On September 4, 2018 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for cancer, respiratory and other diseases, reported that it has dosed the first patient in the Company’s Phase 1 combination clinical trial of PRS-343, its lead proprietary immuno-oncology drug candidate targeting HER2 and 4-1BB, plus atezolizumab (Tecentriq), an approved PD-L1 inhibitor (Press release, Pieris Pharmaceuticals, SEP 4, 2018, View Source [SID1234529394]).

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The trial, a multicenter, open-label, Phase 1 dose escalation study, is designed to determine the safety, tolerability, and potential synergistic anti-tumor effects of PRS-343 plus anti-PD-L1 immunotherapy in patients with advanced or metastatic HER2-positive solid tumors. Elevated HER2 expression is associated with multiple cancers, including gastroesophageal, bladder, breast, and a range of other tumor types. The trial is fully funded and sponsored by Pieris, while Roche is supplying atezolizumab.

"The initiation of the combination trial of PRS-343 with an anti-PD-L1 immunotherapy marks the beginning of Pieris’ investigation into the potential synergistic effects of its 4-1BB-targeted therapy with PD-1/L1 blockade," said Louis Matis, M.D., Senior Vice President and Chief Development Officer of Pieris. "Given evidence from multiple preclinical studies demonstrating synergistic anti-tumor activity from concurrent 4-1BB activation and PD-(L)1 pathway blockade, we believe that combination therapy with PRS-343 and atezolizumab has the potential to provide significant clinical benefit for patients. We are enthusiastic to be initiating this trial and look forward to reporting our findings from this combination study next year."

About PRS-343

PRS-343 is a bispecific monoclonal antibody-Anticalin fusion protein comprised of a HER2 tumor-targeting antibody genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based bispecific therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes, and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

About HER2-Positive Malignancies

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells and is associated with aggressive disease progression. Multiple tumor types can express HER2 including breast, gastroesophageal, bladder, biliary (cholangiocarcinoma), colorectal, endometrial, ovarian, non-small cell lung, pancreatic, head and neck, and other cancers.

On September 4, 2018 Puma Biotechnology, Inc. (Nasdaq:PBYI) reported that the European Commission (EC), has granted marketing authorisation for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy (Press release, Puma Biotechnology, SEPT 4, 2018, View Source [SID1234529268]).

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EC approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Patients (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, for patients with hormone receptor positive, HER2-positive early stage breast cancer patients who were treated within one year after the completion of trastuzumab based adjuvant therapy, invasive disease-free survival (iDFS) was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49; 95% CI: (0.30, 0.78); p=0.002)

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

"Reducing the risk of disease recurrence remains a need for patients, despite advances in the treatment of early stage HER2-positive breast cancer," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to bring this new medicine to patients in Europe and would like to express our appreciation to the patients, caregivers and physicians who contributed to the neratinib clinical development program and, more specifically, the ExteNET trial. We are committed to continuing to expand NERLYNX accessibility to patients worldwide. We expect NERLYNX to be commercially available in Europe in 2019, beginning with our launch in Germany during the first half of 2019 and followed by additional countries throughout Europe in the second half of 2019."

The approval of NERLYNX by the European Commission follows the positive opinion issued by the Committee for Medicinal Products for Human Use of the European Medicines Agency in June 2018.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On September 4, 2018 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported that Marc N. Casper, president and chief executive officer, will present at the Morgan Stanley Global Healthcare Conference on Wednesday, September 12, 2018, at 2:15 p.m. (ET) at the Grand Hyatt New York, New York (Press release, Thermo Fisher Scientific, SEP 4, 2018, View Source [SID1234529458]).

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You can access the live webcast of the presentation via the Investors section of our website, www.thermofisher.com.

On September 4, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported that it will present at 2018 B. Riley FBR Healthcare Conference on Tuesday, September 4th and at the Maxim Rights Offering Conference on Thursday, September 6th, both of which are being held in New York City (Press release, Actinium Pharmaceuticals, SEP 4, 2018, View Source [SID1234529253]).

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The Company’s Chief Medical Officer, Mark Berger, M.D, will participate in a panel at the B. Riley FBR Healthcare Conference. Details of the panel are as follows:

Title:

Antibody-drug Conjugates are a Waning Technology

Date:

September 4, 2018

Time:

12:50 pm ET

Location:

New York Marriott East Side, Stuyvesant Room

On September 4, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the achievement of a development milestone in its collaboration with Eli Lilly and Company (Press release, Zymeworks, SEPT 4, 2018, View Source [SID1234529269]). In accordance with Zymeworks’ 2013 licensing and collaboration agreement with Lilly, Zymeworks will receive a milestone payment of US$2.0 million for Lilly’s submission of an IND application for a bispecific antibody enabled by Zymeworks’ proprietary Azymetric platform. Previously, Zymeworks announced Lilly’s nomination of two bispecific immuno-oncology drug candidates for late-stage preclinical development.

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"The team at Lilly has done an impressive job advancing a novel bispecific therapeutic built on our Azymetric platform to the IND stage in a relatively short period of time," said Ali Tehrani, Ph.D., President and Chief Executive Officer of Zymeworks. "Moving a compound into the clinic is an important step in drug development and we look forward to future progress with Lilly as well as our five other partners."

Under its two licensing and collaboration agreements with Lilly, Zymeworks has granted Lilly worldwide licenses to research, develop and commercialize multiple bispecific therapeutics directed towards Lilly’s targets. To date, Zymeworks has received an upfront licensing payment and multiple research milestone payments under these agreements, in addition to historical equity investments made by Lilly in Zymeworks. Zymeworks is also eligible to receive further development and commercial milestone payments and tiered royalties on global product sales.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.