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.

On October 21, 2019 Acorda Therapeutics, Inc. (NASDAQ:ACOR) reported that it will host a conference call and webcast to report its third quarter 2019 update and financial results on Monday, November 4 at 4:30 p.m. ET (Press release, Acorda Therapeutics, OCT 21, 2019, View Source [SID1234542375]).

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To participate in the conference call, please dial (833) 236-2756 (domestic) or (647) 689-4181 (international) and reference the access code 5464078. The presentation will be available on the Investors section of www.acorda.com.

A replay of the call will be available from 7:30 p.m. ET on November 4, 2019 until 11:59 p.m. ET on December 4, 2019. To access the replay, please dial (800) 585-8367 (domestic) or (416) 621-4642 (international); reference code 5464078. The archived webcast will be available in the Investor Relations section of the Acorda website at www.acorda.com.

On October 21, 2019 Sophiris Bio Inc. (NASDAQ: SPHS) (the "Company" or "Sophiris"), a biopharmaceutical company studying topsalysin (PRX302), a first-in-class, pore-forming protein, in late-stage clinical trials for the treatment of patients with urological diseases, reported that following an End of Phase 2/ Pre-Phase 3 meeting with the United States Food and Drug Administration (FDA), there is agreement regarding the design of a single Phase 3 clinical trial to evaluate the potential of topsalysin as a targeted focal therapy to treat patients with intermediate risk localized prostate cancer (Press release, Sophiris Bio, OCT 21, 2019, View Source [SID1234542392]).

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The Phase 3 study design agreed upon with the FDA is consistent with the design previously agreed upon with the European Medicines Agency, as reported in June of this year. The study will enroll approximately 700 patients with a confirmed diagnosis of localized intermediate risk disease, to be equally randomized to receive a single administration of either topsalysin or placebo. The primary endpoint for the study will be the proportion of patients at 12 months who have failed treatment, defined as histological progression of disease, resulting in the need for alternative therapy, as assessed by an independent central adjudication panel. In addition, the FDA has indicated that in order to receive approval, Sophiris will evaluate all patients that progress to alternative treatments for an additional 12 months, for a total of 24 months of data, post the administration of study drug.

"The meeting with the FDA was positive, confirming the proposed Phase 3 study design is an acceptable approach to targeted focal therapy in the proposed patient population. The FDA’s request to provide data on patients progressing to alternative therapy for an additional 12 months – for a total of 24 months – will, we believe, strengthen the overall data package for approval, providing valuable information on the durability of response following targeted focal therapy with topsalysin," said Professor Hashim Ahmed, Faculty of Medicine Department of Surgery & Cancer, Chair in Urology, Imperial College of London & Imperial College Healthcare NHS Trust and a member of the Scientific Advisory Board at Sophiris.

"The meeting with the FDA was productive and it was clear that if the proposed study were positive and the safety profile were to continue as observed in clinical trials to date, a single study has the potential to provide the clinical data to support regulatory approval in both the US and Europe," said Professor Scott Eggener, Faculty of Surgery and Radiobiology University of Chicago Medicine and a member of the Scientific Advisory Board at Sophiris.

"Now that there is a clear and agreed upon regulatory pathway forward for localized prostate cancer, we can now focus on our plan to fund this study and the Company going forward," said Randall E. Woods, our president and chief executive officer. "With the uncertainty of the regulatory pathway removed, we are advancing our discussions with multiple parties capable of funding the continued development of topsalysin."

About Localized Prostate Cancer

Prostate cancer is the second most common form of cancer in men in the United States with an estimated 175,000 new cases in 2019. Approximately 77 percent of patients in the United States are diagnosed with localized disease. Research has shown that patients with early, localized disease have a low likelihood of the cancer spreading beyond the confines of the prostate; however, many men with clinically-significant localized disease choose to undergo radical treatment. Radical therapies include surgery to remove the entire prostate and/or radiation. Potential toxicities from radical treatments can be significant and permanent and include erectile dysfunction, urinary incontinence and rectal toxicity.

About Topsalysin

Topsalysin (PRX302), an innovative, "First-in-Class" transmembrane pore-forming protein, was genetically modified to be activated only by enzymatically-active PSA, which is produced in large quantities within the prostate of men with prostate cancer. The targeted focal treatment of prostate cancer is in line with current treatment trends for solid tumors such as breast and liver, where the goal is to remove the tumor and preserve as much of the organ and organ function as possible.

Topsalysin has the potential to provide a targeted focal therapy for the ablation of localized prostate cancer lesions while potentially avoiding many of the complications and side effects associated with whole gland radical treatments. The increasing use of multiparametric magnetic resonance imaging (mpMRI) and advances in software to co-register previously obtained mpMRI images with real-time three-dimensional ultrasound images enables urologists to more accurately locate tumors within the prostate when taking biopsies. This increases the accuracy with which men with clinically significant lesions are identified. It also enables the injection of an ablative agent, such as topsalysin, directly into previously identified clinically significant tumors located within the prostate.

On October 21, 2019 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that it will webcast its Quarterly Update Conference Call for the third quarter 2019 on Tuesday, November 12 at 4:30 p.m. ET / 1:30 p.m. PT. Dr. Helen Torley, president and chief executive officer, will lead the call (Press release, Halozyme, OCT 21, 2019, View Source [SID1234542376]). On the same date, Halozyme will release financial results for the third quarter ended September 30, 2019 following the close of trading.

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The call will be webcast live through the "Investors" section of Halozyme’s corporate website and a recording will be made available following the close of the call. To access the webcast and additional documents related to the call, please visit the Investors page of www.halozyme.com approximately fifteen minutes prior to the call to register, download and install any necessary audio software. The live call may be accessed by dialing (877) 824-0907 (domestic callers) or (647) 689-5655 (international callers). A telephone replay will be available after the call by dialing (800) 585-8367 (domestic callers) or (416) 621-4642 (international callers) using replay ID number 6597916.