On January 31 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced that initial results from the company’s ongoing SUMMIT Phase II ‘basket’ clinical trial of PB272 (neratinib) in patients with tumors harboring HER2 or HER3 mutations were published in the journal Nature . The paper, "HER kinase inhibition in patients with HER2- and HER3-mutant cancers," appears in the January 31, 2018 online issue at View Source and will be published in a future print issue of the journal.

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The Phase II SUMMIT trial is a global, multi-histology, open-label, precision-medicine ‘basket’ study evaluating the safety and efficacy of neratinib administered daily to patients with a wide variety of solid tumors with activating HER2 or HER3 mutations. SUMMIT is designed to evaluate the contributions of both genetic mutation and cancer type on individual patients’ response to neratinib. Information generated from the trial will help guide neratinib-based targeted therapy across a broad spectrum of tumor types with HER2 or HER3 mutations, including patients with rare tumors who may not otherwise have access to investigational therapies.

"Publication of the initial SUMMIT data in this prestigious journal reflects the novelty and quality of this precision-medicine trial design, as well as the growing understanding that both tumor type and gene mutations play an important role in individual patients’ response to cancer therapies such as neratinib," said Alan H. Auerbach, Puma’s Chief Executive Officer and President. "The basket trial design utilized for SUMMIT is enabling researchers to evaluate the clinical potential of neratinib in multiple cancer types, rather than limiting exploration to one tumor type at a time. SUMMIT is also significant in that it will provide the largest body of clinical data to date on the use of an irreversible pan-HER inhibitor in patients who have solid tumors with somatic HER2 or HER3 mutations."

The initial SUMMIT results published in Nature comprise data from 141 patients enrolled in the neratinib monotherapy arm of the trial, including 124 patients with HER2 mutations and 17 patients with HER3 mutations. This included patients with 21 unique tumor types, with the most common being breast, lung, bladder and colorectal cancer. Researchers observed 30 distinct HER2 and 12 distinct HER3 mutations among these patients, with the most frequent HER2 variants involving amino acids S310, L755, A755_G776insYVMA and V777.

In the HER2-mutant cohort, clinical responses were observed in tumors with S310, L755, V777, P780_Y781insGSP and A775_G776insYVMA mutations. When stratified by tumor type, responses were observed in patients with breast, cervical, biliary, salivary and non-small-cell lung cancers, which led to cohort expansions in these tumor types. No activity was observed in the HER3-mutant cohort.

The neratinib safety profile observed in the SUMMIT study is consistent with that observed previously in metastatic patients with HER2 amplified tumors. The study showed that the most frequently observed adverse reaction was diarrhea. All patients in the SUMMIT study received prophylactic loperamide (16 mg per day initially) for the first cycle of treatment in order to reduce neratinib-related diarrhea, and with this anti-diarrheal prophylaxis and management, diarrhea was not a treatment-limiting side effect in SUMMIT. For the 141 patients enrolled in the neratinib monotherapy arm with safety data available, 31 patients (22.0%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was two days. Four patients (2.8%) permanently discontinued neratinib and 21 patients (14.9%) had dose interruptions due to diarrhea.

"Results to date from the SUMMIT trial validate the ‘next-generation’ basket trial approach, which has enabled us to efficiently and effectively evaluate neratinib across numerous cancer types as well as individual and sometimes entirely novel HER2 mutations," said David Hyman, M.D., Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSK). "We look forward to completing enrollment in the ongoing cohorts in the study and continuing to utilize the basket trial design to explore the most optimal treatment options for these select patient populations."

Dr. Hyman, who helped pioneer the concept of basket trials at MSK, presented the initial findings from the SUMMIT study at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2017.

"We are very pleased with these initial results," said Mr. Auerbach. "We look forward to advancing neratinib into further clinical development in multiple HER2 mutant tumor types, both as monotherapy and in novel combinations."

On January 31, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) and Cascadian Therapeutics, Inc. (Nasdaq:CASC) reported the signing of a definitive merger agreement under which Seattle Genetics has agreed to acquire Cascadian Therapeutics (Press release, Cascadian Therapeutics, JAN 31, 2018, View Source [SID1234523651]). Under the terms of the agreement, Seattle Genetics will pay $10.00 per share in cash, or approximately $614 million. The transaction was unanimously approved by the Boards of Directors of both companies.

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Cascadian Therapeutics’ most advanced program is tucatinib, an investigational oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2, a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, ovarian and gastric. Tucatinib is currently being evaluated in a randomized global pivotal trial called HER2CLIMB for patients with HER2-positive (HER2+) metastatic breast cancer, including patients with or without brain metastases. Tucatinib has been evaluated as a single agent and in combination with both chemotherapy and other HER2-directed agents including Herceptin (trastuzumab) and Kadcyla (trastuzumab emtansine). Results from phase 1b trials showed that the combination of tucatinib, capecitabine and trastuzumab was generally well-tolerated and demonstrated clinical activity in patients with and without brain metastases. The data support the ongoing pivotal trial and the potential role of tucatinib in earlier lines of metastatic breast cancer.

"This acquisition would enhance our late-stage clinical pipeline with a potentially best-in-class, orally available and highly selective TKI for patients with HER2-positive metastatic breast cancer," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Tucatinib would complement our existing pipeline of targeted cancer therapies, provide a third late-stage opportunity for a commercial product in solid tumors and expand our global efforts in breast cancer. It also leverages our broad expertise and resources to advance and expand the tucatinib program for patients. Beyond breast cancer, we believe there may be opportunities for tucatinib in other tumor types, such as HER2-positive metastatic colorectal cancer. Cascadian’s pipeline also includes a preclinical immuno-oncology agent. We look forward to welcoming the team at Cascadian Therapeutics and continuing the momentum of the tucatinib development program."

"This agreement represents a very positive outcome for patients with HER2-expressing cancers, our employees and for our stockholders," said Scott D. Myers, President and Chief Executive Officer of Cascadian Therapeutics. "Seattle Genetics has the development and commercial capabilities and the resources needed to more fully realize the potential of tucatinib as a new best-in-class treatment option for metastatic breast cancer, colorectal cancer and potentially for other indications."

Terms of the Transaction

Under the terms of the definitive merger agreement, Seattle Genetics will commence a tender offer on or about February 8, 2018 to acquire all of the outstanding shares of common stock of Cascadian Therapeutics for $10 per share in cash. This represents a 69 percent premium to the closing price of Cascadian Therapeutics’ common stock on Tuesday, January 30, 2018, and a 139 percent premium to its 30-day volume weighted average stock price. The tender offer is subject to customary closing conditions, including the tender of at least a majority of the outstanding shares of Cascadian Therapeutics common stock (on a fully diluted basis) and the expiration or early termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Following the closing of the tender offer, a wholly-owned subsidiary of Seattle Genetics will merge with and into Cascadian Therapeutics, with each share of Cascadian Therapeutics common stock that has not been tendered being converted into the right to receive the same $10 per share in cash offered in the tender offer. The transaction is anticipated to close in the first quarter of 2018.

In connection with the transaction, Seattle Genetics has secured a financing commitment in the amount of $400 million from Barclays and JPMorgan-Chase Bank. The balance of the consideration will be provided from cash on hand.

Leerink Partners LLC is acting as lead financial advisor to Seattle Genetics. Barclays and J.P. Morgan Securities LLC are also acting as financial advisors on the transaction. Perella Weinberg Partners LP is acting as financial advisor to Cascadian Therapeutics. Legal counsel for Seattle Genetics is Sullivan & Cromwell LLP and legal counsel for Cascadian Therapeutics is Reed Smith LLP. Goodwin Procter LLP acted as special counsel for the Cascadian Therapeutics Board of Directors and Board transaction committee.

Seattle Genetics Preliminary Financial Results

In conjunction with today’s announcement, Seattle Genetics separately reported preliminary unaudited consolidated financial results as of and for the quarter and year ended December 31, 2017 as follows:

Three Months Ended December 31, 2017 Year Ended December 31, 2017
Total revenues $128 million to $130 million $481 million to $483 million

ADCETRIS net product sales in the U.S. and Canada $82 million to $84 million $306 million to $308 million

Total revenues increased from the comparable periods in 2016 primarily as a result of increased ADCETRIS net product sales. ADCETRIS net product sales increased from the comparable periods in 2016 primarily due to an increase in sales volume and, to a lesser extent, price increases. The increases in sales volumes in both periods were driven primarily by increased use of ADCETRIS across multiple lines of therapy in Hodgkin lymphoma and for the treatment of other malignancies.

In addition, as of December 31, 2017, Seattle Genetics had approximately $413 million in cash and cash equivalents and short-term investments.

Conference Call Details

Seattle Genetics’ management will host a conference call and webcast to discuss the transaction today at 5:30 a.m. Pacific Time (PT); 8:30 a.m. Eastern Time (ET). The live event will be available from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section, or by calling 800-281-7973 (domestic) or 323-794-2093 (international). The conference ID is 7936538. A replay of the discussion will be available beginning at approximately 8:30 a.m. PT today from the Seattle Genetics website or by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 7936538. The telephone replay will be available until 5:00 p.m. PT on Friday, February 2, 2018.

On January 31, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a global Phase 3 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, as a potential second-line treatment in patients with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC) (Press release, BeiGene, JAN 31, 2018, View Source;p=RssLanding&cat=news&id=2329344 [SID1234523649]). Tislelizumab is also being studied in global Phase 3 trials in non-small cell lung cancer and hepatocellular carcinoma and two pivotal Phase 2 trials in China in relapsed/refractory classical Hodgkin lymphoma and urothelial cancer.

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"We are pleased to be leading the third global Phase 3 study of tislelizumab under our strategic collaboration with Celgene. These studies are designed to support regulatory filings both in China and globally, and take advantage of our unique global clinical development organization as well as the recent regulatory reforms in China. In 2018, we look forward to further expanding the development program for tislelizumab and to accomplishing key milestones including a planned NDA submission in China," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"Patients with advanced unresectable or metastatic esophageal carcinomas face poor prognosis, especially those with squamous histology, due to the extremely aggressive nature of the disease. We are hopeful that this Phase 3 trial will establish safety and efficacy of tislelizumab as an important treatment option for these patients," commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene.

The Phase 3, open-label, multi-center, randomized trial is designed to compare the efficacy and safety of tislelizumab compared to investigator-chosen chemotherapy as a second-line treatment in patients with advanced unresectable or metastatic ESCC. Approximately 450 patients are planned to be enrolled in Greater China, Japan, Korea, Belgium, France, Germany, Italy, Spain, the United Kingdom and the United States. Patients will be randomized to receive either tislelizumab at 200 mg every three weeks or one of three single-agent chemotherapies, paclitaxel, docetaxel, or irinotecan, as determined by the investigator.

The trial’s primary endpoint is overall survival, and secondary endpoints include progression-free survival, objective response rate, duration of response, health-related quality of life, safety, and tolerability.

"Treatment options for esophageal squamous cell carcinoma have been limited to chemotherapy. Tislelizumab has shown promising anti-tumor activity and has been generally well-tolerated in clinical trials to date in patients with a variety of cancers, including esophageal cancer, and we are hopeful that data from this Phase 3 trial will lead to a new treatment option where it is so greatly needed," said Professor Lin Shen, M.D., Vice President at the Beijing Cancer Hospital, Beijing, China, and lead investigator of the trial.

For more information about the trial, patients and physicians should email BeiGene at [email protected].

About Esophageal Squamous Cell Carcinoma

Esophageal cancer, which includes squamous cell carcinoma, is considered a serious malignancy with respect to prognosis and a fatal outcome in the great majority of cases. Esophageal carcinoma affects more than 450,000 people worldwide.i Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of death from cancer.ii

Esophageal squamous cell carcinoma occurs at a rate 20 to 30 times higher in China than in the United States.i An esophageal "cancer belt," primarily squamous cell cancers, extends from northeast China to the Middle East.i Advanced esophageal cancer is a rapidly fatal disease. More than two-thirds of patients diagnosed with esophageal cancer will have advanced or metastatic disease, with a median survival of 8-10 months and an expected five-year survival rate of less than five percent.iii These data, combined with the relative lack of highly effective treatment, are indicative of the large unmet medical need in patients diagnosed with esophageal cancer.

About Tislelizumab (BGB-A317)

Tislelizumab is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for tislelizumab for solid tumors outside of Asia (except Japan).

On January 31, 2018 Atossa Genetics Inc. (NASDAQ:ATOS), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods for breast cancer and other breast conditions, reported that it will host a conference call on February 1, 2018 at 4:30 pm EST to discuss additional findings from its Phase 1 study of Atossa’s proprietary oral Endoxifen (Press release, Atossa Genetics, JAN 31, 2018, http://ir.atossagenetics.com/news/detail/836/atossa-genetics-to-host-conference-call-to-presentadditional-findings-from-itsphase-1-study-of-oral-endoxifenthursday-february-1-2018-at-4-30-pm-est [SID1234523648]). Endoxifen is an active metabolite of the FDA-approved drug tamoxifen, which is currently used to treat breast cancer and for breast cancer prevention in high-risk patients.

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The objectives of this double-blinded, placebo-controlled, Phase 1 study of 48 healthy female subjects were to assess the pharmacokinetics of proprietary formulations of both oral and topical Endoxifen dosage forms as single (oral) and repeat (oral and topical) doses, as well as to assess safety and tolerability. Preliminary results from the study, which were announced on September 14, 2017 and October 25, 2017, showed that all objectives of the study were successfully met: there were no clinically significant safety signals and no clinically significant adverse events and both the oral and topical Endoxifen were well tolerated. In the topical arm of the study, low but measurable Endoxifen levels were detected in the blood in a dose-dependent fashion. In the oral arm of the study, participants exhibited dose-dependent Endoxifen levels that met or exceeded the published therapeutic level.

Additional findings from the oral arm of the Phase 1 study will be announced during the conference call on February 1, 2018. Due to expected high call attendance, participants are asked to preregister for the call through the following link: View Source Please note that registered participants will receive their dial in number upon registration and will dial directly into the call without delay. Those without internet access or who are unable to pre-register may dial in by calling: 1-844-824-3830 (domestic), 1-412-317-5140 (international) and Canada Toll Free: 1-855-669-9657. Callers should ask to be joined into the Atossa Genetics call.

The conference call will also be available through a live webcast at www.atossagenetics.com. Details for the webcast may be found on the Company’s IR events page at View Source

Management will answer pre-submitted questions gathered prior to the conference call in the Question and Answer period of the call. Interested parties may submit questions for management’s consideration prior to the call by submitting them in writing to Atossa Genetics’ Investor Relations at [email protected].

A replay of the call will be available approximately one hour after the end of the call through March 1, 2018. The replay can be accessed via Atossa’s website or by dialing 877-344-7529 (domestic) or 412-317-0088 (international) or Canada Toll Free at 855-669-9658. The replay access code is 10116753.

Atossa is developing proprietary Endoxifen with two routes of delivery to potentially address two distinct patient populations: oral Endoxifen for breast cancer survivors and topical Endoxifen for women with a condition called mammographic breast density (or, MBD). When a patient is treated for breast cancer, doctors typically prescribe oral tamoxifen for 5-10 years to reduce the risk of recurrent and new tumors. Tamoxifen can have uncomfortable as well as serious side effects. Perhaps more importantly, not all patients benefit from tamoxifen therapy due to their inability to effectively metabolize tamoxifen into Endoxifen. Recent research continues to confirm the key role Endoxifen plays in reducing the risk of recurrent and new breast cancer in these patients. It is estimated that more than one million breast cancer survivors in the U.S. are recommended to take tamoxifen. Atossa is developing oral Endoxifen for these patients who are "refractory" to tamoxifen meaning that they are not benefiting from tamoxifen.

There is no FDA-approved treatment for MBD, which affects more than ten million women in the U.S. It is well accepted that MBD increases the risk of breast cancer, which is why approximately 30 states now require that a finding of MBD be reported to the patient, physician or both. It is believed that not only does MBD make mammography less effective because MBD can hide cancerous tumors, but also the tissue itself may be more prone to develop cancer. For these reasons, Atossa is developing topical Endoxifen as a potential treatment for MBD.

Results from Atossa’s Phase 1 study have paved the way for upcoming Phase 2 studies: a study using Atossa’s proprietary topical Endoxifen to treat MBD which will be performed at South General Hospital in Stockholm and a study using Atossa’s proprietary oral Endoxifen to treat women who are refractory to tamoxifen. We plan to open both of these studies in the first quarter of 2018.

Atossa has also started a program to deliver Chimeric Antigen Receptor Therapy, or CAR-T, cells into the ducts of the breast for the potential targeted treatment of breast cancer. This is a novel approach using Atossa’s proprietary intraductal microcatheter technology for the potential transpapillary, or "TRAP," delivery of T-cells that have been genetically modified to attack breast cancer cells. We believe this method has several potential advantages including the reduction of toxicity by limiting systemic exposure of the T-cells; improved efficacy by placing the T-cells in direct contact with the target ductal epithelial cells that are undergoing malignant transformation; and, lymphatic migration of the CAR-T cells potentially extending their cytotoxic actions into the regional lymph system, which could limit tumor cell dissemination. We are also using our intraductal microcatheters in a Phase 2 study at Montefiore Medical Center in New York where we are targeting the delivery of Fulvestrant to the site of early stage breast cancer and ductal carcinoma in situ.

Atossa is developing its products to reduce the risk of developing breast cancer and to provide new approaches to effectively treat breast cancer patients in a cost-effective and safer manner. A study conducted by Defined Health, a leading market research firm, estimates that the potential market for Endoxifen exceeds $1 billion in annual sales and the potential market for Atossa’s intraductal microcatheters to delivery therapeutics exceeds $800 million as a treatment and replacement for surgery.

CAR-T has been the subject of much attention recently. In October 2017, pioneer CAR-T company Kite Pharma was acquired for $11.9 billion by Gilead; in August 2017 Novartis received the first FDA approval in the CAR-T field for Kymriah for the treatment of B-cell Acute Lymphoblastic Leukemia; and in January 2018 Celgene Corporation announced the acquisition of Juno Therapeutics for $9 billion.

Atossa’s 2018 potential milestones include:

First quarter of 2018 – opening the Phase 2 Study of topical Endoxifen to treat MBD at Stockholm South General Hospital in Sweden (which we plan to complete in 2018).
First quarter of 2018 – opening the Phase 2 Study of oral Endoxifen to treat patients who are not responding to Tamoxifen (which we plan to complete in 2018).
Second half of 2018 – commencing one or more studies administering TRAP CAR-T with our microcatheters.
Throughout 2018 – continuing our Phase 2 study administering Fulvestrant with our microcatheters.
The American Cancer Society (ACS) estimates that approximately 250,000 women will be diagnosed with breast cancer in the United States this year and that approximately 40,000 will die from the disease. It is the second leading cause of cancer death in American women. Although about 100 times less common than women, breast cancer also affects men. The ACS estimates that the lifetime risk of men getting breast cancer is about 1 in 1,000; 2,470 new cases of invasive breast cancer will be diagnosed; and 460 men will die from breast cancer in 2017.

On January 31, 2018 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on the development of curative therapeutics using CRISPR/Cas9 technology, reported that it will present or host one-on-one meetings at the following upcoming healthcare conferences in February (Press release, Intellia Therapeutics, JAN 31, 2018, View Source [SID1234523712]):

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Wednesday, February 14, 2018

Leerink Partners 7th Annual Healthcare Conference

Who: Tom Barnes, Ph.D., Senior Vice President, Innovation Sciences

Location: New York, New York

Presentation Time: 1:00pm EST

Tuesday, February 27, 2018

Credit Suisse 2018 Global Healthcare Conference

Who: Tom Barnes, Ph.D., Senior Vice President, Innovation Sciences

Location: London, United Kingdom

One-on-one meetings only

A live webcast of Intellia’s presentations will be accessible through the Events and Presentations page of the Investor Relations section of the company’s website at www.intelliatx.com. To access the webcasts, please log on to the Intellia website approximately 15 minutes prior to the start time to ensure adequate time for any software downloads that may be required. A replay of the webcast will be available on Intellia’s website for 14 days following each conference.