1stOncology™: Cancer Intelligence Service – Page 11621 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

VBL Presents Positive Interim Data from the OVAL Phase 3 Pivotal Study in Ovarian Cancer at the ASCO20 Annual Meeting, Showing 58% or Higher Objective Response Rate

On June 1, 2020 VBL Therapeutics (Nasdaq: VBLT), reported the presentation of the positive outcome of pre-planned interim analysis results from the OVAL Phase 3 pivotal clinical trial in platinum-resistant ovarian cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 virtual annual meeting (Press release, VBL Therapeutics, JUN 1, 2020, View Source [SID1234558783]).

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!

The analysis compared the CA-125 objective response rate (ORR) according to GCIG criteria in the treatment and control arms among the first 60 evaluable patients. The CA-125 ORR in those patients was 53%. Assuming a balanced randomization, the response rate in the treatment arm (VB-111 in addition to weekly paclitaxel) was 58% or higher. In patients who had post-dosing fever, which is a marker for VB-111 treatment, the response rate was 69%.

The CA-125 response rate observed in the Phase 3 interim analysis is at least as good as the response rate seen in the prior Phase 2 study, which enrolled a similar patient population and showed overall survival benefit. In the previously reported Phase 2 study of VB-111 in platinum resistant ovarian cancer, 58% of the patients treated with VB-111 and paclitaxel demonstrated a CA-125 response. Those patients with a CA-125 response demonstrated a median overall survival of 808 days, versus 351 days for those patients without a CA-125 response.

"The OVAL interim data are very encouraging as they demonstrate the potential benefit of VB-111 over standard-of-care in a randomized-controlled setting," said Tami Rachmilewitz, M.D., Vice President Clinical Development of VBL Therapeutics. "With over 25% of the patients already enrolled in the study, we look forward to further advancing the OVAL study by expansion to Europe and Japan later this year."

For VBL’s presentation at ASCO (Free ASCO Whitepaper) see: Link

About the OVAL (VB-111-701/GOG-3018) study (NCT03398655)
OVAL is an international Phase 3 randomized, double-blind, placebo-controlled potential registration clinical trial that compares a combination of VB-111 and paclitaxel to placebo plus paclitaxel, in patients with platinum-resistant ovarian cancer. The study is planned to enroll approximately 400 patients. OVAL is conducted in collaboration with the GOG Foundation, Inc., an independent international non-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies.

About VB-111 (ofranergene obadenovec)
VB-111 is a first-in-class, targeted anti-cancer gene-therapy agent that is being developed to treat a wide range of solid tumors. VB-111 is a unique biologic agent that uses a dual mechanism to target solid tumors. Its mechanism combines blockade of tumor vasculature with an anti-tumor immune response. VB-111 is administered as an IV infusion once every 6-8 weeks. It has been observed to be well-tolerated in >300 cancer patients and demonstrated activity signals in an "all comers" Phase 1 trial as well as in three tumor-specific Phase 2 studies. VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission. VB-111 has also received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970).

Protalix BioTherapeutics Reports First Quarter 2020 Financial Results and Business Update

On June 1, 2020 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the first quarter ended March 31, 2020, and provided a business update on recent corporate and clinical developments (Press release, Protalix, JUN 1, 2020, View Source [SID1234558782]). The Company’s management will discuss the financial results and provide a clinical, corporate and financial highlights on a conference call and live webcast scheduled for Monday, June 1, 2020 at 8:30 am Eastern Daylight Time (EDT).

"The first quarter of 2020 has most certainly been transformational for Protalix, despite the COVID-19 pandemic that affected the global markets," said Dror Bashan, Protalix’s President and Chief Executive Officer. "I am proud to say that despite the pandemic, Protalix was able to keep the company running smoothly and adapt quickly to the changing environment."

"During the quarter, we were able to close a $43.7 million private placement," he continued. "Furthermore, the topline results from the completion of our Phase III BRIDGE study and the subsequent BLA submission for PRX-102 announced in May prove that Protalix has actually gained momentum by leaning into this unprecedented challenge. I am convinced now more than ever that our team is positioned for long-term success and look forward to continuing our momentum through the rest of this year and into 2021."

Conference Call and Webcast Information

The Company will host a conference call on Monday, June 1, 2020, at 8:30 am, Eastern Daylight Time, to review the clinical, corporate and financial highlights. To participate in the conference call, please dial the following numbers prior to the start of the call:

The conference call will also be broadcast live and available for replay for two weeks on the Company’s website, www.protalix.com, in the Events Calendar of the Investors section. Please access the Company’s website at least 15 minutes ahead of the conference to register, download, and install any necessary audio software.

First Quarter 2020 and Recent Business Highlights

Clinical and Regulatory Advancements

·On May 28, 2020, the Company and its development and collaboration partner, Chiesi Global Rare Diseases, a unit of Chiesi Farmaceutici S.p.A., or Chiesi, announced the submission on May 27, 2020 of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for pegunigalsidase alfa, or PRX-102, for the treatment of adult patients with Fabry disease via the FDA’s Accelerated Approval pathway. PRX-102 was granted Fast Track designation by the FDA in January 2018. Upon the BLA approval, if approved, the Company will be eligible to receive a milestone payment from Chiesi.

·On May 11, 2020, the Company announced positive topline results following the completion of its Phase III BRIDGE clinical trial of PRX-102 for the treatment of Fabry disease. The Phase III BRIDGE clinical trial, a 12-month open-label, single arm switch-over study evaluating the safety and efficacy of PRX-102, 1 mg/kg infused every two weeks, met its main objectives for safety and efficacy, and topline analysis indicated substantial improvement in renal function as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope) in patients switched from agalsidase alfa to PRX-102.

·On February 6, 2020, Protalix and Chiesi announced the receipt of an agreement letter from the FDA for the Initial Pediatric Study Plan (iPSP) for PRX-102 for the treatment of Fabry disease, outlining an agreed-upon approach to address the needs of pediatric Fabry patients.

Corporate & Financial Developments

·On March 16, 2020, the Company announced that it has agreed to conduct a feasibility study with Kirin Holdings Company, Limited, or Kirin, to evaluate the production of a novel complex protein utilizing ProCellEx. The Company received a non-refundable payment of $1.0 million and Kirin will provide research funding for the Company’s scientists to conduct cell line engineering and protein expression studies on the target protein.

·On March 12, 2020, the Company entered into securities purchase agreements with certain existing and new institutional and other accredited investors in a private placement. Pursuant to such agreements, the Company issued and sold to the purchasers an aggregate of approximately 17.6 million unregistered shares of its common stock at a price per share of $2.485, or aggregate net committed proceeds equal to approximately $41.3 million. Each share of the Company’s common stock issued in the transaction was accompanied by a warrant to purchase an additional share of common stock at an exercise price equal to $2.36.

Financial Results

For the three months ended March 31, 2020, compared to the three months ended March 31, 2019

·The Company recorded revenues from selling goods of $5.0 million during the three months ended March 31, 2020, an increase of $1.5 million, or 43%, compared to revenues of $3.5 million for the same period of 2019. The increase resulted primarily from an increase of $0.8 million in sales of drug product to Brazil as well as an increase of $0.7 million in sales of drug substance to Pfizer Inc.

·Revenues from license and R&D services for the three months ended March 31, 2020, were $16.6 million, an increase of $9.7 million, or 140%, compared to revenues of $6.9 million for the same period of 2019. Revenues from the license agreements represent the revenues recognized in connection with previously announced agreements with Chiesi. The increase is primarily due to revenues recognized in connection with the progress of the Company’s clinical trial that have been performed, and with revenues recognized in connection with an updated costs estimation throughout the trials until completion in the amount of $6.7 million.

·Cost of goods sold was $3.4 million for the three months ended March 31, 2020, an increase of $1.4 million, or 68%, from cost of goods sold of $2.0 million for the same period of 2019. The increase is primarily due to an increase in sales of goods.

·Research and development expenses were $10.3 million for the three months ended March 31, 2020, a decrease of $1.4 million, or 12%, compared to $11.7 million of research and development expenses for the same period of 2019. The decrease was primarily due to a decrease in costs related to manufacturing of our drug in development.

·Selling, general and administrative expenses were $3.2 million for the three months ended March 31, 2020, an increase of $1.0 million, or 43%, compared to $2.2 million for the same period of 2019. The increase resulted primarily from a $0.6 million increase in compensation related costs and a $0.2 million increase in professional fees.

·Net income for the three months ended March 31, 2020 was $1.7 million, or $0.10 per share, basic and diluted, compared to a net loss of $7.3 million, or $0.50 per share, basic and diluted, for the same period of 2019.

Lynparza recommended for approval in EU by CHMP for BRCA-mutated metastatic pancreatic cancer

On June 1, 2020 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported that Lynparza (olaparib) has been recommended for marketing authorisation in the European Union (EU) for the 1st-line maintenance treatment of patients with germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer (Press release, AstraZeneca, JUN 1, 2020, View Source [SID1234558781]).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the Phase III POLO trial, which were published in The New England Journal of Medicine.

The trial demonstrated that Lynparza nearly doubled the time patients with gBRCAm metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months versus 3.8 months on placebo. The safety and tolerability profile of Lynparza in the POLO trial was consistent with previous trials.

José Baselga, Executive Vice President, Oncology R&D, said: "Patients with advanced pancreatic cancer have seen limited treatment advances over the last few decades. We are now one step closer to bringing the first targeted medicine to certain biomarker-selected patients with advanced pancreatic cancer in the EU."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "A pancreatic cancer diagnosis is devastating, and we are committed to research that aims to change the prognosis for patients. The POLO Phase III trial demonstrated that treatment with Lynparza extended time without disease progression in certain patients with advanced pancreatic cancer – we are hopeful that we will be able to bring this treatment to patients in the EU soon."

The CHMP recommendation is for maintenance treatment with Lynparza for adult patients with germline BRCA1/2 mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a 1st-line chemotherapy regimen.

Lynparza is approved in the US and several other countries as a 1st-line maintenance treatment for patients with gBRCAm metastatic pancreatic cancer based on the Phase III POLO trial, with ongoing regulatory reviews in the EU and other jurisdictions.

Lynparza was recently approved in the US for patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. It was also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer.

Pancreatic cancer
Pancreatic cancer is a deadly cancer with a high unmet medical need. The disease has the lowest survival rate of the most common cancers.1 Globally, pancreatic cancer is the 11th-most commonly occurring cancer and the seventh leading cause of cancer death.2,3 There were approximately 460,000 new cases worldwide in 2018.3 As there are often no symptoms, or symptoms may be non-specific in the early stages, it is most commonly diagnosed at an incurable stage.4,5

Around 80% of pancreatic cancer patients are diagnosed when the disease has metastasised, at which point average survival is less than a year.6 Despite advances in treatment, few improvements have been made in diagnosis and treatment in the past few decades.7 Current treatment is surgery (for which approximately only 10-20% of patients are eligible), chemotherapy and radiotherapy, highlighting a critical unmet medical need for more effective treatment options.8

POLO
POLO is a Phase III randomised, double-blinded, placebo-controlled, multi-centre trial of Lynparza tablets (300mg twice daily) as maintenance monotherapy vs. placebo. The trial randomised 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed on 1st-line platinum-based chemotherapy. Patients were randomised (3:2) to receive Lynparza or placebo until disease progression. The primary endpoint was progression-free survival (PFS) and key secondary endpoints included overall survival, time to second disease progression, overall response rate and health-related quality of life.

BRCA mutations
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

Lynparza
Lynparza (olaparib) 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 a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, 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 the US as a 1st-line maintenance treatment with bevacizumab for patients with homologous recombination deficiency (HRD)-positive advanced ovarian cancer. Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US and several other countries for the treatment of germline BRCA-mutated metastatic pancreatic cancer. Lynparza is approved in the US for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several jurisdictions for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 30,000 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.

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 Koselugo (selumetinib), a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

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 six new medicines 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.

Chi-Med Plans to Submit NDA for Surufatinib Following Pre-NDA Meeting with the U.S. FDA

On June 1, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that it has held its pre-New Drug Application ("NDA") meeting with the U.S. Food and Drug Administration ("FDA") for surufatinib for the treatment of patients with advanced neuroendocrine tumors ("NET") (Press release, Hutchison China MediTech, JUN 1, 2020, View Source [SID1234558780]). Chi-Med has reached an agreement with the FDA that the completed SANET-ep (non-pancreatic NET) and SANET-p (pancreatic NET) studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic NET patients, could form the basis to support a U.S. NDA submission.

The FDA granted Fast Track Designation status to surufatinib for the non-pancreatic and pancreatic NET development programs in April 2020. Chi-Med has initiated preparatory work for the U.S. NDA and intends to utilize a rolling submission under Fast Track Designation Status. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. Filing acceptance of the NDA is subject to FDA review of the complete application. The planned start of the NDA submission is late 2020.

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Chi-Med currently retains all rights to surufatinib worldwide.

NET in the U.S., Europe and Japan: In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019. A U.S. FDA NDA submission is being prepared. Regulatory interactions in Europe and Japan are also underway to confirm the clinical development strategy and potential path to registration. All such interactions are based on the robust data from the two positive Phase III studies of surufatinib in NET in China, and the ongoing multi-cohort Phase Ib study in the U.S. that began in November 2015 (clinicaltrials.gov identifier: NCT02549937).

Non-pancreatic neuroendocrine tumors in China: In November 2019, a NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the China National Medical Products Administration (NMPA) and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in patients with advanced non-pancreatic neuroendocrine tumors in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the Independent Data Monitoring Committee ("IDMC") to determine that the study met the pre-defined primary endpoint of progression-free survival ("PFS") and should be stopped early. The positive results of this trial were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress (clinicaltrials.gov identifier: NCT02588170).

Pancreatic neuroendocrine tumors in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET is being prepared for submission, following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821). Study results will be submitted for presentation at an upcoming scientific conference.

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: We have entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317), Tuoyi (toripalimab) and Tyvyt (sintilimab), which are approved in China.

Publication in Nature Communications Highlights the Preclinical Development of SYNB1891 and its Potential as a Dual Innate Immune Activator to Stimulate an Immune Response in Difficult to Treat Tumors

On June 1, 2020 Synlogic, Inc., (Nasdaq: SYBX) a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, reported the publication in Nature Communications of preclinical data supporting its first clinical immuno-oncology program, SYNB1891, which is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors or lymphoma (Press release, Synlogic, JUN 1, 2020, View Source [SID1234558779]). Data described in the publication demonstrate that SYNB1891 treatment cleared tumors and stimulated antitumor immunity in preclinical models of cancer.

"The targeted delivery and dual immune stimulatory activity of SYNB1891 offer distinct advantages over other approaches," said Aoife Brennan, M.B., Ch. B., Synlogic’s president and chief executive officer. "The preclinical data published today highlight the transformative potential of SYNB1891. Together with the early experience in the clinic demonstrating feasibility and tolerability in the initial cohorts of the clinical trial, these data provide support for the continued development of SYNB1891 as a potential therapeutic option to expand the benefits of immunotherapy to more patients with cancer."

The publication titled, "Immunotherapy with an engineered bacteria by targeting the STING pathway for anti-tumor immunity," details the engineering and characterization of SYNB1891. The work describes preclinical studies that demonstrate anti-tumor activity and generation of immunological memory by SYNB1891 in mouse models of cancer, as well as its robust activation of human antigen presenting cells (APCs) that are key to the generation of an anti-tumoral immune response.

SYNB1891 is an engineered strain of E. coli Nissle, that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an anti-tumor immune response via activation of APCs and presentation of tumor antigens. The bacterial chassis of SYNB1891 also stimulates the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response. A notable advantage of SYNB1891 is that the STING agonist is not released by the bacteria until they have been engulfed by the target cells (APCs) and so there is less risk of deleterious effects on other immune cells such as T-cells. Also, while SYNB1891 has been engineered with safety features that are designed to prevent its replication unless supplemented with specific nutrients, the bacteria remain active for several days within the injected tumor to stimulate a local immune response.

Intra-tumorally administered SYNB1891 is being evaluated as a monotherapy in an ongoing Phase 1 open-label, multicenter, dose escalation clinical trial (NCT04167137) in patients with advanced solid tumors or lymphoma. Synlogic expects to release data from the monotherapy arm of this study in late 2020. After establishing a maximum tolerated dose for SYNB1891 as monotherapy, Synlogic expects to initiate a second arm of the trial in which subjects will receive escalating dose levels of SYNB1891 in combination with a fixed dose of the checkpoint inhibitor, atezolizumab (Tecentriq), to establish a recommended dose for the combination regimen.

The DOI for the paper is 10.1038/s41467-020-16602-0.