On January 5, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX), a clinical-stage biopharmaceutical company, reported that it is reshaping its strategy and operations to prioritize its emerging clinical and preclinical immuno-oncology portfolio (Press release, Dynavax Technologies, JAN 5, 2017, View Source [SID1234517380]). The company has implemented significant organizational restructuring and cost reductions to align around its immuno-oncology business, while allowing it to advance HEPLISAV-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)], its investigational hepatitis B vaccine candidate, through the U.S. Food and Drug Administration (FDA) review process and an approval decision. Dynavax continues to believe that HEPLISAV-B is an approvable product and plans to submit its response to the FDA’s outstanding questions shortly.

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To achieve these savings, Dynavax has suspended manufacturing for HEPLISAV-B and reduced its global workforce by 38 percent. The company will incur restructuring costs, currently estimated to be $3.0 million, primarily in the first quarter of 2017. The company estimates that its cash, cash equivalents and marketable securities were approximately $81.4 million as of December 31, 2016. Going forward, it expects HEPLISAV-B costs prior to any FDA decision to be less than $1 million per month, and all other operating costs to be less than $60 million per year to support continued development of its oncology program. This restructuring is currently estimated to result in approximately a 40 percent reduction in cash burn. The company will continue to evaluate the possibility of a partnership to support HEPLISAV-B as it increasingly concentrates its own strategic focus on oncology.

"We value all of our colleagues, so reducing our workforce is a sad and difficult decision. But it is one we believe is necessary to align our organization to reflect that of a clinical R&D-stage company with a promising immuno-oncology pipeline, which has become a strategically important area of our business and one we believe can potentially benefit thousands of people with cancer," said Eddie Gray, chief executive officer of Dynavax. "These measures will increase our financial strength and position us well to create significant long-term clinical and financial value. They also will allow us to advance HEPLISAV-B toward approval while we continue to evaluate the possibility of a partnership to support its approval and launch. We are grateful to all affected employees for their dedication to bringing us this far."

Prioritizing Diversified Immuno-Oncology Pipeline
Dynavax has made notable progress in the rapidly advancing area of immuno-oncology, and is focusing on two promising compounds that have shown potential to enhance the immune response against cancer.

The company’s lead clinical candidate, SD-101, an investigational cancer immunotherapeutic, is currently being studied in several Phase 1/2 studies evaluating its potential to be broadly effective against multiple solid tumors and hematologic malignancies. SD-101, an intratumoral TLR9 agonist, has shown encouraging early clinical data in metastatic melanoma.

At the Society for Melanoma Research conference in November 2016, Dynavax announced the first findings from an ongoing Phase 1/2 study of SD-101 in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 treatment. Early results evaluating 13 patients with metastatic melanoma for efficacy and 19 patients for safety were reported. In patients naïve to anti-PD-1 treatment, objective responses were observed in four of five patients (80 percent), including one complete response and three partial responses. In a small number of patients with progressive disease stable disease was observed while receiving Keytruda and SD-101 in combination. The combination of the two drugs was well-tolerated with no dose-limiting toxicities. These encouraging clinical data will be enhanced by a dose-expansion phase to further explore the efficacy of this combination.

Dynavax is also developing a second TLR9 agonist, DV281, which has completed preclinical testing in models for lung cancer. Lung cancer remains an area of high unmet need, with fewer than 20 percent of patients responding to the most recently-approved immunotherapies. DV281 will be administered as an inhaled therapeutic. Dynavax intends to begin Phase 1 studies of DV281 in the second quarter of 2017.

The company expects to present additional data from its immuno-oncology portfolio at medical conferences throughout 2017, including at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).

Continuing to Advance HEPLISAV-B while Maintaining Manufacturing Capacity at Reduced Cost
Dynavax plans to respond this month to the November 2016 Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for HEPLISAV-B, and will advance the vaccine through an expected six-month FDA review period. The company remains confident that the existing clinical data package meets the requirements for approval. During the regulatory review period, Dynavax will retain, but furlough, the majority of the workforce supporting its manufacturing facility in Germany. This approach will enable the company to leverage the existing stockpiled inventory of HEPLISAV-B, while providing it with the ability to re-activate and scale for commercial launch activities.

Conference Call Details
The Dynavax management team will host a conference call and webcast today, Thursday, January 5, 2017, at 4:30 p.m. Eastern Time, to provide more information about the restructuring. The live call can be accessed by phone by dialing (877) 479-1857 (domestic) or +1 (503) 343-6309 (international) and specifying conference call code 47911578. A link to the live webcast may be accessed by visiting the "Investors" section of the Dynavax website or directly at www.dynavax.com. A replay of the conference call may be accessed for one week following the call by dialing (855) 859-2056 (domestic) or +1 (404) 537-3406, and using the passcode 47911578.

About SD-101
SD-101 is Dynavax’s proprietary CpG-C class oligodeoxynucleotide. SD-101 is a potent activator of dendritic cells, activating them to mature and produce Type 1 interferons through specific binding to TLR9, a key recognition receptor in the innate immune system. SD-101 is delivered directly to the tumor, where it can stimulate highly effective immune responses to tumor antigens. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

About DV281
DV281, a newly developed TLR9 agonist, is a CpG-C class oligodeoxynucleotide developed specifically for inhaled delivery to lung tumors that are not easily accessible for intratumoral injection. Inhaled DV281 induces dendritic cell activation and tumor microenvironment changes comparable to intratumoral injection of SD-101. Studies in animal models of lung tumors show that DV281 dramatically reduces lung tumor burden and leads to immune-mediated control of tumor metastases outside the lung. Dynavax intends to initiate a Phase 1 study in the second quarter of 2017.

About HEPLISAV-B
HEPLISAV-B is an investigational adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary TLR 9 agonist to enhance the immune response. HEPLISAV-B is administered in two doses over one month. In Phase 3 trials, HEPLISAV-B demonstrated higher and earlier protection with fewer doses than a currently licensed hepatitis B vaccine. The investigational vaccine’s safety profile is based on clinical trials that generated safety data from more than 14,000 participants. The most frequently reported local reaction was injection site pain. The most common systemic reactions were fatigue, headache and malaise, all of which were similar to an existing vaccine.

Dynavax has worldwide commercial rights to HEPLISAV-B.

On January 5, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, rreported its 2016 year-end cash balance and reviewed key anticipated events for 2017 (Press release, OncoMed, JAN 5, 2017, View Source [SID1234517304]).

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OncoMed ended 2016 with approximately $184.6 million in cash. OncoMed’s current cash is estimated to be sufficient to fund operations through at least the third quarter of 2018, without taking into account future potential milestone payments from partners. Full-year cash expenses for 2016 were approximately $115 million, in accordance with the company’s 2016 guidance. OncoMed expects 2017 operating cash burn to be less than $100 million, before considering potential milestones/opt-ins.

"2017 represents a potentially transformational year for our company," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "Phase 2 clinical trial results for demcizumab and tarextumab are anticipated in the first half of the year, and together those investigational drugs will be eligible for potential partner opt-ins totaling close to $100 million. Three additional programs, vantictumab, ipafricept and anti-RSPO3, are also eligible for potential partner opt-ins this year, and OncoMed could receive more than $170 million in total 2017 partner opt-in payments. At the same time, our earlier-stage programs are making progress in the clinic, we will be reporting on that progress, our two novel immuno-oncology candidates, anti-TIGIT and GITRL-Fc trimer are advancing into the clinic, and we continue to discover and develop additional novel agents directed at new immuno-oncology targets."

End-of-Year Accomplishments

In December 2016, OncoMed achieved the following:

Filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for anti-TIGIT (previously "I/O#2"). TIGIT (T cell immunoglobulin and ITIM domain protein) is an inhibitory receptor that stops T-cells from attacking tumor cells. Anti-TIGIT is part of OncoMed’s collaboration with Celgene Corporation.

Enrolled the first patient in a Phase 1b clinical trial of anti-DLL4/VEGF bispecific antibody (OMP-305B83) plus FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy for the treatment of second-line metastatic colorectal cancer. The anti-DLL4/VEGF bispecific antibody is part of OncoMed’s collaboration with Celgene.
2017: Anticipated Key Financial Milestones and Pipeline Progress by Program

Demcizumab (anti-DLL4, OMP-21M18)

Report top-line results in the first half of 2017 from the Phase 2 YOSEMITE clinical trial of demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine for the treatment of first-line metastatic pancreatic cancer.
OncoMed anticipates that the top-line data will include response rate, progression-free survival (PFS), interim overall survival (OS) and safety results. Subsequent analyses of event-driven OS data will be conducted mid-year and at year-end.

Submit demcizumab Phase 2 data package in the first half of 2017 to Celgene for opt-in consideration.
The Phase 2 YOSEMITE PFS, interim OS, response rate, and exploratory biomarker data are expected to form the basis of a demcizumab data package. In the first half of 2017, OncoMed will also provide Celgene with response, PFS and safety data from the Phase 2 DENALI clinical trial of demcizumab plus carboplatin and pemetrexed in first-line non-small cell lung cancer (NSCLC), as well as interim safety and efficacy data from the ongoing Phase 1b clinical trial of demcizumab plus pembrolizumab (anti-PD1, Keytruda). Additional data analyses for each of these studies will be conducted as each trial matures, with planned and final analysis of OS from the DENALI trial at year-end.
OncoMed will be entitled to a $70 million opt-in payment if Celgene exercises its option on demcizumab. Following option exercise, OncoMed and Celgene will co-develop and co-commercialize demcizumab in the U.S., sharing profits 50/50, while Celgene will lead development and commercialization outside the U.S.

Complete enrollment in the Phase 1b demcizumab plus pembrolizumab clinical trial.

Present interim data from the Phase 2 YOSEMITE and the Phase 1b demcizumab plus pembrolizumab dose-escalating trial and expansion arms at medical oncology meetings during the second half of 2017, pending abstract acceptance.
Tarextumab (anti-Notch 2/3, OMP-59R5)

Report top-line progression-free survival, overall survival, and biomarker-driven efficacy data in the first half of 2017 from the Phase 2 PINNACLE clinical trial of tarextumab in combination with cisplatin/carboplatin and etoposide for the treatment of first-line small cell lung cancer (SCLC).

Submit a tarextumab data package in the first half of 2017 to GlaxoSmithKline (GSK). GSK then has the opportunity to review the data package and consider exercising its option.
If GSK exercises its option on tarextumab, OncoMed would be entitled to receive a $25 million payment. GSK would then lead and fully fund further development and commercialization.

Present data from the Phase 2 PINNACLE clinical trial at a medical oncology meeting during the second half of 2017, pending abstract acceptance.
Wnt programs — Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

Submit data package for both programs in the first half of 2017 to Bayer for opt-in consideration.
Data package will include Phase 1b clinical trial data from the ongoing studies of both vantictumab and ipafricept.
OncoMed will be entitled to receive a $25 million payment for vantictumab and a $15 million payment for ipafricept if Bayer exercises its options on the investigational drugs. Upon option exercise, Bayer will lead and fully fund further development and commercialization.

Present Phase 1b data from the ongoing clinical trials at medical oncology meetings during 2017, pending abstract acceptance.
Anti-RSPO3 (OMP-131R10)

Continue enrollment in the Phase 1a biomarker-selected expansion cohort of the Phase 1a clinical trial and the Phase 1b trial of anti-RSPO3 in combination with FOLFIRI chemotherapy in patients with colorectal cancer, including biomarker-positive subjects.

Submit a data package upon the achievement of certain enrollment objectives to Celgene for opt-in consideration.
OncoMed will be entitled to receive a $37.75 million payment if Celgene exercises its option on anti-RSPO3. Upon option exercise, OncoMed and Celgene would co-develop and co-commercialize anti-RSPO3 in the U.S., sharing profits 50/50, while Celgene would lead development and commercialization outside the U.S.
Anti-DLL4/VEGF bispecific (OMP-305B83)

Initiate second Phase 1b clinical trial of the anti-DLL4/VEGF bispecific antibody in combination with paclitaxel for the treatment of platinum-resistant ovarian cancer.
Brontictuzumab (anti-Notch1, OMP-52M51)

Begin patient enrollment in the first half of 2017 of planned Phase 1b clinical trial of brontictuzumab combined with trifluridine and tipiracil tablets (Lonsurf) in third-line colorectal cancer. The trial includes enrollment of biomarker-positive patients whose tumors express the activated form of Notch1.
Immuno-oncology Pipeline

Initiate Phase 1 clinical trial in the first half of 2017 of anti-TIGIT (OMP-313M32).
Celgene will have an option to license anti-TIGIT at the end of the Phase 1a clinical trial.

File an IND in the first half of 2017 for OncoMed’s wholly owned GITRL-Fc (OMP-336B11) trimer program.

Present preclinical data related to anti-TIGIT, pending abstract acceptance.
In future years, OncoMed is eligible for more than $4 billion in total potential milestone and option payments from its partners under its collaboration agreements with Celgene, Bayer, and GSK. To date, OncoMed has received over $465 million from its existing partners.

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 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.