On September 27, 2016 Galera Therapeutics, Inc., a clinical-stage biotechnology company developing new treatments for cancer patients, reported the presentation of final data, including one-year tumor control, from a Phase 1b/2a clinical trial of GC4419, an investigational drug candidate for the reduction of severe chemoradiation-induced oral mucositis (OM), in an oral presentation at the American Society of Radiation Oncology (ASTRO) Annual Meeting (Press release, Galera Therapeutics, SEP 27, 2016, View Source [SID:SID1234515442]). The OM efficacy data from this study in head and neck cancer patients were previously presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June and demonstrated marked reductions in the incidence, severity and duration of severe OM when compared to historical experience.

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The new one-year tumor control follow-up data presented today in Boston, Massachusetts further shows that local and distant tumor control, progression-free survival and overall survival compared well with historical experience for patients receiving chemoradiation for head and neck cancers.

This Phase 1b/2a trial assessed the safety and pharmacokinetics of GC4419, administered intravenously prior to each dose of standard intensity modulated radiotherapy (IMRT) and cisplatin therapy, in 46 head and neck cancer patients. The study demonstrated that, compared to historic controls, GC4419 delayed the onset, reduced the incidence, shortened the duration and reduced the intensity of severe OM (defined as WHO Grades 3 and 4 OM). Furthermore, only 4.3% of patients required breaks in IMRT of 5 consecutive fractions or more, as opposed to published rates of 15% in historical studies. In combination, GC4419 had a safety profile consistent with the underlying IMRT and cisplatin regimen.

Now with a full one year of follow-up in all consenting patients (44/46), investigators further report that the overall 1-year local-regional control, the 1-year distant metastasis-free rate and the 1-year overall survival were each 93%. The 1-year progression-free survival was 84%. These rates compare favorably with historic controls.

"We are encouraged to see that after one year of follow-up, tumor control in these patients appears to be maintained," said J. Mel Sorensen, MD, President and CEO of Galera. "These findings support the continuing development of GC4419, now in a randomized double-blinded Phase 2 trial for this patient population. As radiation oncologists know well, severe OM is a debilitating side effect that can result in treatment interruptions of potentially life-saving chemoradiation therapy. We look forward to advancing our clinical development program for GC4419, as well as our pipeline of orally active dismutase mimetics."

About Oral Mucositis (OM)
Oral mucositis is a common debilitating side effect of radiation treatment in head and neck cancer (HNC) patients. Severe OM, defined as Grade 3 or 4 OM on the World Health Organization Oral Mucositis Scale, occurs in 60 to 80 percent of HNC patients who receive radiation therapy. Importantly, severe OM may result in interruptions in radiation treatment, which can compromise the otherwise good prognosis for tumor control in many of these patients. In addition, patients suffer significant pain, may develop serious infections, and may be unable to eat solid food or even drink liquids. Further, the costs of managing these side effects are substantial, particularly when hospitalization and/or surgical placement of PEG tubes to maintain nutrition and hydration is required. There is currently no drug approved to prevent or treat severe OM in head and neck cancer patients.

About GC4419
GC4419 is a superoxide dismutase mimetic, a small molecule drug that is designed to convert superoxide to hydrogen peroxide and oxygen. This mechanism is thought to block the large burst of superoxide induced by radiotherapy, the initiating step in the development of OM, and has been shown to be protective of normal tissue but not tumor in preclinical models. In preliminary clinical studies, GC4419 markedly delayed the onset, shortened the duration and decreased the incidence of severe OM when administered intravenously prior to each dose of intensity modulated radiotherapy (IMRT) and cisplatin. GC4419 has now entered randomized Phase 2 development to reduce the incidence, severity and duration of severe OM in patients receiving radiation and chemotherapy for the treatment of head and neck cancer.

On September 27, 2016 Biothera Pharmaceuticals, Inc. reported the presentation of clinical data demonstrating the mechanism of action of Imprime PGG, the Company’s Phase 2 cancer immunotherapy drug, in healthy human volunteers (Press release, Biothera, SEP 27, 2016, View Source [SID:SID1234515441]). These are the first data to show that when administered intravenously to healthy human subjects, Imprime PGG drives the immunopharmacodynamic (IPD) responses observed in ex vivo human and in vivo mouse studies. Specifically, the study demonstrated that formation of an immune complex between Imprime PGG and endogenous anti-beta glucan antibodies (ABA) was critical to elicit Imprime-induced immune activating events in humans. These findings provide additional evidence that ABA levels may be a particularly useful biomarker for selecting patients most likely to respond to Imprime-based therapy. These data, as well as additional preclinical research demonstrating Imprime’s ability to reshape the suppressive immune microenvironment of the tumor and elicit robust anti-tumor immunity, were presented in poster presentations during the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), taking place in New York City, September 25-28, 2016.

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"For the first time we are showing that Imprime PGG elicits multiple innate immune-activating events after systemic dosing in humans. These immune-activating events are the same events necessary for efficacy in preclinical models," said Jeremy Graff, Ph.D., Biothera’s Chief Scientific Officer and Senior Vice President, Research. "These data also further bolster our extensive research to show that pre-treatment ABA levels represent a viable, non-invasive, mechanism-based patient selection biomarker that will be deployed in our upcoming clinical trials."

Imprime PGG is a Pathogen Associated Molecular Patterning (PAMP) molecule that acts therapeutically as an immunological "ignition switch" to enlist the functionality of the innate immune system and to enhance the efficacy of tumor targeting, anti-angiogenic, and immune checkpoint inhibitor antibodies. Biothera and Merck are advancing a phase 2 clinical research collaboration to evaluate Imprime PGG and Merck’s anti-PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with either advanced melanoma or metastatic triple negative breast cancer. Biothera and Merck are also collaborating with the Big Ten Cancer Research Consortium to commence an Imprime PGG plus KEYTRUDA Phase 1b/2 study in patients with non-small cell lung cancer.

In a second poster presentation at the conference, Biothera presented preclinical data further demonstrating the ability of Imprime PGG to re-orient the immunosuppressive tumor microenvironment, disabling the immunosuppression that shields cancer cells from immune attack. Imprime PGG promotes the differentiation of human myeloid-derived suppressor cells (MDSCs), significantly upregulating the expression of co-stimulatory molecules (iNOS, CD80, CD86) that drive anti-tumor activity and relieving MDSC-mediated inhibition of T Cell proliferation. Previous preclinical studies have reported that Imprime PGG also promotes repolarization of M2 macrophages to an anti-tumor, M1-like orientation while triggering maturation of critical antigen presenting cells (i.e. dendritic cells) to enable antigen-specific T cell expansion and the production of the potent anti-tumor cytokine interferon gamma. Collectively, these data show that Imprime PGG treatment can reshape the tumor microenvironment favoring robust anti-tumor immune responses.

On September 27, 2016 Rasna Therapeutics, Inc. (OTCQB:RASP) (the "Company") (formerly Active With Me, Inc.), a development stage biotechnology company focused on the development of cancer drugs, reported it has implemented a 3.25-for-1 forward split of its common stock in effect for trading on a split-adjusted basis on Tuesday, September 20, 2016 as well as a name change and trading symbol change from Active With Me, Inc. and "ATVM" to Rasna Therapeutics, Inc. and "RASP", effective as of September 27, 2016 (Press release, Rasna Therapeutics, SEP 27, 2016, View Source [SID:SID1234515438]).

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As a result of the stock split, every one share of issued and outstanding common stock of the Company will be converted into 3.25 shares of common stock. Proportional adjustments will be made to the Company’s options and warrants. Any fractional shares resulting from the forward stock split will be rounded up to the next whole share.

On September 27, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported data from the Company’s GALE-301 Phase 1/2a clinical trial was presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in New York, NY (Press release, Galena Biopharma, SEP 27, 2016, View Source [SID:SID1234515437]). The focus of the presentation was on the association between clinical outcomes and folate binding protein (FBP) expression. GALE-301 is administered with the adjuvant granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in disease-free ovarian and endometrial cancer patients.

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Poster #B007, entitled, "Improved disease-free survival in endometrial and ovarian cancer patients with low folate binding protein expression after treatment with the E39 peptide vaccine in a phase I/IIa trial," reported clinical outcomes based on FBP expression level. The data revealed a disease free survival (DFS) benefit in patients with low FBP expression (FBPlo), but not in patients with high FBP expression (FBPhi).

"The results presented today are quite informative to our program as little is known about the effects of FBP expression levels on FBP-directed therapies, including the GALE-301 (E39) vaccine," said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "The fact that the low expressors appeared to show a better DFS benefit may be due to immunotolerance from significantly higher endogenous exposure to the FBP antigen. This is also something we explored with our GALE-302, or attenuated version, of the peptide. These findings warrant further study as they may help inform the design and target patient populations for the next clinical trial for our folate binding protein development programs."

Thirty-eight enrolled patients underwent FBP expression testing, and there were no clinicopathologic differences between the vaccine group (VG n=18) and the control group (CG n=20) or within FBPhi (VG n=10; CG n=9) and FBPlo (VG n=8; CG n=11;) (p≥0.1). There were significantly more primary tumors in FBPlo vs. FBPhi (p=0.027) and median follow up for the study was 16.3 months. While there was no significant difference in overall DFS between the CG and the VG (34.6% vs. 34.6%, p=0.208), in FBPlo patients, there was improved DFS in the VG at 85.7% vs. the CG at 17.5% (p=0.01). There was no such difference in FBPhi patients (VG 13.9% vs. CG 44.4%, p=0.83). Though groups were small, there was a dose-dependent effect in the FBPlo patients receiving 1000mcg (n=4) having improved DFS compared to the <1000mcg patients (n=4) and the CG (n=3) (100% vs. 66.7% vs.17.5%, respectively, p=0.03). Comparing FBPlo and FBPhi patients in the VG, the FBPlo patients had improved DFS (85.7% vs. 13.9%, p=0.052). In the CG, FBPlo patients did worse (17.5% vs. 44.4% in FBPhi, p=0.371).

Disease-free, HLA-A2-positve patients were vaccinated, while HLA-A2-negative patients were followed as untreated controls. The vaccine group received six monthly inoculations of GALE-301+GM-CSF, including either 100, 500, or 1000 mcg of peptide and 250mcg of GM-CSF. FBP expression testing was performed by immunohistochemistry and the results were graded 0-4+ based on the percentage of positively staining cells. Patient’s tumors were then categorized as FBPlo if scored 0-1+ or FBPhi if 2-4+. The patients were monitored for evidence of clinical recurrence through the standard of care follow-up by their treating oncology team. Demographics, FBP expression, and DFS were analyzed using appropriate statistical tests.

About GALE-301

GALE-301 is a cancer immunotherapy that consists of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting. FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers. FBP is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Enrollment has been completed in the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial in two gynecological cancers: ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696).

About Ovarian/Endometrial Cancers

New cases of ovarian cancer occur at an annual rate of 11.9 per 100,000 women in the U.S., with an estimated 22,280 new cases and 14,240 deaths in 2016. Approximately 46.2% of ovarian cancer patients are expected to survive five years after diagnosis. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their lifetime (2011 – 2013 data). The prevalence data from 2013 showed an estimated 195,767 women living with ovarian cancer in the United States.

Due to the lack of specific symptoms, the majority of ovarian cancer patients are diagnosed at later stages of the disease, with an estimated 75% of women presenting with advanced-stage (III or IV) disease. These patients have their tumors routinely surgically debulked to minimal residual disease, and then are treated with platinum- and/or taxane-based chemotherapy. While many patients respond to this treatment regimen and become clinically free-of-disease, the majority of these patients will relapse. Depending upon their level of residual disease, the risk for recurrence after completion of primary therapy ranges from 60% to 85%. Unfortunately for these women, once the disease recurs, treatment options are limited and the disease remains incurable.

New cases of endometrial cancer occur at an annual rate of 25.4 per 100,000 women in the U.S., with an estimated 60,050 new cases and 10,470 deaths in 2016. Approximately 81.7% of endometrial cancer patients are expected to survive five years after diagnosis. Approximately 2.8% of women will be diagnosed with ovarian cancer at some point during their lifetime (2010 – 2013 data). The prevalence data from 2013 showed an estimated 635,437 women living with endometrial cancer in the United States.

Source: National Cancer Institute Surveillance, Epidemiology, and End Results Program

On September 27, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported two posters presented at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (CRI-AACR) in New York (Press release, Aduro BioTech, SEP 27, 2016, View Source;p=RssLanding&cat=news&id=2206156 [SID:SID1234515423]). The preclinical data demonstrate positive changes in the tumor microenvironment and induction of a tumor-specific immune response by Aduro’s LADD (listeria-based immunotherapy construct) and STING (Stimulator of Interferon Genes) Pathway Activator immunotherapy platform technologies. Importantly, adding a PD-1 blockade to either immunotherapy regimen significantly bolstered antitumor efficacy.

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"These preclinical data demonstrate the underlying mechanisms by which our LADD and STING immunotherapy platforms activate the immune system and induce robust innate immunity, facilitating a change in the tumor microenvironment which results in effective destruction of cancer cells in several preclinical models," said Thomas Dubensky, Jr., Ph.D., chief scientific officer of Aduro. "Importantly, the combination data are even more impressive, showing increased efficacy when our LADD and STING platforms are combined with an anti-PD1 checkpoint inhibitor to combat the tumor’s ability to hide from the immune system. These data support our strategy to combine our immunotherapy regimens with checkpoint inhibitors for greater anti-tumor activity, looking toward the ultimate goal of better, more effective patient care."

The following posters were presented at the meeting:

Poster A013: Favorable changes in the tumor microenvironment following intravenous dosing with live attenuated Listeria monocytogenes-based immunotherapy.
In a poster session on Sunday, September 25, 2016, Meredith Leong, Ph.D., a scientist at Aduro, presented data from multiple preclinical studies using Aduro’s LADD immunotherapy platform. The data demonstrated that a combination of LADD with an anti-PD1 checkpoint inhibitor results in improved anti-tumor efficacy in multiple tumor models. In addition, analyses of biopsies from patients given CRS-207, a LADD immunotherapy, showed enhancement of infiltrating CD8+ T cells, mature dendritic cells, macrophages and natural killer cells, all specialized immune system cells involved in eradicating tumor cells. Consistent with this clinical data, the preclinical findings showed that LADD induced a potent favorable change in the tumor microenvironment including increased CD8+ T cells, infiltration of neutrophils, and a reduction of regulatory T cells, creating an environment for the tumor susceptible to anti-cancer treatments.

Poster B020: STING activation in the tumor microenvironment using a synthetic human STING-activating cyclic dinucleotide induces potent anti-tumor immunity
In a poster session on Monday, September 26, 2016, Sarah McWhirter, Ph.D., a scientist at Aduro, presented preclinical data on ADU-S100, a STING Pathway Activator. The data demonstrate that ADU-S100 stimulates the production of interferon-beta by all human STING alleles. Importantly, the results showed that injecting ADU-S100 directly into the tumor microenvironment induced T cells with tumor-specific antigenic repertoire leading to durable anti-tumor immunity. In addition, the combination of STING activation in the tumor microenvironment and PD-1 blockade enhances antitumor efficacy. There is an ongoing Phase 1 first-in-human clinical study to evaluate the safety, tolerability and possible anti-tumor activity of ADU-S100 in patients with cutaneously-accessible advanced metastatic solid tumors or lymphomas.

About the Tumor Microenvironment
The tumor microenvironment is the cellular environment in which the tumor exists, and, along with cancerous cells, includes support cells, immune cells, surrounding blood vessels, and the extracellular matrix. The tumor cells and the surrounding microenvironment are closely related and interact constantly. Tumors influence the microenvironment by releasing signals that promote tumor growth, immune tolerance and immune suppression. When tumors initially form, the body’s immune system recruits and activates a host of immune cells to fight the invading tumor. However, in cases where cancer develops, tumors are eventually able to evade the immune system by changing their microenvironment to inhibit the ability of the immune system to recognize and destroy the tumor thus allowing for tumor outgrowth and formation of metastasis.

About LADD and CRS-207
LADD is Aduro’s proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to generate a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.

CRS-207 is one of a family of product candidates based on Aduro’s LADD immunotherapy platform that has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.

About STING Pathway Activator Platform
The Aduro-proprietary STING Pathway Activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.