On September 4, 2018 Aduro Biotech, Inc. (NASDAQ:ADRO) reported that preclinical data for its first-in-class anti-APRIL antibody BION-1301 was presented at the 5TH European Congress of Immunology in Amsterdam, The Netherlands. Data from the preclinical studies demonstrated that BION-1301 was well-tolerated (Press release, Aduro Biotech, SEP 4, 2018, View Source;p=RssLanding&cat=news&id=2365988 [SID1234529284]). In addition, pharmacological activity of BION-1301 binding to APRIL (A Proliferation-Inducing Ligand), a ligand for the receptors BCMA (B cell maturation antigen) and TACI (transmembrane activator and cyclophilin ligand interactor), was established in a dose-dependent fashion. The pharmacokinetics (PK) and target engagement biomarkers were used to predict the first-in-human dose. APRIL mediates important B-cell functions including activation, survival and maturation. Serum levels of APRIL are enhanced in patients diagnosed with multiple myeloma (MM) and correlate with a poor prognosis. APRIL in the bone marrow triggers a cascade of events to support human MM to proliferate, survive, induce resistance to standard-of-care drugs in MM cells and provide an immune protective environment.

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"The pioneering work on the mechanism of action, PK and pharmacodynamics presented today has paved the way for the first clinical evaluation of BION-1301, an ongoing Phase 1/2 trial in patients with multiple myeloma," commented Hans van Eenennaam, Ph.D., executive vice president antibody research and site head, Aduro Biotech Europe.

Aduro is conducting a Phase 1/2 multi-center, open-label study (see www.clinicaltrials.gov, identifier NCT03340883) designed to evaluate the safety and activity of BION-1301 in patients with relapsed or refractory MM whose disease has progressed after at least 3 prior systemic therapies, including immunomodulatory drugs, proteasome inhibitors, chemotherapies, or monoclonal antibodies.

About BION-1301
Aduro is currently evaluating BION-1301, its most advanced proprietary B-select monoclonal antibody, as a novel therapy for MM. Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In preclinical studies, Aduro has established that APRIL plays a crucial part in the protective bone marrow tumor microenvironment. In these studies, APRIL, through BCMA, was shown to be critically involved in the survival, proliferation and chemoresistance of MM, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. In addition, BION-1301 also demonstrated the ability to inhibit immune suppressive effects of regulatory T cells via TACI but not BCMA in MM blood and bone marrow. BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM.

On September 4, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported the publication of a peer reviewed paper in Leukemia authored by scientists from the Dana Farber Cancer Institute and Aduro as part of their ongoing collaboration to study the role of APRIL (A PRoliferation Inducing Ligand) in multiple myeloma (MM) (Press release, Aduro Biotech, SEP 4, 2018, View Source;p=RssLanding&cat=news&id=2366001 [SID1234529283]). The authors profile the impact that APRIL, acting through its receptor TACI (transmembrane activator and cyclophilin ligand interactor), has on immune regulatory T cells (Tregs) in MM. The paper further reports that APRIL binding to TACI contributes to the immunosuppressive and treatment resistant MM bone marrow microenvironment, an effect that could potentially be mitigated by anti-APRIL antibody, BION-1301. Aduro is currently advancing BION-1301 in a Phase 1/2 dose escalation trial for the treatment of MM.

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Key findings from the study include the observation that TACI expression is significantly higher in Tregs than conventional T cells from the same patient. APRIL significantly stimulates proliferation and survival of these Tregs, whereas a neutralizing anti-APRIL antibody (BION-1301) may inhibit these effects. Furthermore, the paper explained how APRIL specifically augments Tregs to enhance MM cell survival.

"It is now well-known that APRIL acts through its two receptors TACI and BCMA (B cell maturation antigen), the most specific MM antigen expressed at high levels in malignant plasma cells/B cells of all MM patients. Our newest findings from this study indicate that an anti-APRIL antibody such as BION-1301 may have the potential to treat MM through a differentiated mechanism of action, not only by inhibiting APRIL binding to BCMA, but also stimulating immunity to cancer by blocking APRIL binding to TACI," commented Dr. Yu-Tzu Tai, lead author and Principal Scientist in Medical Oncology at the Dana-Farber Cancer Institute.

The paper entitled "APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications," can be accessed at View Source

About APRIL
APRIL is a member of the tumor necrosis factor superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA and TACI to stimulate a wide variety of responses that promote MM growth and survival and suppress the immune system so that the tumor cells are protected and sustained in the bone marrow.

About BION-1301
Aduro is currently evaluating BION-1301, its most advanced proprietary B-select monoclonal antibody, as a novel therapy for MM. Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In preclinical studies, Aduro has established that APRIL plays a crucial part in the protective bone marrow tumor microenvironment. In these studies, APRIL, through BCMA, was shown to be critically involved in the survival, proliferation and chemoresistance of MM, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. In addition, BION-1301 also demonstrated the ability to inhibit immune suppressive effects of regulatory T cells via TACI but not BCMA in MM blood and bone marrow. BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM.

On September 4, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the achievement of a development milestone in its collaboration with Eli Lilly and Company (Press release, Zymeworks, SEPT 4, 2018, View Source [SID1234529269]). In accordance with Zymeworks’ 2013 licensing and collaboration agreement with Lilly, Zymeworks will receive a milestone payment of US$2.0 million for Lilly’s submission of an IND application for a bispecific antibody enabled by Zymeworks’ proprietary Azymetric platform. Previously, Zymeworks announced Lilly’s nomination of two bispecific immuno-oncology drug candidates for late-stage preclinical development.

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"The team at Lilly has done an impressive job advancing a novel bispecific therapeutic built on our Azymetric platform to the IND stage in a relatively short period of time," said Ali Tehrani, Ph.D., President and Chief Executive Officer of Zymeworks. "Moving a compound into the clinic is an important step in drug development and we look forward to future progress with Lilly as well as our five other partners."

Under its two licensing and collaboration agreements with Lilly, Zymeworks has granted Lilly worldwide licenses to research, develop and commercialize multiple bispecific therapeutics directed towards Lilly’s targets. To date, Zymeworks has received an upfront licensing payment and multiple research milestone payments under these agreements, in addition to historical equity investments made by Lilly in Zymeworks. Zymeworks is also eligible to receive further development and commercial milestone payments and tiered royalties on global product sales.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.

On September 4, 2018 Puma Biotechnology, Inc. (Nasdaq:PBYI) reported that the European Commission (EC), has granted marketing authorisation for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy (Press release, Puma Biotechnology, SEPT 4, 2018, View Source [SID1234529268]).

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EC approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Patients (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, for patients with hormone receptor positive, HER2-positive early stage breast cancer patients who were treated within one year after the completion of trastuzumab based adjuvant therapy, invasive disease-free survival (iDFS) was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49; 95% CI: (0.30, 0.78); p=0.002)

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

"Reducing the risk of disease recurrence remains a need for patients, despite advances in the treatment of early stage HER2-positive breast cancer," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to bring this new medicine to patients in Europe and would like to express our appreciation to the patients, caregivers and physicians who contributed to the neratinib clinical development program and, more specifically, the ExteNET trial. We are committed to continuing to expand NERLYNX accessibility to patients worldwide. We expect NERLYNX to be commercially available in Europe in 2019, beginning with our launch in Germany during the first half of 2019 and followed by additional countries throughout Europe in the second half of 2019."

The approval of NERLYNX by the European Commission follows the positive opinion issued by the Committee for Medicinal Products for Human Use of the European Medicines Agency in June 2018.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On September 4, 2018 Tempest Therapeutics Inc., a development-stage biotechnology company advancing small molecules that modulate anti-tumor immunity pathways, reported that Ginna Laport, M.D., joined the company as Chief Medical Officer (Press release, Tempest Therapeutics, SEPT 4, 2018, View Source [SID1234529267]). Dr. Laport brings significant expertise in hematology, oncology and clinical drug development, and will lead the evaluation and clinical development of Tempest’s portfolio of novel first-in-class drug candidates in patients with advanced malignancies.

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"We are very excited to welcome Ginna to the Tempest team. She has an impressive academic and biotech pedigree together with a track record of advancing multiple modalities of cancer therapeutics. Ginna will be integral in the transition of Tempest into a clinical-stage biotechnology company in 2019," said CEO Tom Dubensky, Ph.D.

Prior to joining Tempest, Dr. Laport served as vice president of clinical development at Corvus Pharmaceuticals, where she led the clinical development of small molecules and antibodies targeting the adenosine pathway to treat advanced solid tumors. Additionally, Dr. Laport was a member of the Executive Committee and oversaw clinical development and operations.

Before Corvus, Dr. Laport was faculty in the Stanford University School of Medicine, most recently as professor of medicine in the Division of Blood and Marrow Transplantation (BMT). Her research focused on adoptive immunotherapies for malignant diseases and she served as director of clinical research in the BMT Division and as an associate director of the Stanford Cancer Institute. Prior to Stanford, Dr. Laport was an assistant professor in hematology/oncology at the University of Pennsylvania. Dr. Laport served on the FDA’s Oncologic Drugs Advisory Committee (ODAC), was national chair of the NIH-sponsored BMT Clinical Trials Network that directs multicenter clinical trials, and has co-authored over 80 publications.

Dr. Laport received her M.D. from the University of Texas-Houston and a B.A. from Baylor University. She completed her internal medicine residency and fellowship in hematology/oncology at The University of Chicago.

In addition, Tempest has promoted Dr. Alicia Levey to Chief Business Officer. Dr. Levey previously was Tempest’s VP of business development and strategy. Prior to Tempest, she was VP of business development at Inception Sciences, a small molecule drug discovery company formed in collaboration with Versant Ventures, a global venture capital firm focused primarily on early stage investing and biotechnology company creation.

Dr. Levey is an operating principal at Versant where she has led the diligence on multiple deals including several that have been acquired or are now public. She holds a Ph.D. from the Stanford University School of Medicine.

"We are delighted to have Alicia in the CBO role," said Dr. Dubensky. "She has been a critical component in establishing Tempest and has a deep track record of successful business development."