-1 blockade is critical to successful synergy with OX40 costimulation in preclinical mammary tumor models.
Oral
Immunology
Potentiating Immunotherapy Responses with Generation Agents and Combinatorial Partners
Tuesday 19 Apr 15:00-17:00
New Orleans Theater B, Morial Convention Center
Abstract #4361

Stewart R
Generation and Characterisation of MEDI1873 A Novel Hexameric GITRL Fusion Protein and Potent Agonist of the GITR Receptor
Poster
Immunology
Immune Modulating Agents 1
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 26
Poster Board #22, Abstract #561

Mullins S
Local immune activation resulting in tumor growth inhibition with MEDI9197 – an intratumorally administered TLR7/8 agonist
Poster
Immunology
Immune Modulation Agents and Therapeutic Antibodies
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 25
Poster Board #6, Abstract #1475

Ghadially H
Analysis of expression MHC class I chain-related gene A and B (MICA/B) in normal and tumour tissue
Poster
Immunology
Immune Microenvironment and Antitumor Immunity
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 24
Poster Board #12, Abstract #1451

Ratcliffe M
A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative
Poster
Late-Breaking Research: Immunology
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 10
Poster Board #18, Abstract #LB-094

Sola C
NKG2A immune checkpoint blockade enhances the antitumor efficacy of PD1/PD-L1 inhibitors in a preclinical model
Poster
Immunology
Immune Checkpoints 1
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 26
Poster Board #26, Abstract #2342

Odate S
Inhibition of STAT3 with oligonucleotide antisense molecule, AZD9150 increases the chemosensitivity and decreases tumorigenicity of neuroblastoma
Poster
Tumor Biology
Pediatric Cancer Molecular Pathways
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 31
Poster Board #2, Abstract #2439

Harper J
Exploring the oncolytic potential of Newcastle Disease virus
Poster
Clinical Research
Adoptive Cell Therapy, Immune Checkpoints, and Vaccines
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 21
Poster Board #26, Abstract #2234

Jiang L
PD-L1 expression and its relationship with other driver genes in non-small cell lung cancer (NSCLC
Poster
Tumor Biology
Immunomodulation and Immunotherapy
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 31
Poster Board #26, Abstract #5140

Leyland R
A Mouse GITRL Fusion Protein Drives T-Cell Activation and Antitumor Activity in Preclinical Mouse Models of Cancer
Poster
Immunology
Immune Response Monitoring: Preclinical
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 23
Poster Board #13, Abstract #4902

Bossi, G
ImmTACs in combination with anti-CTLA-4 and anti-PD-L1 antibodies can re-direct the immune system more efficiently to eradicate cancer
Poster
Immunology
Immune Modulation Agents 2
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 22
Poster Board #14, Abstract #4873

Huff CA
Clinical cancer stem cell targeting in multiple myeloma: An early phase trial of the anti-CD19 monoclonal antibody, MEDI-551, in combination with lenalidomide and dexamethasone
Poster
Phase II, III, and Special Population Clinical Trials
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 13
Poster Board #2, Abstract #CT102

Tumour Drivers & Resistance

Noble R
Evaluating the consequences of MCT1 inhibition in Burkitt lymphoma following treatment with AZD3965
Poster
Experimental and Molecular Therapeutics
Novel Antitumor Agents
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 17
Poster Board #6, Abstract #325

Avivar-Valderas A
Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer
Poster
Experimental and Molecular Therapeutics
Cellular Processes and Responses to Therapy
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 14
Poster Board #6, Abstract #240

Sandi C
Dual mTOR inhibitor, AZD2014, and castration induce immunogenic effects and anti-tumour activity in prostate cancer mouse model
Poster
Experimental and Molecular Therapeutics
PI3K/AKT Inhibitors
Sunday 17 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 19
Poster Board #20, Abstract #389

Feng S
AZD4547 and AZD5363 synergistically inhibit prostate cancer progression by modulating MAPK and AKT activation
Poster
Molecular and Cellular Biology/Genetics
Oncogenes and Tumor Suppressor Genes and Pathways
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 9
Poster Board #24, Abstract #1174

Barry E
Targeting MET Exon 14 mutations with the selective small molecule inhibitor Savolitinib
Poster
Molecular and Cellular Biology/Genetics
Oncogene Function, Regulation and Targeting
Monday 18 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 8
Poster Board #30, Abstract #1150

Diallo B
The MEK1/2 inhibitor selumetinib appears as an efficient targeted therapy when used in an adjuvant setting in Patient-Derived Xenografts of Uveal Melanoma
Poster
Experimental and Molecular Therapeutics
Experimental Therapeutics
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 16
Poster Board #8, Abstract #2087

Rodrik-Outmezguine VS
Overcoming mTOR Resistance Mutations with a new generation mTOR inhibitor
Poster
Experimental and Molecular Therapeutics
New Drugs, Therapeutic Targets, and Treatment Approaches
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 18
Poster Board #17, Abstract #2147

Yang Z
Anti-tumor activities of AZD3759, a novel EGFR inhibitor with excellent penetration cross central nervous system (CNS), in pre-clinical animal models
Poster
Session Category TBD
Late-Breaking Research: Experimental and Molecular Therapeutics 2
Monday 18 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 12
Poster Board #24, Abstract #LB-217

Searle EJ
Treatment with the novel Akt inhibitor AZD5363 following radiotherapy improves tumor control in mouse models of head and neck cancer
Poster
Experimental and Molecular Therapeutics
Preclinical Radiotherapeutics
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 18
Poster Board #2, Abstract #3042

Greenawalt D
Your targeted population might not be what you predict: Changes in tumor genetic landscapes post standard of care
Poster
Clinical Research
Molecular Classification and Genomic Applications
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 23
Poster Board #5, Abstract #3168

Greer Y
MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonist, induces apoptotic cell death in breast cancer cells
Poster
Molecular and Cellular Biology/Genetics
Cell Death 1
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 2
Poster Board #4, Abstract #3494

De Velasco MA
The Jak1/2 inhibitor AZD1480 suppresses tumor growth and metastasis in genetically engineered mouse models of PTEN-deficient prostate cancer
Poster
Experimental and Molecular Therapeutics
Targeting Protein Kinases, Death Pathways, and the Tumor Microenvironment
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 19
Poster Board #26, Abstract #3864

Deng J
Pre-clinical study using KRAS mutant mouse models for lung cancer immunotherapy
Poster
Tumor Biology
Mechanisms of Tumorigenesis in Animal Models of Cancer 2
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 32
Poster Board #22, Abstract #4184

McEachern K
Predicting response to Mcl-1 targeting agents in NSCLC and Multiple Myeloma
Poster
Molecular and Cellular Biology/Genetics
Cell Death 3
Tuesday 19 Apr 13:00-17:00
Convention Center, Halls G-J, Poster Section 4
Poster Board #8, Abstract #3558

Palakurthi S
Utilizing NSCLC PDXs derived from patients on osimertinib (AZD9291) clinical trials to further refine therapeutic strategies
Poster
Tumor Biology
Therapeutic Studies in Patient-derived Xenografts
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 33
Poster Board #18, Abstract #5192

Nilsson M
Beta blockers abrogate EGFR TKI resistance induced by adrenergic receptor-mediated upregulation of IL-6 and modulation of the LKB1/AMPK/mTOR axis
Poster
Experimental and Molecular Therapeutics
Combination Therapies and Approaches to Sensitizing Cancer Cells to Drugs
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 15
Poster Board #3, Abstract #4662

Chen H
Therapeutic activity of bivalent BRD4 inhibitor AZD5153 in haematological cancers
Poster
Experimental and Molecular Therapeutics
Epigenetic Agents
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 16
Poster Board #16, Abstract #4705

Capasso A
A phase IB study of the combination of AZD6244 hydrogen sulfate (selumetinib) and cyclosporin A (CsA) in patients with advanced solid tumors with an expansion cohort in metastatic colorectal cancer
Poster
Phase I Clinical trials 2
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 13
Abstract # CT146

Cortes J
Phase I studies of AZD1208, a PIM kinase inhibitor, in patients with recurrent or refractory acute myelogenous leukemia or advanced solid tumors
Poster
Phase I Clinical Trials 2
Wednesday 20 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 13
Poster Board #8, Abstract #CT147
Antibody Drug Conjugates

Li J
MEDI4276, a HER2-targeting antibody tubulysin conjugate, displays potent in vitro and in vivo activity in preclinical studies
Poster
Experimental and Molecular Therapeutics
Monoclonal Antibodies and Antibody-Drug Conjugates
Tuesday 19 Apr 08:00-12:00
Convention Center, Halls G-J, Poster Section 15
Poster Board #16, Abstract #2970

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 6 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 New Oncology as one of AstraZeneca’s six Growth Platforms 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, the genetic drivers of cancer 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.

LAM-002 is an exquisitely selective first-in-class kinase inhibitor that is cytotoxic for specific cancers with little to no effect on normal cells. LAM Therapeutics advanced LAM-002 into a Phase 1 trial in relapsed or refractory B-cell non-Hodgkin lymphoma within one year of discovery (Company Pipeline, LAM Therapeutics, APR 14, 2016, View Source [SID:1234510762]).

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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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LAM-002 is also being evaluated in pre-clinical models of neurological disease.

The mechanisms underlying discrimination between "self" and "non-self", a central immunological principle, require careful consideration in immune oncology therapeutics where eliciting anti-cancer immunity must be weighed against the risk of autoimmunity due to the self origin of tumors. Whole cell vaccines are one promising immunotherapeutic avenue whereby a myriad of tumor antigens are introduced in an immunogenic context with the aim of eliciting tumor rejection. Despite the possibility collateral damage to healthy tissues, cancer immunotherapy can be designed such that off target autoimmunity remains limited in scope and severity or completely non-existent. Here we provide an immunological basis for reconciling the safety of cancer vaccines, focusing on tumor endothelial cell vaccines, by discussing the following topics: (a) Antigenic differences between neoplastic and healthy tissues that can be leveraged in cancer vaccine design; (b) The layers of tolerance that control T cell responses directed against antigens expressed in healthy tissues and tumors; and, (c) The hierarchy of antigenic epitope selection and display in response to whole cell vaccines, and how antigen processing and presentation can afford a degree of selectivity against tumors. We conclude with an example of early clinical data utilizing ValloVax, an immunogenic placental endothelial cell vaccine that is being advanced to target the tumor endothelium of diverse cancers, and we report on the safety and efficacy of ValloVax for inducing immunity against tumor endothelial antigens.

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!