On June 22, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the results from a small trial of just 18 rectal cancer patients in complete remission using an immunotherapy called dostarlimab are "impressive," whilst acknowledging there’s more work to be done (Press release, Propanc, JUN 22, 2022, View Source [SID1234616184]). Chief Scientific Officer and Co-Founder, Dr Julian Kenyon MD, MB, ChB, believes that the field’s biggest challenge remains that immunotherapies work inconsistently across cancers. Oncologists estimate a response rate of 20% across cancer types, according to the Wall Street Journal ("WSJ"). The drugs can wipe out cancers from some people, but fail to work for others. It is also uncertain whether the cancer may eventually return once a patient is in remission, even after a prolonged period of time.

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Immunotherapies like dostarlimab, known as a checkpoint inhibitor, seek to inhibit key regulators of the immune system that when stimulated, reduces the body’s immune response to fight cancer. Given that immunotherapies target specific gene sequences, it often means they can encounter resistance, due to mutations that occur and genetic variation even within the primary tumor of a patient. As a result, Dr Cercek, from Memorial Sloan Kettering, who conducted the study for dostarlimab, estimates only 10% of rectal cancer patients and about 4% of all cancers will respond to treatment, according to the WSJ.

"For many cancers, multiple factors can drive growth, making it hard to effectively match one biomarker, or a particular gene sequence, to a single drug. On the other hand, a therapeutic approach like our lead product candidate, PRP, which alters the characteristics of the cancer cell, by enforcing it to express proteins it normally wouldn’t, means the treatment is less likely to encounter resistance through mutations, which is what we have observed in the lab as well as in clinical practice," said Dr Julian Kenyon.

In addition to specifically selecting the 18 rectal cancer patients according to their genetic biomarker, the trial included patients that were pre-metastatic, where tumors were locally advanced in one area, but not spread to other organs. This means patients identified with metastatic cancer were excluded from the trial. Therefore, the treatment and prevention of metastatic cancer, the main cause of patient death for sufferers, still remains the unsolved, final frontier. Cancer stem cells, which are the cells responsible for spreading to other parts of the body, remains a key focus for Dr Kenyon.

Dr Kenyon said, "PRP is a proenzyme treatment that targets and eradicates cancer stem cells by altering multiple pathways of a cancerous cell rather than a single genetic sequence. We’ve observed that once they are treated with PRP, the effects are irreversible and are more easily recognizable by the immune system, therefore potentially improving the response rates of standard approaches like immunotherapy, to overcome advanced cancers. We look forward to testing the utility of PRP with these approaches as we further advance into the clinic."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

On June 22, 2022 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to MB-106, Mustang’s CD20-targeted, autologous CAR T cell therapy for the treatment of Waldenstrom macroglobulinemia ("WM" or "Waldenstrom"), a rare type of B-cell non-Hodgkin lymphoma ("B-NHL") (Press release, Mustang Bio, JUN 22, 2022, View Source [SID1234616183]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch") to treat patients with relapsed or refractory B-NHLs and chronic lymphocytic leukemia ("CLL").

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The FDA grants Orphan Drug Designation to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers. If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are very pleased to receive Orphan Drug Designation from the FDA, as it is an important regulatory milestone for Mustang’s MB-106 program for the treatment of Waldenstrom macroglobulinemia, a rare B-NHL with a significant unmet medical need. We look forward to dosing the first patient in our multicenter Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and CLL under Mustang’s IND shortly. In the Phase 1 portion of this trial, MB-106 dose escalation will proceed in three separate arms, and Waldenstrom patients will be included in the indolent lymphoma arm in parallel with accrual of patients to the aggressive lymphoma and CLL arms."

MB-106 data presented earlier this month at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress continue to demonstrate high efficacy and a very favorable safety profile across all five dose levels. The overall response ("ORR") was 96% across all dose levels and all indications (n=26). In particular, the 100% complete response rates by PET scan of patients with WM (n=2) as well as of patients with B-NHL previously treated with CD19-directed CAR T cell therapy (n=2) underscore the potential for MB-106 to treat these patient populations with high unmet needs. Durable responses were observed in a wide range of hematologic malignancies including follicular lymphoma, CLL, diffuse large B-cell lymphoma and WM. The possible outpatient administration of this therapy makes it potentially even more compelling. Currently no CAR T therapy is specifically approved for WM.

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

About Waldenstrom Macroglobulinemia
Waldenstrom macroglobulinemia ("WM"), also known as lymphoplasmacytic lymphoma, is a rare type of non-Hodgkin lymphoma ("NHL"), a malignant disorder of the bone marrow and lymphatic tissues. The proliferation of cancer cells can crowd out normal cells in these tissues, leading to low levels of red blood cells, white blood cells, and platelets which, in turn, causes fatigue, shortness of breath, infections, bruising, and bleeding. In addition, the cancer cells make large amounts of the large antibody protein immunoglobulin M, or IgM, which cause the blood to become thick. This hyperviscosity of the blood affects its flow through the smaller blood vessels, leading to some of the other manifestations of the disease, such as visual and neurological symptoms. WM is a rare disorder with an incidence of approximately 3 per million people per year, and 1,400 new cases are diagnosed in the U.S. each year. The median age at diagnosis is 70 years.

About MB-106 (CD20-targeted autologous CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody. MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch will be used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial that is now open to enrollment under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on these trials can be found at View Source using the identifier NCT05360238 for the Mustang multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch.

On June 22, 2022 ProMIS Neurosciences Inc. (TSX: PMN) (OTCQB: ARFXF) ("ProMIS" or the "Company"), a biotechnology company focused on the discovery and development of antibody therapeutics targeting misfolded proteins such as toxic oligomers, implicated in the development of neurodegenerative diseases, reported that it has amended its articles to authorize the issuance of 70,000,000 Series 1 Preferred Shares ("Series 1 Shares") which it intends to use in settlement of its outstanding debentures (Press release, ProMIS Neurosciences, JUN 22, 2022, View Source [SID1234616182]).

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Holders of Series 1 Shares will be entitled to participate, on an as-converted basis, in dividend payments only if the Company declares, pays or sets aside any dividends on shares of any other class or series of capital stock. The Series 1 Shares are not subject to mandatory redemption or other redemption provisions and do not confer any voting rights or privileges to the holders. Holders of the Series 1 Shares shall be entitled to a liquidation preference in an amount per share equal to US$0.10.

Series 1 Shares are convertible at the option of the holder, in a 1:1 ratio, into the Company’s Common Shares ("Common Shares"). All outstanding Series 1 Shares shall automatically convert into Common Shares, at the effective conversion rate, upon the closing of one or more sales of equity securities resulting in at least US$30 million of gross proceeds to the Company.

On June 22, 2022 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for VBI-1901, a bivalent gB/pp65 immunotherapeutic vaccine candidate for the treatment of glioblastoma (GBM) (Press release, VBI Vaccines, JUN 22, 2022, View Source [SID1234616181]). In June 2021, the FDA also granted Fast Track Designation for VBI-1901 for the treatment of recurrent GBM in patients with first tumor recurrence.

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"This orphan drug designation is another significant milestone for our VBI-1901 program, and it underscores the urgency of our effort to develop meaningful new treatment options for patients with this devastating cancer," said Jeff Baxter, President and CEO of VBI. "As recently presented at ASCO (Free ASCO Whitepaper), we continue to see strong tumor response data and improvements in overall survival data compared to historical controls in the Phase 2a study of VBI-1901. With this orphan drug status, we look forward to working closely with the FDA and clinical investigators to build on that data, advancing the potential of this program to be a valuable part of the fight against GBM."

Though classified as a rare disease, GBM is the most common primary brain cancer with approximately 14,000 new cases diagnosed in the United States each year, and a low median overall survival of 15-18 months after diagnosis of primary GBM.1 Glioblastomas are stage IV brain tumors – they are an exceptionally aggressive form of brain cancer, with high recurrence rates and a five-year survival rate around 10%.2 Standard of care in the frontline setting includes surgical resection, chemotherapy, and radiation therapy. There is no effective standard of care in the recurrent setting – median overall survival in this patient population is approximately eight months.3

About FDA Orphan Drug Designation

The FDA’s Office of Orphan Products Development grants orphan drug designation to investigational drugs and biologics intended to prevent, diagnose, or treat rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for qualified clinical trials, exemptions from certain FDA fees, and the potential for seven years of post-approval marketing exclusivity.

About FDA Fast Track Designation

The Fast Track program facilitates the expedited development and review of new drugs or biologics that are intended to: 1) treat serious or life-threatening conditions, and 2) demonstrate the potential to address unmet medical needs. A therapeutic that receives Fast Track Designation is eligible for some or all of the following: 1) more frequent meetings with FDA to discuss the development plan and data needed to support approval, 2) more frequent written communication from FDA relating to the design of the proposed clinical trials and use of biomarkers, 3) Accelerated Approval and Priority Review, if relevant criteria are met, and 4) Rolling Review, which means the company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, instead of waiting until all sections of the application are completed.

Fast Track Designation was granted to VBI-1901, adjuvanted with granulocyte macrophage colony-stimulating factor (GM-CSF), for the treatment of first-recurrent GBM in June 2021.

About VBI-1901 and GBM

VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 14,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality.

To learn more about VBI’s ongoing Phase 1/2a study and the INSIGhT trial, visit clinicaltrials.gov (Respective Identifiers: NCT03382977 and NCT02977780).

On June 22, 2022 TriSalus Life Sciences, an immunotherapy company on a mission to extend and improve the lives of patients with liver and pancreatic tumors, reported that highlighted a series of updates from clinical and pre-clinical studies that help support the company’s immunotherapy platform approach for treating liver and pancreatic tumors (Press release, TriSalus Life Sciences, JUN 22, 2022, View Source [SID1234616180]).

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Since acquiring its first therapeutic candidate in 2020, TriSalus has initiated two Phase I clinical trials and numerous pre-clinical studies with leading cancer institutes across the U.S. These studies are evaluating the company’s immunotherapy platform, which integrates an investigational class C TLR9 agonist, SD-101, and the proprietary Pressure-Enabled Drug Delivery (PEDD) method of administration to overcome critical treatment barriers that can prevent immunotherapeutic uptake in hard-to-treat tumors.

"Patients with liver and pancreatic tumors can experience poor outcomes due to tumor-induced immunosuppression and high intratumoral pressure that often prevent therapeutics, such as immunotherapy drugs, from reaching their targets. Existing treatment approaches, including direct needle injections and intravenous immunotherapy alone, often fail to address these barriers in a comprehensive way. By engineering new approaches to meet these challenges, we may be able to improve the treatment paradigm for liver and pancreas tumor patients," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus.

Dr. Katz continued, "The TriSalus immunotherapy platform combines the well-studied, investigational immunotherapy, SD-101, administered via PEDD, an innovative vascular delivery method leveraged by FDA-cleared devices. Pre-clinical and early clinical data from studies examining this novel approach are promising and give us hope that we will be able to offer liver and pancreas tumor patients a better chance of responding more reliably to immunotherapy. While our approach is highly innovative, the delivery technology has been used in over 16,000 cases and SD-101 has been studied through Phase 2 trials in other indications. As such, we are building upon reassuring safety data for both SD-101 and PEDD and hope that, by integrating the two into a single platform, we can enable better responsiveness to systemic immunotherapy."

Clinical Development Update for Liver and Pancreas Immunotherapy Platform

Pressure-Enabled Regional Immuno-Oncology (PERIO-01) Clinical Study

In June, the Pressure-Enabled Regional Immuno-Oncology (PERIO-01) clinical trial’s Principal Investigator, Dr. Sapna Patel, an Associate Professor and Director of the Uveal Melanoma Program and Melanoma Fellowship Program at the University of Texas MD Anderson Cancer Center, delivered an oral presentation at the 20th Congress of the International Society of Ocular Oncology. During this presentation, Dr. Patel discussed the innovative approach being taken in the PERIO-01 trial and reviewed early data that supports the safety of SD-101 and immunologic effects within liver tumors at various dose levels.

The PERIO-01 clinical trial (NCT04935229) seeks to evaluate whether the TriSalus immunotherapy platform approach can improve the performance of systemic checkpoint inhibitors in patients with uveal melanoma with liver metastases, a rare form of eye cancer that frequently spreads to the liver. The clinical trial is underway at leading academic medical centers, including MD Anderson Cancer Center, Columbia University Irving Medical Center, Thomas Jefferson University Hospital, Massachusetts General Hospital, and University of Pittsburgh Medical Centers. Since enrollment of the first patient in the PERIO-01 trial, TriSalus has fully enrolled patients at four dose levels in Cohort A, which is evaluating the safety of SD-101, and started enrollment for Cohort B to evaluate the safety of SD-101 in combination with nivolumab, a checkpoint inhibitor.

Early data from the PERIO-01 study, also presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Tumor Immune Microenvironment Workshop, suggest SD-101 delivered via PEDD has enabled immunologic activity within the liver metastases’ tumor microenvironment in metastatic uveal melanoma patients. This data bolsters evidence that suggests this integrated approach may support better immune checkpoint inhibitor performance in uveal melanoma patients and other intrahepatic indications, within the liver and potentially at other disease sites. These clinical data resonate well with a newly published pre-clinical study in Cancer Gene Therapy that suggests administering a class C TLR9 agonist via PEDD can improve responsiveness to systemic checkpoint inhibition for liver tumors through elimination of a highly immunosuppressive cell type known as myeloid derived suppressor cells (MDSC).

Pressure-Enabled Regional Immuno-Oncology (PERIO-02) Clinical Study

In May, TriSalus announced the first patient enrolled in its second immunotherapy platform study, PERIO-02 (NCT05220722). The trial is evaluating SD-101 in adults with locally advanced, metastatic, or unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Since then, TriSalus has fully enrolled patients in the first dose level of Cohort A, which is evaluating the safety of SD-101 in this patient population. The trial was initiated at MD Anderson Cancer Center with additional sites planned. Cohort B is expected to open over the summer and will test SD-101 via PEDD in combination with systemic pembrolizumab, a checkpoint inhibitor. Importantly, testing the therapeutic platform of SD-101 delivered via PEDD across multiple indications to enable systemic checkpoint inhibition has the potential to provide data to support the broad application of this innovative approach for patients with liver or pancreas tumors.

Pre-Clinical Studies Leveraging Proprietary Infusion Technology

TriSalus’ clinical leadership team also recently presented new pre-clinical data at the Society of Interventional Radiology (SIR) 2022 Annual Scientific Meeting. In one abstract presentation, TriSalus highlighted data that suggests the PEDD method was more effective in delivering SD-101 into liver tissue than direct needle injection. To further support these findings, TriSalus is collaborating with Massachusetts General Cancer Center on an investigator-initiated clinical trial (NCT05128032) to evaluate whether PEDD improves the delivery of radioactive microspheres during radioembolization treatment for liver cancer, compared to a standard microcatheter.

In a second abstract presentation at SIR 2022, TriSalus highlighted new data on the development of a trans-venous approach for the regional treatment of pancreatic tumors, called pancreatic retrograde venous infusion (PRVI). This pre-clinical data is the first of its kind to demonstrate that the PRVI approach can improve uptake and tumor response for pancreatic tumors. Unlike the liver, using the arterial systemic for drug delivery in the pancreas poses significant anatomic challenges. TriSalus has developed a novel approach to leverage the PEDD method in venous branches using a new FDA-cleared device designed for highly targeted intra-pancreatic delivery of SD-101.

Expanded Strategic Research Collaborations

TriSalus has also announced several strategic collaborations with top-tier cancer institutions and research centers to further efforts to develop innovative treatment options. In January, TriSalus announced a three-year strategic research collaboration with the University of Colorado Anschutz Medical Campus to advance research of immuno-oncology treatments for patients with liver and pancreatic tumors, and in April, the company shared it is developing a new immunotherapeutic research laboratory on the campus of Lifespan Health System to further develop its therapeutic platform. These announcements build upon the strategic research collaboration established in 2021 with the University of Texas MD Anderson Cancer Center to evaluate TriSalus’ platform approach for the treatment of liver and pancreatic tumors.