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 4, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported guidance for the current estimated timing of interim and final overall survival analysis from the PROSPECT study – a placebo controlled Phase 3 study designed to investigate the efficacy of PROSTVAC to prolong the survival of men with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Bavarian Nordic, JAN 4, 2017, View Source [SID1234517268]).

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The company maintains its previous guidance that full data is expected within this year, albeit in the second half of 2017, with the third interim analysis likely to occur around mid-2017. This estimate is based on a decline in the number of average monthly events currently seen in the PROSPECT study.

"As there has been speculation that the third interim could occur during first quarter of 2017, we believe it is important to update the market on the current estimated timelines for readout of the Phase 3 study" said Paul Chaplin, President and CEO of Bavarian Nordic.

While the company remains blinded to all patient specific data, the latest estimates have been provided by the independent Data Monitoring Committee (DMC) following a routine analysis of the current survival data.

"While we will have to await the final read out of the PROSPECT study to establish the efficacy of PROSTVAC, we are encouraged that the current monthly event rate has declined. This is great news for the patients. Not only is this consistent with an improvement in the standard of care for patients with mCRPC, which has been observed in recent years, but could also be indicative of a therapeutic effect of PROSTVAC as well" said Paul Chaplin.

About the PROSPECT study
PROSPECT is a global, randomized, double-blind, placebo-controlled phase 3 study being conducted under a Special Protocol Assessment (SPA) from the FDA. The objective of the study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival. The study has been fully enrolled with 1,297 asymptomatic or minimally symptomatic mCRPC patients as of January 2015. Patients were enrolled at more than 200 sites in 15 countries. Both the first and second interim analyses confirmed that the study would continue as planned. Final study data requires 534 events in both comparisons of treatment arms versus placebo, and the third interim analysis will occur at 427 events.

About PROSTVAC
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec, or "rilimogene") is a prostate specific antigen (PSA)-targeted immunotherapy candidate designed to enhance or stimulate the body’s immune response, specifically T cells that will home to and kill prostate cancer cells, altering the course of the disease and improving overall survival (OS) of patients with prostate cancer. A robust data package has been established that includes 18 ongoing or completed clinical studies, comprising more than 2,000 patients of which more than 1,100 patients have been actively treated with PROSTVAC, which has been generally well-tolerated. A randomized, placebo-controlled Phase 2 trial demonstrated the potential of PROSTVAC to extend the median overall survival by 8.5 months in patients with advanced prostate cancer. These results led to the initiation of the PROSPECT pivotal Phase 3 study.

PROSTVAC is being developed in collaboration with the National Cancer Institute under a Cooperative Research and Development Agreement.

On January 4, 2017 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing Pentarins as a new class of potent and selective anti-cancer medicines, reported highlights from 2016 and outlined expected milestones for 2017 (Press release, Tarveda Therapeutics, JAN 4, 2017, View Source [SID1234517285]).

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"2016 was a year of transformative progress for Tarveda’s Pentarin platform and acceleration in the development of our novel treatments to improve the effectiveness of cancer therapies for patients with solid tumors. The company raised substantial capital and strengthened its premier venture capital syndicate, completed the in-licensing of PEN-866, which will be in a Phase I clinical trial in 2017, and embarked on our first-in-human trial for our lead drug candidate PEN-221," said Drew Fromkin, President and Chief Executive Officer of Tarveda. "We have constructed an attractive pipeline of novel, anti-cancer medicines, built a solid foundation on which to create true value for patients and our Company’s stakeholders, and look forward to achieving additional, validating milestones in 2017."

Key 2016 Accomplishments

Secured $38 million in Series C financing co-led by Novo A/S and New Enterprise Associates (NEA) with Flagship Pioneering, NanoDimension and Eminent Venture Capital also participating

Concentrated the Company’s development and discovery resources on Tarveda’s Pentarin Platform through the spin-off of BTP-114 to Placon Therapeutics. BTP-114 is a next-generation, platinum-based chemotherapy that is now in a Phase I clinical trial in collaboration with a domestic pharmaceutical partner

Expanded clinical program and R&D expertise with the appointment of Leila Alland, M.D. to Chief Medical Officer. Dr. Alland brings more than 15 years of pharmaceutical drug development experience including her most recent leadership roles in oncology clinical development at AstraZeneca and Bristol-Myers Squibb

In-licensed the broad Heat Shock Protein 90 (HSP90) targeting conjugate platform, including lead drug PEN-866, from Madrigal Pharmaceuticals

Miniaturized HSP90 targeting drug conjugates are designed to have high affinity for the well-characterized intracellular target, HSP90, and increase the killing of cancer cells while reducing collateral damage to normal cells

PEN-866 accumulates and is retained in xenograft tumors, releasing over time the potent tumor-killing payload SN-38, the active component of the approved anticancer medicine, irinotecan

PEN-866 has shown efficacy and durability of response in multiple preclinical tumor models including small cell lung, pancreatic, and ovarian cancers, sarcoma and patient derived tumor models

Presented preclinical data for PEN-221 demonstrating complete and sustained tumor regressions in hard-to-treat, somatostatin receptor 2 (SSTR2) positive cancer models

Miniaturized size and unique design of Pentarins such as PEN-221 allow for rapid penetration deep into solid tumors to drive efficacy
PEN-221 binds with high affinity to the cell surface target, SSTR2, internalizes into the tumor cell and releases its DM1 payload, which is retained in the tumor cell long after PEN-221 is cleared from circulation

Initiated a first-in-human Phase 1/2a trial of PEN-221 at multiple, premier clinical sites in the United States

The Phase 1/2a study of PEN-221 selects patients most likely to respond to PEN-221 by using FDA approved imaging diagnostics to identify those with tumors expressing SSTR2

Expected Key 2017 Milestones
Complete PEN-221 Phase 1 dose escalation and identify the recommended Phase 2 dose of PEN-221 in patients with SSTR2 expressing neuroendocrine tumors and small cell lung cancer in 2017

Initiate the first-in-human trial of PEN-866 in 2017, a Phase 1/2a dose escalation/expansion study evaluating safety and efficacy of PEN-866 in advanced, topoisomerase-1 sensitive cancer patients

Report preclinical data in 2017 on new Pentarins that bind to intracellular and cell-surface targets and drive anti-tumor activity
Announce the Tarveda Scientific Advisory Board in the first quarter of 2017

About Pentarins
Tarveda is developing Pentarins, potent and selective miniaturized drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cell killing agent through a chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for effective penetration and distribution into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell killing payload inside the cancer cells for efficacy.