On August 17, 2020 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company") reported that all proposals related to the proposed merger between DelMar and Adgero were approved by DelMar’s stockholders at a special meeting held on August 14, 2020 (Press release, DelMar Pharmaceuticals, AUG 17, 2020, View Source [SID1234563744]). The holders of a majority of the outstanding shares of common stock of Adgero have also issued their written consent approving the merger. The proposed merger remains subject to further customary closing conditions. DelMar expects the closing of the merger to occur in August 2020.

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Upon closing of the transaction, the combined company will change its name to "Kintara Therapeutics, Inc." and it is anticipated that the shares will commence trading on the Nasdaq Capital Market under the ticker symbol "KTRA."

The final voting results for DelMar’s special meeting of stockholders will be filed with the Securities and Exchange Commission in a Form 8-K.

On August 17, 2020 Immunomedics, Inc. (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported that the U.S. Food and Drug Administration (FDA) has approved the Prior Approval Supplement (PAS) for Samsung Biologics to produce commercial-scale hRS7, the antibody used in Trodelvy (sacituzumab govitecan-hziy), at its manufacturing facilities in Incheon, South Korea (Press release, Immunomedics, AUG 17, 2020, View Source [SID1234563743]).

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"We want to thank the FDA for working collaboratively with us in expediting this PAS approval in the midst of the COVID-19 pandemic," said John Stubenrauch, Senior Vice President of Global Product Supply. "This approval enhances our ability to supply commercial product to the U.S. market, where the unmet need across our lead indications is very high. We have been using drug product that were produced with antibody manufactured by Samsung in clinical trials in the U.S. over the course of 2020, and we now look forward to further scaling our commercial supply of Trodelvy globally."

Trodelvy is the first ADC the FDA has approved for the treatment of people with metastatic triple-negative breast cancer. It contains the hRS7 antibody that binds to Trop-2, a cell-surface protein expressed in many solid cancers, and helps Trodelvy deliver the anti-cancer drug, SN-38, to kill the cancer cells.

"The Samsung partnership highlights our overall strategy to scale our supply chain and help ensure we can meet our commitments to patients globally as we seek to broaden the availability of Trodelvy geographically and across tumor types," commented Dr. Behzad Aghazadeh, Executive Chairman of Immunomedics.

On August 17, 2020 Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing that enables in vitro diagnostics, pre-clinical nucleic acid-based therapeutic drug candidates, supply chain security, anti-counterfeiting and anti-theft technology, reported that it has filed a nonprovisional patent application with the United States Patent and Trademark Office (USPTO) entitled "Methods and Systems of PCR-Based Recombinant Adeno-Associated Virus (AAV) Manufacture" (the "Patent") (Press release, Applied DNA Sciences, AUG 17, 2020, View Source [SID1234563742]). The Patent claims priority to a previously filed provisional patent application filed with the USPTO in August of 2019.

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AAV is utilized to deliver a therapeutic gene of interest to a patient or a patient’s cells to cause the expression of the necessary protein to address a targeted disease. Reflective of its potential as one of the most promising delivery vehicles for genetic medicines, there are approximately 80 active or enrolling clinical trials that utilize AAV. With its new patent application, Applied DNA seeks to leverage its LinearDNA platform to give gene and redirected cell therapy developers the ability to greatly improve the manufacture and quality of their AAV-vectored medicines that have the potential to address many diseases, including COVID-19.

"AAV is generally accepted as the preferred vector for gene therapy, and so, has an enormous breadth as a therapeutic gene delivery system. AAV vectors are manufactured utilizing multiple plasmid DNAs as starting materials, and as the number of gene therapy programs increase, and with improving levels of clinical success and progression of therapies into late-phase clinical studies, the field is being challenged by the need for larger manufacturing scales," said Dr. James A. Hayward, president and CEO of Applied DNA Sciences. "At Applied DNA, we believe we have solved the linear DNA production challenge and can make the DNA sequences at scale for gene therapies. Utilizing our LinearDNA platform to manufacture amplicons, we can deliver gene therapy constructs that potentially lower the risks that come with the use of plasmid-based AAV manufacture. As one of the only companies in the marketplace commercializing a scaled linear DNA manufacturing platform, we believe we are uniquely positioned to deliver linear DNA as an alternative to plasmids, and with this patent filing, we expand our addressable market to including AAVs."

AAV is manufactured by the triple transfection of three plasmid DNA constructs into packaging cell lines to produce recombinant adeno-associated virus. This triple transfection requires large amounts of DNAs that are currently manufactured via plasmids – circular DNA constructs which are propagated in bacteria. The three DNA constructs necessary for successful AAV production are: (i) AAV Rep and Cap; (ii) AAV Helper; and (iii) the therapeutic cargo (transgene) flanked on either side by inverted terminal repeat sequences (ITR). The manufacture of plasmid DNA for the production of AAV, however, presents a number of significant challenges, including scalability, fidelity, mis-incorporation of plasmid-derived DNA sequences, high costs, and long lead times for cGMP production.

Concluded Dr. Hayward, "The ITRs serve as the viral origins of replication and for packaging signals to assemble AAV in the host cell. But the triple transfection of the required plasmids, and in the strict stoichiometries required for AAV assembly, we believe adds enormously to the cost of traditional AAV manufacturing, limiting the availability of many gene therapies. Our success in simplifying the production of the critical plasmid genes for AAV production we believe enable AAV production with minimal or absent plasmids, potentially greatly enhancing production and lowering costs. The use of LinearDNA potentially lowers the risks that come with plasmids, including off-target DNA, contamination by the genes for antimicrobial resistance or other bacterial DNA, endotoxin contamination and the use of antibiotics."

The Patent claims methods for the use of specialized LinearDNATM amplicons, instead of plasmids, to manufacture AAV. The patent also claims methods and systems for the PCR-based manufacturing of AAV transgene constructs flanked on either side by the necessary ITR sequences via the Company’s LinearDNA platform. Due to their complex secondary structures, the ITR sequences necessary for AAV production have historically been very challenging to amplify via PCR. Leveraging the Company’s PCR expertise, the methods and systems claimed in the Patent utilize specialized PCR techniques and primer designs to mitigate the challenges caused by the ITR secondary structures, allowing for the high yield and high-fidelity manufacture of transgene –ITR amplicons.

On August 17, 2020 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that Jarrod Longcor, chief business officer of Cellectar, presented a poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) VIRTUAL MEETING: ADVANCES IN MALIGNANT LYMPHOMA being held August 17-19, 2020 (Press release, Cellectar Biosciences, AUG 17, 2020, View Source [SID1234563740]). The abstract was submitted April 2, 2020.

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The poster, entitled: "CLR 131 Demonstrates 100% Overall Response Rate in Relapsed or Refractory Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom’s Macroglobulinemia (WM): Initial Results from Ongoing Phase 2 trial, CLOVER-1 Study" reviews data from four patients enrolled in the Phase 2a portion of the ongoing Phase 2 CLOVER-1 study of CLR 131. The presentation featured efficacy and safety data highlighting;

-100% overall response rate,
-25% complete response rate,
-75% major response rate (patients achieving partial response or better), and
-Mean duration of response exceeding 17 months (8.4 – 31.7 months); duration of response continues to increase for all patients

The safety profile in these highly pretreated patients with relapsed or refractory LPL/ WM was predictable and adverse events were similar to those observed in previous CLR 131 clinical studies in B-cell malignancies. The predominate treatment emergent adverse event remains cytopenias with all patients recovering. Importantly, no patients experienced adverse events that are frequently associated with treatments prescribed for LPL/WM patients such as atrial fibrillation, peripheral neuropathy, ocular toxicities, bleeding events, liver toxicities, renal toxicities or other "off-target" effects.

"CLR 131’s ability to treat various LPL/WM patients including those who do not respond to or are intolerant of ibrutinib is a potentially important therapeutic advance. The potential for patients to have a long term drug treatment holiday whereby there is no requirement for taking a pill once or twice a day for years is clinically meaningful," said study investigator Sikander Ailawadhi, M.D., Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida.

"The overall product profile and achievement of a complete response as a monotherapy, along with the extended duration of responses in patients that are refractory to at least one prior therapy and have also received multiple lines of treatment is highly encouraging," said Jarrod Longcor. "These patients currently have limited treatment options and CLR 131 may represent an important potentially disease modifying improvement in the LPL/WM treatment paradigm. We plan to initiate our pivotal study and potentially report additional LPL/WM data later this year."

There is currently only one approved drug for the treatment of relapsed or refractory LPL/WM. In May of this year, the U.S. Food and Drug Administration granted Fast Track Designation for CLR 131 in treatment of relapsed or refractory LPL/WM. The company currently continues to enroll patients in the Phase 2b portion of the CLOVER-1 study and plans to initiate a pivotal study in LPL/WM in the fourth quarter of 2020.

About CLOVER 1

The Phase 2 CLOVER-1 study is an open-label study designed to determine the efficacy and safety of CLR 131 in select B-cell malignancies. The CLOVER-1 Phase 2 study completed the Part A dose-exploration portion, conducted in relapsed/refractory (r/r) B-cell malignancies, and is now enrolling in the Part B expansion cohorts evaluating a two cycle dosing regimen that provides approximately 100mCi total body dose of CLR 131 in r/r multiple myeloma (MM) and lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM). Patients with LPL/WM must have received at least two prior treatment regimens, unless ineligible to receive standard agents, and have measurable disease, as defined by either a nodal lesion of > 15 mm, an extranodal lesion of > 10 mm, or measurable IgM. Prior external beam radiation therapy was allowed. The median age of the four LPL/WM patients enrolled in the study was 70 (range 54-81) and included 2 females and 2 males who had a median of two prior regimens (range 1-5). CLR 131 was administered intravenously, up to 30 minutes at total body doses (TBD) of <50mCi, ~50 mCi, and ~75mCi.

A copy of the presentation materials can be accessed on the Events and Presentations section of the Cellectar website once the presentations conclude.

About CLR 131

CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and a Phase 1 dose-escalating clinical study in pediatric solid tumors and lymphomas. The company recently completed a Phase 1 dose-escalation clinical study in r/r multiple myeloma. The FDA granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r diffuse large B-cell lymphoma and Orphan Drug Designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia, neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. CLR 131 was also granted Rare Pediatric Disease Designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Earlier this year, the European Commission granted an ODD for r/r multiple myeloma and most recently, the U.S. Food and Drug Administration granted Fast Track Designation for CLR 131 in lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM) in patients having received two prior treatment regimens or more.

On August 17, 2020 The University of Texas MD Anderson Cancer Center reported that In a Phase II trial led by researchers , the combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, achieved a 51% overall response rate (ORR) in patients with cholangiocarcinoma marked by the BRAF V600E mutation (Press release, MD Anderson, AUG 17, 2020, View Source [SID1234563739]).

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This trial represents the first prospective study for patients with BRAF-mutated cholangiocarcinoma, or bile duct cancer, and suggests this targeted therapy combination could serve as a much-needed treatment option for patients with treatment-resistant advanced disease. The trial results were published today in Lancet Oncology.

"In this study, we saw that the dabrafenib and trametinib combination demonstrates clinical benefit and should be considered as a therapeutic option for these patients ," said lead author Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics. "These findings also reinforce the need for routine testing of BRAF mutations in patients with biliary tract cancers. As we move forward with precision oncology, we’re seeing that alterations present in these rare cancers are actionable and the patients do benefit from targeted therapies."

This study is part of an ongoing Phase II, open-label, multicenter trial testing the efficacy and safety of the combination therapy in patients with a variety of BRAF V600E-mutated rare cancers. The bile duct cohort enrolled 43 patients, all of whom had received at least one prior line of therapy.

Trial participants were 91% Caucasian, 5% Asian (Japanese heritage), 2% Asian (East Asian heritage) and 2% white (Arabic/North African). The median age was 57, with women accounting for 56% and men 44% of participants.

Bile duct cancer is a rare disease diagnosed in about 8,000 people each year in the U.S. Most cases are diagnosed at advanced stages, and thus clinical outcomes are generally poor, with a five-year survival rate below 20%. Standard of care includes surgery, when possible, and chemotherapy.

In patients with advanced disease, median overall survival with chemotherapy treatment is less than one year, so there is a significant unmet need for effective new treatment approaches, explained Subbiah.

Mutations in the BRAF gene are found in 5-7% of those diagnosed with bile duct cancer, and patients with the BRAF V600E mutation are more likely to have poor outcomes. Trials with single-agent therapies targeting BRAF have been effective for treating these patients, but have shown significant toxicities, including secondary malignancies.

However, combining these agents with MEK inhibitors, which act downstream in the same signaling pathway, have proven effective and are FDA-approved for use in other cancer types, including melanoma, lung cancer and anaplastic thyroid cancer. These agents are not currently approved by the FDA to treat cholangiocarcinoma.

In the current trial, the combination therapy achieved an ORR of 51% (22 patients) according to investigator assessments. The median duration of response was 8.7 months, with seven patients seeing an ongoing response beyond 12 months.

Median progression-free survival was 9.1 months and median overall survival was 13.5 months, with 56.4% and 35.8% of patients still alive at 12 months and 24 months, respectively.

All patients experienced at least one adverse event, with the most common being fever, nausea, vomiting, diarrhea and fatigue. Twenty-four patients (56%) experienced a Grade 3 or 4 adverse event, the most common of which was an increase in gamma-glutamyltransferase, an enzyme found in the liver and bile ducts. According to the authors, these side effects were consistent with those seen previously from this combination in other cancer types.

"The trajectory of cholangiocarcinoma is changing rapidly," said co-author Milind Javle, M.D., professor of Gastrointestinal Medical Oncology. "Targeted therapy has made meaningful inroads, and this study is an excellent example of that. This is an important development for patients with cholangiocarcinoma and BRAF V600E mutations, who often have limited treatment options."

This research was supported by GlaxoSmithKline and Novartis. Co-authors from MD Anderson include Milind Javle, M.D., of Gastrointestinal Medical Oncology. A full list of co-authors and disclosures can be found with the full paper here.