On October 28, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to inform disease management decisions and improve patient outcomes, reported that the DecisionDx-Melanoma integrated test result (ITR) now includes i31-GEP for Risk of Recurrence (i31-ROR) (Press release, Castle Biosciences, OCT 28, 2021, View Source [SID1234592136]). Designed to improve the precision of treatment plans for better patient care, the i31-ROR predicts patient-specific five-year outcomes for melanoma-specific survival (MSS), distant metastasis-free survival (DMFS) and recurrence-free survival (RFS).

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DecisionDx-Melanoma is a gene expression profile (GEP) test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples.

Earlier this year, Castle launched the ITR for DecisionDx-Melanoma, which included i31-GEP Sentinel Lymph Node Biopsy (i31-SLNB). i31-SLNB is an independently validated algorithm that integrates clinicopathologic features with the 31-GEP score. i31-SLNB is designed to provide a more precise and personalized prediction of sentinel lymph node (SLN) positivity to guide discussions and recommendations, within current risk-based guidelines, for the SLN biopsy (SLNB) surgical procedure.

Castle has now completed independent validation of a new, separate algorithm, i31-ROR, that integrates DecisionDx-Melanoma’s 31-GEP score with the specific Breslow thickness, mitotic rate, SLN status, ulceration status and location (head and neck, extremities, trunk) of the individual patient’s tumor. The additional endpoints of RFS and DMFS, which are not currently provided by the American Joint Committee on Cancer Eighth Edition (AJCC8) staging system, are anticipated to be helpful when determining appropriate treatment pathways for each patient’s disease. The new upgraded ITR now provides both this new i31-ROR result as well as the i31-SLNB, in addition to the traditional class designation obtained with DecisionDx-Melanoma.

"Clinicians and patients look to our tests to provide clinically actionable information that better informs cancer management decisions, such as intensity of surveillance and follow-up frequency," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "And we are committed to continually reviewing this process to improve patient care, as evidenced by the introduction of our new i31-GEP for Risk of Recurrence test result.

"With this additional information, DecisionDx-Melanoma results are not only designed to provide a more precise, personalized likelihood of SLN positivity, but now also include a more individualized risk assessment, rather than an average, population-based risk estimate, that we believe can help personalize patient management decisions and overall risk assessments beyond standard melanoma staging."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated DecisionDx-Melanoma test result.

Through June 30, 2021, DecisionDx-Melanoma has been ordered 78,277 times for use in patients with cutaneous melanoma. More information about the test and disease can be found at www.CastleTestInfo.com.

On October 28, 2021 Exicure, Inc. (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported presentations at the following scientific conferences during the month of November (Press release, Exicure, OCT 28, 2021, View Source [SID1234592135]):

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TIDES EU
Title: "Development of Spherical Nucleic Acids Targeting SCN9A For the Treatment of Neuropathic Pain"
Presented by: Bart Anderson, Senior Director, R&D
Date: November 16, 2021
Time: 8:45am CET / 1:45am U.S. CST

Neuroscience 2021 (The Society for Neuroscience)
Poster 1: "Spherical Nucleic Acids Targeting FXN Induce Frataxin Expression in Models of Friedreich’s Ataxia"
Presented by: Grant Corbett, Group Lead, Neuroscience
Poster 2: "Biodistribution of Spherical Nucleic Acids in the Mouse CNS Following ICV, ICM and IT Delivery"
Presented by: Lauren Moore, Senior Scientist, Neuroscience
November 8-11, 2021

On October 28, 2021 Novocure (NASDAQ: NVCR) reported that the final patient has been enrolled in phase 3 pivotal INNOVATE-3 trial evaluating the efficacy of Tumor Treating Fields (TTFields) together with paclitaxel for treatment of patients with platinum-resistant ovarian cancer (Press release, NovoCure, OCT 28, 2021, View Source [SID1234592134]).

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"This is a major step forward for our clinical trial program and an important achievement for patients, trial investigators and our company," said William Doyle, Novocure’s Executive Chairman. "Ovarian cancer is the fifth leading cause of cancer death in women, impacting nearly 100,000 patients annually in the U.S., Europe and Japan, alone. INNOVATE-3 is the largest abdominal trial to complete enrollment in Novocure history, and we are excited to be enhancing the clinical field in support of people with this deadly disease."

Following the completion of enrollment, an independent Data Monitoring Committee (DMC) will conduct the pre-specified interim analysis pursuant to the trial protocol. Final data from the INNOVATE-3 trial is anticipated in 2023.

INNOVATE-3 is a randomized, open-label study which was designed to enroll 540 adult patients with recurrent, platinum-resist ovarian cancer. Patients have been randomized to receive either weekly paclitaxel alone or weekly paclitaxel concomitant with TTFields tuned to 200 kHz until progression. The primary endpoint is overall survival. Secondary endpoints include progression free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. The European Network for Gynecological Oncological Trials (ENGOT) and The GOG Foundation, Inc. collaborated with Novocure on the design and facilitation of this trial.

About Ovarian Cancer

In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old. Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease. Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy. Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases. Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence. Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor.

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 are 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 network of preclinical collaborators and 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 20,000 patients have been treated with TTFields.

On October 28, 2021 Novocure (NASDAQ: NVCR) reported financial results for the quarter ended September 30, 2021, highlighting commercial strength and strategic investment across clinical, product development and commercial initiatives intended to fuel future growth (Press release, NovoCure, OCT 28, 2021, View Source [SID1234592133]). Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer by developing and commercializing its innovative therapy, Tumor Treating Fields (TTFields). TTFields are electric fields that disrupt cancer cell division.

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(1) Adjusted EBITDA is a non-U.S. GAAP measurement of earnings before interest, taxes, depreciation, amortization and share-based compensation.

(2) An "active patient" is a patient who is receiving treatment under a commercial prescription order as of the measurement date, including patients who may be on a temporary break from treatment and who plan to resume treatment in less than 60 days.

(3) A "prescription received" is a commercial order for Optune or Optune Lua that is received from a physician certified to treat patients for a patient not previously on Optune or Optune Lua. Orders to renew or extend treatment are not included in this total.

"The third quarter was another period of solid execution at Novocure," said William Doyle, Novocure’s Executive Chairman. "We generated $134 million in net revenues and invested $48 million across our research, clinical and product development initiatives. We recently completed enrollment in our phase 3 INNOVATE-3 trial and our phase 2 EF-31 trial, and announced a new collaboration with global oncology leader, Roche. The fundamentals of our business are strong, and we are energized by the opportunities before us to help many more cancer patients and to drive the growth of our company."

"As we look ahead, we are nearing a key inflection point for patients and our organization as several of our late-stage clinical trials approach full enrollment," added Asaf Danziger, Novocure’s Chief Executive Officer. "We have completed enrollment in our INNOVATE-3 trial studying recurrent ovarian cancer, and our LUNAR trial studying non-small cell lung cancer is expected to enroll the final patient by year-end. As this cycle of late-stage trials nears conclusion, we are eager to further explore the efficacy of TTFields in new indications, together with other treatment modalities, and in partnerships with global oncology leaders."

Third quarter 2021 financial update

For the quarter ended September 30, 2021, net revenues were $133.6 million, representing 1% growth compared to the third quarter 2020.

In the United States, net revenues totaled $88.0 million in the quarter ended September 30, 2021, representing a 5% decrease compared to the same period in 2020.
In EMEA markets, net revenues totaled $30.3 million in the quarter ended September 30, 2021, representing 7% growth compared to the same period in 2020.
In Japan, net revenues totaled $8.8 million in the quarter ended September 30, 2021, representing 17% growth compared to the same period in 2020.
In Greater China, net revenues totaled $6.5 million in the quarter ended September 30, 2021, representing 52% growth compared to the same period in 2020.
For the three months ended September 30, 2021, the increase in net revenues from the third quarter of 2020 resulted primarily from an increase of 141 active patients in our currently active markets and the launch of Optune in China.

We recorded $10.6 million in revenues from Medicare fee-for-service beneficiaries in the third quarter 2021, an increase of 9% from the $9.7 million recognized in the same period in 2020. We believe we have completed the administrative ramp-up associated with processing Medicare claims and efficiently pursuing appeals. In the third quarter of 2021, we did not record a material amount of incremental net revenue resulting from the successful appeal of previously denied claims for Medicare fee-for-service beneficiaries billed prior to established coverage.

Cost of revenues for the three months ended September 30, 2021 was $30.2 million compared to $28.4 million for the same period in 2020, representing an increase of 6%. The increase in cost of revenues was primarily due to the cost of shipping transducer arrays to a higher volume of commercial patients and increasing shipments of equipment to Zai Lab. Gross margin was 77% for the three months ended September 30, 2021 compared to 79% for the three months ended September 30, 2020.

Research, development and clinical trials expenses for the three months ended September 30, 2021 were $48.1 million compared to $32.8 million for the same period in 2020, representing an increase of 47%. This was primarily due to an increase in clinical trial and personnel expenses for our phase 3 pivotal and label expansion trials, an increase in development and personnel expenses to support our product development programs, and increased investments in preclinical research and the expansion of our medical affairs activities.

Sales and marketing expenses for the three months ended September 30, 2021 were $32.6 million compared to $29.4 million for the same period in 2020, representing an increase of 11%. This was primarily due to an increase in personnel and professional services costs as we continue to enhance our commercial capabilities in anticipation of potential future approvals in new indications.

General and administrative expenses for the three months ended September 30, 2021 were $31.2 million compared to $27.1 million for the same period in 2020, representing an increase of 15%. This was primarily due to an increase in personnel costs and professional services.

Net loss for the three months ended September 30, 2021 was $13.1 million compared to net income of $9.3 million for the same period in 2020.

At September 30, 2021, we had $933.8 million in cash, cash equivalents and short-term investments, an increase of $91.2 million compared to $842.6 million at December 31, 2020. The increase in our cash, cash equivalents and short-term investments was primarily due to the cash flow from operations and the exercise of options.

Third quarter 2021 operating statistics

There were 3,502 active patients at September 30, 2021, representing 4% growth compared to September 30, 2020.

In North America, there were 2,223 active patients at September 30, 2021, representing no change compared to September 30, 2020.
In EMEA markets, there were 987 active patients at September 30, 2021, representing 9% growth compared to September 30, 2020.
In Japan, there were 292 active patients at September 30, 2021, representing 21% growth compared to September 30, 2020.
Additionally, 1,380 prescriptions were received in the quarter ended September 30, 2021, representing 1% growth compared to the same period in 2020.

In North America, 931 prescriptions were received in the quarter ended September 30, 2021, representing a 3% decrease compared to the same period in 2020.
In EMEA markets, 339 prescriptions were received in the quarter ended September 30, 2021, representing 3% growth compared to the same period in 2020.
In Japan, 110 prescriptions were received in the quarter ended September 30, 2021, representing 28% growth compared to the same period in 2020.
Third quarter 2021 non-U.S. GAAP measures

We also measure our performance based upon a non-U.S. GAAP measurement of earnings before interest, taxes, depreciation, amortization and shared-based compensation ("Adjusted EBITDA"). We believe Adjusted EBITDA is useful to investors in evaluating our operating performance because it helps investors compare the results of our operations from period to period by removing the impact of earnings attributable to our capital structure, tax rate and material non-cash items, specifically share-based compensation.

Adjusted EBITDA was $19.9 million for the three months ended September 30, 2021, a decrease of $17.4 million, or 47%, from $37.3 million for the three months ended September 30, 2020. The decrease was driven by increased investments in research and development activities intended to further our exploration of TTFields therapy, and in sales and marketing readiness initiatives in anticipation of future potential launches in new indications. Adjusted EBITDA as a percentage of net revenues reached 15% in the quarter, despite research and development investment reaching 36% of third quarter net revenues. We believe these focused investments are critical to our efforts to realize the long-term potential of the TTFields platform.

Recent achievements

In September, the FDA granted breakthrough device designation to the NovoTTF-200T system for the treatment of advanced liver cancer, in part based on clinical data from Novocure’s phase 2 HEPANOVA trial. Our team, along with trial investigators, are actively designing a phase 3 pivotal trial studying the efficacy of TTFields together with atezolizumab and bevacizumab for the first-line treatment of patients with unresectable or metastatic liver cancer.
In September, we announced a clinical trial collaboration with Roche to evaluate the use of TTFields together with atezolizumab for the treatment of metastatic pancreatic cancer.
In October, we announced the last patient had been enrolled in our phase 2 pilot EF-31 trial for the treatment of gastric cancer.
Today, we announced that the last patient was enrolled in our phase 3 pivotal INNOVATE-3 trial for the treatment of recurrent ovarian cancer.
Anticipated clinical milestones

Data from phase 2 pilot EF-31 trial in gastric cancer (2022)
Data from phase 2 pilot EF-33 trial with high-intensity arrays in recurrent glioblastoma (2022)
Final data from phase 3 pivotal LUNAR trial in NSCLC (2022)
Last patient enrollment in phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2023)
Data from phase 3 pivotal METIS trial in brain metastases (2023)
Final data from phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer (2023)
Final data from phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer (2024)
Conference call details

Novocure will host a conference call and webcast to discuss second quarter 2021 financial results at 8 a.m. EDT today, Thursday, October 28, 2021. Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 6394785.

The webcast, earnings slides presented during the webcast and the corporate presentation can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call. Novocure has used, and intends to continue to use, its investor relations website, as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

On October 28, 2021 Takeda Pharmaceutical Company Limited (TOKYO:4502/NYSE:TAK) ("Takeda") reported that its Board of Directors resolved today to engage in the acquisition of its own shares pursuant to the provision of its Articles of Incorporation in accordance with Article 459, paragraph 1 of the Companies Act of Japan, as detailed below (Press release, Takeda, OCT 28, 2021, View Source [SID1234592132]).

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"At our current share price, we see an opportunity to buy back our shares at a substantial discount to what we perceive is their underlying value," said Costa Saroukos, director and Chief Financial Officer of Takeda. "We expect that this share buyback of up to 100B yen will not impact our deleveraging plans, and that we will remain firmly on track to deliver on our target for 2x (‘low twos’) net debt to Adjusted EBITDA by the end of FY23. We are also maintaining our existing dividend policy and updating our capital allocation policy to allow for share buybacks in the future when appropriate. This underscores our business’ strong cash generation ability, our confidence in our fundamental growth driven by the 14 global brands, and our belief that the R&D strategy with ~40 new molecular entities in the pipeline, will deliver for the long term."

This buyback of shares will be funded by Takeda’s operating cash flow driven by growth in our 14 global brands and working capital improvements.

1. Reason for acquisition of its own shares

To enhance capital efficiency and improve shareholder returns.

2. Details of acquisition

(1) Class of shares to be acquired:

Shares of common stock

(2) Number of shares to be acquired:

Up to 35 million shares

(equivalent to 2.23% of the total number of shares outstanding excluding treasury shares)

(3) Total amount of shares to be acquired:

Up to JPY 100 billion

(4) Schedule of acquisition:

From November 2, 2021 to April 29, 2022

(5) Method of acquisition:

Open-market repurchase through a trust bank

(Reference)

Treasury shares held by Takeda as of September 30, 2021
Aggregate number of issued shares (excluding treasury shares)

1,572,829,854 shares

Number of treasury shares

9,422,671 shares

Updated Capital Allocation Policy

Takeda is delivering on its financial commitments and has a strong cash flow outlook driven by business momentum, cost synergies, and non-core asset divestitures. Guided by our values and our commitment to Patients, People and Planet, we will allocate capital to maximize value for patients and shareholders.

Takeda’s policy in the allocation of capital is as follows:

• Invest in growth drivers;
• Deleverage rapidly; and
• Shareholder returns.

In respect of "Invest in growth drivers", Takeda makes disciplined and focused investments in value-creating business opportunities including R&D, new product launches, including in China, and plasma-derived therapies. With regards to "Deleverage rapidly", Takeda is targeting a 2x (i.e. "low-twos") net debt/adjusted EBITDA ratio within fiscal years ending March 2022 – March 2024 and has committed to maintaining solid investment grade credit ratings. In respect of "Shareholder returns", Takeda maintains its well-established dividend policy of 180 yen per share annually, alongside share buybacks when appropriate. We expect underlying growth momentum to continue over the mid-term.