On July 7, 2020 Novocure (NASDAQ: NVCR) reported that the last patient has been enrolled in the HEPANOVA trial, a phase 2 pilot trial testing Tumor Treating Fields in combination with sorafenib in patients with advanced liver cancer (Press release, NovoCure, JUL 7, 2020, View Source [SID1234561725]). The final data collection date is six months after the last patient in.

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"Tumor Treating Fields therapy has demonstrated efficacy in in vitro and in vivo models of hepatocellular carcinoma," said Asaf Danziger, Novocure’s Chief Executive Officer. "We believe that Tumor Treating Fields’ mechanism of action is broadly applicable to solid tumor cancers. We look forward to seeing results from the HEPANOVA trial and further exploring the potential of Tumor Treating Fields as a treatment for advanced liver cancer."

The open-label trial includes 25 patients with advanced hepatocellular carcinoma that are not eligible for surgical resection or local treatments. HEPANOVA’s primary endpoint is overall response rate. Second endpoints include in-field control rate, progression free survival rate at 12 months, overall survival rate at 1 year and distant metastases free survival rate at 1 year. The sample size was based on the ability to detect an overall response rate of 20 percent in patients treated with Tumor Treating Fields compared to the 4.5 percent overall response rate calculated from historical controls.

Tumor Treating Fields have demonstrated efficacy in in vitro and in vivo models of hepatocellular carcinoma and can be delivered to the abdominal region. In preclinical studies, Tumor Treating Fields delivered at 150 kHz reduced both HepG2 and Huh-7D12 cell counts (53 percent to 64 percent) and clonogenic potential (~70 percent). The combined treatment of Tumor Treating Fields and sorafenib led to a significant reduction in the number of HepG2 and Huh-7D12 cells (p<0.001) versus each treatment alone.1 Tumor Treating Fields delivered at 150 kHz plus sorafenib led to reduced viability and clonogenicity, as well as increased apoptosis and autophagy in vitro and to a significant reduction in tumor volume in vivo.2

Treatment with Tumor Treating Fields is not approved for liver cancer. The safety and effectiveness of treatment with Tumor Treating Fields for liver cancer has not been established.

About Liver Cancer

Liver cancer is a leading cause of cancer deaths worldwide and is the fifth leading cause of cancer deaths annually in the U.S. The incidence of liver cancer is approximately 38,000 new cases annually in the U.S., approximately 82,500 new cases annually in Europe, and approximately 35,500 new cases annually in Japan. The five-year survival rate with existing standards of care is less than 18 percent.

Hepatocellular carcinoma is the most widespread type of cancer that originates from the liver. Advanced liver cancer has spread either to the lymph nodes or to other organs, and because these cancers are widespread, they cannot be treated with surgery. The current common standard treatment for patients with advanced disease and those who progress on loco-regional therapy is systemic therapy with sorafenib.

About Tumor Treating Fields

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and potentially causing cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with glioblastoma and in the U.S. for mesothelioma, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Use of Tumor Treating Fields for the treatment of liver cancer is investigational only.

On July 7, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported the e-publication of results from a Phase 1 company-sponsored study of oral rigosertib in combination with standard dose azacitidine in the treatment of patients diagnosed with either higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML) in the international hematological malignancy journal Leukemia Research (Press release, Onconova, JUL 7, 2020, View Source [SID1234561724]).

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"A key strategy emerging in the treatment of MDS is the identification of safe and effective combinations, particularly those involving oral agents. The results from this Phase 1 study represent Onconova’s first efforts to explore oral rigosertib in combination with azacitidine to address the unmet medical need in patients with MDS and AML. We anticipate meeting with the FDA, in conjunction with the pivotal data readout from the INSPIRE Trial, for alignment with the agency on a registration trial for the combination of oral rigosertib plus azacitidine in HMA-naïve HR-MDS," said Steven M. Fruchtman, M.D., President and CEO of Onconova.

"These results coupled with preliminary data from the phase II studies, support further clinical development of this novel combination with a manageable safety profile and efficacy in patients with MDS both those HMA naïve and after HMA failure," said study principal investigator Lewis R. Silverman, M.D., Director, Translational Research Center for the Myelodysplastic Syndrome, Associate Professor, Medicine, Hematology, and Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "The oral administration of rigosertib is not just more convenient for patients, but may improve treatment compliance, leading to improved clinical outcomes."

This publication reports the results of an open-label, dose-escalating Phase 1 study with the combination oral of rigosertib and standard dose azacitidine administered sequentially to patients diagnosed with HR-MDS following HMA-failure, or relapsed/refractory AML. The study objectives were to assess safety and determine the recommended Phase 2 dose (RP2D) for future studies. The study evaluated three dose cohorts of oral rigosertib with no dose-limiting toxicities reported. In addition, the oral rigosertib/azacitidine combination demonstrated an overall response rate of 7/9 (78%) in patients with HR-MDS and 2/7 (29%) in patients with AML. The Phase 2 part of the study is ongoing. Additional details are available on www.clinicaltrials.gov (NCT01926587).

"We believe this combination could eventually prove very beneficial for patients with higher-risk MDS. In addition to its oral formulation and thus ease of administration, rigosertib is potentially an attractive partner for a variety of combination approaches due to its novel mechanism of action as a RAS mimetic that differentiates it from other MDS therapies," said Richard C. Woodman, M.D., Chief Medical Officer of Onconova.

About Rigosertib

Rigosertib, Onconova’s lead candidate, is a proprietary Phase 3 small molecule. A key publication in a preclinical model reported rigosertib’s ability to block cellular signaling by targeting RAS effector pathways (Divakar, S.K., et al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling." Cell 165, 643). Onconova is currently in the clinical development stage with oral and IV rigosertib, including clinical trials studying single agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in HMA naive and refractory higher-risk MDS patients (Phase 2). Patents covering oral and injectable rigosertib have been issued in the US and are expected to provide coverage until at least 2037.

On July 7, 2020 Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built proteins known as DARPin therapeutics, reported that it has successfully placed 5,528,089 registered shares (the New Shares), corresponding to approximately 25% of the company’s currently registered share capital, by way of an accelerated bookbuilding process (the Offering), at an offering price of CHF 14.50 per share (Press release, Molecular Partners, JUL 7, 2020, View Source(SIX%3A%20MOLN,25%25%20of%20the%20company’s%20currently [SID1234561723]). The gross proceeds of the Offering, before deducting commissions and offering expenses, amount to approximately CHF 80.2 million (~USD 85.1 million). The offering included participation by new and existing institutional investors in Switzerland, the United States and the European Union, including Suvretta Capital Management, LLC, Camber Capital Management LP, BVF Partners L.P., Federated Hermes Kaufmann Funds and Monashee Investment Management LLC.

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The New Shares will be issued from existing authorized share capital of the company under exclusion of the existing shareholders’ pre-emptive rights.

SVB Leerink LLC, Cowen and Company, LLC, Credit Suisse AG and Van Lanschot Kempen Wealth Management N.V. acted as Joint Bookrunners. HC Wainwright & Co. and Octavian AG served as Financial Advisors.

The New Shares are expected to be listed and admitted to trading on SIX Swiss Exchange as of July 9, 2020. Payment and settlement is expected to take place on the same date. Molecular Partners AG intends to use the net proceeds from the Offering to fund R&D activities, in particular to accelerate
its early stage pipeline, as well as for general corporate purposes.

The company, members of the board of directors and members of the management board have agreed to a 90-day lock-up period after settlement of the New Shares, subject to certain customary exceptions.

The New Shares were offered exclusively to (a) professional investors in Switzerland on the basis of applicable exemptions from the prospectus requirements under the Swiss Financial Services Act and outside of the United States in compliance with Regulation S under the U.S. Securities Act of 1933, as amended (the U.S. Securities Act), (b) certain qualifying investors outside of Switzerland and outside of the United States by way of private offerings in reliance on Regulation S under the U.S. Securities Act and exemptions from prospectus, registration and/or filing requirements available under local securities laws and (c) a limited number of persons within the United States who are reasonably believed to be qualified institutional buyers in a private placement pursuant to Section 4(a)(2) of the U.S. Securities Act or pursuant to another exemption from, or in a transaction not subject to, the registration requirements of the U.S. Securities Act.

On July 7, 2020 Pacira BioSciences, Inc. (Nasdaq: PCRX) reported that it intends to offer, subject to market and other conditions, $300.0 million aggregate principal amount of convertible senior notes due 2025 (the "notes") in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Pacira Pharmaceuticals, JUL 7, 2020, View Source [SID1234561722]). Pacira also intends to grant the initial purchasers of the notes a 30-day option to purchase up to an additional $45.0 million aggregate principal amount of notes.

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The terms of the notes, including the interest rate, initial conversion rate and other terms, will be determined by negotiations between Pacira and the initial purchasers of the notes.

Pacira intends to use a portion of the net proceeds from the offering to repurchase a portion of its outstanding 2.375% Convertible Senior Notes due 2022 (the "2022 Notes") concurrently with the pricing of the offering in privately negotiated transactions effected through one of the initial purchasers of the notes or its affiliate, as Pacira’s agent. Pacira intends to use the remainder of the net proceeds from the offering for general corporate purposes, including working capital, research and development expenditures and the license or acquisition of complementary products and/or technologies. Holders of the 2022 Notes that are repurchased in the concurrent repurchases described above may purchase shares of Pacira’s common stock in the open market to unwind any hedge positions they may have with respect to the 2022 Notes. These activities may affect the trading price of Pacira common stock and, if conducted concurrently with this offering, may result in a higher initial conversion price for the notes Pacira is offering.

This offering is being made to qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the notes and the shares of Pacira common stock, if any, issuable upon conversion of the notes have not been and will not be registered under the Securities Act or any state securities laws, and, unless so registered, the notes and such shares may not be offered or sold in the United States or to U.S. persons except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws.

On July 7, 2020 Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS) reported a reduction in workforce of approximately 30% of its head count to focus on development of its first-in-class PDK1 inhibitor SNS-510 (Press release, Sunesis, JUL 7, 2020, View Source [SID1234561720]).

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The reduction in workforce is to right size the Company to achieve its objectives and preserve cash resources. The reduction in workforce is expected to be completed during the current quarter and will provide the Company sufficient cash to fund its operations into the second quarter of 2021.

"The changes we are undertaking will extend our cash runway and provide us with the necessary resources to execute on our PDK1 program, while also allowing the flexibility to explore opportunities for additional value creation," said Dayton Misfeldt, Interim Chief Executive Officer of Sunesis. "We thank our affected employees for their contributions and wish them success in their future endeavors."

The Company also plans to review strategic alternatives to maximize shareholder value that can include asset in-licensing, partnering, acquisitions and mergers. There can be no assurance that the strategic review will result in any transaction or other outcome. The Company does not currently intend to publicly discuss or disclose further developments of the strategic review unless and until its Board of Directors has approved a transaction or otherwise determined that further disclosure is appropriate.

"We are committed to evaluating strategic alternatives that enhance value for shareholders as the development organization is focused on advancing SNS-510 to an IND. We are also continuing to explore a path forward for vecabrutinib," said Mr. Misfeldt.

About SNS-510

SNS-510 is a PDK1 inhibitor licensed from Millennium Pharmaceuticals, Inc. ("Takeda Oncology"), a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited. SNS-510 interaction with PDK1 inhibits both PI3K signaling and PIP3-independent pathways integral to many malignancies, and PDK1 can also be overexpressed in breast, lung, prostate, hematologic and other cancers. Evaluation of SNS-510 in the Eurofins Oncopanel, a panel of >300 genomically profiled cancer cell lines from diverse tissue origins, indicated that CDKN2A-mutated tumors are particularly sensitive to SNS-510. CDKN2A alterations are common in human cancers and may prove to be useful biomarkers for broad investigation of SNS-510 as a monotherapy and in combination with other anticancer agents. Sunesis is conducting an Investigational New Drug ("IND")-enabling program for SNS-510.