1stOncology™: Cancer Intelligence Service – Page 16095 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Evotec expands collaboration with STORM Therapeutics on its RNA epigenetic platform

On July 27, 2017 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) reported an integrated drug discovery collaboration with STORM Therapeutics ("STORM") to develop new small molecule epigenetic drugs for oncology and other therapeutic areas (Press release, Evotec, JUL 27, 2017, View Source [SID1234519900]). The focus will be on a range of newly discovered RNA modulating enzyme targets.

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!

Evotec and STORM have been collaborating since 2016 in high-throughput screening and structural biology to identify hits against two of Storm’s RNA modulating targets. The agreement has been expanded to support STORM’s chemistry efforts on additional novel targets. Evotec will use its broad drug discovery platform to develop the compounds against these novel RNA targets.

STORM was founded based on pioneering work in the Kouzarides & Miska labs at the University of Cambridge to tackle diseases through drugging of RNA modulating enzymes. STORM is the only company harnessing the power of RNA epigenetics as a new area of important biology.

Dr Mario Polywka, Chief Operating Officer of Evotec, commented: "We are excited to be part of this extended drug discovery collaboration with STORM which is targeting this novel class of RNA modulating enzymes. This integrated drug discovery collaboration showcases our industry leading drug discovery platform and expertise and shows how it can be applied to the most novel drug targets."

Keith Blundy, CEO of STORM Therapeutics, added: "We are very happy to further expand this relationship with Evotec. At STORM, our vision is to become the world’s first company to deliver a disease-modifying agent that works by targeting RNA modulating enzymes. The combination of our understanding of the unique biology of our multiple targets and the infrastructure we have in place with Evotec will enable us to accelerate the development of novel small molecule drug candidates."
No financial details were disclosed.

RNA AND RNA EPIGENETICS
RNA (ribonucleic acid) is the only direct product of the human genome and as mRNA acts as the template for the synthesis of all proteins, the molecular machines of the cell. RNA is also known to be a key player in cellular decision-making, particularly in the form of non-coding RNA (ncRNA) such as microRNA, piRNA and long non-coding RNA. Almost all of this RNA is chemically modified: over 100 different chemical modifications have been identified to date, catalysed by several large families of RNA-modifying enzymes. The discovery of reversible chemical modifications of RNA and their role in changing RNA activity and regulating key processes within the cell gave rise to the concept of RNA epigenetics. There is a growing understanding of the importance of RNA modifications in the development of cancer and other diseases, providing a wealth of novel therapeutic targets for drug discovery.

TESARO AND TAKEDA ENTER INTO EXCLUSIVE LICENSING AGREEMENT TO DEVELOP AND COMMERCIALIZE NOVEL CANCER THERAPY NIRAPARIB IN JAPAN

On July 27, 2017 TESARO, Inc. (NASDAQ: TSRO) and Takeda Pharmaceutical Company Limited (TSE:4502) reported an exclusive licensing agreement for the commercialization and clinical development of niraparib, a novel poly ADP-ribose polymerase (PARP) inhibitor (Press release, TESARO, JUL 27, 2017, View Source [SID1234519902]). This agreement includes the development of niraparib for the treatment of all tumor types in Japan, and all tumor types excluding prostate cancer in South Korea, Taiwan, Russia and Australia. Niraparib, first marketed in the U.S. in April under the brand name ZEJULA, has quickly become the most frequently prescribed PARP inhibitor in the U.S.

Under the terms of this agreement, TESARO will receive a $100 million upfront payment and is eligible to receive additional milestone payments of up to $240 million related to the achievement of certain regulatory and commercial goals. TESARO will also be eligible to receive from Takeda tiered royalties based on a double digit percentage of net product sales. Takeda gains exclusive commercial rights for all potential future niraparib indications in Japan, and rights excluding prostate cancer in South Korea, Taiwan, Russia and Australia. Takeda will be responsible for development of niraparib in Japan and the four specified countries, including all associated expenses. Additional terms of this agreement were not disclosed.

"The niraparib development program addresses many of the most prevalent and devastating cancers worldwide. We must continue to make new treatments available to patients and, through research, further our knowledge into the full utility of this molecule," said Christophe Bianchi, President of Takeda Oncology.

"We are pleased to be collaborating with TESARO, a company we admire for its high caliber oncology expertise. This agreement represents another step in our goal of building Takeda’s robust portfolio in solid tumors and, more importantly, our commitment to patients living with cancer who desperately want — and need — new, innovative therapies."

Once-daily niraparib is the first and only PARP inhibitor that has received approval for the maintenance treatment of women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status. TESARO’s development plan currently includes clinical trials of niraparib in patients with ovarian, breast, and lung cancer. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

"TESARO is devoted to providing transformative therapies for people bravely facing cancer, and this partnership enables us to continue to globalize our mission," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "As the largest pharmaceutical company in Japan, Takeda is recognized as a leader in oncology, and we are excited to work with the Takeda team to quickly advance niraparib for patients who are in need of new treatment options."

Niraparib is not currently approved for use in Japan, South Korea, Russia, Taiwan or Australia.

About ZEJULA (Niraparib)

ZEJULA (niraparib) is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect. Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in patients treated with ZEJULA. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia), as well as cardiovascular effects (hypertension and hypertensive crisis) have been reported in patients treated with ZEJULA. Monitor complete blood counts to detect hematologic adverse reactions, as well as to detect cardiovascular disorders, during treatment. ZEJULA can cause fetal harm and females of reproductive potential should use effective contraception. Please see full prescribing information, including additional important safety information, available at www.zejula.com.

Tagrisso significantly improves progression-free survival in the Phase III FLAURA trial for lung cancer

On July 27, 2017 AstraZeneca reported that the Phase III FLAURA trial showed a statistically-significant and clinically-meaningful progression-free survival (PFS) benefit with Tagrisso (osimertinib) compared to current 1st-line standard-of-care treatment (erlotinib or gefitinib) in previously-untreated patients with locally-advanced or metastatic epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519898]).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The strong results from the FLAURA trial are very exciting news for patients with EGFR mutation-positive non-small cell lung cancer, providing physicians with a potential new first-line treatment option to improve outcomes in this disease. We will now initiate discussions with global health authorities on the data and regulatory submissions."

The efficacy, safety and tolerability profiles for Tagrisso, erlotinib and gefitinib were consistent with current knowledge. A full evaluation of the FLAURA data is ongoing. Further results will be presented at a forthcoming medical meeting.

About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR-TKI treatment leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M. Tagrisso targets this secondary mutation that leads to disease progression. There is also a need for agents with improved CNS efficacy since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso is a third generation, irreversible EGFR tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations, with clinical activity against central nervous system (CNS) metastases. Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablets have been approved in more than 50 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.

About FLAURA

FLAURA assessed the efficacy and safety of Tagrisso 80mg once-daily treatment versus standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously untreated patients with locally advanced or metastatic EGFR mutation-positive NSCLC. The trial was a double-blinded, randomised study, with 556 patients across 30 countries.

The primary endpoint of the trial was PFS, and secondary endpoints included overall survival, objective response rate, duration of response, disease control rate, safety and measures of health-related quality of life (HRQoL).

About AstraZeneca in Lung Cancer

AstraZeneca is using ground-breaking science to develop a wide range of medicines for patients with lung cancer. We are pioneering precision medicines that target molecular mutations in tumour cells, as well as those that aim to boost the power of the immune response against cancer. We are committed to transforming outcomes for patients with lung cancer, whose treatment options are currently limited.

AstraZeneca and Merck establish strategic oncology collaboration

OnJuly 27, 2017 AstraZeneca and Merck & Co., Inc., (Merck; known as MSD outside of the US and Canada) reported that they have entered a global strategic oncology collaboration to co-develop and co-commercialise AstraZeneca’s Lynparza (olaparib) for multiple cancer types. Lynparza is an innovative, first-in-class oral poly ADP ribose polymerase (PARP) inhibitor currently approved for BRCA-mutated ovarian cancer in multiple lines of treatment (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519892]).

Lynparza’s pipeline has grown significantly in the last few years, with 14 indications currently being developed across several tumour types, including breast, prostate and pancreatic cancers. The strategic collaboration is expected to further increase the number of treatment options available to patients.

The companies will develop and commercialise Lynparza jointly, both as monotherapy and in combination with other potential medicines. Independently, the companies will develop and commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab).

The companies will also jointly develop and commercialise AstraZeneca’s selumetinib, an oral, potent, selective inhibitor of MEK, part of the mitogen-activated protein kinase (MAPK) pathway, currently being developed for multiple indications including thyroid cancer.

Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "Our strategic collaboration builds on scientific evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumours. By bringing together the expertise of two leading oncology innovators, we will accelerate Lynparza’s potential to become the preferred backbone of many immuno-oncology combination therapies as the world’s first and leading PARP inhibitor. This is a truly exciting step and we are pleased to work with Merck, a company that shares our passion for science to deliver new medicines for cancer patients."

Kenneth C. Frazier, Chief Executive Officer of Merck, said: "This global collaboration between AstraZeneca and Merck, two oncology leaders, will increase the possibilities for patients to have more treatment options for more cancers. Merck continues to build its leadership in immuno-oncology with Keytruda as foundational in monotherapy and combination therapy, and this collaboration expands our oncology leadership into the growing targeted therapies of PARP and MEK inhibitors. We look forward to working with AstraZeneca to create greater value for patients and shareholders than if both companies worked independently."

Financial considerations
Under the terms of the agreement, AstraZeneca and Merck will share the development and commercialisation costs for Lynparza and selumetinib monotherapy and non-PD-L1/PD-1 combination therapy opportunities. Gross profits from Lynparza and selumetinib Product Sales generated through monotherapies or combination therapies will be shared equally.

Merck will fund all development and commercialisation costs of Keytruda in combination with Lynparza or selumetinib. AstraZeneca will fund all development and commercialisation costs of Imfinzi in combination with Lynparza or selumetinib.

AstraZeneca will continue to manufacture Lynparza and selumetinib.

As part of the agreement, Merck will pay AstraZeneca up to $8.5 billion in total consideration, including $1.6 billion upfront, $750 million for certain license options and up to $6.15 billion contingent upon successful achievement of future regulatory and sales milestones. Under the terms of the agreement, AstraZeneca anticipates approximately $1 billion to be recorded under Externalisation Revenue in 2017.

AstraZeneca will book all Product Sales of Lynparza and selumetinib; gross profits due to Merck under the collaboration will be recorded under Cost of Sales. The initial, regulatory and commercial milestone payments will be recorded under Externalisation Revenue. The transaction does not impact AstraZeneca’s 2017 financial guidance. AstraZeneca continues to anticipate that the sum of Externalisation Revenue and Other Operating Income in FY 2017 will be ahead of that in FY 2016.

The collaboration agreement was completed upon signing on 26 July 2017.

For the purposes of the UK Listing Authority’s Listing Rule LR 10.4.1 R (Notification of class 2 transactions), the book value of gross assets subject to the license and collaboration is approximately $242 million. In view of the development and early growth phase of the medicines, a pre-tax loss of $231 million was attributable to Lynparza and selumetinib in aggregate in the year to 31 December 2016.

NOTES TO EDITORS

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DDR pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines that target DDR mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed BRCA-mutated (germline and/or somatic), high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as a monotherapy for patients with deleterious, or suspected deleterious, germline BRCA-mutated (as detected by a US FDA test) advanced ovarian cancer, who have been treated with three or more lines of chemotherapy.

The Company recently presented positive results for Lynparza from its Phase III OlympiAD trial that showed a statistically-significant and clinically-meaningful improvement in progression-free survival for patients treated with Lynparza tablets (300mg twice daily), compared to treatment with physician’s choice of a standard of care chemotherapy. OlympiAD, a randomised, open label, multi-centre Phase III trial assessing the efficacy and safety of Lynparza in patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are predicted or suspected to be deleterious, was the first positive Phase III trial to evaluate the efficacy and safety of PARP inhibitor beyond ovarian cancer. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III trial called OLYMPIA. This trial is still open and recruiting patients internationally.

Lynparza generated Product Sales in 2016 of $218 million.

About selumetinib
Selumetinib, licensed by AstraZeneca from Array BioPharma Inc. in 2003, inhibits the MEK enzyme in the RAS/RAF/MEK/ERK pathway in cancer cells to prevent the tumour from growing. Selumetinib is in Phase III development for differentiated thyroid cancer, for which it was granted Orphan Drug Designation by the FDA in May 2016.

Selumetinib is also being tested in a separate Phase II trial in patients with paediatric neurofibromatosis type-1, and in a Phase I trial with patients suffering from advanced solid tumours.

About AstraZeneca in Oncology

AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer

On July 27, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported progression-free survival (PFS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy or Imfinzi in combination with tremelimumab versus platinum-based standard-of-care (SoC) chemotherapy in previously-untreated patients with metastatic (Stage IV) 1st-line non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519897]).

The combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving PFS compared to SoC in patients whose tumours express PD-L1 on 25% or more of their cancer cells (as determined by the VENTANA PD-L1 (SP263) assay).

As a secondary endpoint, although not formally tested, Imfinzi monotherapy would not have met a pre-specified threshold of PFS benefit over SoC in this disease setting.

The trial will continue to assess two additional primary endpoints of overall survival (OS) for Imfinzi monotherapy and OS for the Imfinzi plus tremelimumab combination. Final OS data from both primary endpoints are expected during the first half of 2018.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "While the results from the MYSTIC trial for progression-free survival in first-line Stage IV non-small cell lung cancer compared with standard of care are disappointing, the trial was designed to assess overall survival and we look forward to evaluating the remaining primary endpoints of overall survival for both mono- and combination therapy."

AstraZeneca recently received accelerated approval from the US FDA for Imfinzi in previously-treated patients with locally advanced or metastatic urothelial carcinoma (mUC).

About MYSTIC

The MYSTIC trial is a randomised, open-label, multi-centre, global Phase III trial of Imfinzi monotherapy or Imfinzi in combination with tremelimumab versus SoC in treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally-advanced or metastatic (Stage IV) 1st-line NSCLC. Lung cancer is an unapproved use of Imfinzi.

The trial is being conducted in 167 centres across 17 countries, including the US, Canada, Europe, parts of Asia including Japan, Korea, Thailand, Taiwan and Vietnam, and in Russia and Australia. Primary endpoints include PFS and OS.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.

Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in immuno-oncology. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in mUC and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in mUC, NSCLC, SCLC and HNSCC and in Phase I/II trials in hepatocellular carcinoma (HCC) and haematological malignancies.

About Tremelimumab

Tremelimumab is an investigational human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being investigated in an extensive clinical trial programme in combination with Imfinzi, in NSCLC, mUC, HNSCC, HCC and blood cancers.

About AstraZeneca in NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of NSCLC across all stages of disease and lines of therapy. We aim to address unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and ongoing FLAURA and ADAURA trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with NSCLC without a known genetic mutation. Our portfolio includes Imfinzi (durvalumab), an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT, PACIFIC, MYSTIC, PEARL and ARCTIC trials) and in combination with tremelimumab, an anti-CTLA-4 (MYSTIC, NEPTUNE and POSEIDON trials).