On August 14, 2019 AstraZeneca reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for Calquence (acalabrutinib) as a monotherapy treatment for adult patients with chronic lymphocytic leukaemia (CLL), one of the most common types of leukaemia in adults (Press release, AstraZeneca, AUG 14, 2019, View Source [SID1234538721]).1

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José Baselga, Executive Vice President, Oncology R&D, said: "This is an important regulatory milestone for our work in haematology and for patients living with chronic lymphocytic leukaemia, a life-threatening disease. The Breakthrough Therapy Designation acknowledges the growing body of evidence that supports Calquence as a highly-selective Bruton tyrosine kinase inhibitor with the potential to offer patients a new, differentiated, chemotherapy-free treatment option with a favourable safety profile."

The FDA granted the BTD based on positive results from the interim analyses of the ELEVATE-TN and ASCEND Phase III clinical trials. Together the trials showed that Calquence alone or in combination significantly increased the time patients lived without disease progression or death, with safety and tolerability that was consistent with its established profile.

This is the 10th BTD that AstraZeneca has received from the FDA since 2014. An FDA BTD is designed to accelerate the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown encouraging early clinical results which may demonstrate substantial improvement on a clinically-significant endpoint over currently-available medicines.

Calquence is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, Qatar, the United Arab Emirates, Mexico, Argentina and recently Singapore and is being developed for the treatment of CLL and other blood cancers. The positive results from both the ELEVATE-TN and ASCEND trials will serve as the foundation for regulatory submissions later this year.

About ELEVATE-TN

ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence alone or in combination with obinutuzumab vs. chlorambucil in combination with obinutuzumab in previously-untreated patients with CLL. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg twice daily until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity).2

The primary endpoint is progression-free survival (PFS) in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment and overall survival.2

About ASCEND

ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in previously-treated patients with CLL.2 In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received physician’s choice of either rituximab in combination with idelalisib or rituximab in combination with bendamustine.3,4

The primary endpoint is PFS assessed by an IRC, and key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as overall survival, patient-reported outcomes and time to next treatment.3,4

About Calquence

Calquence (acalabrutinib) was granted accelerated approval by the US FDA in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Calquence is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.5 In beta (B) cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 26 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenström macroglobulinaemia, follicular lymphoma, and multiple myeloma and other haematologic malignancies. Several Phase III clinical trials in CLL are ongoing, including ASCEND, ELEVATE-TN, ELEVATE-RR (ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in patients with previously-treated high-risk CLL, and ACE-CL-311 evaluating acalabrutinib in combination with venetoclax and with/without obinutuzumab in patients with previously-untreated CLL without 17p deletion or TP53 mutation.

About chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is one of the most common type of leukaemia in adults, with an estimated 105,000 new cases globally and 20,720 new cases in the US annually, and prevalence that is expected to grow with improved treatment.1,6,7,8 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.1 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.1 This could result in anaemia, infection and bleeding.1 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration that included Innate Pharma licensing the US commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.

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, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investment that accelerate the delivery of our strategy, as illustrated by the 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 August 14, 2019 M2Gen, a health informatics solutions company focused on accelerating the discovery, development and delivery of precision medicine, reported the appointment of Helge Bastian, Ph.D., as president and chief executive officer (CEO) (Press release, M2Gen, AUG 14, 2019, View Source [SID1234538740]). Bastian succeeds M2Gen Executive Chair William S. Dalton, M.D., Ph.D., who has served as interim CEO since September 2018.

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"Dr. Bastian has a proven track record of building profitable and sustainable businesses in the life sciences and healthcare sectors including many years of experience in leading clinical research and biobanking organizations supporting precision medicine approaches. We are excited to have Dr. Bastian join M2Gen and lead our company to the next level as we deliver health information solutions that link patient-specific clinical and molecular data with the objective of developing and delivering personalized medicine for patients. With Dr. Bastian at the helm, M2Gen will continue to grow and advance the company’s mission to learn from each patient and proactively develop therapeutic options to meet patient needs," said Dalton.

Dr. Bastian is an experienced executive and scientific leader with more than 27 years of international experience while contributing to the growth of leading life science and healthcare companies in Germany, Switzerland and the USA. His expertise spans, molecular and synthetic biology including game-changing technologies such as genome editing, gene synthesis and re-programming, molecular and companion diagnostics, clinical research, drug development, pharmaceutical manufacturing and biobanking. As M2Gen’s new CEO, he will focus on expanding the company’s business portfolio and growing the Oncology Research Information Exchange Network (ORIEN), an alliance of biopharmaceutical companies and leading cancer centers, powered by M2Gen’s data and informatics platforms that work in collaboration to address the greatest challenges in oncology drug development. He will also join M2Gen’s Board of Directors.

"I am very excited about M2Gen’s revolutionizing data-driven approach to precision medicine in such an important area as oncology that affects so many people’s lives. I look forward to bringing my leadership experiences from the life science and healthcare industry to M2Gen and taking the company to the next level of its exciting growth strategy," said Bastian. "Understanding a patient’s genetic predisposition and the real-time molecular patterns in a patient’s tumor in combination with his / her clinical data is paramount to unravel the molecular mechanisms responsible for cancer development, and for developing new drugs and therapies as well as for accurate patient enrolling to clinical trials and even for developing strategies for cancer prevention. M2Gen’s initiative to build this unique and growing healthcare ecosystem of cancer centers to support clinical and molecular data sharing from a large number of cancer patients via M2Gen’s platforms is designed to fundamentally change the way cancer is being studied and treated, and will accelerate the discovery and development of precision treatment options for patients."

Dr. Bastian joins M2Gen from Thermo Fisher Scientific, Inc., where he led the Sample Preparation and Synthetic Biology businesses as Vice President and General Manager since 2014. Before Thermo Fisher Scientific, Dr. Bastian held a number of senior leadership positions and served as a member of several executive leadership teams, including Managing Director and Chief Commercial Officer at Indivumed, an integrated oncology company; Vice President Global Marketing, Business Development and Strategy at Sigma-Aldrich (now Merck KGaA); Executive Vice President Life Science Services for SGS, the world’s leading inspection, verification, testing and certification company. Prior to SGS, he held various management positions during his 11-plus years at Qiagen including Vice President Molecular Diagnostics, Vice President Global Strategic Marketing, and Vice President PreAnalytiX, a QIAGEN / Becton Dickinson joint venture. Dr. Bastian earned his diploma in biology / biochemistry from Georg-August University and holds a Ph.D. in molecular and cell biology performed at the Max-Planck Institute for Biophysical Chemistry. From 2014-2018, Dr. Bastian served as a board member to the International Gene Synthesis Consortium (IGSC). Dr. Bastian has recently been appointed to the board of directors at enzymatic gene synthesis pioneer Molecular Assemblies, Inc., San Diego, and is an alumnus from the Max-Planck-Network and the Columbia Business School.

On August 14, 2019 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported financial results for the three and six months ended June 30, 2019 and provided an update on its development programs for ThermoDox and GEN-1 (Press release, Celsion, AUG 14, 2019, View Source [SID1234538760]). The Company’s lead program is ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin currently in Phase III development (the OPTIMA Study) for the treatment of hepatocellular carcinoma (HCC), or primary liver cancer. The Company’s immunotherapy candidate, GEN-1, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. GEN-1 is currently in Phase I/II development (the OVATION 2 Study) for the localized treatment of newly diagnosed Stage III/IV ovarian cancer.

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"With a clear focus on shareholder value, Celsion continues to execute its business plan for our ongoing clinical development programs with ThermoDox and GEN-1. We are exceptionally well positioned on the fundamentals with a strong balance sheet that is expected to fund our clinical programs through transformative milestones over the next 18 months," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We look forward to the first of two preplanned interim efficacy analyses for the OPTIMA Study expected in October 2019. At the current event rate, the second interim analysis, if needed, is expected to occur in early 2020. This global, pivotal study completed patient enrollment in August 2018 at more than 65 clinical sites in 14 countries, including all the major markets for primary liver cancer."

"The first cohort of patients in the dose-escalation portion of our OVATION 2 Study in newly diagnosed ovarian cancer has been enrolled. We continue to work through the activation of up to 30 clinical sites in the U.S. and Canada by the end of this year. Importantly, enrollment of patients in the Phase I portion of the study is expected to be completed and initial data reported by the end of 2019. This promising clinical development program in immunotherapy has generated impressive results in previous trials," Mr. Tardugno added.

Recent Developments

ThermoDox

Results of the National Institutes of Health Analysis of ThermoDox Published in the Journal of Vascular and Interventional Radiology. On August 13, 2019, the Company announced that results from an independent analysis of the Company’s ThermoDox HEAT Study conducted by the National Institutes of Health (NIH) were published in the peer-reviewed publication, Journal of Vascular and Interventional Radiology. The analysis was conducted by the intramural research program of the NIH and the NIH Center for Interventional Oncology (CIO), with the full data set from the Company’s HEAT Study. The analysis evaluated the full data set to determine if there was a correlation between baseline tumor volume and radiofrequency ablation (RFA) heating time (minutes/tumor volume in milliliters), with or without ThermoDox treatment, for patients with HCC. The NIH analysis was conducted under the direction of Dr. Bradford Wood, MD, Director, NIH Center for Interventional Oncology and Chief, NIH Clinical Center Interventional Radiology.

The article titled, "RFA Duration Per Tumor Volume May Correlate With Overall Survival in Solitary Hepatocellular Carcinoma Patients Treated With RFA Plus Lyso-thermosensitive Liposomal Doxorubicin," discussed the NIH analysis of results from 437 patients in the HEAT Study (all patients with a single lesion representing 62.4% of the study population). The key finding was that increased RFA heating time per tumor volume significantly improved overall survival (OS) in patients with single-lesion HCC who were treated with RFA plus ThermoDox, compared to patients treated with RFA alone. A one-unit increase in RFA duration per tumor volume was shown to result in about a 20% improvement in OS for patients administered ThermoDox, compared to RFA alone. The authors conclude that increasing RFA heating time in combination with ThermoDox significantly improves OS and establishes an improvement of over two years versus the control arm when the heating time per milliliter of tumor is greater than 2.5 minutes. This finding is consistent with the Company’s own results, which defined the optimized RFA procedure as a 45-minute treatment for tumors with a diameter of 3 centimeters. Thus, the NIH analysis lends support to the hypothesis underpinning the OPTIMA Study.

Data Lock for First Prespecified Interim Analysis in OPTIMA Phase III Study of ThermoDox in Primary Liver Cancer. On August 5, 2019, the Company announced the prescribed number of events has been reached for the first prespecified interim analysis of the OPTIMA Phase III Study with ThermoDox plus radiofrequency ablation (RFA) in patients with HCC. Following preparation of the data, the first interim analysis will be conducted by the Independent Data Monitoring Committee (iDMC). The iDMC meeting is expected to occur by mid-October. This timeline is consistent with the Company’s stated expectations and is necessary to provide a full and comprehensive data set that may represent the potential for a successful trial outcome. The iDMC recommendations will be announced as soon as possible after the meeting.

In accordance with the statistical plan, this initial interim analysis has a target of at least 118 events, or 60% of the total number required for the final analysis. At the time of the data cutoff, the Company received reports of 128 events. The hazard ratio for success at 128 events is approximately 0.63, which represents a 37% reduction in the risk of death compared with RFA alone, and is consistent with the 0.65 hazard ratio that was observed in the prospective HEAT Study subgroup, which demonstrated a two-year overall survival advantage and a median time to death of more than seven and a half years.

The OPTIMA Study was fully enrolled in August 2018 with 556 subjects from 65 clinical sites in 14 countries. The design of the OPTIMA Study is based on the Company’s HEAT Study, in which a subgroup analysis of 285 subjects with a single lesion of 3-7 cm in size received a single ThermoDox administration in combination with a 45-minute or longer RFA procedure. Followed prospectively for over 2.5 years, patients treated with ThermoDox demonstrated a median survival of more than 7.5 years and a survival benefit of more than two years over the control group. These data were published in the October 2017 issue of the peer-reviewed journal Clinical Cancer Research, and are available here.

IRB Approval to Begin a Clinical Study of ThermoDox Plus High Intensity Focused Ultrasound in Breast Cancer Patients at University Medical Center Utrecht in the Netherlands. On June 20, 2019, the Company announced that the University Medical Center Utrecht in the Netherlands received Institutional Review Board (IRB) approval to begin a Phase I study to determine the safety, tolerability and feasibility of ThermoDox in combination with Magnetic Resonance Guided High Intensity Focused Ultrasound (MR-HIFU) hyperthermia and cyclophosphamide therapy for the local treatment of the primary tumor in metastatic breast cancer (mBC). The secondary objective of this study is to assess radiological objective response of distant metastases and of the primary breast tumor.

This single-site, investigator-sponsored study – image-guided targeted doxorubicin delivery with hyperthermia to optimize loco-regional control in breast cancer; the i-GO Feasibility Study – will enroll up to 12 newly diagnosed mBC patients. Study subjects will receive up to six cycles of the following regimen at three-week intervals:

●60 minutes of MR-HIFU hyperthermia at 40oC to 42oC delivered to the primary tumor;
●50 mg/m2 of ThermoDox as a 30-minute intravenous (IV) infusion during hyperthermia; and
●600 mg/m2 of cyclophosphamide as a 15-minute IV infusion after hyperthermia.

This study further reinforces the broad potential of ThermoDox to treat a range of solid tumors with multiple localized heating sources.

Issuance of New U.S. Patent for ThermoDox. On April 17, 2019, the Company announced that the United States Patent and Trademark Office granted U.S. Patent No. 10,251,901 B2 – Thermosensitive Nanoparticle Formulations and Method of Making the Same – which is directly applicable to the method of treating cancer using a new ThermoDox formulation. The claim covers a method for preparing (as well as the composition of) a doxorubicin sulfate temperature-sensitive liposome and extends protection for the ThermoDox patent portfolio to 2033. This new patent broadens the ThermoDox intellectual property portfolio and provides for lifecycle management well into the future.

Corporate Development

Celsion Participated in Two Investor Conferences. During May 2019, the Company attended the ThinkEquity Conference in New York City and the Deutsche Bank 44th Annual Health Care Conference in Boston. A webcast of Celsion’s presentation at the ThinkEquity Conference may be accessed by visiting the "News & Investors" section of Celsion’s corporate website. The format of the Deutsche Bank Health Care Conference was comprised of one-on-one and small group meetings with leading institutional investors.

Second Quarter Financial Results

For the quarter ended June 30, 2019, Celsion reported a net loss of $5.9 million ($0.29 per share), compared with $8.2 million ($0.46 per share) in the same period of 2018. Operating expenses were $5.7 million in the second quarter of 2019, which represented a $2.4 million (30%) decrease from $8.1 million in the same period of 2018. During the second quarter of 2019, the Company incurred $0.6 million in non-cash stock option expense, compared with $3.2 million in the comparable prior-year period.

Research and development expenses decreased $1.0 million to $3.6 million in the second quarter of 2019, compared with $4.6 million in the second quarter of 2018. Clinical development costs for the Phase III OPTIMA Study decreased $0.8 million to $1.2 million in the second quarter of 2019, compared with $2.0 million in the second quarter of 2018, due to the completion of enrollment in this 556-patient trial in August 2018. Costs associated with the startup of the OVATION 2 Study were $0.1 million in the second quarter of 2019. Other costs related to clinical supplies and regulatory support for the ThermoDox and GEN-1 clinical development programs increased by $0.3 million in the second quarter of 2019 compared with the prior-year period. In the second quarter of 2019, non-cash stock compensation expense decreased $2.6 million compared with the same period of 2018.

General and administrative expenses were $2.1 million in the second quarter of 2019, compared with $3.5 million in the same period of 2018. The decrease was primarily attributable to a $1.8 million decrease in non-cash stock compensation expense, offset by a $0.2 million increase in professional fees primarily related to recruiting fees for several new positions to support the anticipated regulatory and commercialization efforts for ThermoDox.

The Company realized $0.1 million of interest income from its short-term investments during the second quarters of 2019 and 2018. In connection with the Company’s venture debt facility with Horizon entered in late June 2018, the Company incurred interest expense of $0.3 million during the second quarter of 2019. This compares with interest expense of $15,000 in the comparable prior-year period.

The Company ended the second quarter of 2019 with $21.8 million in cash, investment securities and interest receivable. With $21.8 million in cash at June 30, 2019 coupled with future sales of the Company’s New Jersey NOL’s, the Company believes it has sufficient capital resources to fund its operations into the first quarter of 2021.

Six Month Financial Results

For the six months ended June 30, 2019, the Company reported a net loss of $8.3 million ($0.42 per share), compared with $12.7 million ($0.73 per share) in the same period of 2018. Operating expenses were $10.7 million during the first six months of 2019, which represented a $1.8 million (15%) decrease from $12.5 million in the same period of 2018. During the first half of 2019, the Company incurred $1.3 million in non-cash stock option expense, compared with $3.4 million in the comparable 2018 period.

Net cash used for operating activities was $10.7 million in the first six months of 2019, compared with $8.8 million in the same period in 2018. This was in line with the Company’s projected cash utilization for 2019 of approximately $18 million, or an average of approximately $4.5 million per quarter. Cash provided by financing activities was approximately $4.5 million during the first six months of 2019.

Research and development expenses decreased $1.0 million to $6.3 million in the first half of 2019 from $7.3 million in the first half of 2018. Clinical development costs for the Phase III OPTIMA Study decreased $1.2 million to $2.1 million in the first half of 2019, compared with $3.3 million in the first half of 2018, due to the completion of enrollment in this 556-patient trial in August 2018. Costs associated with the startup of the OVATION 2 Study were $0.2 million in the first half of 2019. Other costs related to clinical supplies and regulatory support for the ThermoDox and GEN-1 clinical development programs increased by $0.2 million in the first half of 2019 compared with the same prior-year period. In the first half of 2019, non-cash stock compensation expense decreased $2.1 million compared with the same period of 2018.

Other expenses in the first half of 2019 included a non-cash gain of $2.6 million, net of a $0.4 million charge for the issuance of 200,000 warrants related to an amendment for the potential milestone payments for the GEN-1 ovarian product candidate, compared with a non-cash charge of $0.5 million for the comparable prior-year period.

The Company realized $0.2 million of interest income during the first half of 2019 and 2018. In connection with the Company’s venture debt facility with Horizon entered in late June 2018, the Company incurred interest expense of $0.7 million during the first six months of 2019, compared with interest expense of $15,000 in the comparable prior-year period.

Conference Call

The Company is hosting a conference call to provide a business update and discuss its second quarter 2019 financial results at 11:00 a.m. EDT on Thursday, August 15, 2019. To participate in the call, dial 1-800-367-2403 (Toll-Free/North America) or 1-334-777-6978 (International/Toll) and use conference ID 2816618. The call will also be broadcast live on the internet at www.celsion.com. The call will be archived for replay until August 29, 2019 and can be accessed at 1-719-457-0820 or 1-888-203-1112 using conference ID 2816618. An audio replay will also be available for 90 days at www.celsion.com.

On August 14, 2019 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported positive results from the Phase III PAOLA-1 trial in women with advanced ovarian cancer (Press release, AstraZeneca, AUG 14, 2019, View Source [SID1234538722]). The trial, in the 1st-line maintenance setting, compared Lynparza (olaparib) added to standard-of-care (SoC) bevacizumab vs. bevacizumab alone in women with or without BRCA gene mutations.

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The trial met its primary endpoint in the intent-to-treat* population with a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS), increasing the time women taking Lynparza plus bevacizumab lived without disease progression or death vs. those taking bevacizumab alone. The results, including biomarker sub-group analyses, will be presented at a forthcoming medical meeting. The safety and tolerability profiles observed in PAOLA-1 were generally consistent with those known for each medicine. PAOLA-1 is the second positive Phase III trial with Lynparza in 1st-line advanced ovarian cancer.

José Baselga, Executive Vice President, Oncology R&D, said: "The positive results from the PAOLA-1 trial demonstrate a clear potential benefit of adding Lynparza to the standard-treatment bevacizumab for women with advanced ovarian cancer. Following positive results from the SOLO-1 trial for women with a BRCA gene mutation, the PAOLA-1 trial marks yet another positive Phase III trial for Lynparza as a 1st-line maintenance treatment for women with advanced ovarian cancer. We look forward to discussing the results with global health authorities as soon as possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "The Phase III PAOLA-1 trial demonstrates MSD’s and AstraZeneca’s continued commitment to improving clinical outcomes for women with advanced ovarian cancer. In this co-operative group trial sponsored by ARCAGY Research, maintenance treatment with Lynparza when added to a standard-of-care treatment was evaluated in an environment representative of real clinical practice. By studying Lynparza in this broader patient population, we have learned more about how it may help even more patients with advanced ovarian cancer in the future."

Eric Pujade-Lauraine, Medical Director of ARCAGY Research, said: "The PAOLA-1 trial is a positive example of the strength and promise of academia-industry collaboration in advancing science and new treatment options for patients. We greatly appreciate the commitment of AstraZeneca and MSD in working with academic cooperative groups in ENGOT and look forward to sharing the full PAOLA-1 results at a forthcoming medical meeting."

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYnécologiques) on behalf of GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specialising in clinical and translational research in patients’ cancers and a member of the GCIG (Gynecologic Cancer InterGroup).

About PAOLA-1

PAOLA-1 is a randomised, double-blind Phase III trial testing the efficacy and safety of Lynparza added to SoC bevacizumab vs. bevacizumab alone, as a 1st-line maintenance treatment for newly-diagnosed advanced FIGO Stage III-IV high grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. The intent-to-treat* population refers to all patients randomised in the trial.

About ovarian cancer

Ovarian cancer is the eighth most common cause of death from cancer in women worldwide. In 2018, there were nearly 300,000 new cases diagnosed and around 185,000 deaths.1 Most women are diagnosed with advanced (Stage III or IV) ovarian cancer and have a five-year survival rate of approximately 30%.2 For newly-diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.3,4,5,6

About Lynparza

Lynparza is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair, such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in 64 countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer, regardless of BRCA status. It is approved in the US, the EU, Japan and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 43 countries, including the US and Japan, for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally-advanced breast cancer. Regulatory reviews are underway in other jurisdictions for ovarian, breast and pancreatic cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for the treatment of advanced ovarian cancer and metastatic breast cancer and has been used to treat over 25,000 patients worldwide. Lynparza has the broadest and most advanced clinical-trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

About GINECO

GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein) is the French Cooperative Group in Oncology labelled by INCA (Institut National du Cancer, or French NCI) developing and conducting gynaecological and metastatic breast cancer clinical trials at the national and international level. Founded in 1993, the GINECO group is a member of international consortia such as ENGOT and GCIG.

About ENGOT

ENGOT (European Network for Gynaecological Oncological Trial groups) is a research network of the European Society of Gynaecological Oncology (ESGO). Founded in 2007, ENGOT includes 21 cooperative groups from 25 European countries.

About GCIG

The GCIG (Gynecological Cancer InterGroup) aims to promote and facilitate high quality clinical trials in order to improve outcomes for women with gynaecological cancer. Founded in 1998, GCIG includes 23 cooperative groups from 28 countries worldwide.

About the AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

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, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investment that accelerate the delivery of our strategy, as illustrated by the 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 August 14, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the pricing of its previously announced registered underwritten public offering of 10,810,810 shares of its common stock at a price to the public of $37.00 per share (Press release, Deciphera Pharmaceuticals, AUG 14, 2019, View Source [SID1234538741]). The gross proceeds to Deciphera from the offering, before deducting the underwriting discounts and commissions and other estimated offering expenses, are expected to be $400.0 million. The offering is expected to close on or about August 19, 2019, subject to customary closing conditions. In addition, Deciphera has granted the underwriters a 30-day option to purchase up to 1,621,621 additional shares of its common stock.

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J.P. Morgan, Piper Jaffray and Jefferies acted as joint book-running managers for the offering. Guggenheim Securities acted as lead manager for the offering. SunTrust Robinson Humphrey acted as co-manager for the offering.

Deciphera intends to use the net proceeds of the offering to fund: clinical trials for ripretinib, including the expansion stage of its current Phase 1 clinical trial, its ongoing pivotal Phase 3 clinical trials, and additional clinical trials, as well as clinical research outsourcing and manufacturing of clinical trial material, and pre-commercialization manufacturing process development and validation; clinical trials for DCC-3014, including the expansion stage of its current Phase 1 clinical trial, as well as clinical research outsourcing and manufacturing of clinical trial material; clinical trials for rebastinib, including its current Phase 1b/2 clinical trial, as well as clinical research outsourcing and manufacturing of clinical trial material; Investigational New Drug-enabling studies and the potential development of DCC-3116; new and ongoing research activities for future drug candidates using its proprietary kinase switch control inhibitor platform; continued growth of its commercial and medical affairs capabilities to support its transition from a development-stage company toward a commercial-stage company; and working capital purposes, including general operating expenses.

A shelf registration statement relating to the shares of common stock offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) and was declared effective by the SEC on October 12, 2018. The securities may be offered only by means of a written prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. A final prospectus supplement and accompanying prospectus will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained from J.P. Morgan Securities LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Piper Jaffray & Co., 800 Nicollet Mall, J12S03, Minneapolis, Minnesota, 55402, Attention: Prospectus Department, by telephone at (800) 747-3924 or by email at [email protected]; and Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.