On October 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has received a second Breakthrough Therapy Designation (BTD) from the United States Food and Drug Administration (FDA) for its ALK inhibitor, Alecensa (alectinib) (Press release, Hoffmann-La Roche , OCT 4, 2016, View Source [SID:SID1234515583]). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.

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"The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "The decision by the FDA to grant a second breakthrough therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor."

This second breakthrough therapy designation is based on the results of the open-label, randomised phase III J-ALEX study, which were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. J-ALEX compared the efficacy and safety of Alecensa with crizotinib in 207 Japanese people with ALK-positive, advanced or recurrent NSCLC who either had not been treated with chemotherapy or had received one prior line of chemotherapy. Results from the study demonstrated that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66% compared to crizotinib, whilst maintaining a favourable tolerability and safety profile consistent with that observed in previous studies.

The FDA’s Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible. Alecensa received its first FDA BTD in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.

Alecensa is currently available in the US and Israel to ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib, and in Japan to ALK-positive unresectable, recurrent or advanced NSCLC patients. In addition, an ongoing global, randomised phase III trial called ALEX is comparing Alecensa to Xalkori as an initial (first-line) treatment for people with advanced ALK-positive NSCLC.

About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomised Phase III study that compared the efficacy and safety of Alecensa to crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK inhibitor. People were randomised to the Alecensa group or the crizotinib group in a one-to-one ratio. Results include:

Alecensa reduced the risk of disease worsening or death (PFS) by 66 percent compared to crizotinib (HR=0.34, 99 percent CI: 0.17-0.70, p<0.0001).

Median PFS was not reached in the Alecensa arm (95 percent CI: 20.3 months-not estimated) versus 10.2 months in the crizotinib arm (95 percent CI: 8.2-12.0).

Grade 3-4 adverse events (AE) occurred with lesser frequency in the Alecensa arm compared to the crizotinib arm (27 percent vs. 51 percent).

The most common AE occurring with > 30 percent frequency with Alecensa was constipation (36 percent). The most common AEs for crizotinib were nausea (74 percent), diarrhoea (73 percent), vomiting (59 percent), visual disturbance (55 percent), alteration in taste (dysgeusia, 52 percent), constipation (46 percent), and an elevation in liver enzymes called alanine transaminase (ALT, 32 percent) and aspartate transaminase (AST, 31 percent).

About Alecensa
Alecensa (RG7853/AF-802/CH5424802) is an oral medicine created at Chugai Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In two key phase II studies, NP28761 and NP28673, Alecensa shrank tumours in up to 44% of people with ALK-positive NSCLC who progressed on crizotinib. Alecensa also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain
Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord.

One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise
Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III studies of Alecensa include a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

About ALK-positive non-small cell lung cancer
Lung cancer is the biggest cancer killer, causing 1.59 million deaths globally each year. NSCLC is the most common type of lung cancer, and is the leading cause of cancer-related deaths in Europe and across the world, accounting for approximately 85% of lung cancer cases. ALK-positive NSCLC occurs in approximately 5% of patients with advanced NSCLC, translating to about 75,000 patients being diagnosed with the disease annually. It is almost always found in people with a specific type of NSCLC called adenocarcinoma, and is more common in light or non-smokers.

On October 4, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that its board of directors has approved a plan for a reverse split of the Company’s common stock to increase its share price and reduce the number of authorized and outstanding shares (Press release, Cascadian Therapeutics, OCT 4, 2016, View Source [SID:SID1234515581]).

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"The board and management have worked diligently on several facets of the Company this year to position it for the future, including bringing in new management, and solidifying our product development and regulatory strategies. With this action, we are helping ensure that the necessary financial structure is in place to execute our plans," said Scott Myers, President and CEO of Cascadian Therapeutics. "We believe this proposed change will make our stock accessible to a wider range of institutional investors, benefiting all stockholders."

Cascadian is advancing tucatinib (ONT-380), its lead product candidate in Phase 2 development for HER2+ metastatic breast cancer patients, with and without brain metastases. The Company plans to report updated clinical data from its Phase 1b tucatinib combination study with capecitabine and trastuzumab at the San Antonio Breast Cancer Symposium in December. It also expects to provide an update during the fourth quarter on its regulatory strategy for tucatinib.

Cascadian plans to hold a special meeting on November 18, 2016 at the Company’s headquarters to obtain stockholder approval of the reverse split, proposed at a ratio of not less than 1-for-4 and not greater than 1-for-10, and to reduce the total authorized shares of the Company’s common stock by a ratio of two times (2x) the reverse split ratio. The Company believes these proposals will provide shares to operate and fund the Company’s programs. The Cascadian board of directors will set the exact range and timing of the reverse split and share reduction of authorized common stock at its discretion following approval by stockholders and before December 31, 2016. The Company filed a preliminary proxy statement regarding the special meeting with the U.S. Securities and Exchange Commission. The preliminary proxy statement and the Company’s 2015 annual report can be accessed for free at www.sec.gov. The Company’s 2015 annual report can also be accessed for free on SEDAR in Canada. Investors are encouraged to read the preliminary proxy statement because it includes important information regarding the special meeting.

Our board of directors is soliciting proxies in connection with this special meeting. Directors and executive officers of Cascadian have no substantial interests, directly or indirectly, in the matters to be voted upon at the special meeting, except to the extent of their ownership of shares of Cascadian’s common stock and securities convertible to or exercisable for common stock.

On October 4, 2018 Catalent, the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products, and Triphase Accelerator Corporation, a company dedicated to acquiring and developing novel therapeutics for the treatment of cancer, reported that Triphase will obtain worldwide rights to further develop Catalent’s proprietary CD22-4AP Antibody-Drug Conjugate (ADC), which has been developed by Catalent’s wholly owned subsidiary, Redwood Bioscience, Inc., using its SMARTagTM technology platform (Press release, Catalent, OCT 4, 2016, https://biologics.catalent.com/index.php/news-events/news/Catalent-Biologics-and-Triphase-Accelerator-Corporation-Announce-License-Agreement-to-Advance-SMARTag-ADC-to-Clinic [SID1234530208]).

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Catalent will receive an upfront payment and has the potential to earn additional development and commercial milestone payments, plus a royalty on product sales. Triphase will also contract with Catalent for development, manufacturing and analytical services to support a fast path to clinic.

CD22-4AP is a novel, site-specific ADC, targeting CD22, a B-cell restricted sialoglycoprotein that is an important modulator of B-cell signaling and survival, which is expressed on 90% of B-cell malignancies. CD22 is a clinically validated ADC target with potential in Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphoid Leukemia (ALL). Catalent’s ADC, CD22-4AP, is a site-specific modified humanized antibody conjugated to a toxin payload using Catalent’s proprietary Hydrazino-Pictet-Spengler (HIPSTM ) chemistry and proprietary 4AP linker.
Pre-clinical data has shown that this optimization of payload placement and linker composition, combined with the stability afforded by HIPS chemistry, leads to better tolerability and expanded therapeutic index.

Dr. Mohit Trikha, Chief Scientific Officer, Executive Vice President and Head of R&D at Triphase, commented, "Given our deep experience in investigating potential treatment for blood cancers and oncology clinical drug development, it is a logical progression for us to explore other approaches for other hematologic tumors. We believe in the potential of Catalent`s SMARTag technology and look forward to advancing CD22-4AP to clinical proof of concept studies.

"Triphase has demonstrated expertise and a track record in advancing pre-clinical oncology candidates to clinical proof of concept," added Mike Riley, Catalent Biologics’ Vice President & General Manager. "We look forward to leveraging Triphase`s expertise in combination with our proprietary SMARTag technology and supporting infrastructure to bring this potentially transformational treatment to patients."

ABOUT THE SMARTAGTM TECHNOLOGY
The proprietary SMARTag site-specific protein-modification and linker technologies were developed by Redwood Bioscience to enable the generation of homogenous bioconjugates engineered to enhance potency, safety and stability. The technology employs natural post-translational modifications found in human cells to create one or more aldehyde tags at designated sites on protein molecules. These chemical "handles" are then stably conjugated to payloads (e.g., cytotoxic or effector) to prevent their systemic release. The SMARTag platform provides precise payload positioning, stable, site-specific conjugation and defined stoichiometry of drug-protein ratios. The control afforded by the technology enables identification of superior drugs from libraries of differentially designed conjugates. Catalent acquired Redwood Bioscience in 2014.

On October 4, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN) and The US Oncology Network (The Network) reported that The Network has selected Myriad Genetic Laboratories as its preferred provider laboratory for hereditary cancer testing (Press release, Myriad Genetics, OCT 4, 2016, View Source [SID:SID1234515587]). The US Oncology Network is one of the nation’s largest networks of integrated, community-based, and independent physician practices dedicated to advancing high-quality, evidence-based cancer care. With more than 1,000 affiliated physicians in 19 states, providers in The Network treat over 800,000 patients every year.

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As part of the collaboration, Myriad and The US Oncology Network will work together to perform hereditary cancer research through the Genetic Risk Evaluation and Testing (GREAT) program within The Network affiliated practices. Under this program, the two organizations will collaborate to create a database that links patient outcomes with genetic test results. Principal among the research aims of this program is to better understand the genotype-phenotype correlation, gene prevalence, and research related to improving patient counselling and access to testing. The scale achieved by combining the largest hereditary cancer testing laboratory in the world with the more than 350 sites of care affiliated with The US Oncology Network will lead to unprecedented insights into the field of oncology.

"We are excited to work with Myriad as they have been a pioneer in personalized medicine for more than 25 years and have an unmatched reputation for diagnostic accuracy and customer service," said Michael Seiden, MD, PhD, chief medical officer of The US Oncology Network. "Additionally, Myriad’s expertise and scientific leadership, having authored or co-authored over 50 peer-reviewed publications in the last three years, makes them an ideal research collaborator for The US Oncology Network."

"We are exceptionally pleased to work with The US Oncology Network, and are honored by their recognition of Myriad as a preferred provider laboratory," said Johnathan M. Lancaster, MD, PhD, chief medical officer of Myriad Genetic Laboratories, Inc. "We share with The Network an absolute commitment to the highest possible quality of clinical care. We will continue to invest in both research and customer service, which set Myriad apart as the industry gold-standard for hereditary cancer testing."

On October 3, 2016, Clovis Oncology, Inc. ("Clovis") and Lonza Ltd ("Lonza") reported that it entered into a Manufacturing Services Agreement (the "Agreement") for the long term manufacture and supply of the active pharmaceutical ingredient ("API") for rucaparib (Press release, Clovis Oncology, OCT 3, 2016, View Source [SID:SID1234515608]). The terms and conditions of the Agreement are contingent upon the approval by the U.S. Food and Drug Administration of the initial New Drug Application for rucaparib, unless triggered earlier by Clovis. Clovis and Lonza are parties to a Development and Manufacturing Agreement, dated February 8, 2013, as amended, under which Lonza has supplied rucaparib API for clinical development.

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The Agreement provides that Lonza will be a non-exclusive manufacturer of the rucaparib API during the term of the Agreement, which expires on December 31, 2025, unless extended by mutual written consent of the parties. Under the Agreement, Lonza will construct, in an existing Lonza facility, a production train that will be exclusively dedicated to the manufacture of the rucaparib API. The dedicated production train will provide manufacturing capacity to meet Clovis’ currently anticipated needs for commercial supply of rucaparib API.

Clovis is obligated to make scheduled capital program fee payments towards capital equipment and other costs associated with the construction of the dedicated production train and, once the facility is operational, Clovis is obligated to pay a fixed facility fee each quarter for the duration of the Agreement.

Pursuant to the terms of the Agreement, Lonza will manufacture and store an advanced intermediate to be used in the subsequent production of the rucaparib API. Clovis will pay fixed fees on a per kilogram basis for quantities of the advanced intermediate and the rucaparib API ordered by Clovis under the Agreement, subject to certain adjustments. Until the dedicated facility is completed and operationally qualified, Lonza will manufacture the rucaparib API in existing Lonza facilities at pricing established in the Agreement.

Either party may terminate the Agreement due to a material breach of the Agreement by the other party, subject to prior written notice and a cure period. Clovis may terminate the Agreement, subject to 90 days’ prior written notice, in the event rucaparib is withdrawn from the market for certain reasons. In the event of such a termination by Clovis, or termination by Lonza due to material breach by Clovis, Clovis is obligated to compensate Lonza for any services rendered, or for which costs have been incurred by Lonza in anticipation of services to be provided to Clovis, and to pay to Lonza the remaining amount of any capital program fees and quarterly fixed facility fees for the remainder of the term of the Agreement. In the event the Agreement is terminated by Clovis due to material breach by Lonza, Lonza is obligated to repay all or a portion of the capital program fees previously paid by Clovis.

The foregoing is only a summary of certain provisions of the Agreement and is qualified in its entirety by the terms of the Agreement, a copy of which will be filed as an exhibit to Clovis’ annual report on Form 10-K for the year ending December 31, 2016. Clovis intends to submit a Confidential Treatment Request to the SEC pursuant to Rule 24b-2 under the Securities Exchange Act of 1934, as amended, requesting confidential treatment of certain portions of the Agreement.