On August 23, 2018 Rakuten Aspyrian, a biotechnology company developing precision-targeted cancer therapies based on its proprietary Photoimmunotherapy platform, reported that it has raised $150 million in a Series C financing (Press release, Aspyrian Therapeutics, AUG 23, 2018, View Source [SID1234529073]). This round, as with previous rounds, was led by Hiroshi Mikitani, CEO of Rakuten Inc., a leading global innovation company in e-commerce, communications and fintech, and chairman of Rakuten Aspyrian. The Series C brings the company’s total fundraising to approximately $238 million in equity.

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"Developing treatments for cancer patients is a mission I began to pursue years ago and is the motivation behind my investment in Rakuten Aspyrian," said Mr. Mikitani, chairman of Rakuten Aspyrian. "Rakuten Aspyrian’s approach of combining a biologic with laser-activation to target tumors holds the potential to offer an alternative treatment option to help cancer patients fight their disease. Our company has advanced rapidly in developing this technology and is now poised to start Phase 3 studies. My vision is to develop and commercialize a strong pipeline of treatments based on Photoimmunotherapy to create a new platform for cancer treatments."

"With this financing we will advance our lead compound ASP-1929, a treatment that received Fast Track designation by the FDA, into a global, pivotal Phase 3 trial to evaluate the efficacy and safety to treat recurrent head and neck squamous cell carcinomas," said Miguel Garcia-Guzman, Ph.D., president and CEO of Rakuten Aspyrian. "I congratulate the Rakuten Aspyrian team for their excellence and commitment to rapidly advancing ASP-1929 into a Phase 3 study by the end of this year."

The financing will also support manufacturing scale-up for the commercialization of ASP-1929 and corporate growth including the initial buildup of commercial operations to support the launch of ASP-1929 in the United States, Japan and Europe.

In addition, this funding will support the expansion of R&D efforts to evaluate the safety and efficacy of ASP-1929 and other therapies in a range of cancer types, including the initiation of two additional Phase 2 proof of concept studies of ASP-1929 in other cancer types before the end of 2018.

"We are honored to be working with Hiroshi Mikitani, a visionary leader who supports our long-term corporate mission of conquering cancer," said Dr. Garcia-Guzman. "With this influx of capital, we are well positioned to advance our company to the next phase towards developing a fully integrated R&D and commercial biopharmaceutical corporation advancing first-in-class precision tumor-targeted therapies."

About ASP-1929

ASP-1929, a conjugate of cetuximab and IRDye 700DX, targets epidermal growth factor receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck squamous cell carcinomas, esophagus, lung, colon, pancreas and other cancers. This first-in-class therapy targets cancer cells, after which it is locally activated with red light using a proprietary investigational laser and fiber optics. The local activation of the tumor-selective conjugate targets the tumor but not surrounding normal tissues and structures.

Interim results of the Phase 1/2 trial in patients with head and neck squamous cell carcinoma showed a clinically meaningful improvement in the overall response rate, and potential improvements in progression free survival and overall survival when compared to historical data for the standard of care treatments currently available to this patient population. Top line results of the Phase 1/2 trial are expected later this year.

ASP-1929 is an investigational compound that is not approved for any use in any country.

On August 23, 2018 GlobeNewswire /Protalix BioTherapeutics, Inc. (NYSE American:PLX, TASE:PLX), a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell-based expression system, ProCellEx, reported that the Company will present at the 20th Annual Rodman & Renshaw Global Investment Conference, sponsored by H.C. Wainwright & Co., LLC (Press release, Protalix, AUG 23, 2018, View Source;p=RssLanding&cat=news&id=2364579 [SID1234529053]). The conference is being held on September 4-6, 2018 at the St. Regis New York Hotel in New York City.

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Mr. Moshe Manor, the Company’s President and Chief Executive Officer, will provide a corporate overview on Wednesday, September 5 at 2:10 pm ET and will be available to participate in one-on-one meetings with investors who are registered to attend the conference.

If you are an institutional investor, and would like to attend the Company’s presentation, please click on the following link (www.rodmanevents.com) to register for the conference. Once your registration is confirmed, you will be prompted to log into the conference website to request a one-on-one meeting with the Company.

A live and archived webcast of the presentation will be available at www.protalix.com, on the event calendar page.

On August 23, 2018 Novartis reported the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL719 (alpelisib) has met the primary endpoint showing an improvement in progression-free survival (PFS) (Press release, Novartis, AUG 23, 2018, View Source [SID1234529033]). SOLAR-1 is evaluating BYL719 in combination with fulvestrant compared to fulvestrant alone in postmenopausal women and men with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) PIK3CA-mutant advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor[1].

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"BYL719 is the only alpha-specific PI3K inhibitor and the first one to show potential increased benefit and acceptable tolerability for patients," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We are encouraged by the results observed in the SOLAR-1 study and look forward to submitting the data to an upcoming medical congress and starting discussions with health authorities worldwide."

Currently, there are no approved PI3K inhibitors for HR+ advanced breast cancer. The PI3K pathway plays an important role in regulating cell processes and is the most frequently altered pathway promoting tumor growth, disease progression and treatment resistance in HR+ advanced breast cancer[4],[5].

Adverse events observed with investigational BYL719 in combination with fulvestrant in SOLAR-1 were generally consistent with those observed in previous BYL719 and fulvestrant studies[1]. The SOLAR-1 trial will continue to assess data for secondary endpoints. Novartis will begin discussions with global health authorities based on these results.

About PI3K inhibition in advanced breast cancer
Studies have established the role of PI3K signaling in several processes critical for cancer progression, including cell metabolism, growth, survival and motility[9]. Activation of the PI3K pathway in breast cancer is associated with resistance to endocrine therapy, disease progression and poorer prognosis[4],[6].

Proteins in the PI3K pathway consist of four smaller parts called isoforms[7]. Approximately 40% of HR+ advanced breast cancer patients have genetic mutations that activate the alpha isoform, called PIK3CA mutations[2]. Mutations in the three other isoforms are typically not associated with advanced breast cancer[7].

About SOLAR-1
SOLAR-1 is a global, Phase III randomized, double-blind, placebo-controlled trial studying investigational BYL719 in combination with fulvestrant for postmenopausal women and men with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following prior aromatase inhibitor treatment with or without a CDK4/6 inhibitor[10].

The trial randomized 572 patients in a 1:1 ratio to receive continuous oral treatment with BYL719 300mg or placebo once daily in combination with fulvestrant 500mg intramuscular injections on days 1 and 15 on the first cycle and day 1 of each subsequent 28-day cycle as per fulvestrant prescribing information. Patients were allocated based on tumor tissue assessment to either a PIK3CA-mutant cohort or a PIK3CA non-mutant cohort. Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment[10].

The primary endpoint is PFS for patients with the PIK3CA mutation. Secondary endpoints include but are not limited to: overall survival, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutant cohort, safety and tolerability[10].

About BYL719 (alpelisib)
BYL719 is an investigational, orally bioavailable, alpha-specific PI3K inhibitor. In breast cancer cell lines harboring PIK3CA mutations, BYL719 has been shown to potentially inhibit the PI3K pathway and have antiproliferative effects. In addition, cancer cell lines with PIK3CA mutations were more sensitive to BYL719 than those without the mutation across a broad range of different cancers[11].

On August 23, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported the Toca 5 pivotal Phase 3 trial continues without modification following a planned first interim analysis of data conducted by an Independent Data Monitoring Committee (IDMC) (Press release, Tocagen, AUG 23, 2018, View Source;p=RssLanding&cat=news&id=2364611 [SID1234529156]). The IDMC completed its analysis at 50% of events occurring in patients with brain cancer and recommended the trial continue without modification. The global trial is enrolling robustly and nearing full enrollment.

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"We are pleased with the outcome of the interim analysis of the Toca 5 trial by the independent Data Monitoring Committee and the global trial continues. The Toca 5 trial is nearing completion of full enrollment of patients ahead of the projected schedule. We plan to conduct the second interim analysis in the first half of 2019 after 75% of events have occurred," said Asha Das, M.D., senior vice president and chief medical officer of Tocagen.

Toca 5 is a Phase 3, randomized, multi-center study evaluating the safety and efficacy of Toca 511 & Toca FC compared to standard of care in patients undergoing resection for recurrent high grade glioma (HGG). The primary endpoint of the trial is overall survival (OS). The statistical plan for the primary endpoint assumes a median OS of 9.8 months for the control arm versus 14.3 months for the Toca 511 & Toca FC arm. A total of 257 events will provide the study with 85% power to detect a hazard ratio of 0.685. The U.S. Food and Drug Administration (FDA) has granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of recurrent HGG and the European Medicines Agency (EMA) has granted Toca 511 PRIME (PRIority MEdicines) designation for the treatment of glioma. More information about the Toca 5 trial can be found on ClinicalTrials.gov using the clinical trial identifier NCT02414165.

About Toca 511 & Toca FC
Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprised of an investigational biologic, Toca 511 and an investigational small molecule, Toca FC. Toca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered, extended-release formulation of the prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment resulting in anti-cancer immune activation and subsequent tumor killing.

On August 22, 2018 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported it has acquired the drug candidate momelotinib from Gilead Sciences (Press release, Sierra Oncology, AUG 22, 2018, View Source [SID1234529036]). Momelotinib has been investigated in two completed Phase 3 trials for the treatment of myelofibrosis and has demonstrated a potentially differentiated therapeutic profile encompassing anemia-related benefits, as well as achieving substantive spleen and constitutional symptom control.

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"The majority of myelofibrosis patients have anemia at diagnosis or develop it during treatment with other therapies, including ruxolitinib. Anemia is the most significant negative prognostic indicator in myelofibrosis patients and, as a result, one of the most important disease consequences to address," said Dr. Srdan Verstovsek, Medical Oncologist and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas. "The therapeutic focus in myelofibrosis has traditionally been on treating the enlarged spleen and constitutional symptoms common to the disease. However, optimal drug therapy would also address disease-related cytopenias, including anemia and transfusion dependency, while also improving splenomegaly and symptoms. The Phase 3 clinical data for momelotinib demonstrate clinical benefits in all of these categories and I believe the drug candidate warrants further development. Given its anemia benefit, momelotinib could potentially become an important option for the treatment of myelofibrosis."

"Opportunistically adding this compelling Phase 3 asset to our existing pipeline of next generation oncology drug candidates, SRA737 and SRA141, helps establish Sierra as a diversified late-stage drug development company with a commercial orientation," said Dr. Nick Glover, President and CEO of Sierra Oncology. "The company is uniquely positioned to advance momelotinib towards potential registration with several members of the Sierra senior management team having played key roles in the development of momelotinib from its discovery through to Phase 3 clinical trials. The body of clinical data generated from more than 1,200 patients dosed to date will guide and support our momelotinib development strategy. We believe an additional clinical study likely will be required to consolidate these clinical data, and over the coming months we plan to engage with key opinion leaders and regulators to further define an expeditious regulatory path for momelotinib."

"Unlike other JAK inhibitors, momelotinib addresses myelofibrosis-related anemia. The Phase 2 and Phase 3 data to date demonstrate that momelotinib consistently improves the anemia that frequently occurs in advanced myelofibrosis, postulated via ACVR1 inhibition. ACVR1 is a member of the TGFβ superfamily of receptors that regulate the iron metabolism pathway. ACVR1 activates the transcription of hepcidin, which leads to decreased erythropoiesis. Demonstrable splenic responses and constitutional symptom control have also been achieved with momelotinib, suggesting that the compound is able to address a spectrum of unmet medical needs in myelofibrosis," noted Dr. Barbara Klencke, Chief Development Officer for Sierra Oncology. "Momelotinib also has a well-defined, predictable safety profile, with more than 180 patients still remaining on active long-term therapy, some benefitting from treatment for more than seven years, reinforcing its potential durable efficacy and favorable long-term tolerability."

Deal terms

Sierra will pay Gilead a $3 million upfront fee for momelotinib and potential aggregate milestone payments of up to $195 million, which are largely associated with commercial sales of the drug. Sierra will also pay Gilead royalties on any sales of momelotinib, which will be tiered based on commercial success and range from mid-teens to high-twenties. Sierra will assume all currently ongoing clinical studies with momelotinib following a transition period.

Fenwick & West LLP served as legal counsel to Sierra in connection with the transaction. Mizuho Securities USA LLC served as exclusive financial advisor to Gilead. Skadden, Arps, Slate, Meagher & Flom LLP served as legal counsel to Gilead.

Analyst & Investor Call Thursday, August 23st at 4:00 p.m. Eastern Time (1:00 p.m. Pacific Time)
Sierra will host an Analyst and Investor conference call on Thursday, August 23st at 4:00 p.m. ET where the company will introduce momelotinib and respond to questions. Members of the professional investment community may participate by phone by calling (866) 548-4713 (Toll-free in North America) or (323) 794-2093 (International Dial-in) and enter the Conference ID number: 6356543. The call will be webcast live and will be accessible through the company’s website at www.sierraoncology.com. An archived replay of the webcast will also be available.

About momelotinib
Momelotinib is a potent, selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a differentiated therapeutic profile in myelofibrosis encompassing a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, as well as achieving substantive spleen and constitutional symptom control. More than 1,200 subjects have received momelotinib since clinical studies began in 2009. Momelotinib is covered by patents anticipated to provide exclusivity to 2035 in the U.S. and 2033 in the EU.

Momelotinib was discovered and initially developed at Cytopia Ltd., an Australian biotechnology company whose CSO, Dr. Andrew Wilks, discovered the JAK1 and JAK2 kinases while at the Ludwig Institute for Cancer Research. Cytopia was acquired in 2011 by YM BioSciences Inc. (YM), a drug development company. Dr. Nick Glover, President & CEO of Sierra Oncology, previously led YM where he and his team advanced momelotinib through Phase 1/2 studies that first identified momelotinib’s unique anemia benefit. YM was acquired by Gilead in 2013. Current members of Sierra’s management team have prior experience developing momelotinib while at Cytopia, YM and Gilead.