On August 12, 2019 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported its financial results for the second quarter ended June 30, 2019, and provided a business update (Press release, Phio Pharmaceuticals, AUG 12, 2019, View Source [SID1234538607]).

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"Our focus in 2019 remains on execution of our new development strategy, as we continue to advance and expand our immuno-oncology pipeline," said Dr. Gerrit Dispersyn, Phio’s President and CEO. "During the first half of the year, we’ve continued to accelerate our R&D efforts and have made significant progress with our lead candidates. We are now are on track to initiate up to three clinical programs in 2020. Our novel sd-rxRNA for silencing PD-1 receptor expression by T cells is approaching the clinic for both ex vivo application to enhance adoptive cell transfer efficiency and for direct local administration into the tumor micro-environment. In parallel, we are advancing our sd-rxRNA compound designed to overcome immune exhaustion and activate T cells and natural killer cells. As we complete clinical translation for these lead assets, we also expect to announce additional pipeline updates in the near future."

Mid-Year Review

Organization: In March 2019, Dr. Dispersyn was appointed as the Company’s President and CEO, and in April 2019, Dr. John A. Barrett joined the Company as Chief Development Officer. With more than 25 years of experience in research and development, most recently at Ziopharm Oncology, Inc., Dr. Barrett has made an immediate and significant positive impact. Under his leadership, the Company is continuing to build its research and development team to accelerate its internal activities.

Collaborations: Phio has established a number of strong collaborations with leading academic and corporate institutions. Results from several of these collaborators validate and build upon internal results for PH-762, supporting its progress toward clinical translation. In addition, the Company entered into new collaborations supporting the research and development of sd-rxRNA-based products beyond T-cells, including an agreement with Glycostem Therapeutics BV to support the evaluation of sd-rxRNA in adoptive cell therapy using natural killer (NK) cells.

Pipeline Advancements: The Company’s current pipeline products are based on clinically validated targets. Lead product candidate PH-762 is designed to elicit checkpoint blockade by inhibiting PD-1 receptor expression in T cells. Internal data, and data generated by collaborators, showed that silencing mRNA for PD-1 with PH-762 results in enhanced T cell activation and tumor cytotoxicity. Based on these positive preclinical results, Phio is advancing PH-762 for two distinct clinical applications: one for use in adoptive cell transfer of T cells and one for direct administration within the tumor micro-environment. The Company expects to start clinical studies for both of these pipeline products based on PH-762 in 2020.

The Company’s next pipeline product, PH-804, is designed to silence the expression of immune exhaustion target TIGIT by NK cells and T cells resulting in them becoming "weaponized." To date, Phio has shown that reduction of TIGIT by PH-804 leads to an increase in the cytotoxic capacity of NK cells. The Company plans to enter the clinic with PH-804 in the second half of 2020.

To further support the development of Phio’s immuno-oncology pipeline, the Company is working to validate and prioritize additional pipeline products focusing on adoptive cell therapy, the tumor micro-environment, as well as direct tumor applications. The Company’s additional pipeline products include sd-rxRNA compounds that impact the PD-1/PD-L1 axis and compounds that otherwise increase immune cell activity, for example by improving cell metabolism (e.g. increased spare respiratory capacity) and by impacting cell differentiation. We expect to advance additional sd-rxRNA candidates into preclinical and clinical development in the second half of 2019.

Corporate Developments: The Company entered into a purchase agreement with Lincoln Park Capital Fund, LLC ("Lincoln Park") on August 7, 2019, in which the Company has the right to sell to Lincoln Park up to $10 million in shares of the Company’s common stock, subject to the terms of the agreement. This investment by Lincoln Park is a continuation of its prior investment in the Company. The Company believes that this will provide the Company with access to capital at more favorable terms, as the Company controls the timing and amount of any future sales to Lincoln Park, while also providing Phio with a flexible funding option to advance its immuno-oncology programs into the clinical development phase.
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Cash Position

At June 30, 2019, the Company had cash of $10.8 million as compared with $14.9 million at December 31, 2018. The Company expects its cash to provide funding for at least the next twelve months.

Research and Development Expenses

Research and development expenses for the quarter ended June 30, 2019, were $1.1 million as compared with $1.2 million for the quarter ended June 30, 2018. The decrease was primarily due to a reduction in licensing fees.

General and Administrative Expenses

General and administrative expenses for the quarter ended June 30, 2019, were $0.9 million as compared with $0.8 million for the quarter ended June 30, 2018. The increase was primarily due to an increase in legal fees.

Net Loss

Net loss for the quarter ended June 30, 2019, was $2.0 million or $0.08 per share, compared with $1.9 million or $0.46 per share for the quarter ended June 30, 2018. The increase was primarily due to changes in operating expenses, as discussed above.

On August 12, 2019 Propanc Biopharma, Inc. (OTC: PPCB) ("Propanc"), a biopharmaceutical company developing new cancer treatments for patients suffering from recurring and metastatic cancer, reported that the company’s scientific researchers, together with its joint research partners, Universities of Jaén and Granada, published key data in a peer reviewed journal, Scientific Reports, confirming the mechanism of proenzymes and its anti-cancer effects against cancer stem cells (CSCs) (Press release, Propanc, AUG 12, 2019, View Source [SID1234538605]). From the publishers of Nature, it is an online, open access journal, which publishes primary research from all areas of the natural and clinical sciences. The article is entitled "Pancreatic proenzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumor engrafting," and can be accessed via the company website under the link: View Source

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"We are excited to publish this paper on our work with PRP and CSCs, where these cells drive cancer," said Dr Julian Kenyon, Propanc’s Chief Scientific Officer. "We were able to destroy these cells in significant numbers. Remarkably, we observed at least 13 genes that induce cancer were downregulated by PRP. Also, genes implicated in metastasis were downregulated and 7 genes related to cell adhesion, which is the normal state of healthy tissue, were upregulated. In summary, PRP has multiple modes of action, quite unlike any other cancer drug and is clearly in a class of its own. This is likely to translate into PRP being effective in many different cancer types and reducing the recurrence rate after standard treatments."

"Importantly, we proved that PRP impaired engrafting of human derived pancreatic CSC tumors in nude (immune compromised) mice, whilst also displaying an antigrowth effect toward initiated xenografts (grafted, human derived tumors), showing a decreased amount of tumor surrounding fibrotic tissue of treated mice," said Dr. Perán, Acting Professor at the Department of Health Sciences, University of Jaén and Propanc’s Scientific Advisor. "As cancer treatment moves towards more personalized medicine, proven therapies that target and treat specifically CSCs may prove to be a useful method for reducing recurrence after drug treatment failures."

The data provides the strongest evidence that proenzymes could be an effective tool in the fight against metastatic cancer, the single biggest cause of patient death for sufferers. The company’s lead product candidate, PRP, is a formulation of two proenzymes, designed to act synergistically against solid tumors which are malignant. PRP is currently in preparation for a First-In-Human study in advanced cancer patients which the company plans to commence in 2020.

To explain the significance of the discovery, people often have the misconception that tumors are made up from the same type of malignant cell that grows uncontrollably and exponentially. Although that could be the first impression when a tumors progress rapidly, in fact, tumors are a very complicated kind of new organ that develops an intricate organization with its own blood supply and an intricate communication system with the rest of the organism that facilitates the cancer dispersion. In addition, there are different types of cells within a tumor mass, it is true that all of them have a common feature, they are undifferentiated cells, but some of them are more "ancestral" than others. These cells are named cancer stem cells, or CSCs, and are responsible for tumor metastasis and tumor relapse. The strength of these particular cells is that they do not replicate, so conventional therapies that only affect growing cells, do not harm CSCs.

Other important facts about tumors is their ability to change their surroundings, inducing neighboring cells to become malignant, and even more worrisome, its ability to corrupt distant tissue cells creating a future tumor microenvironment.

After more than 10 years collaboration with Propanc’s prestigious, joint scientific researchers with significant experience in cancer, the company now understands the mechanism of action of PRP, a formulation containing a synergistic combination of two pancreatic proenzymes. The "beauty" of this naturally derived formulation is that the body has designed enzymes to perform a specific role on the cells to orchestrate gradual changes. In the same pathways that active enzymes work on healthy cells, PRP, once converted to the activated enzyme form, changes the malignant nature of cancer cells toward a differentiated state in which cells return to be what they were. Some of the company’s scientific studies have already been published in high impact journals, demonstrating that PRP decreases cell proliferation and migration, induces cell differentiation and impairs angiogenesis. In short, tumors cannot grow after PRP treatment, as demonstrated by in vivo studies with mice models.

This latest achievement has demonstrated that PRP also has a significant effect on that population of cells within the tumor that keep a dormant state and a stemness nature. As stated above, those cells, called CSCs, are not eradicated by conventional therapies and are responsible for generating a new tumor in other organs, a process known as metastasis, which is the main cause of patient death for sufferers.

"In collaboration with the Universities of Jaén and Granada, we have performed a detailed study on the effects of PRP upon these tumor-initiating cells and we are excited to reveal that our results are very encouraging," said Mr. James Nathanielsz, Propanc’s Chief Executive Officer. "In addition, we have proven a beneficial impact of our novel treatment, PRP, on tumor initiation and progression as well as on the tumor microenvironment, which is of great scientific interest."

The company has also been working with its research partners with the aim of enhancing the effects of PRP, whilst also maximizing a better-quality and safer product. The project is progressing well and on track to produce an optimized version of PRP which could be effectively reproduced with enhanced effects, compared to the naturally derived proenzymes. Further work is currently being undertaken to ensure the product is comparable in structure to PRP.

About the University of Jaén:

The University of Jaén is among the Top 50 of the best young universities in the world according to THE (Times Higher Education). Likewise, the University of Jaén received the EFQM 500+ European Seal of Excellence, the highest level of recognition awarded by the Excellence in Management Club, as the official representative of the European Foundation for Quality Management (EFQM) in Spain. It also stands out in the field of computing, since the University of Jaén is among the 75 best universities in the world, according to Academic Ranking of World Universities (ARWU) 2017. The University of Jaén is repeatedly in the top 4% of universities worldwide, according to the Ranking Center for World University Rankings (CWUR), which annually collects the thousand best and most valued among the more than 25,000 existing universities. In addition, it is the fourth Spanish university that has obtained the highest score in the ranking of international student satisfaction, published by the STEXX International Studyportals Organization, in its 2016 version.

About the University of Granada:

The University of Granada is widely recognized internationally for its quality in higher education, teaching, research and outreach. National and international rankings reflect the University Granada’s position among the top universities in Spain and among the best in the world. In 2018, the University of Granada has further consolidated this dominant position – taking 278th place in the world and 3rd in Spain in the recently published Shanghai Academic Ranking of World Universities (ARWU 2018). Viewed from the perspective of its performance in specific academic subjects, the UGR has also set a new record, with a further 34 subjects taught at the University featuring in the 2018 ARWU — 12 more than in 2017. Furthermore, 5 of the University Granada’s subjects feature among the world top 100, marking another significant milestone.

On August 12, 2019 Harvard University and Merck are reported a collaboration that will provide significant research funding for up to four years to support immuno-oncology research led by Arlene Sharpe, MD, PhD, at Harvard Medical School (HMS) (Press release, Merck & Co, AUG 12, 2019, View Source [SID1234538604]). Sharpe, the George Fabyan Professor of Comparative Pathology and chair of the HMS Department of Immunology, will collaborate with researchers at Merck on a major project aiming to discover novel aspects of the immune system that may be targeted in future treatments for cancer.

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"This collaborative project aims to discover and validate novel regulators of immune responses," said Dr. Sharpe. "Immunotherapies such as checkpoint inhibitors have revolutionized the treatment of cancer, but my lab is deeply interested in understanding why some patients do not respond or develop resistance to those interventions. My hope is that by defining mechanisms that inhibit immune responses to tumors, we will identify very important druggable targets and new approaches to improve cancer immunotherapy."

The funding will support the work of scientists in the lab of Dr. Sharpe, who is a renowned leader in the field of tumor immunology. She is a member of the National Academy of Sciences and the National Academy of Medicine, and the recipient of numerous awards including the Warren Alpert Foundation Prize in 2017 for her contributions to the discovery of the PD-1 pathway.

"Crucial insights into patient responses and outcomes may be gained through the study of fundamental biological mechanisms," said Isaac Kohlberg, Harvard’s Chief Technology Development Officer and Senior Associate Provost. "The complexity and promise of immuno-oncology presents a prime opportunity for Harvard’s top scientists to advance discovery through an academic-industry collaboration. Through this project, the Sharpe Lab is setting its sight on innovations that may contribute to dramatic improvements in patient care."

Under the agreement spearheaded by Harvard’s Office of Technology Development, Merck will have the option to negotiate an exclusive license to innovations arising from the research collaboration to develop these discoveries toward potential treatments for patients.

"Collaboration with leading scientific groups is an integral part of Merck’s discovery strategy," said Dr. Nick Haining, vice president for oncology discovery at Merck Research Laboratories. "We look forward to working with Dr. Sharpe’s team to investigate new ways to harness the immune system for therapeutic advances."

On August 12, 2019 Saul Priceman, Ph.D., City of Hope assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, and his research team have received a $9.28 million award from the California Institute for Regenerative Medicine (CIRM) to support a chimeric antigen receptor (CAR) T cell phase 1 clinical trial for the treatment of women with HER2-positive breast cancer that has spread to the brain (Press release, City of Hope, AUG 12, 2019, View Source [SID1234538603]).

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HER2 refers to a protein – human epidermal growth factor receptor-2 – which is found on the cell surface of breast cancer cells and drives cancer progression. About 20% of breast cancer patients are HER2-positive, according to the American Cancer Society.

The trial, which opened for enrollment in the fall of 2018 and whose lead clinical investigator is Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research, is testing the safety and effectiveness of the CAR T cell therapy for breast cancer patients with brain metastases who are not effectively being controlled with other therapies. It is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases.

"Our team’s goal is to develop a novel therapy for breast cancer patients with brain metastases who currently have no other effective treatments," Priceman said. "This is a beautiful example of how early support from private donors and foundations helped to develop a therapy and initiate a trial we were desperate to bring to patients, and now this CIRM award funds the entire clinical trial and helps to leverage the knowledge gained here to further advance this therapy."

CAR T cells are a cell-based type of immunotherapy in which a patient’s own T cells are reprogrammed to actively seek out and destroy cancerous cells. For this trial, the patient’s T cells will be isolated from the blood and genetically engineered to express a CAR that allows these immune cells to target and eradicate HER2-positive cancer cells. Patients receive CAR T cells directly to the ventricles of their brains, which is an administration route that was first attempted successfully at City of Hope. City of Hope patents covering the HER2 CAR were licensed to Mustang Bio in 2017.

City of Hope, a recognized leader in CAR T cell therapies, has treated more than 350 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world – it currently has 20 ongoing CAR T cell clinical trials, and has just initiated trials for patients with solid tumors, including prostate cancer.

The trial’s key investigators include City of Hope’s Stephen J. Forman, M.D., director, T Cell Therapeutics Research Laboratory and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., deputy director, T Cell Therapeutics Research Laboratory and the Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of City of Hope’s Division of Neurosurgery and Heritage Provider Network Professor in Gene Therapy. The award also includes City of Hope’s Russel Rockne, Ph.D., Vanessa Jonsson, Ph.D., Ammar Chaudhry, M.D., as well as collaborations with University of Southern California’s Peter Kuhn, Ph.D., and California Institute of Technology’s Lior Pachter, Ph.D.

CIRM funded early preclinical work related to this study, which was important in optimizing the therapy for the eventual Food and Drug Administration approval for permission to start a clinical trial. City of Hope also highlights Eli Khouri, Steve Meringoff, Zach Horowitz, Jody and Gary Marsh, The Kenneth T. and Eileen L. Norris Foundation and Gateway for Cancer Research for their support of this program.

On August 12, 2019 LineaRx, Inc. ("LineaRx"), a majority-owned subsidiary of Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company") reported that, in a decision rendered on August 7, 2019, the Centers for Medicare and Medicaid Services (CMS) approved chimeric antigen receptor (CAR) T-cell therapies that fit the CMS criteria for Medicare beneficiaries nationwide (Press release, LineaRx, AUG 12, 2019, View Source [SID1234538602]). LineaRx believes its unique method of manufacturing DNA is well poised to benefit from the increasing demand for nucleic-acid dependent therapies, like CAR T, as biotechnology companies pursue their gene and cell therapies with reimbursement assured by the CMS decision.

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CAR T-based treatments involve extracting and genetically altering a patient’s T cells to attack a protein on the surface of cancer cells. The cells are then infused back into the patient. All approved CAR T and other redirected cell therapies are manufactured using DNA that is bacterially derived and then delivered to the patient’s T cells by a virus. Such plasmids-based treatments require about three weeks to grow and are acknowledged to have the potential for unintended side-effects. LineaRx offers a cleaner, potentially higher-performing alternative to plasmid DNAs with linear DNAs produced by PCR (Polymerase Chain Reaction) that are used to reprogram CAR T cells. Applications for redirected cells are broadly anticipated with more than 850 trials globally listed on clinicaltrials.gov.

"The oncology community has greeted CAR T cell therapy with extraordinary enthusiasm, but the use of these novel therapies to combat cancer has been constrained by pricing and reimbursement. With the CMS decision, redirected cell therapies are now a permanent part of the toolbox of modern medicine, and with LineaRx, we believe we have a more desirable manufacturing process than plasmids, that will enable biotech companies to accelerate their commercialization efforts," stated Dr. James Hayward, president and CEO of LineaRx. "With the LineaRx ability to provide massive ultrapure DNA with shorter lead times than plasmids, its manufacturing technology should enable gene therapy companies to shorten time-to-market for their therapies and in a much more cost-efficient manner. Patients will also benefit by a more rapid turnaround. Moreover, we believe that our recent acquisition of Vitatex, which just closed last week, facilitates our development of redirected cell therapies by enabling us to study the lymphocytes that we capture alongside the circulating tumor cells from the blood of cancer patients. We believe these studies will guide us toward optimal design of the engager that allows CAR T cells to recognize their host’s cancer at a molecular level."

Full text of CMS decision: Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N)