On July 1, 2021 Novocure (NASDAQ: NVCR) reported final results from its phase 2 pilot HEPANOVA trial in liver cancer testing the safety and efficacy of Tumor Treating Fields (TTFields) together with sorafenib for the treatment of advanced hepatocellular cancer (Press release, NovoCure, JUL 1, 2021, View Source [SID1234584553]). In 21 evaluable patients, the disease control rate was 76% in a patient population with poor prognosis and limited exposure to study treatments. The objective response rate for the intent-to-treat population was 9.5%. In patients who completed at least 12 weeks of TTFields treatment, the disease control rate was 91% with an objective response rate of 18%. The final HEPANOVA results will be presented at the virtual ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer on July 1.

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The HEPANOVA trial enrolled 27 patients with unresectable hepatocellular cancer. Fourteen of the 27 patients, or 52%, had a Child-Turcotte-Pugh (CTP) score of 7 or 8, representing significant liver dysfunction. Six patients, or 22% of the study population, survived less than 12 weeks. The median sorafenib treatment duration was only nine weeks, a much shorter treatment duration than the referenced historical controls1. The median treatment duration of TTFields was 10 weeks.

"We are very encouraged by the HEPANOVA results, especially in light of the poor prognosis of the study population and low treatment exposure," said Dr. Uri Weinberg, Novocure’s Chief Science Officer. "We intend to initiate a randomized controlled trial as soon as possible and are working with key opinion leaders to finalize a protocol incorporating the evolving treatment landscape in advanced liver cancer. We are particularly interested in the potential to use TTFields together with immunotherapy in this aggressive disease given in vivo data which suggest that using TTFields together with anti-PD-1 therapy results in increased tumor response versus either therapy alone."

The objective response rate reached 9.5% in the 21 evaluable patients, more than double the historical controls. The disease control rate was 76%, a much higher rate than the historical controls of 43% to 52%. For the 11 patients who completed at least 12 weeks of TTFields therapy, the objective response rate was 18%. The disease control rate for patients who completed at least 12 weeks of TTFields therapy was 91%. The objective response rate is defined as the percentage of patients who achieved complete or partial response. The disease control rate includes the percentage of responders plus the patients who achieved stable disease. In the intent-to-treat population, median progression free survival was 5.8 months and median time-to-progression was 8.9 months, higher than the historical, sorafenib alone control for both endpoints. No increase in the toxicity of sorafenib and no device-related serious adverse events were reported.

"Hepatocellular cancer is a particularly aggressive disease," said Professor Anca-Ligia Grosu, Medical Director at the University of Freiburg, and the principal investigator of the HEPANOVA trial. "A clear unmet need remains for safe and effective combination treatments. These data show that Tumor Treating Fields have the potential to extend survival in advanced liver cancer without increasing side effects. I look forward to further exploration of efficacy in a randomized, controlled trial."

About Liver Cancer
Liver cancer is a leading cause of cancer deaths worldwide and is the sixth leading cause of cancer deaths annually in the U.S. The incidence of liver cancer is approximately 42,000 new cases annually in the U.S. The five-year survival rate with existing standards of care is less than 20%.

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 progressed on loco-regional therapy is systemic therapy with sorafenib, lenvatinib, or atezolizumab plus bevacizumab.

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

About Tumor Treating Fields
Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.

On July 1, 2021 Celsion Corporation (NASDAQ: CLSN), Celsion GmbH, a wholly owned subsidiary of Celsion Corporation, a clinical-stage biotechnology company, reported commencement of enrollment in Oxford University’s Phase I PanDox study with ThermoDox in conjunction with Focused Ultrasound in patients with pancreatic cancer (Press release, Celsion, JUL 1, 2021, View Source [SID1234584552]). ThermoDox is Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin.

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This investigator-led study sponsored by the University of Oxford and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre has now received ethics, MHRA and institutional R&D approval to commence (ClinicalTrials.gov Identifier: NCT04852367). PanDox is being carried out as a multi-disciplinary collaboration between Celsion, the Oxford University Institute of Biomedical Engineering, the Oncology Clinical Trials Office (OCTO) and the Oxford University Hospitals NHS Foundation Trust. Prof. Mark Middleton, MD, Head of the Department of Oncology at the University of Oxford is the chief clinical investigator and Prof. Constantin Coussios, FREng, PhD, Director of the Institute of Biomedical Engineering, is the lead scientific investigator.

The primary endpoint of the two-arm 18-subject PanDox study is enhanced uptake of doxorubicin in pancreatic tumors using ThermoDox and Focused Ultrasound (FUS), compared to systemic delivery of free doxorubicin. ThermoDox, a heat activated liposomal doxorubicin, will be administered intravenously in 12 patients with non-resectable pancreatic ductal adenocarcinoma (PDAC) and locally activated by focused ultrasound-mediated hyperthermia. This will be compared to conventional systemic delivery of doxorubicin without FUS in 6 patients.

Secondary endpoints include:

Comparing radiologically assessed tumor activity and response with ThermoDox and FUS to free drug alone.
Examining the impact on patient symptoms of ThermoDox plus FUS.
Assessing the safety profile of both FUS and ThermoDox.
The PanDox study is expected to be completed by December 2022 and is similar in design to Oxford’s 10-patient TARDOX study, which demonstrated that ThermoDox plus focused ultrasound increased doxorubicin tumor concentrations by up to 10-fold and enhanced nuclear drug uptake in patients with liver tumors. The findings of the TARDOX study are published in Lancet Oncology (Lyon et al., 2018) and Radiology (Gray et al., 2019).

Preclinical studies conducted at the University of Washington and published in the International Journal of Hyperthermia describe similarly compelling results from experiments performed in a murine model of pancreatic cancer. Those studies demonstrated that ThermoDox plus focused ultrasound increased localized concentration and nuclear uptake of doxorubicin 23-fold compared with a 2-fold increase for hyperthermia and free doxorubicin.

Commenting on the PanDox clinical study, Dr. Laura Spiers, lead oncology clinical research fellow on the PanDox study, said, "Pancreatic cancer has a low five-year survival rate of approximately 10% and drug-based treatments remain less effective than in other cancers, in part due to the unique challenges presented by the stroma surrounding pancreatic tumors. Therefore, finding innovative and effective means of delivering high concentrations of anti-cancer agents such as doxorubicin may lead to a breakthrough for this difficult-to-treat cancer."

Dr. Michael Gray, lead biomedical engineering research fellow, added, "Based on the patient-specific treatment planning approaches developed and validated during the TARDOX trial, PanDox will deliver focused ultrasound mild hyperthermia without either MR-based or invasive thermometry. The ultimate goal is to develop a cost-effective and scalable approach that can be rapidly deployed for the benefit of pancreatic cancer patients".

"This Phase 1 study at Oxford University is the first new trial to be performed under the auspices of Celsion’s wholly owned subsidiary Celsion GmbH, which was recently established to manage all current and future investigator-sponsored trials with ThermoDox," said Andreas Voss, M.D., managing director of Celsion GmbH. "We look forward to providing ThermoDox and other support to Professor Coussios as he and his colleagues strive to provide options to pancreatic cancer patients, as well as to other investigators pursuing compelling possibilities with ThermoDox."

On July 1, 2021 Pulse Biosciences, Inc. (Nasdaq: PLSE), a novel bioelectric medicine company commercializing the CellFX System powered by Nano-Pulse Stimulation (NPS) technology, reported that it has entered into a stock purchase agreement with Robert W. Duggan, an experienced life sciences executive and the Company’s Board Chairman, for the purchase of 3,048,780 shares of the Company’s common stock at a price of $16.40 per share, the last reported sale price of the Company’s common stock on June 30, 2021, the immediately preceding trading day (Press release, Pulse Biosciences, JUL 1, 2021, View Source [SID1234584551]). All indebtedness owed by the Company to Mr. Duggan pursuant to the loan agreement between Mr. Duggan and the Company dated as of March 11, 2021, including the principal balance of $41.0 million and accrued and unpaid interest of $0.6 million, will be paid through the cancellation and extinguishment of such indebtedness and the issuance of the common stock shares in the private placement. As part of the private placement, Mr. Duggan will invest an additional $8.4 million as new capital.

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"This capital strengthens our balance sheet and enables greater flexibility to drive our top business priorities, the CellFX System Controlled Launch Program and the ongoing product development and initiatives to expand the clinical applications for NPS technology," said Darrin Uecker, President and CEO of Pulse Biosciences. "We appreciate the continued support and leadership from the Chairman of our Board of Directors. The entire team at Pulse Biosciences is excited and committed to deliver the clinically differentiated benefits of Nano-Pulse Stimulation technology to as many patients as possible, starting in aesthetic dermatology."

Mr. Duggan, who currently owns approximately 46% of the Company’s outstanding common stock, will become the beneficial owner of approximately 51% of the Company’s outstanding common stock after giving effect to the private placement. Accordingly, after the closing of the private placement, the Company will be considered a "controlled" company under applicable Nasdaq Stock Market rules.

No warrants will be provided, or other discounts given, to Mr. Duggan in the private placement, and the private placement is being facilitated directly by the Company. As such, no investment banking or placement fees are being incurred by the Company. The private placement is expected to close on or about July 7, 2021, subject to the satisfaction of customary preclosing conditions.

This announcement is neither an offer to sell nor a solicitation to buy any securities, nor shall there be any offer, solicitation or sale of any securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

The shares of common stock being issued in the private placement have not been registered under the Securities Act of 1933, as amended (the "Act"), or any state securities laws, and unless so registered, may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Act and applicable state laws.

On July 1, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company developing novel cancer therapies for patients who are failing or are resistant to current treatment regimens, reported topline data results from the recurrent arm of its open-label, Phase 2 clinical study of its lead compound VAL-083 being conducted at the MD Anderson Cancer Center (MD Anderson) in Houston, Texas (Press release, Kintara Therapeutics, JUL 1, 2021, View Source [SID1234584550]).

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The Phase 2 trial is a two-arm, biomarker-driven study testing VAL-083 in glioblastoma multiforme (GBM) patients who have an unmethylated promoter of the methylguanine DNA-methyltransferase (MGMT) gene. The recurrent arm of the study addressed patients who have been pre-treated with temozolomide prior to disease recurrence.

The recurrent arm of the trial enrolled 89 patients, with 35 patients (35 efficacy evaluable) initially receiving a dose of VAL-083 at 40 mg/m2/day, and 54 patients (48 efficacy evaluable) initially receiving the treatment dose of 30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle. This 30 mg dose corresponds to the dose being studied in the recently initiated and currently enrolling VAL-083 study arm of the GBM AGILE study.

Summary of results:

– Median overall survival (mOS) for the 48 efficacy evaluable patients initially receiving the treatment dose of 30 mg/m2/day is 8.0 months (95% confidence interval: CI 5.9-9.9 months). While this is not a head-to-head trial, historically, lomustine, which is the most commonly used chemotherapy for these patients, has demonstrated mOS of 7.2 months*

– Consistent with prior studies, myelosuppression was the most common adverse event. In the 30 mg/m2/day starting dose cohort, five patients experienced a serious adverse event (SAE) possibly related to VAL-083

– For the 83 efficacy evaluable patients who have completed at least one cycle of treatment mOS was 7.5 months (CI 6.1-9.0 months)

"I’m extremely pleased with the outcome of the recurrent arm of the study as it provided important safety and efficacy data to support further evaluation of VAL-083 for the treatment of GBM," said Saiid Zarrabian, Kintara’s Chief Executive Officer. "The study of VAL-083 continues in GBM AGILE, an adaptive registration study where it is currently the only therapeutic agent being evaluated for all three GBM patient subtypes: newly-diagnosed methylated MGMT, newly-diagnosed unmethylated MGMT, and recurrent."

Dr. Barbara O’Brien, the Principal Investigator for the Phase 2 study at MD Anderson added, "These data continue to support VAL-083’s compelling potential as a potent DNA targeting cytotoxic agent for the treatment of GBM, which remains a deadly disease with an urgent need for improved treatment options."

VAL-083 is independent of the MGMT resistance mechanism and has been assessed in over 40 Phase 1 and Phase 2 clinical trials in multiple indications sponsored by the U.S. National Cancer Institute (NCI). Published pre-clinical and clinical data indicate that VAL-083 has activity against a range of tumor types, including lung, brain, cervical, and ovarian tumors and hematologic (blood) cancers. VAL-083 has been granted Orphan Drug Designation for GBM by the FDA and EMA and has also been granted Orphan Drug Designations for medulloblastoma and ovarian cancer by the FDA. In addition, the FDA has granted Fast Track Designation for VAL-083 in recurrent GBM. VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer. VAL-083 has not been approved for any indications outside of China.

* Wick et al N.Eng.J.Med . 377:1954 1963 (2017)

On July 1, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported financial results for the quarter ended March 31, 2021, and provided an update on clinical and corporate progress (Press release, Affimed, JUL 1, 2021, View Source [SID1234584549]).

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"As we continue to build momentum with our clinical programs, we see growing interest in the important work that we are doing in the emerging field of innate immuno-oncology. We published clinical data for AFM13 that is supporting our three-pronged development strategy of our ICE as monotherapy, in combination with NK cells and in combination with a checkpoint inhibitor," said Dr. Adi Hoess, CEO of Affimed. "Over the next several months, we have a number of value-creating events on AFM13, AFM24, where we expect to initiate several clinical studies, and AFM28, and are allocating capital across our portfolio to develop multiple opportunities for shareholder value creation."

Clinical Stage Program Updates
AFM13 (CD30/CD16A)

Affimed is continuing to recruit patients in the REDIRECT study (AFM13-202) after reporting positive results from the preplanned interim futility analysis in March 2021; the trial combined the high- and low-CD30 expressing cohorts into one. Affimed expects to complete enrollment in the study in the first half of 2022. REDIRECT is a phase 2, registration-directed study of AFM13 as monotherapy in patients with relapsed or refractory CD30-positive peripheral T-cell lymphoma (PTCL).
Affimed reported all three dose escalation cohorts in the investigator sponsored trial (IST) at The University of Texas MD Anderson Cancer Center of AFM13 precomplexed with natural killer (NK) cells (AFM13-104) are now fully enrolled. The study is evaluating increasing doses of cord-blood derived NK cells pre-complexed with AFM13 followed by three weekly infusions of AFM13 monotherapy in patients with recurrent or refractory CD30-positive lymphomas.
Preclinical data published in Clinical Cancer Research support the therapeutic potential of AFM13, demonstrating that AFM13 in combination with NK cells improved tumor recognition and enhanced tumor cell killing in vitro and in vivo compared to NK cells alone. This data supported the Investigational New Drug (IND) application for the ongoing phase 1 clinical study of AFM13 pre-complexed with NK cells.
AFM24 (EGFR/CD16A)

AFM24-101, the phase 1/2a clinical trial of AFM24, the EGFR/CD16A targeted ICE for patients with EGFR-expressing solid tumors, completed dose cohort 5 (320 mg) and patients are currently being enrolled and treated in dose cohort 6 (480 mg). Affimed expects to determine the recommended phase 2 dose and initiate dose expansion cohorts in the second half of 2021.
The phase 1/2a combination study of AFM24 with NKGen Biotech’s autologous NK cell therapy, SNK01, a first-in-human proof of concept trial with EGFR-expressing solid tumors is on track to start in the second half of 2021.
The phase 1/2a combination study of AFM24 with the PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) with EGFR-expressing solid tumors is on track to start in the second half of 2021.
Preclinical and Partnered Programs
Affimed expects to disclose the target of its preclinical asset AFM28 and publish initial preclinical data in the second half of 2021. The company remains on track to file an IND application for AFM28 in the first half of 2022.
Genentech has completed the dose escalation portion of the phase 1 study of RO7297089 (anti-BCMA/CD16A). No dose limiting toxicities were observed during the study. However, due to broader portfolio considerations, Genentech decided to stop the phase 1 study of RO7297089. The decision does not impact the development of other targets pursuant to the collaboration agreement with Genentech.
First Quarter 2021 Financial Highlights
As of March 31, 2021, cash and cash equivalents totaled €240.7 million compared to €146.9 million on December 31, 2020. Based on its current operating plan and assumptions, Affimed anticipates that its cash and cash equivalents will support operations into the second half of 2023.
Net cash used in operating activities for the quarter ended March 31, 2021, was €16.0 million compared to €16.5 million for the quarter ended March 31, 2020.
Total revenue for the quarter ended March 31, 2021, was €11.7 million compared with €5.1 million for the quarter ended March 31, 2020. Revenue predominately relates to the Genentech and Roivant collaborations.
Research and development expenses for the quarter ended March 31, 2021, remained flat at €11.4 million compared to the quarter ended March 31, 2020.
General and administrative expenses increased 27.3% from €3.5 million in the quarter ended March 31, 2020, to €4.5 million in the quarter ended March 31, 2021. The increase relates largely to higher personnel expenses, higher premiums for our Directors and Officers liability insurance and higher legal and consulting expenses.
Net finance income for the quarter ended March 31, 2021, increased by 242% from €1.6 million in the quarter ended March 31, 2020, to €5.5 million. This increase is largely due to foreign exchange gains related to assets denominated in U.S. dollars as a result of the strengthening of the U.S. dollar against the Euro during the quarter.
Net income for the quarter ended March 31, 2021, was €1.4 million, or €0.01 per common share compared with a net loss of €8.3 million, or loss €0.11 per common share, for the quarter ended March 31, 2020.
The weighted number of common shares outstanding for the quarter ended March 31, 2021, was 116.2 million.
Additional information regarding these results will be included in the notes to the consolidated financial statements as of March 31, 2021, of Affimed’s filings with the U.S. Securities and Exchange Commission (SEC).

Note on International Financial Reporting Standards (IFRS)
Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the International Accounting Standards Board. None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles in the United States. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information
Affimed will host a conference call and webcast today, July 1, 2021, at 8:30 a.m. EDT to discuss first quarter 2021 financial results and recent corporate developments. The conference call will be available via phone and webcast. To access the call, please dial +1 (409) 220-9054 for U.S. callers, or +44 (0) 8000 323836 for international callers, and reference passcode 4485380 approximately 15 minutes prior to the call. A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be accessible at the same link for 30 days following the call.