On September 19, 2018 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported an update from the ongoing Phase I study of small activating RNA (saRNA) candidate MTL-CEBPA in advanced liver cancer patients (Press release, MiNA Therapeutics, SEP 19, 2018, View Source [SID1234529492]). The Chief Investigator of the trial reported observations of tumour responses in three patients when administered approved liver cancer therapies subsequent to treatment with MTL-CEBPA. These responses corroborate emerging pre-clinical research on the potential for MTL-CEBPA to enhance the benefit of other cancer therapies and to modulate the tumour immune microenvironment. The update from the MiNA clinical trial was presented at the 12th Annual Conference of the International Liver Cancer Association in an oral presentation titled "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a Small Activating RNA (saRNA) Targeting the Transcription Factor C/EBP-α in Patients with Advanced Liver Cancer" in the Novel Targets and Markers session held on Sunday, September 16, 2018.

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"Although these instances are anecdotal, complete responses of tumours are a rarity in primary liver cancer," said Dr. Debashis Sarker, the Chief Investigator of the study and Principal Investigator at the National Institute for Health Research Clinical Research Facility at Guy’s and St Thomas’ and King’s College London. "Observing two patients responding in this manner to approved cancer therapies subsequent to treatment with MTL-CEBPA is very encouraging. I am pleased that MiNA is seeking to modify its ongoing trial to include investigations on the combination in additional patients and I look forward to the opportunity to further evaluate MTL-CEBPA."

In three patients investigators initiated off-study treatment with tyrosine kinase inhibitors, 0 – 3 months after completion of on-study treatment with MTL-CEBPA. Two patients administered with sorafenib experienced confirmed complete tumour responses together with marked decreases in alpha-fetoprotein tumour marker. One of these two patients also experienced resolution of both lung and peritoneal metastases. One patient administered with lenvatinib experienced a partial tumour response. In a published Phase III study of sorafenib as a single agent, complete responses were observed in 0% of patients and partial responses were observed in 2% of patients1. In a published Phase III study of lenvatinib as a single agent, complete responses were observed in 0% of patients and partial responses were observed in 18% of patients based on RECIST 1.1 criteria2.

"These exciting observations by study investigators together with an emerging understanding of the role of CEBPA in the tumour immune microenvironment present the opportunity to evaluate a novel regimen with disease modifying potential," said Robert Habib, CEO of MiNA Therapeutics. "Having characterised in patients the safety, tolerability and saRNA proof of mechanism in a single agent setting, MTL-CEBPA is well positioned for further investigation in combination with other cancer therapies. We are in active discussions with the regulatory authorities to amend our ongoing Phase I trial to include further studies of MTL-CEBPA in combination."

The potential for MTL-CEBPA to enhance the benefits of other cancer therapies is supported by emerging pre-clinical research. In a chemically induced model of cirrhotic hepatocellular carcinoma in rats, treatment of MTL-CEBPA for one week followed by sorafenib for one week demonstrated a significant improvement in anti-tumour activity compared to either two weeks of sorafenib alone or two weeks of MTL-CEBPA alone. Durable activity of MTL-CEBPA for several weeks after treatment was previously demonstrated in pre-clinical models of liver disease3.

In 2017 the National Cancer Institute reported pre-clinical studies demonstrating that loss of function of C/EBP-α resulted in an increase in Myeloid Derived Suppressor Cells (MDSCs) in the tumour immune microenvironment resulting in augmented tumour growth in mouse models of cancer4. MDSCs have been identified as key players in promoting a range of diseases, including in cancer where MDSCs may provide tumours resistance to cancer therapies.

The Phase I clinical trial of MTL-CEBPA is ongoing at multiple sites in the United Kingdom and Asia. Enrolment has been completed evaluating MTL-CEBPA as a single agent. Enrolment is expected to begin in Q4 2018 evaluating MTL-CEBPA in combination with sorafenib. For more information, please contact us at [email protected].

About MTL-CEBPA
MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES liposomal nanoparticle and is designed to activate the CEBPA gene. By restoring CEBPA expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse liver disease in a range of pre-clinical studies including models of liver cancer, liver cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). MTL-CEBPA is currently under evaluation in OUTREACH, a multi centre first-in-human Phase I clinical study in

patients with severe liver cancer. In preliminary results from the OUTREACH study, MTL-CEBPA was generally well tolerated in patients with both healthy and impaired liver function was found to mediate RNAa activity in white blood cells. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov

On September 19, 2018 Abzena, plc (AIM: ABZA, Abzena’), the life sciences group providing services and technologies to enable the development and manufacture of biopharmaceutical products, reported that it has signed an antibody humanisation agreement with Tmunity Therapeutics (Tmunity), a clinical stage T cell therapy company and a leader in the development of new Chimeric Antigen Receptor T Cell (CAR-T) therapies for the treatment of solid and hematological cancers (Press release, Abzena, SEP 19, 2018, View Source [SID1234529491]).

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Under the agreement Abzena will humanize monoclonal antibodies using its Composite Human Antibody technology. This technology combines humanization and deimmunisation technologies to generate fully-humanized therapeutic antibodies devoid of CD4+ T cell epitopes.

Tmunity will use the humanised antibodies to develop CAR-T engineered products. CAR-T therapy is an innovative therapeutic form of personalised medicine in which a patient’s own T-cells are genetically modified to express an antigen recognizing CAR on the surface of the T cell. When the CAR-T encounters a cancer cell expressing the cognate antigen, the CAR-T is activated releasing cytokines that kill the cancer cell. CAR-T therapies have been successfully developed for the treatment of hematological cancers, a success that Tmunity is seeking to duplicate in solid tumors and other hematological malignancies.

The research and license agreement between Abzena and Tmunity also includes developability assessment to assess for any potential sequence liabilities that would affect quality of the product and EpiScreen, Abzena’s ex-vivo immunogenicity assessment platform.

Under the terms of the licence agreement Abzena will also be due milestone payments should products containing any of the humanized antibody sequences reach IND acceptance.

Campbell Bunce, SVP Scientific Operations of Abzena, said:

"We are delighted to be working with such an innovative organisation as Tmunity, to use our Composite Human Antibody platform to help design superior CARs for their CAR-T products. We believe that reducing the risk of immunogenicity of the receptor will contribute to a reduced risk profile for this exciting and potent treatment for cancer."

"Innovative use of our proprietary technology for an emerging and revolutionary drug platform like CAR-T, and utilisation of our protein engineering, immunology and bioanalytics expertise, is a great example of our ability to provide world-class support to our partners."

On September 19, 2018 Aurinia Pharmaceuticals Inc., (NASDAQ:AUPH)(TSX:AUP) reported its Chairman and CEO, Richard Glickman, will present a company overview at two upcoming investor conferences (Press release, Aurinia Pharmaceuticals, SEP 19, 2018, View Source [SID1234529490]).

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The presentations will be webcast live and can be accessed via the investor section of the Aurinia website, www.auriniapharma.com. A replay of each presentation will also be archived on the site following the event.

Monday, October 1, 2018, Aurinia will present at the Cantor Fitzgerald 4th Annual Healthcare Conference in New York City at 8:55am ET.

Tuesday, October 2, 2018, Aurinia will present at the LEERINK Partners Roundtable Series: Rare Disease & Immuno-Oncology in New York City at 3:30pm ET.

On September 19, 2018 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc Biopharma" or the "Company"), a clinical stage biopharmaceutical company focusing on development of new and proprietary treatments for cancer patients suffering from solid tumors, such as pancreatic, ovarian and colorectal cancers, reported the execution of a research collaboration agreement with the University of Jaén, Spain, for the provision of research services and scientific technical advice for the Company’s POP1 drug discovery program (Press release, Propanc, SEP 19, 2018, View Source [SID1234529489]). The goal for the program is to synthesize and develop a backup clinical compound to the Company’s lead product candidate, PRP. The development of the backup compound will be used for treating patients with limited therapeutic options for the treatment of solid tumors,

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The specific objectives for the collaboration include:

The identification of a suitable backup clinical compound to PRP;
The validation of the anti-carcinogenic properties of the new drug candidate through in vitro testing;
The validation of the anti-carcinogenic properties of the new drug candidate through in vivo testing;
The production of the new synthetic drug candidate in compliance with FDA’s "current good manufacturing practice" (cGMP) conditions, in order for it to be used in human trials.
Dr. Macarena Perán Quesada, Professor at the University of Jaén, will be in charge of management and coordination of the working team and will be the scientific consultant in charge of the project run by the University of Jaén. Dr. Perán is the lead author of several scientific papers jointly published with the Company regarding the anti-cancer and anti-tumor effects of PRP, as well as a co-inventor of several patents in the Company’s intellectual property portfolio, including the discovery of PRP as a targeted, cancer stem cell therapy.

"We are truly delighted to be working with Dr. Perán, as we look to discover and develop new compounds which support our lead product candidate, PRP, which is progressing towards human trials," said Mr. James Nathanielsz, Propanc Biopharma’s Chief Executive Officer. "Our vision is to establish a new therapeutic drug class for the treatment and prevention of metastatic cancer, by targeting and eradicating cancer stem cells. We look forward to executing this important project with Dr. Perán and the Department of Health Sciences at the University of Jaén."

"The collaboration between public institutions and biotech companies is key to overcoming therapeutic challenges," said Dr. Perán. "We are excited to commence this new project with the hope of providing an effective treatment against aggressive cancers, like pancreatic cancer."

On September 19, 2018 Exelixis, Inc. (NASDAQ:EXEL) reported that its partner Ipsen Biopharmaceuticals Canada Inc. received approval from Health Canada of CABOMETYX (cabozantinib) tablets for the treatment of adults with advanced renal cell carcinoma (RCC) who have received prior vascular endothelial growth factor (VEGF) targeted therapy (Press release, Exelixis, SEP 19, 2018, View Source;p=irol-newsArticle&ID=2368033 [SID1234529488]). Health Canada granted CABOMETYX priority review status, which provided an accelerated review of Ipsen’s new drug submission.

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"The approval of CABOMETYX in Canada helps address a significant unmet need for patients with advanced kidney cancer whose disease has progressed on first-line therapy and who have limited treatments available," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "We are glad to be partnering with Ipsen to bring this much needed treatment option to these patients and look forward to our continued collaboration."

The Health Canada approval was based on results of the phase 3 pivotal METEOR trial in which CABOMETYX provided a statistically significant and clinically meaningful improvement in overall survival, progression-free survival and objective response rate as compared with everolimus in patients with advanced RCC who have received prior anti-angiogenic therapy.

Under the terms of the Collaboration Agreement with Ipsen, Exelixis will receive a milestone payment of $5 million for the Health Canada approval. The payment will be made by Ipsen within the next 70 days.

Please see Important Safety Information below and full U.S. prescribing information at View Source

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 The Canadian Cancer Society estimates that kidney cancer is among the top ten most common forms of kidney cancer in Canada, with approximately 6,600 new cases diagnosed in 2017.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.4 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment, and an estimated 14,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.4

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About the Exelixis and Ipsen Collaboration

In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. Under the terms of the Collaboration Agreement with Ipsen, Exelixis is entitled to receive a tiered royalty of 22 percent to 26 percent of annual net sales.

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced RCC. CABOMETYX tablets are also approved in: the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union for previously untreated intermediate- or poor-risk advanced RCC; and in Canada for adult patients with advanced RCC who have received prior VEGF targeted therapy. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC. On March 28, 2018, Ipsen announced that the European Medicines Agency validated its application for a new indication for cabozantinib as a treatment for previously treated advanced HCC in the European Union. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.