On April 16, 2018 Leap Therapeutics, Inc. (NASDAQ:LPTX) reported that presented nonclinical and clinical data on DKN-01, Leap’s anti-DKK1 monoclonal antibody, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting (Press release, Leap Therapeutics, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342693 [SID1234525349]). The presentation highlighted the immunomodulatory activity of DKN-01 in nonclinical experiments and preliminary results from the dose escalation phase of the clinical study evaluating DKN-01 in combination with the Merck (known as MSD outside the United States and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced esophagogastric cancer.

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Nonclinical Data:
Nonclinical studies demonstrated the activity of DKK1 inhibition in enhancing innate immunity and the potential for combination with immune checkpoint inhibitors. mDKN-01, the murine form of DKN-01, reduced myeloid-derived suppressor cells (MDSCs), increased PD-L1 levels on MDSCs, and enhanced expression of T-cell chemoattractants. These innate mechanisms, promoting an inflammatory tumor microenvironment, are complementary to immune checkpoint inhibition. In a syngeneic tumor model, mDKN-01 had additive activity with anti-PD-1 therapy as compared to either antibody administered alone.

Clinical Data:
Preliminary results from the dose escalation phase of the clinical study evaluating the combination of DKN-01 and KEYTRUDA in patients with advanced esophagogastric cancer demonstrated that the combination was well tolerated with early signals of clinical activity:
Four out of five patients enrolled at the highest tested dose of DKN-01 were naïve to anti-PD-1/PD-L1 therapy and evaluable for response. One patient had a partial response with a 66% reduction in target tumor volume. This patient had progressed on two prior systemic therapies and had a tumor that was known to be KRAS amplified, microsatellite stable (MSS), and PD-L1 negative; a phenotype typically less responsive to anti-PD-1 therapy. Three patients had stable disease, two of whom remain on study through at least four cycles.

Two patients enrolled in the escalation phase were refractory to anti-PD-1/PD-L1 therapy and currently have had a best response of stable disease. One of these patients also had a tumor that was KRAS amplified, MSS, and PD-L1 negative and has been on study for six cycles with an initial 10% reduction in tumor burden.
The DKN-01 and KEYTRUDA expansion combination continues to enroll patients who are naïve to anti-PD-1/PD-L1 therapy (n=40) and patients who are refractory to anti-PD-1/PD-L1 therapy (n=15).

On April 16, 2018 Humanigen, Inc. (OTCQB: HGEN), a biopharmaceutical company pursuing cutting-edge science to develop its proprietary monoclonal antibodies for immunotherapy and oncology treatments, reported it has signed an agreement with The University of Texas MD Anderson Cancer Center to begin investigator-led research on lenzilumab and its potential to support chimeric antigen receptor T cell (CAR-T) therapy (Press release, Humanigen, APR 16, 2018, View Source [SID1234525348]). Lenzilumab is a first-in-class Humaneered recombinant monoclonal antibody that targets and is an antagonist of soluble granulocyte-macrophage colony-stimulating factor (GM-CSF).

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Preclinical work assessing lenzilumab’s action on one of the mechanisms in the inflammatory cascade induced by CAR-T will proceed in parallel with a planned study that could potentially qualify as a registration study, testing lenzilumab as a potential prophylaxis for neurotoxicity induced by CAR-T therapy. Neutralization of circulating GM-CSF has the potential to blunt or prevent an inflammatory cascade that can result in serious and life-threatening CAR-T-induced side effects – neurotoxicity and Cytokine Release Syndrome.

"With this agreement, we are excited that the team at MD Anderson Cancer Center is beginning to investigate lenzilumab’s potential to make groundbreaking CAR-T therapy safer, better and more routine," said Cameron Durrant, M.D., chairman and chief executive officer of Humanigen. "CAR-T science has moved quickly in the past few years with the two currently marketed CAR-T therapies having been approved based on single Phase 1/2 studies. We look forward to adding to the burgeoning, cutting-edge science studying lenzilumab as a potential critical CAR-T support therapy."

The preclinical study will measure the ability of lenzilumab to block patient CD19-CAR-T cells-treatment-derived GM-CSF induction of human leukocyte antigen-DR (HLA-DR) expression on CD14+ monocytes. It will assess the inhibitory effect of lenzilumab on GM-CSF-induced HLA-DR expression on CD14+ cells, plus other phenotypic and functional monocyte assays.

About Lenzilumab

Lenzilumab is a first-in-class, novel Humaneered recombinant monoclonal antibody designed to target and neutralize circulating granulocyte-macrophage colony-stimulating factor (GM-CSF), the myeloid inflammation factor involved in the recruitment of myeloid cells to a tumor and a central actor in leukocyte differentiation, autoimmunity and inflammation. There is also extensive evidence linking GM-CSF expression to serious and potentially life-threatening side effects in chimeric antigen receptor T-cell (CAR-T) therapy, such as neurotoxicity and Cytokine Release Syndrome (CRS). Humanigen is working with leading CAR-T experts to develop lenzilumab as a potential prophylactic treatment to minimize neurotoxicity associated with CAR-T cancer therapy. In addition, lenzilumab is currently being evaluated as a potential treatment for rare leukemias in a phase 1 trial (NCT02546284) in patients with chronic myelomonocytic leukemia (CMML) with additional potential in juvenile myelomonocytic leukemia (JMML), a rare pediatric cancer. In previous clinical trials, lenzilumab has shown to be safe and well-tolerated in more than 100 patients, including those with rheumatoid arthritis, asthma and healthy volunteers. It is a potent inhibitor of GM-CSF in vivo.

On April 16, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that it has entered a new worldwide collaboration with Bristol-Myers Squibb Company on a program to develop and commercialize Factor XIa (FXIa) inhibitors, including BMS-986177, for the prevention and treatment of major thrombotic conditions (Press release, Johnson & Johnson, APR 16, 2018, View Source [SID1234525347]). Under the agreement, Janssen Pharmaceuticals, Inc. and Bristol-Myers Squibb Company will advance BMS-986177 into Phase 2 clinical trials and establish a broad development program across multiple therapeutic indications.

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The development of novel oral anticoagulants has been a major step forward in the prevention and treatment of thrombosis. The goal for next-generation anticoagulants is to achieve the same efficacy as the current standard of care while substantially lowering the risk of bleeding. Early clinical research has shown that

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FXIa inhibition has the potential to reduce the risk of thrombotic events with a significantly lower risk of bleeding compared to currently available therapies.

"Janssen has built deep knowledge in the anticoagulation space through our extensive experience researching and developing innovative cardiovascular therapies," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Janssen Research & Development, LLC. "We look forward to applying our expertise to this collaboration with Bristol-Myers Squibb to explore the full potential of BMS-986177 through Factor XIa inhibition to provide a wider safety window for anticoagulation than current therapies."

"With the addition of a Factor XIa inhibitor program to our pipeline, Janssen continues to live up to our long-standing commitment of working tirelessly to bring truly transformational therapies to patients worldwide," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "With this new collaboration we have the potential to improve the standard of care for patients with cardiovascular conditions characterized by pathologic thrombosis."

The companies will share development costs and commercial profits and losses. Additional terms of the agreement were not disclosed

On April 16, 2018 Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported the additional information from the Company’s successfully completed Phase 2 clinical trial of Brilacidin-OM (see NCT02324335) for the indication of decreasing the incidence of Severe Oral Mucositis (SOM) (WHO Grade ≥3) in Head and Neck Cancer (HNC) patients receiving chemoradiation (Press release, Innovation Pharmaceuticals, APR 16, 2018, View Source [SID1234525346]).

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These additional data align with previously released Brilacidin-OM results showing a risk reduction in the incidence of SOM, including up to an 80.3% risk reduction in the incidence of SOM among patients receiving more aggressive chemotherapy. Other previously released results indicate Brilacidin-OM also delayed onset of SOM. The Company is developing Brilacidin-OM under FDA Fast Track designation as a convenient, and clearly differentiated, therapy aimed to decrease incidence of SOM.

Secondary Endpoint: Duration of SOM

Brilacidin outperformed placebo in both the Initial Instance Duration of SOM and the Overall Duration of SOM, as shown below.

Exploratory Endpoint: Unplanned Office Visits, Emergency Department Visits, and/or Hospital Admissions Due to OM
Positive OM assessment endpoints are additionally supported by zero (0) of the patients in the Brilacidin-OM group having unplanned office visits, ED visits, or hospital admissions due to OM, compared to four (4) patients in the placebo group.

Other Study Observations
·Regardless of the oral sites irradiated (at least two sites from: buccal mucosa, floor of mouth, ventral/lateral tongue, and soft palate), the incidence by patient of Severe OM on Brilacidin-OM relative to placebo was consistently reduced.

·Across cumulative radiation dose intervals, patients in the Brilacidin-OM group consistently reported less often feeling the sensation "swollen" (approximately half of that reported for the placebo group). "Burning" sensation also was reported consistently less frequently in the Brilacidin treatment group.

· Patients in the Brilacidin-OM group appeared to trend more favorably over the course of chemoradiation treatment according to Eastern Cooperative Oncology Group (ECOG) Performance Status—a common set of criteria used in oncology trials to assess debility.

On April 16, 2018 Idera Pharmaceuticals, Inc. ("Idera") (NASDAQ:IDRA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel oligonucleotide therapeutics for oncology and rare diseases, reported it has entered into a clinical development support agreement with Pillar Partners Foundation ("Pillar Partners") (Press release, Idera Pharmaceuticals, APR 16, 2018, View Source [SID1234525345]). Under the terms of the agreement Pillar Partners will provide direct funding to support three investigator initiated clinical trials to further strategically expand the clinical research of IMO-2125, Idera’s toll-like receptor ("TLR") 9 agonist into broader melanoma populations and other solid tumors. For these trials, Idera will provide IMO-2125. Idera is currently enrolling a Phase 3 ("ILLUMINATE-301") trial of intratumoral administration of IMO-2125 in combination with ipilimumab in patients with anti-PD-1 refractory metastatic melanoma.

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The three trials within the terms of this agreement are:
A Phase 1/2 open label study of intratumoral IMO-2125 in combination with intratumoral ipilimumab and IV nivolumab in a protocol open to multiple tumor types including non-small cell lung cancer ("NSCLC"), melanoma, squamous cell carcinoma of the head and neck and urothelial carcinoma. The principal investigator initiating this trial is Aurélien Marabelle, MD, PhD, Clinical Director of the Cancer Immunotherapy Program at Institut Gustave Roussy, Villejuif, France.

A Phase 2 study of intratumoral IMO-2125 in combination with IV pembrolizumab in patients with NSCLC. The principal investigator initiating this trial is Arafat Tfayli, MD, FRCP, Professor of Clinical Medicine, Director of Research, NK Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon.

A Phase 2 placebo controlled study of intradermal administration of IMO-2125 in patients with T3/T4 primary melanoma scheduled to undergo a combined re-excision and sentinel node biopsy procedure. The principal investigators initiating this trial are Bas Koster, MD, Fons van den Eertwegh MD, PhD, and Tanja de Gruijl, PhD, who is Professor of Translational Tumor Immunology and Co-Director of the Cancer Immunology Program at the VU University Medical Center, Cancer Center Amsterdam, The Netherlands.
"We are eager to expand our knowledge and understanding of the various cancer types and combinations in which IMO-2125 can play a significant role in improving outcomes beyond our current registrational focus with our ILLUMINATE 301 program," stated Joanna Horobin, M.B., Ch. B., Idera’s Chief Medical Officer. "We look forward to working with these investigators to provide the support they need to initiate these trials before the end of the year," said Shah Rahimian, MD, Idera’s Oncology Medical Lead. "
"We have long believed and understood that the mechanism for IMO-2125 has broad potential and plays a central role in IO combinations beyond PD-1 refractory melanoma and through this financial grant, we are able to help light the spark to further expand our ability to test this hypothesis in multiple tumor types with expert clinical investigators," stated Youssef El Zein, Managing Partner, Pillar Invest Corporation.