On October 21, 2019 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported the completion of enrollment in CONTESSA, a multinational, multicenter, randomized, Phase 3 study investigating tesetaxel as a potential treatment for patients with HER2 negative, hormone receptor positive metastatic breast cancer (Press release, Odonate Therapeutics, OCT 21, 2019, View Source;a-phase-3-study-of-tesetaxel-in-patients-with-metastatic-breast-cancer-4b01a676-a578-4c38-a3a8-f70cc4daa7aa [SID1234542388]). The Company expects to report top-line results from CONTESSA in the third quarter of 2020.

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About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies. Tesetaxel currently is the subject of three studies in breast cancer, including a multinational, multicenter, randomized, Phase 3 study in patients with metastatic breast cancer, known as CONTESSA.

About CONTESSA

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with metastatic breast cancer (MBC). CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally for 14 days of each 21-day cycle) in approximately 600 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Patients with central nervous system (CNS) metastases are eligible. The primary endpoint is progression-free survival (PFS) as assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival (OS), objective response rate (ORR) as assessed by the IRC and disease control rate (DCR) as assessed by the IRC.

On October 21, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported the results of the Phase III IMbrave150 study, evaluating Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a treatment for people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Chugai, OCT 21, 2019, View Source [SID1234542373]).

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The combination of Tecentriq and Avastin improved overall survival (OS) and progression-free survival (PFS), the co-primary endpoints of the study, providing a statistically significant and clinically meaningful improvement compared with standard-of-care sorafenib. Safety for the combination of Tecentriq and Avastin was consistent with the known safety profiles of the individual medicines, with no new safety signals identified. Data from the IMbrave150 study will be presented at an upcoming medical meeting.

"We are very pleased that Tecentriq and Avastin in combination became the first treatment regimen containing immunotherapy to show positive results in a pivotal study with HCC patients," said Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. "Systemic therapy is the standard treatment for people with HCC who are not eligible for surgery or topical therapy. HCC is still a disease with poor prognosis, and new treatment options are awaited. We will be working together with Roche to provide patients with this new treatment option as early as possible."

About IMbrave150 study
IMbrave150 is a global Phase III, multicenter, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People are randomized 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. People receive the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints were OS and PFS by independent-review facility (IRF) per RECIST v1.1. Secondary efficacy endpoints included objective response rate (ORR), time to progression (TTP) and duration of response (DOR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (PROs), safety and pharmacokinetics.

About hepatocellular carcinoma (HCC)
HCC accounts for over 90% of liver cancer and an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide. 1, 2) In Japan, about 40 thousand people are diagnosed with a liver cancer every year and the number of deaths accounts for about 28 thousands per year. 3) HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage. 1) The prognosis for unresectable HCC remains limited, with few systemic therapeutic options and a 1-year survival rate of less than 50%. 4)

Trademarks used or mentioned in this release are protected by law.

[References]
1: Llovet J et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.
2: Liver Cancer Study Group of Japan. The 20th follow-up survey of nation-wide research for primary liver cancer 2008-2009. Kanzo. 60(8): 258-293 (2019)
3: Cancer Registry and Statistics. Cancer Information Service, National Cancer Center Japan [Internet; cited Ocotober 2019] Available from: View Source
4: Giannini G et al. Prognosis of untreated hepatocellular carcinoma. Hepatology. 2015;61(1):184-190.

On October 21, 2019 BIOLASE, Inc. (NASDAQ: BIOL), the global leader in dental lasers, reported select unaudited preliminary financial results for the third quarter ended September 30, 2019 (Press release, Biolase Technology, OCT 21, 2019, View Source [SID1234542390]).

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Select Preliminary Third Quarter 2019 Unaudited Financial Results:

Revenue is expected to be in the range of $8.5 million to $8.8 million.
Loss from operations is expected to be in the range of ($4.8) million to ($5.2) million as the Company increased its allowance for doubtful accounts by approximately $1.1 million to fully reserve for payments still owed to it by its Chinese distributor.
Net loss is expected to be in the range of ($5.4) million to ($5.8) million.
Third quarter adjusted EBITDA is anticipated to be in the range of ($2.7) million to ($3.1) million. The Company continues to expect to be adjusted EBITDA break-even in the fourth quarter of 2019, which is historically the Company’s strongest quarter.
Estimates of financial results are inherently uncertain and subject to change, and actual results may differ materially due to the completion of management’s final review, final adjustments and other developments that may arise before the Company’s financial results for the quarter ended September 30, 2019 are finalized.

Non-GAAP Disclosure

In addition to the financial information prepared in conformity with generally accepted accounting principles in the U.S. ("GAAP"), this press release includes certain historical non-GAAP financial information. Management believes that these non-GAAP financial measures assist investors in making comparisons of period-to-period operating results and that, in some respects, these non-GAAP financial measures are more indicative of the Company’s ongoing core operating performance than their GAAP equivalents.

Adjusted EBITDA is defined as net loss before interest, taxes, depreciation and amortization, stock-based compensation and allowance for doubtful accounts. Management uses adjusted EBITDA in its evaluation of the Company’s core results of operations and trends between fiscal periods and believes that these measures are important components of its internal performance measurement process. Therefore, investors should consider non-GAAP financial measures in addition to, and not as a substitute for, or as superior to, measures of financial performance prepared in accordance with GAAP. Further, the non-GAAP financial measures presented by the Company may be different from similarly named non-GAAP financial measures used by other companies.

The Company’s outlook for fourth quarter of 2019 earnings is provided on a non-GAAP basis because certain reconciling items are dependent on future events that either cannot be controlled, such as interest rates, or reliably predicted, such as stock-based compensation. Any such reconciling items may be significant.

Conference Call Information
BIOLASE, Inc. will host a conference call on November 6, 2019 at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time) to discuss its financial results for the third quarter ended September 30, 2019, and to answer questions. For both "listen-only" participants and those participants who wish to take part in the question-and-answer portion of the call, the dial-in number in the U.S./Canada is 800-458-4148. For international participants outside the U.S./Canada, the dial-in number is 323-794-2093. For all callers, refer to the Conference ID 9068935. To access the live webcast, visit the Investor Relations section of the BIOLASE website at www.biolase.com and see "Investor Events".

An audio archive of the webcast will be available for 30 days on the Investor Relations section of the BIOLASE website.

On October 21, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported positive topline results from the HER2CLIMB trial, a randomized, double-blind, placebo-controlled, active comparator pivotal trial evaluating tucatinib (Press release, Seattle Genetics, OCT 21, 2019, View Source [SID1234542374]). The trial compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1), and 47 percent of the patients enrolled in the trial had brain metastases at the time of enrollment. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

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The trial met the primary endpoint of progression-free survival (PFS), showing that the addition of tucatinib was superior to trastuzumab and capecitabine alone, with a 46 percent reduction in the risk of disease progression or death (hazard ratio (HR)=0.54 (95% Confidence Interval (CI): 0.42, 0.71); p<0.00001). The trial also met the two key secondary endpoints at interim analysis. The tucatinib arm demonstrated an improvement in overall survival, with a 34 percent reduction in the risk of death (HR=0.66 (95% CI: 0.50, 0.88); p=0.0048) compared to trastuzumab and capecitabine alone. For patients with brain metastases at baseline, the tucatinib arm also demonstrated superior PFS, with a 52 percent reduction in the risk of disease progression or death compared to those who received trastuzumab and capecitabine alone (HR=0.48 (95% CI: 0.34, 0.69); p<0.00001).

Tucatinib in combination with trastuzumab and capecitabine was generally well tolerated with a manageable safety profile. The most frequent adverse events in the tucatinib arm included diarrhea, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting. Grade 3 or greater adverse events in the tucatinib arm compared to the control arm included diarrhea (12.9 vs. 8.6 percent), increased aspartate aminotransferase (AST) (4.5 vs. 0.5 percent), increased alanine aminotransferase (ALT) (5.4 vs. 0.5 percent) and increased bilirubin (0.7 vs. 2.5 percent). There was no requirement for prophylactic antidiarrheals. Adverse events leading to discontinuations were infrequent in both the tucatinib arm and the control arm (5.7 and 3.0 percent). Additional results are scheduled to be presented on December 11 at the 2019 San Antonio Breast Cancer Symposium.

"There is significant unmet medical need following treatment with trastuzumab, pertuzumab and T-DM1 in patients with metastatic HER2-positive breast cancer," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "The addition of tucatinib to the commonly used doublet of trastuzumab and capecitabine represents a potential significant clinical advance for patients with metastatic HER2-positive breast cancer, importantly, including those with brain metastases. Based on these findings, we plan to unblind the trial and offer tucatinib to patients on the control arm. We also plan to submit a New Drug Application (NDA) to the FDA in the first quarter of 2020, with the goal of bringing a much-needed new medicine to patients."

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Approximately 30 to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival as well as progression-free survival in patients with brain metastases at baseline. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally-advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. The trial is being conducted in North America, Europe and Asia and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-

positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at www.clinicaltrials.gov.

Conference Call Details

Seattle Genetics’ management will host a conference call and webcast to discuss topline results from the HER2CLIMB clinical trial of tucatinib. The event will be held today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The live event will be simultaneously webcast and available for replay from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 800-367-2403 (domestic) or 334-777-6978 (international). The conference ID is 9551838. A replay of the audio only will be available by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 9551838. The telephone replay will be available until 5:00 p.m. PT on October 24, 2019.

On October 21, 2019 Bruker Corporation (Nasdaq: BRKR) reported it will report third quarter 2019 financial results on Thursday, October 31, 2019, after the market closes (Press release, Bruker, OCT 21, 2019, View Source [SID1234542391]). The Company will host a conference call and webcast at 4:30 p.m. Eastern Time to discuss the results and current business trends.

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To listen to the webcast, investors can go to View Source and click on the "Earnings Webcast" hyperlink in the "Latest Results" section. A slide presentation will be referenced during the webcast and will be posted to the company’s website shortly before the webcast begins.

Investors can also listen to the earnings webcast via telephone by dialing 1-888-437-2685 (U.S. toll free) or +1-412-317-6702 (international) and referencing "Bruker’s Third Quarter 2019 Earnings Conference Call".

Bruker is enabling investors to pre-register for the earnings conference call so that they can expedite their entry into the call and avoid the need to wait for a live operator. In order to pre-register for the call, investors can visit View Source and enter their contact information. Investors will then be issued a personalized phone number and PIN to dial into the live conference call. Individuals can pre-register any time prior to the start of the conference call on October 31.

A telephone replay of the conference call will be available by dialing 1-877-344-7529 (U.S. toll free) or +1-412-317-0088 (international) and entering conference number: 10136323. The replay will be available beginning one hour after the end of the conference call through December 1, 2019.