On December 12, 2018 Generex Biotechnology Corporation (OTCQB:GNBT) reported that the FDA had reviewed the company’s investigational new drug (IND) application and given notification that the study can proceed (Press release, Generex, DEC 12, 2018, View Source [SID1234532037]). The study: A Phase II Clinical Trial of Pembrolizumab (Keytruda) in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer, is sponsored by Generex and conducted under a collaboration agreement with Merck and a clinical trial agreement with the NSABP Foundation, Inc. (NSABP).

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The combination study builds on previous clinical studies of both AE37 and Keytruda. AE37, a cancer vaccine, was the subject of a 300 patient prospective, randomized and single-blinded Phase II study in patients with breast cancer. That study showed a strong trend toward reduced relapses,particularly in patients with triple negative breast cancer. Keytruda also has shown encouraging results in patients with triple negative breast cancer when used as monotherapy. The complementary mechanisms of action of the two drugs suggest the combination may have the potential to be better than either alone.

AE37 is unique among therapeutic cancer vaccines in that it ensures specific activation of CD4+ T helper cells, which are critical in generating an effective immune response. Its improved immunological potency, along with an excellent safety profile, offers particular advantages for combination studies. In addition to the Phase II study in breast cancer patients, AE37 also has been tested in a Phase I study in prostate cancer patients. AE37 treated patients have consistently displayed a robust, long-lasting and specific response to the vaccine.

Liesha Emens, M.D., Ph.D., Principal Investigator for the study and Professor of Medicine at the University of Pittsburgh Medical Center commented: "So far, metastatic triple negative breast cancer patients treated upfront with immunotherapy benefit clinically from immune checkpoint immunotherapy only if their tumors contain PDL1+ cells. Increasing the number of patients with immune-activated tumors should bring the benefit of immunotherapy to even more patients. This Phase II trial will test whether the AE37 vaccine may trigger immunity in triple negative breast cancer patients, priming them for clinical benefit from immune checkpoint blockade."

Eric von Hofe, President of NuGenerex-ImmunoOncology commented: "We are gratified to see this important trial moving forward. While we have tested AE37 in breast and prostate cancer patients, there is good rationale for inclusion of AE37 in the treatment regimen of a variety of additional cancer types of high unmet need. Gastric, colon, ovarian and bladder cancers all express the same tumor target expressed in breast and prostate cancer that AE37 activates the immune system to recognize."

About AE37

AE37 is an investigational therapeutic cancer vaccine being developed to treat certain types of breast cancer. It is a combination of portions of two proteins that together stimulate the immune system to fight cancer cells.

Up to 80 percent of breast cancers express some level of a protein called HER2. While treatments exist to target HER2 in breast cancer patients with the highest level of HER2 expression (roughly 25%), the majority of patients who have lower levels of expression have more limited treatment options. AE37 consists of a protein derived from the HER2 protein combined with a portion of the MHC class II associated invariant chain which has been termed Ii-Key.

AE37 does not directly target HER2, but rather acts as a vaccine to activate the immune system to recognize the HER2 protein, which is expressed on cancer cells as foreign. AE37 ensures activation of CD4-positive lymphocytes, immune cells that are important in stimulating both the antibody response (antibodies against HER2) and cellular responses directed against the HER2 protein in breast cancer cells. The Ii-Key peptide is coupled with the HER2 protein to ensure a more robust and long-lasting response.

On December 12, 2018 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported that it has commenced an underwritten public offering of its common shares (Press release, VBI Vaccines, DEC 12, 2018, View Source [SID1234532101]). VBI also intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of common shares offered in the public offering. The offering is subject to market and other conditions and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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BMO Capital Markets, Canaccord Genuity LLC, and Oppenheimer & Co. Inc. are acting as joint book-runners for the underwritten public offering.

VBI intends to use the net proceeds from the offering to progress its research and development programs, which include, among other things, funding the continued clinical development of Sci-B-Vac, including the ongoing Phase 3 clinical program in the United States, Europe and Canada; the Phase 1/2a clinical study of the therapeutic vaccine candidate, VBI-1901, for glioblastoma (GBM); the prophylactic vaccine candidate, VBI-1501, for cytomegalovirus (CMV); and the immuno-therapeutic candidate, VBI-2601, for hepatitis B. The net proceeds will also be used for general corporate purposes, including working capital and capital expenditures.

A shelf registration statement relating to the common shares was previously filed with the Securities and Exchange Commission (the "SEC") and declared effective on June 8, 2017. A preliminary prospectus supplement and accompanying prospectus relating to the underwritten public offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement (when available) and accompanying prospectus may be obtained from BMO Capital Markets Corp., Attention: Equity Syndicate Department, 3 Times Square, 25th Floor, New York, NY 10036 or by e-mail at [email protected], or from Canaccord Genuity LLC, Attention: Equity Syndicate Department 99 High Street, 12th Floor, Boston, MA 02110 or by e-mail at [email protected], or from Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, NY 10004 or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction. Any offer, if at all, will be made only by means of the prospectus supplement and accompanying prospectus forming a part of the effective registration statement.

The securities will not be offered or sold, directly or indirectly, in Canada or to any resident of Canada.

On December 12, 2018 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that Aron Knickerbocker, Chief Executive Officer, will present at the 37th Annual J.P. Morgan Healthcare Conference, Wednesday, January 9, 2019 at 2:00 pm PT (Press release, Five Prime Therapeutics, DEC 12, 2018, View Source [SID1234532039]).

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The presentation will be webcast and may be accessed at the "Events & Presentations" section of the Company’s website at View Source Five Prime will maintain an archived replay of the webcast on its website for 30 days after the conference.

On December 12, 2018 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported highlights from a Key Opinion Leader (KOL) breakfast featuring a presentation by Brian Druker, M.D., Professor of Medicine at the School of Medicine at Oregon Health & Science University (OHSU), Director of OHSU’s Knight Cancer Institute, and Aptose management team (Press release, Aptose Biosciences, DEC 12, 2018, View Source [SID1234532023]).

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The webcast of the presentation will be archived on Aptose’s website here.

William G. Rice, Ph.D., Chairman, President and Chief Executive Officer, first provided a recap on CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor, and included the following key highlights:

CG-806 has a well-differentiated mechanism of action, selectively and potently inhibiting kinase clusters that include all forms of FLT3 and BTK, as well as rescue pathways that can allow resistance to other drugs, and avoiding other kinase clusters associated with toxicity
CG-806 demonstrated superior potency on acute myeloid leukemia (AML) patient cells relative to all other FLT3 inhibitors
CG-806 demonstrated superior potency on B-cell patient cells relative to ibrutinib
In preclinical mouse model studies, CG-806 induced rapid and sustained tumor eradication with no observed toxicity
CG-806’s safety profile remains clean: New results, recently presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting from 28-day GLP toxicity and toxicokinetic studies, continue to demonstrate a highly favorable safety profile with no adverse findings to date
Dr. Druker discussed the evolution of kinase inhibitors as anticancer drugs, reviewed the current treatment landscape in AML and B-cell cancers, emphasizing the medical needs for these patient populations, and highlighted his experience with CG-806 alone and in combination to potentially address these medical needs. Key highlights:

CG-806 potently killed primary malignant cells from patients with diverse hematologic malignancies
CG-806 demonstrated superior killing potency on cells from AML patients compared to five other FLT3 inhibitors
AML patient cells with the FLT3-ITD mutation, found in approximately 30% of AML patients, were highly sensitive to CG-806
Just presented at ASH (Free ASH Whitepaper), AML patient cells with the IDH-1 mutation were unexpectedly sensitive to CG-806, a new finding that further broadens CG-806’s potential use and potential paths for rapid development
CG-806 data demonstrated broad and superior killing potency compared to ibrutinib, which is the current standard of care for B-cell malignancies, on cells from patients with CLL and other B-cell cancers
Drug combination studies with CG-806 and venetoclax on patient bone marrow cells suggest the combination may become the preferred drug combination for patients with AML, CLL, ALL and other hematologic malignancies
"CG-806 is unlike any molecule we have investigated, and it is more than just a FLT3 and BTK inhibitor," said Dr. Druker. "806 has the unusual ability to suppress key driver and rescue pathways and overcome the resistance that develops with other kinase inhibitors, and it has demonstrated potent activity against actual primary cells from patients with hematologic malignancies. We are hopeful that clinical testing will prove it to be a new treatment for a patient population in need of new options."

Stephen B. Howell, M.D., Professor of Medicine at the University of California, San Diego, and Associate Director for Clinical Research at the Moores UCSD Cancer Center, who serves as Aptose’s Acting Chief Medical Officer, wrapped up the prepared remarks of the session with current development plans for CG-806:

IND-enabling GLP toxicology and safety studies with CG-806 are complete
As a result of its robust safety profile, Aptose plans to file an IND in the first quarter of 2019 to begin clinical testing of CG-806 both in healthy volunteers (HVS) and in patients with B-cell malignancies
After a therapeutic dose is identified from the HVS or B-cell malignancy clinical trials, Aptose intends to expand into acutely ill AML patients and other sensitive subpopulations
About CG-806
CG-806 is a preclinical stage oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. It is in development for acute myeloid leukemia (AML) and B cell lymphoma.

Brian J. Druker, M.D.
Brian Druker, M.D., is the director of the Knight Cancer Institute, Associate Dean for oncology of the OHSU School of Medicine, JELD-WEN Chair of Leukemia Research and a Howard Hughes Medical Institute investigator. He revolutionized the treatment of cancer through research that resulted in the development of imatinib, the first drug to target the molecular defect of a cancer while leaving healthy cells unharmed. Marketed under the name Gleevec, his discovery turned a once-fatal cancer, chronic myeloid leukemia, into a manageable condition. This work changed the life expectancy of patients with CML from an average of 3 to 5 years to a 95% five-year survival, and has resulted in a paradigm-shift in cancer treatment from non-specific chemotherapy to highly targeted therapeutic agents. He is a member of the National Academy of Medicine, the National Academy of Sciences and, among numerous awards, is the recipient of the 2009 Lasker-DeBakey Clinical Medical Research Award and most recently, the 2018 Tang Prize in Biopharmaceutical Science.

Dr. Druker currently serves as the Chair of the Scientific Advisory Board for Aptose. He receives compensation from Aptose for this role. He and his team at OHSU, through the BEAT AML collaboration, have directly conducted studies with CG-806 on fresh bone marrow samples from patients with various hematologic malignancies, and data from these studies serve as the cornerstone of presentations made by Aptose Biosciences.

On December 12, 2018 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that the first patient was treated in a phase 1 dose escalation study combining pelareorep and carfilzomib with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) to treat relapsed multiple myeloma patients (Press release, Oncolytics Biotech, DEC 12, 2018, View Source [SID1234532025]). This study is based on findings from the NCI 9603 multiple myeloma study that combined pelareorep with carfilzomib that resulted in objective responses, elimination of multiple myeloma cells and most importantly, an inflamed phenotype with PD-L1 overexpression.

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"Having worked with pelareorep in multiple myeloma and understanding its ability to act as a potentiator of checkpoint blockade, I’m very excited to work with the Oncolytics team on this study," said Dr. Craig Hofmeister, Associate Professor, Department of Hematology and Medical Oncology Emory University School of Medicine. "Pelareorep has proven its ability to create an inflamed phenotype and its potential for upregulation of PD-1 on tumor-infiltrating lymphocytes. My hope is this study leads not only to an effective combination dosing schedule but provides quantitative data describing the expression of PD-1, along with correlative studies that reveal the roles of both immune-mediated and direct cytotoxic myeloma cell killing."

This open-label, phase 1 study, conducted by Dr. Hofmeister at Emory University, will enroll up to 62 patients to examine the side effects and best dosing schedule of pelareorep when given in combination with dexamethasone, carfilzomib, and nivolumab in treating participants with relapsed multiple myeloma. The primary objectives of the study are to determine the maximum tolerated dose of pelareorep in combination with carfilzomib and nivolumab. Secondary outcome measures include time to progression, progression-free survival and overall survival, as well as the characterization of an inflamed phenotype and confirmation of biomarker responses indicative of tumor inflammation.

"We now have our second checkpoint inhibitor combination study enrolling, and I’m excited for the potential of the immune and biomarker data to come from it," said Dr. Rita Laeufle, Chief Medical Officer of Oncolytics Biotech. "These studies, along with our soon to be initiated studies combining pelareorep with Merck’s Keytruda, also in multiple myeloma, and Roche’s Tecentriq in neoadjuvant breast cancer, will provide further evidence that pelareorep has the potential to expand the use of checkpoint inhibitors by priming tumors cells. The confirmation of our predictive biomarkers enhances the likelihood of success in registrational studies, thereby reducing both clinical and commercial risk making pelareorep more attractive to potential partners."

For more information about the study, including a comprehensive list of inclusion and exclusion criteria, please visit: www.clinicaltrials.gov (identifier: NCT03605719).

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.