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Veracyte to Present at the 21st Annual Needham Growth Conference

On January 9, 2019 Veracyte, Inc. (Nasdaq: VCYT) reported that Bonnie H. Anderson, chairman and chief executive officer, is scheduled to present at the 21st Annual Needham Growth Conference in New York City on Tuesday, January 15, 2019 at 8:40 a.m. EST (5:40 a.m. PST) (Press release, Veracyte, JAN 9, 2019, View Source [SID1234532601]).

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A live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 90 days following the conclusion of the live presentation broadcast.

Selexis Expands Strategic Immuno-Oncology Alliance with Agenus

On January 9, 2019 Selexis SA, a pioneering life sciences company and a global leader in mammalian cell line generation technology, reported that it has signed additional commercial license agreements (CLAs) with Agenus Inc., (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune-modulating antibodies, cancer vaccines, and adoptive cell therapies (Press release, Selexis , JAN 9, 2019, View Source [SID1234532600]).1 Under the new CLAs, Agenus will leverage Selexis’ modular SUREtechnology Platform for the rapid, stable, and cost-effective production of its therapeutic proteins.

"It’s gratifying to have the opportunity to play a part in Agenus’ mission to redefine cancer treatment by advancing promising new biologics for individuals living with cancer," said Yemi Onakunle, PhD, MBA, Selexis vice president, licensing and business development. "The Selexis team has a notable track record of success in helping our partners overcome protein-expression challenges and advance products rapidly and safely through the clinic to the market where they can be made available to patients in need."

The Selexis SUREtechnology Platform improves the way mammalian cells are used in the discovery, development and manufacturing of recombinant proteins and drugs. The platform provides key significant advantages over traditional approaches, enabling: speed, high-yield, stability and flexibility.

"Our fully integrated capabilities, from early discovery of protein therapeutics to GMP manufacturing, allows us to rapidly produce and clinically test promising new drug candidates thereby delivering innovation with speed. A critical step in this process is the in-house development of commercially viable cell-lines expressing novel and complex proteins," said Alex Duncan, PhD, chief technology officer at Agenus. "We have successfully used the Selexis’ platform to drive our lead anti-CTLA4 (AGEN1884) and anti-PD1 (AGEN2034) programs, and are excited to partner with them to advance our novel single agent and multi-specific antibody programs."

Adimab Provides 2018 Update on Clinical Pipeline

On January 9, 2019 Adimab, LLC, the global leader in the discovery and optimization of fully human monoclonal and bispecific antibodies, reported that 12 new partner programs entered clinical development in 2018 (Press release, Adimab, JAN 9, 2019, View Source [SID1234532599]). This brings the total number of Adimab partner programs that have entered the clinic to 21.

"We carefully track the progression of our partners’ programs and try to benchmark their success against established industry metrics. At this point we are seeing more than half of our funded discovery programs proceed into product development, which is well above industry average," said Guy Van Meter, Senior Vice President of Business Development.

"It’s one thing to show fancy slides with fantasy data; it’s a very different thing to get actual molecules into clinical development. This year we more than doubled the number of Adimab antibodies in clinical development and saw the approval of our first antibody," said Tillman Gerngross, Chief Executive Officer and Co-Founder of Adimab.

Resulting from a 2013 discovery collaboration, Innovent Biologics received BLA approval for its PD1 program in 2018, making it the most advanced partner program coming from the Adimab Platform. Notably, Innovent was able to go from discovery to BLA approval in five years.

Partners that have initiated clinical development in 2018 include Alector, Five Prime Therapeutics, Innovent Biologics, Merck, Novartis, Potenza Therapeutics (an Astellas Pharma company), Tizona Therapeutics, and others. In 2018, Adimab partners exercised options to 16 commercial licenses to advance programs into product development, bringing the total number of optioned programs to over 50. Partners exercising commercial options in 2018 include Alector, DragonFly Therapeutics, iTeos Therapeutics, Innovent Biologics, Regeneron, Takeda, Tusk Therapeutics, and others.

NantKwest Announces Launch of Merkel Cell Carcinoma Phase II Trial Deploying Novel Triple Combination of off-the-Shelf Natural Killer haNKⓇ Cell Therapy with Superagonist IL-15 Cytokine Therapy and PD-L1 Checkpoint Inhibitor Therapy

On January 9, 2019 NantKwest Inc. (Nasdaq:NK), a leading, clinical-stage, natural killer cell based therapeutics company, reported the launch of a novel triple combination, phase II clinical trial in Merkel cell carcinoma (MCC) (Press release, NantKwest, JAN 9, 2019, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-announces-launch-merkel-cell-carcinoma-phase-ii-trial?field_nir_news_date_value[min]=2019 [SID1234532598]).

NantKwest’s phase II immunotherapy trial builds upon the company’s earlier phase II single-combination study using its proprietary, off-the-shelf aNKTM natural killer cell therapy and IL-15/Fc superagonist (N-803), which produced an objective responses in 3 of 7 patients.

In this new clinical trial, patients will be dosed with: (i) the novel chemotherapy-free combination of our haNK cell therapy, which are aNK cells that are genetically engineered to express the high-affinity variant of the CD16 receptor (V158 FcγRIIIa), (ii) avelumab, a PD-L1 targeting checkpoint inhibitor, and (iii) N-803, a superagonist IL-15/Fc cytokine therapy, in a regimen designed to synergistically optimize the therapeutic potential of each agent.

Commenting on the initiation of this novel triple combination trial in MCC, Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest said, "Even in a heavily pretreated patient population, including patients who have failed checkpoint inhibitor therapy, we were encouraged to see our combination of aNK cell and N-803 therapy exhibit preliminary clinically meaningful antitumor activity, including objective response in this resistant setting."

Dr. Soon-Shiong continued, "Building upon this human clinical trial data, we are pleased to announce the transition of this earlier study to include haNK cell therapy in combination with the IL-15 superagonist N-803 and the PD-L1 checkpoint inhibitor avelumab, which we believe, when used together, will offer synergies and the potential to improve response rates for patients with MCC that may also potentially translate to a number of additional solid tumor indications."

In preclinical and human clinical studies conducted by NantKwest, the combination of haNK cells with a number of different therapeutic antibodies, including avelumab, led to enhanced tumor cell killing when compared to the use of the antibody alone. The IL-15/Fc superagonist N-803, developed by NantCell, Inc., an affiliate company, has been shown to synergistically activate NK and T cells and enhance cancer cell killing in both single agent and combination therapy. The PD-L1 checkpoint inhibitor avelumab, a monoclonal antibody developed by Merck KGaA and approved in 2017 by the FDA, targets the programmed death-ligand 1 protein (PD-L1), commonly expressed on a wide range of cancer cells. Avelumab works by blocking PD-L1 from binding PD-1 receptors on T-cells, resulting in an increase in CD8+ T-cell immune responses. This effect is amplified with the addition of N-803 and haNK cells.

With encouraging preclinical and clinical responses already demonstrated for aNK as a single agent therapy or in combination, we believe this existing dataset provides validation for our novel, triple combination clinical trial design.

MCC is a rare and aggressive skin cancer that arises from uncontrolled growth of cells in the skin. Increasing in incidence, approximately 2,500 new cases are reported in the U.S. each year. Patients with metastatic or locally advanced MCC have an extremely poor prognosis, with less than 20% of patients surviving longer than five years. Typically these patients are treated with a range of drugs, including chemotherapy, which can result in significant side effects. Although new immune therapies have the potential to improve survival, MCC is still fatal for a majority patients who have progressed on or after treatment with a checkpoint inhibitor and represents an unmet medical need.

Study Design

The Phase II clinical study will evaluate a combination therapy with our off-the-shelf CD16-targeted natural killer cells (haNK), the IL-15 superagonist (N-803), and avelumab, without the use of cytotoxic chemotherapy, in subjects with MCC that have progressed on or after treatment with a checkpoint inhibitor. The combination of these agents have been safely studied in our previous clinical trials for other solid cancer indications. The goal of combining these therapies is to synergistically maximize the killing of cancer cells while attempting to spare patients from chemotherapy and its associated adverse side effects.

haNK Cell Therapy Platform

NantKwest’s haNK cell therapy platform is a natural killer cell therapy that was developed to optimize the key role of natural killer cells in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improve anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC is an important component of the human immune system associated with the synergistic interaction of natural killer cells with antibodies to directly kill a target cell that has been identified by an antigen-specific antibody. ADCC represents one of the key mechanisms that antibodies utilize to target and kill cancer cells. Engineered to express the high-affinity variant of the CD16, high affinity Fc receptor (V158 FcγRIIIa), in preclinical studies, the combination of haNK cells with a number of different therapeutic antibodies led to enhanced tumor cell killing when compared to the use of the antibody as a single therapeutic agent, providing strong support for this novel combination immunotherapeutic approach.

N-803 Superagonist IL-15 Cytokine Therapy

Interleukin-15 (IL-15) is a critical factor controlling the development, proliferation and activation of effector natural killer (NK) cells and CD8+ memory T cells. In preclinical and clinical studies, this cytokine has exhibited potent antitumor activities against well-established tumors. N-803, developed by NantCell, an affiliate company, is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. In preclinical and clinical studies, N-803 has shown improved biological activity, longer persistence in lymphoid tissues and enhanced anti-tumor activity by simultaneously mobilizing both the innate and adaptive arms of the immune system. This robust immunostimulatory capacity is believe to elicit rapid and durable responses against cancer cells compared to native, non-complexed IL-15 in vivo.

For additional information regarding this MCC clinical trial please visit, www.clinicaltrials.gov and for additional information on NantKwest, please visit www.nantkwest.com

Seattle Genetics Announces Publication of North American Subgroup Data from ECHELON-1 Phase 3 Clinical Trial of ADCETRIS® (Brentuximab Vedotin) in Newly Diagnosed Advanced Hodgkin Lymphoma

On January 9, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported the publication of data from the ECHELON-1 phase 3 clinical trial online in the journal Clinical Cancer Research (Press release, Seattle Genetics, JAN 9, 2019, View Source [SID1234532597]). The publication, titled "Brentuximab Vedotin Plus Chemotherapy in North American Patients with Newly Diagnosed Stage III or IV Hodgkin Lymphoma," reports data from the North American patient population from ECHELON-1 evaluating ADCETRIS (brentuximab vedotin) in combination with AVD (Adriamycin, vinblastine and dacarbazine) in newly diagnosed stage III or IV classical Hodgkin lymphoma (HL). These data were previously presented in a poster presentation at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In March 2018, the U.S. Food and Drug Administration (FDA) approved ADCETRIS in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical HL based on the positive results of the ECHELON-1 phase 3 clinical trial. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival.

"Prior to the FDA approval of ADCETRIS in combination with AVD, up to 30 percent of patients with advanced stage HL would not respond or would relapse following frontline treatment with ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine)," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "In this pre-specified analysis of 497 patients with HL treated in North America, similar to overall trial results, ADCETRIS plus AVD was associated with a lower risk of a progression event compared to ABVD. This is important information for North American healthcare providers to have when making treatment decisions, where there is access to supportive care, and treatment patterns and physician familiarity with treating patients with ADCETRIS."

Of the 1,334 advanced stage classical HL patients who participated in the ECHELON-1 clinical trial, 497 patients were treated in North America, with 250 patients in the ADCETRIS plus AVD arm and 247 patients in the ABVD control arm. The manuscript presents the North American results which include:

A pre-specified sensitivity analysis showed per Independent Review Facility (IRF) assessment, the two-year modified progression-free survival (PFS) rate for patients in the ADCETRIS plus AVD arm was 84.3 percent compared to 73.7 percent in the control arm (HR 0.596; 95% CI: 0.40, 0.90), which corresponds to a difference of 10.6 percent.
On the ADCETRIS plus AVD arm, peripheral neuropathy events were observed in 80 percent of patients compared to 56 percent on the ABVD arm. In the ADCETRIS plus AVD arm, the majority of peripheral neuropathy events were Grade 1 or 2 (41 percent and 21 percent, respectively). Grade 3 events were reported in 17 percent of patients. In the ABVD arm, Grade 3 events were reported in less than one percent of patients. There were no Grade 4 events on either arm. Across both arms of the study, approximately 75 percent of the patients with peripheral neuropathy reported resolution or improvement at last follow-up.
Febrile neutropenia during treatment was reported in 20 percent of patients in the ADCETRIS plus AVD arm compared with nine percent in the ABVD arm. In the ADCETRIS plus AVD arm, 14 percent (35 patients) received primary prophylactic G-CSF within five days of starting treatment and nine percent (three patients) reported febrile neutropenia.
Pulmonary toxicity was reported in three percent of patients in the ADCETRIS plus AVD arm versus ten percent of patients in the ABVD arm. Grade ≥3 events were reported in two percent versus six percent of patients, in the ADCETRIS plus AVD and ABVD arms, respectively.
About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Classical Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the American Cancer Society, approximately 8,500 cases of Hodgkin lymphoma will be diagnosed in the United States during 2018 and more than 1,000 will die from the disease. Approximately half of all newly diagnosed Hodgkin lymphoma patients have Stage III/IV disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma. The phase 3 CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma is ongoing.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, and adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.