On January 5, 2017 Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported an overview of recent progress for its investigational drug portfolio in addition to several anticipated key objectives for 2017 (Press release, Cascadian Therapeutics, JAN 5, 2017, View Source [SID1234517272]).

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"In 2016, we refocused our resources on the development of our small molecule HER2 inhibitor, tucatinib, and have entered 2017 with clear priorities and with an enhanced team that has late-stage development experience," said Scott D. Myers, President and Chief Executive Officer of Cascadian Therapeutics. "In the fourth quarter of 2016, following a very collaborative meeting with the FDA, we amended the ongoing HER2CLIMB Phase 2 trial of tucatinib so that, if successful, HER2CLIMB could serve as a single pivotal registration trial. Updated data from the ongoing Phase 1b Triplet combination study continues to show a tolerable safety profile and encouraging anti-tumor activity in a heavily pre-treated population, including those with and without brain metastases. With a clear, accelerated regulatory pathway for the advancement of tucatinib in the United States, a solid balance sheet and an expanded talented leadership team, we plan to spend more time on our ex-U.S. strategy for tucatinib and to continue building for success in 2017 and beyond."

Recent Progress Update

Tucatinib — targeted HER2 inhibitor

In December 2016, Cascadian announced that following a recent meeting with the U.S. Food and Drug Administration (FDA) it has amended the HER2CLIMB Phase 2 clinical trial of its investigational product, tucatinib, by increasing the sample size so that, if successful, the trial could serve as a single pivotal study to support registration. HER2CLIMB is a randomized (2:1), double-blind, controlled pivotal clinical trial comparing tucatinib in combination with capecitabine and trastuzumab vs. placebo in combination with capecitabine and trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab and T-DM1. The primary endpoint is progression-free survival (PFS) based upon independent radiologic review, and the sample size is increased to approximately 480 patients, including patients who enrolled in HER2CLIMB to date. Patients will also be followed for overall survival, which is a secondary endpoint. Key objectives related to assessing activity in brain metastases include a secondary endpoint of PFS in a subset of patients with brain metastases.
In December 2016, researchers presented updated results from the Company’s ongoing Phase 1b Triplet combination study (tucatinib with capecitabine and trastuzumab) at the 2016 San Antonio Breast Cancer Symposium (SABCS). Results showed that tucatinib continues to be well tolerated in this combination, with an updated median progression-free survival (PFS) of 7.8 months, an overall response rate (ORR) of 61 percent and a median duration of response (DoR) of 10 months. Patients treated with the Triplet combination previously received a median of 3 HER2-targeted agents, such as trastuzumab, pertuzumab, lapatinib and T-DM1.
CASC-578 – a novel Chk1 cell cycle inhibitor

During the fourth quarter and during 2016, the following progress was made in the CASC-578 program:

Non-GLP repeat dose tolerability studies were conducted in rats and cynomolgus monkeys to establish drug tolerability and identify dose ranges to test in future IND enabling GLP toxicology studies.
A GLP safety pharmacology study was conducted in cynomolgus monkeys to evaluate multiple cardiovascular safety endpoints. The results of this study indicate CASC-578 has an acceptable safety profile at the doses tested and support further development of the drug.
CASC-578 was evaluated in vitro in a large panel of tumor derived cell lines to define its activity as a single agent in both solid and hematological cancers and to identify potential biomarkers to define tumor genotypes most likely to respond to the drug. The results of this study demonstrated CASC-578 can inhibit the growth of a subset of tumor derived cell lines from both solid and hematological malignancies with IC50 values as low as 30 nM and several candidate biomarkers were identified that correlate with potency in responsive cell lines.
To better define the pharmacological activity and therapeutic index of CASC-578, several in vivo studies were conducted in mice using human xenograft models of acute leukemia, mantle cell lymphoma and non-small cell lung cancer. The results of these experiments showed CASC-578 inhibited, and in some cases, regressed established tumors as a single agent.
Corporate Update

In January 2017, the Company announced the appointment of Marc L. Lesnick, Ph.D., as Senior Vice President, Regulatory Affairs and Quality.

As of September 30, 2016, cash, cash equivalents and investments totaled $71.6 million and no debt. The Company plans to provide 2017 guidance in its fourth quarter and year-end 2016 results announcement.
2017 Key Objectives Planned

Focus on HER2CLIMB pivotal trial enrollment: Expand the HER2CLIMB trial to sites in Europe, Australia and Israel in the first half of 2017.

Report new data at scientific meetings: Report new data analyses from tucatinib and the Chk1 cell cycle inhibitor at scientific meetings in 2017.

Explore tucatinib’s utility in other clinical settings: Support the initiation of select investigator-sponsored combination trials, including trials in HER2-positive amplified, metastatic colorectal cancer and in combination with palbociclib and letrozole in HER2-positive, hormone-receptor positive metastatic breast cancer.

Define next steps for CASC-578: Complete pharmacology studies in the first half of 2017 and make go/no-go decision on IND-enabling studies for CASC-578 in the second half of 2017.

Pursue capital options: Evaluate all available financing vehicles, including non-dilutive options such as out-licensing tucatinib regional rights.

On January 5, 2017 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell-based therapies, reported that the first patient of the Therapeutic Immunotherapy with NKR-2 (THINK) trial started cell processing in Belgium (Press release, Celyad, JAN 5, 2017, View Source [SID1234517408]). Blood was collected from this patient and first CAR-T NKR-2 dose level infusion (3×108 cells) is expected in January 2017.

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"We are pleased to announce that the first patient has been registered in our Belgian Phase Ib trial of CAR-T NKR-2. After witnessing evidence of activity in our initial safety studies, we are enthusiastic about reporting data from this trial in 2017," said Christian Homsy, CEO of Celyad. "We look forward to expanding the trial to U.S.-based institutions and I would like to thank our clinical partners, and the Celyad team for enabling this milestone."

Dr. Frédéric Lehmann, VP Clinical Development & Medical Affairs at Celyad: "This is an important moment for Celyad. The THINK trial is aimed to demonstrate that CAR-T NKR-2 cells can deeply transform the way we treat cancer patients. The team keeps on showing its awe-inspiring ability to deliver in Research and Development, and the Company has now reached a cardinal inflection point to emerge as a key player in the CAR-T space."

On January 5, 2017 Kite Pharma, Inc. (Nasdaq:KITE) reported that Ian T. Clark, former Chief Executive Officer, Head of Commercial Operations and member of the Board of Directors for Genentech Inc., a member of the Roche Group, has been appointed to its Board of Directors (Press release, Kite Pharma, JAN 5, 2017, View Source [SID1234517275]). Clark brings extensive commercialization experience to the Board as Kite plans for key milestones in 2017, including potential approval and launch in the United States of its engineered chimeric antigen receptor (CAR) T cell therapy, axicabtagene ciloleucel, as a treatment for patients with refractory aggressive B-cell non-Hodgkin lymphoma (NHL).

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In addition to Clark’s appointment as an independent director to Kite’s Board, he was also appointed to serve as the Chairman of Kite’s newly established Commercialization Committee and will join Kite’s Audit Committee.

"We are very pleased to have Ian join our Board of Directors as we embark on potential approval and commercialization of axicabtagene ciloleucel by the U.S. FDA," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "Ian, with his tenure at the helm of Genentech and road-tested experience launching 15 new drugs, including the immunotherapy Tecentriq, strengthens our board’s breadth of talent and background. His expertise will bolster our already impeccable commercial team led by Shawn Tomasello. We look forward to drawing on his significant experience and strong track record developing and executing commercial strategies in oncology."

"I have watched history begin to unfold as Kite has emerged as one of the leaders in cell therapy," said Ian Clark. "I look forward to lending my expertise to the teams at Kite, the management and my fellow Board members as Kite solidifies its position in immunotherapy."

Clark joined Genentech in 2003 as Senior Vice President and General Manager, BioOncology. In August 2005 he was named Senior Vice President, Commercial Operations and in January 2006, Clark was named Executive Vice President, Commercial Operations and became a member of the Executive Committee. Clark was named Head of Global Product Strategy and Chief Marketing Officer of Roche in April 2009.

Prior to joining Genentech, Clark served as General Manager of Novartis Canada, overseeing all of the company’s country operations. Before assuming his post in Canada, Clark served as Chief Operating Officer for Novartis United Kingdom. Clark worked in executive positions in sales and marketing for Sanofi and Ivax in the United Kingdom, France and Eastern Europe. Clark began his career at Searle, where he held management positions in both sales and marketing. He has served on the Board of Directors of the Biotechnology Industry Organization (BIO) since 2009 as well as on the boards of TerraVia, the Gladstone Foundation and as a member of the Federal Reserve Bank of San Francisco’s Economic Advisory Council. Clark received a Bachelor of Science degree and honorary doctorate in Biological Sciences from Southampton University in the United Kingdom.

About axicabtagene ciloleucel

Kite Pharma’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

On January 5, 2017 Avidity Biosciences reported the completion of a $16 million Series B financing round to support the development of its Antibody-siRNA Conjugate (ASC) platform (Press release, Avidity Biosciences, JAN 5, 2017, View Source [SID1234521096]). The Series B round includes investment of $10 million in new capital and conversion of $6 million in convertible debt. Takeda Pharmaceuticals, through its venture group, led the Series B round, and both new and existing investors participated, including Alethea Capital, Alexandria Real Estate Equities, Brace Pharma, EcoR1 Capital, F-Prime Capital, Moore Venture Partners and Tavistock Life Sciences.

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"Our ASC platform unites two of the most impactful innovations over the past twenty years – monoclonal antibodies and oligonucleotides – to create a new class of precision medicines," said Troy Wilson, Ph.D., J.D., president and chief executive officer of Avidity Biosciences. "Although siRNA-based therapeutics have demonstrated significant clinical and commercial promise, conventional approaches are limited to targeting diseases of the liver. Because ASCs use antibodies to overcome barriers of delivering siRNA, they have the potential to impact a broader range of therapeutic areas. Our goal is to partner with leading pharmaceutical and biotechnology companies to deliver a pipeline of ASCs targeting genetic drivers of disease."

ASCs link a monoclonal antibody—designed against a specific molecular target—with a siRNA therapeutic payload, allowing the conjugate to have unmatched specificity and selectivity. In preclinical models, ASCs have shown potential to knockdown messenger RNA levels in multiple important cell types and tissues, including tumor, muscle, heart, lung, liver and B cells. In addition, ASCs have drug-like properties comparable to antibodies and antibody-drug conjugates.

In connection with the financing, Avidity Biosciences annouced that Michael Martin, Ph.D., global head of Takeda Ventures Inc., and Todd Brady, director of finance and investments of Brace Pharma Capital, will join its board of directors. Tony Hsu, founder and chief investment officer of Alethea Capital, will also join the board as a non-voting member.

"We believe Avidity’s ASC platform offers a compelling approach that builds on successes with antibodies, ADCs and oligonucleotide-based therapeutics," said Dr. Martin. "Avidity has recruited a top-notch team and made significant progress against its scientific and business goals. We look forward to working with the company to realize the promise of ASCs as a new class of precision medicines."

On January 5, 2017 Neon Therapeutics, an immuno-oncology company developing neoantigen-based therapeutic vaccines and T cell therapies to treat cancer, reported the successful completion of a $70 million Series B financing (Press release, Neon Therapeutics, JAN 5, 2017, View Source [SID1234517277]). Proceeds from the financing will be used to advance Neon Therapeutics’ lead program NEO-PV-01, a fully personalized neoantigen vaccine, through an ongoing Phase 1b clinical trial. In addition, this investment will support preclinical development of NEOPTC-01, a personalized adoptive T cell program, and the Shared Neoantigen Program.

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The Series B financing was led by Partner Fund Management. Joined by existing investors Third Rock Ventures and Access Industries, additional new investors included Fidelity Management & Research Company, Wellington Management Company, Inbio Ventures and Nextech Invest.

"The investor quality in this financing reflects the promise of the neoantigen biology platform, as well as our leading position," said Hugh O’Dowd, chief executive officer of Neon Therapeutics. "This capital is a testament to our strong team and our approach to neoantigen-based therapeutics, and will provide important resources to bring potentially life-changing medicines to cancer patients in need."