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Vivoryon Therapeutics AG enters myeloid immune checkpoint drug discovery, and collaborates with the University of Kiel to select cancer therapy candidates from its QPCTL inhibitor portfolio

On June 27, 2019 Vivoryon Therapeutics AG, (Euronext Amsterdam: currently PBD, to be changed to VVY, ISIN: DE0007921835) reported that they have entered into a research collaboration with University Medical Center Schleswig-Holstein, Campus Kiel, to discover and develop first-in-class therapeutics in cancer immunotherapy (Press release, Vivoryon Therapeutics, JUN 27, 2019, View Source [SID1234537422]). Professor Thomas Valerius and his group will qualify Vivoryon’s broad portfolio of small molecule QPCTL inhibitors for their use as modulators of the CD47/SIRP-alpha myeloid immune checkpoint. These inhibitors, some of which have already been clinically tested, originated from the Company’s Alzheimer’s disease drug development program which remains to be a core focus for Vivoryon Therapeutics. Besides, these inhibitors also offer interesting therapeutic options in immuno-oncology.

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Recently published and internal research has shown that the Glutaminyl-peptide cyclotransferase-like (QPCTL) enzyme is a powerful therapeutic target to silence the "do not eat me" signal provided by the interaction of CD47 (expressed on cancer cells), with the protein SIRP-alpha (expressed on macrophages and other myeloid cells). Tumor immunotherapy that targets this interaction is a current focus of innovation in cancer drug development. Combining a therapeutic tumor-targeted antibody of choice with the inhibition of the CD47/SIRP-alpha interaction is expected to lead to significant therapeutic improvements. By possessing the broadest portfolio of small molecule QPCTL inhibitors and the clinically most advanced compounds in that field, Vivoryon Therapeutics is uniquely positioned. QPCTL inhibitors are expected to have considerable therapeutic advantages compared to antibody approaches that are currently explored in clinical studies to silence the CD47/SIRP-alpha interactions.

Dr. Michael Schaeffer, CBO of Vivoryon Therapeutics said: "We are very pleased to partner with the University Medical Center Schleswig-Holstein, who is -like us- truly dedicated to accelerating innovative cures for cancer. Professor Valerius is a renowned expert in the field of myeloid effector cells in immunotherapy. This collaboration allows us to engage multiple targets and fully exploit our unique patent position. Undoubtedly, we are now entering into one of the most exciting fields of current drug development."

Within this collaboration Vivoryon Therapeutics will fund focused research with the clear goal of further qualifying its QPCTL inhibitors in cellular cancer models. Vivoryon’s highly active compounds will be tested individually and in combination with therapeutic antibodies.

Prof. Dr. Thomas Valerius, Senior Physician at the Department of Internal Medicine II – Hematology, Oncology of the University Hospital Schleswig-Holstein, added: "Our partnership with Vivoryon Therapeutics fits well with our goal of advancing early-stage therapeutic innovation. We are delighted that we are working on some of the most exciting compounds in myeloid checkpoint inhibition today and are convinced that these molecules could lead to significant improvements in cancer immunotherapy."

The development partners confirm that the cooperation has no effect on sales transactions of the University Medical Center Schleswig-Holstein – in particular procurement processes – and there are no expectations in this connection.

For more information, please contact:

Vivoryon Therapeutics AG
Dr. Ulrich Dauer, CEO
Email: [email protected]

Universitätsklinikum Schleswig-Holstein, Campus Kiel
Medizinische Klinik II, Sektion für Stammzell- und Immuntherapie
Prof. Dr. med. Thomas Valerius
Email: [email protected]

MC Services AG
Anne Hennecke, Susanne Kutter
Tel: +49 (0) 211 529 252 27
Email: [email protected]

INmune Bio Announces Publication of Data on INKmune Primed NK cells in Peer-Reviewed Journal PLOS ONE

On June 27, 2019 INmune Bio, Inc. (NASDAQ: INMB), an immunotherapy company developing treatments that harness the patient’s innate immune system to fight disease, reported that the peer-reviewed open access scientific journal PLOS ONE published an article titled, "Tumor- and cytokine-primed human natural killer cells exhibit distinct phenotypic and transcriptional signatures," summarizing the different effects between NK cell activation in response to tumor cells and cytokine-mediated activation (Press release, INmune Bio, JUN 27, 2019, View Source [SID1234537326]).

Co-authored by Dr. Mark Lowdell, Chief Scientific Officer and co-founder at INmune Bio, the paper defines the response of natural killer (NK) cells following their encounters with tumor cells and provides insight into tumor-specific NK cell responses; helping the transition toward harnessing their therapeutic potential in cancer. The paper identifies a unique signaling "fingerprint" expressed by NK cells after binding to CTV-1 tumor cells, which is the parent clone of INmune Bio’s own INB16 cells.

Through these observational data, researchers are able to use that knowledge to apply the strategy to build immunotherapy treatments. Priming NK cells with controlled exposure to tumor cells – which is the mechanism of action of INKmune – in the patient is potentially more effective against cancer targets with potentially fewer side effects than the administration of cytokines such as IL-2 or IL-15.

"We are delighted to be sharing these data describing the unique molecular pathways triggered within human NK cells upon priming with INmune Bio’s own INB16 (INKmune) cell line," says Dr. Lowdell. "These data confirm that the primed NK cells generated by INB16 stimulation upregulate genes, which are crucial to NK-mediated killing of patients’ cancer cells, such as CD70 and CXCL10. These differences in gene expression may explain the greater cytotoxic activity of INB16 primed NK cells in vitro compared to cytokine primed cells which may lead to greater clinical efficacy."

"This work has combined expertise across many groups, and it was important to publish these data in a highly-regarded open access journal to ensure that they are available to the widest possible audience," concludes Dr. Lowdell.

Sierra Oncology Launches Campaign Exploring Non-Dilutive Strategic Options to Support Development of its DDR Assets

On June 27, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported plans to prioritize its existing resources on the development of momelotinib, its differentiated Phase 3 drug candidate for the treatment of patients with myelofibrosis (Press release, Sierra Oncology, JUN 27, 2019, View Source [SID1234537322]). Sierra also announced it has launched a campaign exploring non-dilutive strategic options to support the future continued development of its portfolio of potent and selective DDR (DNA Damage Response) assets, consisting of SRA737 (Chk1 inhibitor) and SRA141 (Cdc7 inhibitor).

"We recently reported compelling proof-of-concept clinical efficacy data for SRA737 at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting, demonstrating that this drug candidate has notable anti-cancer activity in multiple indications and a defined clinical path forward towards potential initial registration for the treatment of anogenital cancer, an indication with considerable unmet need. For SRA141, we have demonstrated a potentially novel mechanism of cytotoxicity and successfully completed the IND process with the FDA enabling the commencement of clinical trials," said Dr. Nick Glover, President and CEO of Sierra Oncology. "While we continue to advance the assets in our DDR portfolio and view them as promising oncology drug candidates that warrant further development, we are prioritizing our resources on our lead drug, momelotinib. To support the continued development of SRA737 and SRA141 in the future, we intend to seek non-dilutive strategic options."

About Sierra’s DDR assets: SRA737 (targeting Chk1) and SRA141 (targeting Cdc7)
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). Tumors with high levels of replication stress become reliant on Chk1 to mitigate the potentially catastrophic consequences of excess genomic instability. Intrinsic sources of replication stress can include genetic alterations in tumor suppressors, oncogenes or DNA Damage Repair genes. SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine (LDG) acts as a potent extrinsic inducer of replication stress.

At the 2019 ASCO (Free ASCO Whitepaper) Annual meeting, Sierra reported preliminary efficacy data for SRA737 including a 30% Overall Response Rate in patients with anogenital cancer treated with SRA737+LDG , an indication for which the second line metastatic setting represents a significant unmet medical need with no approved therapies and very poor life expectancy. Additionally, subjects whose tumors harbored FA/BRCA gene network mutations displayed favorable outcomes across multiple indications, with an Overall Response Rate of 25% and Disease Control Rate of 81%.

Sierra has conducted preclinical research demonstrating SRA737 synergy in combination with other DDR-targeted agents including poly ADP-ribose polymerase (PARP) inhibitors, as well as with immuno-oncology therapeutics. Sierra has an agreement with Janssen Research & Development, LLC (Janssen), under which Janssen has agreed to supply the PARP inhibitor niraparib, facilitating the potential initiation of a combination trial with SRA737 that Sierra has designed for the treatment of prostate cancer. Sierra reported preclinical data in a late-breaking poster presented at the AACR (Free AACR Whitepaper) Annual Meeting 2019 demonstrating that SRA737+LDG activates innate immune signaling and establishes an anti-tumor immune microenvironment that profoundly synergizes with immune checkpoint inhibitors. Sierra has reported having management support from a major immuno-oncology company to potentially supply their leading immunotherapeutic agent to run a combination study with SRA737.

SRA141 is a potent, selective, orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7). Sierra reported preclinical data in a late-breaking poster presented at the AACR (Free AACR Whitepaper) Annual Meeting 2019 highlighting a possible novel mechanism of cytotoxicity for SRA141 that is distinct from other agents, in which SRA141 alters DNA replication dynamics and delays cell cycle progression, leading to apoptotic tumor cell death. This differentiated mechanism of action may support a unique spectrum of clinical opportunities for SRA141 as both monotherapy and in combination with pro-apoptotic and mitotic disrupting agents. Sierra has successfully completed the IND process with the U.S. Food and Drug Administration (FDA) for SRA141 and has designed a potential Phase 1/2 trial with this drug candidate.

Sierra Oncology retains the global commercialization rights to SRA737 and SRA141.

About Sierra Oncology
Sierra Oncology is a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with unmet medical needs in hematology and oncology.

Momelotinib, Sierra’s lead drug candidate, is a potent, selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a differentiated therapeutic profile in myelofibrosis encompassing robust constitutional symptom improvements, a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, and comparable spleen control to ruxolitinib. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including more than 800 subjects treated for myelofibrosis.

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in Q4 2019 to support potential registration of the momelotinib on a global basis. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic, anemic and have been treated previously with a JAK inhibitor. Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the MOMENTUM trial.

Momelotinib is wholly owned by Sierra Oncology and is covered by patents anticipated to provide potential exclusivity to 2040 in the U.S. The FDA has granted Fast Track designation to momelotinib for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.

Kitov Successfully Completes IND-enabling Studies to advance NT219 for the Treatment of Patients with Recurrent or Metastatic Head and Neck Cancers

On June 27, 2019 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a pharmaceutical company focused on advancing first-in-class oncology therapies to overcome tumor drug resistance, increase treatment response rate, and slow tumor progression, reported that it has successfully completed the laboratory phase of the IND-enabling studies for NT219, a first-in-class, dual-inhibitor small molecule, designed to prevent and overcome cancer drug resistance (Press release, Kitov Pharmaceuticals , JUN 27, 2019, View Source [SID1234537321]). The preclinical GLP toxicology studies have demonstrated good tolerability at the highest dose levels expected to be tested in Kitov’s planned Phase 1/2 study treating patients with squamous cell carcinoma of the head and neck (SCCHN).

"We are excited with the completion of the IND-enabling studies for NT219 which advances our growing oncology pipeline to the clinic," stated Isaac Israel, chief executive officer of Kitov. "Our planned development of NT219 is based on strong preclinical evidence demonstrating that the combination of NT219 with the EGFR antibody cetuximab has potential clinical benefits for patients with recurrent or metastatic SCCHN whose cancer has not responded or has become resistant to early-line immuno-oncology or chemotherapy treatments. Pending a smooth regulatory review process, we look forward to initiating a Phase 1/2 trial with NT219 and cetuximab in the U.S. by the end of 2019."

Kitov is preparing for completion of the GMP manufacturing of the drug product and submission of an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) to initiate a dose-escalation Phase 1/2 study to treat SCCHN cancer patients with the combination of NT219 and cetuximab.

About NT-219

NT219, is a first-in-class small molecule designed to prevent and overcome cancer drug resistance. NT-219 is an inhibitor of two signaling proteins involved in drug resistance, Insulin Receptor Substrate 1 and 2 (IRS1/2) and Signal Transducer and Activator of Transcription 3 (STAT3). Efficacy of NT-219 was demonstrated in PDX models in combination with targeted therapies, chemotherapies and immuno-oncology therapies in delaying onset and reversing resistance to anti-cancer drugs in head and neck, colon, lung, and pancreatic cancers. Kitov is planning to initiate a Phase 1/2 open label multi-center study of NT-219 in combination with cetuximab (ErbituxTM) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) by the end of 2019.

Genmab Announces U.S. FDA Approval of DARZALEX® (daratumumab) in Combination with Lenalidomide and Dexamethasone in Frontline Multiple Myeloma

On June 27, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) (Press release, Genmab, JUN 27, 2019, View Source [SID1234537320]). The supplemental Biologics License Application (sBLA) for this indication was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., under the Real-Time Oncology Review (RTOR) pilot program. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"The combination of lenalidomide and dexamethasone is broadly used by newly diagnosed patients with multiple myeloma ineligible for ASCT in the United States. We are extremely pleased that physicians can now offer their patients the option to add DARZALEX to this regimen in the U.S.," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on data from the Phase III MAIA (MMY3008) study of daratumumab in combination with lenalidomide and dexamethasone as treatment for patients with newly diagnosed multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from this study was presented as a Late-Breaking Abstract at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide was administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue treatment with lenalidomide and dexamethasone until disease progression or unacceptable toxicity. The primary endpoint of the study is progression free survival.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.