On April 3, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported its data from its poster presentation at the AACR (Free AACR Whitepaper) or American Association of Cancer Research annual Meeting 2019 demonstrating that the targeted radiation delivered by Actimab-A to CD33 expressing cells can deplete MCL-1 levels in tumor cells, thereby removing a mechanism of resistance and rendering them more susceptible to venetoclax (Press release, Actinium Pharmaceuticals, APR 3, 2019, View Source [SID1234534939]). Further, the induction of direct AML cell death via double-stranded DNA breaks by Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Actimab-A is an ARC or Antibody Radiation Conjugate comprised of the anti-CD33 monoclonal antibody lintuzumab and the potent alpha-particle emitting radioisotope Ac-225 or Actinium-225. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML or Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, and Small Lymphocytic Leukemia. The poster can be viewed on Actinium’s website here.

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Highlight’s of Actinium’s poster presentation are as follows:

Actimab-A treatment of venetoclax resistant AML cells led to a decrease in MCL-1 levels. MCL-1 is a protein in the BCL-2 family of anti-apoptotic proteins, which is overexpressed in relapsed or refractory AML cells and has been shown to mediate resistance to venetoclax.
The same Actimab-A treatment reduced BCL-XL. BCL-XL is another protein in the BCL-2 family and also been proposed to mediate resistance to venetoclax.
Additional studies demonstrated that Actimab-A produced double-stranded DNA breaks in two cell lines resistance to venetoclax.
At all dose levels and time points, Actimab-A significantly increased double-stranded DNA breaks compared to cells treated with lintuzumab alone.
In a venetoclax resistant AML in vivo tumor model, statistically significant reduction in tumor size was observed in animals receiving the combination of Actimab-A and venetoclax compared to venetoclax alone.
At evaluation on day 38, complete responses were reported in 3 of 5 animals receiving the combination of Actimab-A and venetoclax while no animals receiving venetoclax alone achieved a complete response at any time point.
100% survival at day 40 was observed in cohorts receiving Actimab-A and venetoclax while no animals treated with venetoclax alone survived beyond day 30.
Dr. Dale Ludwig, Actinium’s Chief Scientific Officer, said, "The results of these studies further our enthusiasm for the combination of Actimab-A and venetoclax. Expanding on our previous in vitro work, it is validating to observe multiple synergies derived from Actimab-A’s unique targeted radiation mechanism of action including MCL-1 reduction. Given the role this protein plays in AML cell resistance to venetoclax, it is exciting to see its depletion with Actimab-A, resulting in increased cell death and tumor control in these studies. We are also excited to demonstrate that Actimab-A causes double-stranded DNA breaks for which there is no known resistance or repair mechanism. It is important to note that these findings were observed in cell lines and xenograft animal models based on venetoclax resistant cell lines. These data further support the advancement of the combination of Actimab-A and Venetoclax into clinical trials as we are doing with two distinct clinical trials."

Actinium has filed a patent on the combination of a targeted alpha-emitting therapeutic such as Actimab-A together with a BCL-2 inhibitor, which includes venetoclax, as a method to treat cancer. Actinium has initiated a Phase 1/2 trial that is studying Actimab-A in combination with venetoclax for patients with relapsed or refractory AML and is planning a Phase 1/2 trial that will study Actimab-A and venetoclax with a hypomethylating agent also for patients with relapsed or refractory AML, which is expected to be initiated in the first half of 2019.

Sandesh Seth, Actinium’s Chairman and CEO, said, "As we advance towards the clinic with our second Actimab-A venetoclax combination trial, it is encouraging to see multiple synergies in robust pre-clinical models. With many patients not responding to or having limited duration of their responses with venetoclax treatment, these important findings together with our extensive clinical data with Actimab-A will be beneficial to the advancement of our two combination trials. This work also showcases Actinium’s integration of our research and development and clinical development efforts that can result in rapid translation to the clinic. With a robust intellectual property portfolio around our AWE technology platform, we see a multitude of opportunities to leverage targeted radiation via our ARC’s in combination with other therapeutic modalities to generate potential therapies for patients with high unmet medical needs that are underserved by current therapeutic approaches."

On April 3, 2019 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that it will present at the 18th Annual Needham Healthcare Conference (Press release, Oncolytics Biotech, APR 3, 2019, View Source [SID1234534938]). The presentation, by Dr. Matt Coffey, President & CEO of Oncolytics, will take place at 1:30 pm ET, on Wednesday, April 10, 2019 at the Westin Grand Central Hotel in New York City.

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A live audio link to the webcast session will be available on the Company’s website at View Source It is recommended that listeners log on 10 minutes in advance of the live session to register and download any necessary software. An audio replay will be accessible approximately two hours following the presentation on the Oncolytics website.

On April 2, 2019 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President and CEO: Hiroshi Nomura hereinafter called "Sumitomo Dainippon Pharma") has reported that on March 29 the company applied for a partial change in the marketing approval previously acquired in Japan for RETHIO 100 mg for I.V. infusion (generic name, thiotepa; hereinafter called "RETHIO") (Press release, Sumitomo Dainippon Pharma, FEB 2, 2019, View Source [SID1234605564]). The change applied for this time involves an additional indication of RETHIO for conditioning treatment prior to autologous hematopoietic stem cell transplantation (auto-HSCT) for malignant lymphoma.

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RETHIO is a drug indicated for conditioning treatment prior to auto-HSCT for pediatric malignant solid tumors. Sumitomo Dainippon Pharma obtained the marketing approval for this drug on March 26, 2019 and plans to launch it after NHI drug price listing.

Malignant lymphoma, a hemocytes-derived cancer, is a disease that lymphocytes, a subpopulation of leukocytes (white blood cells), become cancerous. This disease occurs typically in lymphoid tissues, such as lymph nodes, spleens, and tonsils, but it also often develops in other sites. It has been reported that the incidence of malignant lymphoma is around ten in 100,000 persons in Japan annually, the most common hematapostema in Japanese adults. As with conditioning treatment prior to autologous HSCT for pediatric malignant solid tumors, the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs of the Ministry of Health, Labour and Welfare (MHLW) determined similarly high medical need in conditioning treatment prior to auto-HSCT for malignant lymphoma. Thus, Sumitomo Dainippon Pharma conducted Phase 1 trials in Japan and subsequently applied for the additional indication.

Sumitomo Dainippon Pharma believes that, upon approval of its additional indication, this drug will contribute to improved healthcare as a new treatment option for patients indicated for conditioning treatment prior to auto-HSCT for malignant lymphoma, a therapeutic area with high unmet medical need.

About autologous hematopoietic stem cell transplantation (auto-HSCT)
Autologous hematopoietic stem cell transplantation is a therapy that aims to reconstruct hematopoietic capacity via intravenous transfusion of normal hematopoietic stem cells of the patient himself/herself after eradicating intractable cancers by conditioning myeloablative treatment prior to transplantation using maximum levels of anti-cancer drugs or radiation.

About the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs
The Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs is a committee established to promote the development of unapproved or off-label drugs by pharmaceutical companies that are approved for use in Europe and the United States, etc., but not approved in Japan. It is organized under the Ministry of Health, Labour and Welfare of Japan and consists of academic experts in medical and pharmaceutical fields.

On April 2019 RhoVac AB ("RhoVac") reported that all prostate cancer patients who participated in the clinical phase I / II study with RhoVac’s drug candidate RV001, have completed their 9- and 12-month’s follow-ups (Press release, RhoVac, APR 2, 2019, View Source [SID1234555933]). This marks the completion of the clinical phase I / II study for the participating patients.

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RhoVac’s clinical phase I / II study was conducted during the period of Q1 2017 to Q1 2019. The 22 patients recruited for this study had been diagnosed with prostate cancer and been treated with prostatectomy. Blood samples were drawn before, during and after the study to analyze the product-mediated immune response to the treatments. The results, reported in August 2018, showed a significant immune response in 86% of patients. The patients also participated in 3-, 6-, 9- and 12-month’s follow-ups to study the duration of the immune response. This follow-up phase is now completed as all 22 patients have had their final follow-up visit at the clinical site.

The last samples from the 9- and 12-month’s follow-up phase have now been sent to the University of Tübingen for immunological analysis. RhoVac expects to report these results mid-2019.

CEO Anders Ljungqvist comments:

– The company’s first clinical study, RhoVac-001, is now completed and only analyzes and final reporting of the follow-up phase remain. I am proud that RhoVac has completed this study within the set timeframe. A result we have largely achieved thanks to the highly dedicated patients who have participated in the study. This combined with an outstanding collaboration with Copenhagen Prostate Cancer Center at University Hospital, Copenhagen; Phase I unit Zelo at Bispebjerg and Frederiksberg Hospital, DanTrials ApS and T-cell Monitoring Group, the Department of Immunology at the University of Tübingen, Germany have all ensured that we have been able to communicate conclusive results according to time frame. Thank you very much to all the participants.

On April 2, 2019 LIDDS AB reported that Clinical data shows that intratumoral delivery of TLR agonists in combination with immune checkpoint inhibitors can effectively treat solid cancers (Press release, Lidds, APR 2, 2019, View Source [SID1234555907]). NanoZolid technology is very suitable to provide sustained intratumoral release and minimize the need for repeated injections. LIDDS has performed pre-clinical studies with promising results using a TLR9 agonist formulated with NanoZolid.

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Toll-like receptors (TLR) are a key target for the pharmaceutical industry in the fight against cancer. TLRs are expressed on various immune cells, including dendritic cells, and they initiate the body’s immune response. TLR activation can lead to an immunologically active or inflamed tumor environment which then recruits the cytotoxic T-cells necessary for an anti-tumor response in immunotherapy.

-The NanoZolid technology addresses key issues in developing TLR agonists as repeated intratumoral injections are needed using standard formulations, says Monica Wallter, CEO LIDDS.

-We will be focusing our project on TLR9, one of the most promising targets for increasing response and reversing resistance to immunotherapies. TLR9 agonists have been shown to be most effective when injected directly into a tumor, says Monica Wallter.

-A preclinical programme is ongoing to broaden the results obtained to date and we are now preparing for a Phase I clinical trial using NanoZolid combined with a TLR9 agonist. The first human study is planned to commence in 2020, says Monica Wallter.

Preclinical studies have shown that activation of TLR pathways can lead to potent immunological effects that generate anti-tumor immunity and shrink tumors. Most importantly, these effects can act in synergy with immune checkpoint inhibitors.

-There is significant commercial potential in this area of research and drug development and the market for TLR agonists is expected to be worth hundreds of millions of dollars over the coming years, says Monica Wallter.

The most relevant target cancers for the TLR9 project are head and neck cancer, prostate cancer and lymphomas. These cancers are diagnosed in around 2 million patients each year.

Toll-like receptors have been studied for many years and the emerging clinical data suggests that their time has come as important anti-cancer agents when used in combination with immune checkpoint inhibitors.