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Galena Biopharma Presents GALE-301 Folate Binding Protein Expression Data at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference

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

Aduro Biotech Presents Encouraging Preclinical Data Showing Combination Synergy of its Immunotherapy and Checkpoint Inhibitors to Increase Antitumor Efficacy

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.

Provectus Biopharmaceuticals Announces Acceptance of Abstract for Poster Presentation at 31st SITC Annual Meeting

On September 27, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.provectusbio.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or the "Company"), reported that the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) has accepted an abstract for a poster presentation related to the use of PV-10, an investigational ablative immunotherapy under development by Provectus for solid tumor cancers, in the treatment of pancreatic cancer (Press release, Provectus Pharmaceuticals, SEP 27, 2016, View Source [SID:SID1234515422]).

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The abstract, "Intralesional injection with Rose Bengal and systemic chemotherapy induces anti-tumor immunity in a murine model of pancreatic cancer," describes research undertaken at Moffitt Cancer Center by a team of scientists led by Shari Pilon-Thomas. The exact time and place of the poster presentation has yet to be determined. The full abstract will be available on line at SITC (Free SITC Whitepaper)ancer.org on November 8 according to conference organizers.

The 31st SITC (Free SITC Whitepaper) Annual Meeting and Associated Programs will be held November 9-13 at the Gaylord National Hotel & Convention Center in National Harbor, Maryland.

ProNAi Licenses Oncology Drug Targeting DNA Damage Response Checkpoint Kinase 1 (Chk1) from CRT Pioneer Fund, UK

On September 27, 2016 ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage drug development company advancing targeted therapeutics for the treatment of patients with cancer, reported that it has obtained an exclusive license from the CRT Pioneer Fund LP for worldwide rights to develop and commercialize PNT737 (formerly CCT245737), a highly selective, orally available, small molecule inhibitor of Checkpoint kinase 1 (Chk1) (Press release, ProNAi Therapeutics, SEP 27, 2016, View Source [SID:SID1234515467]). PNT737 is being investigated in two recently initiated Phase 1 clinical trials, currently sponsored and managed by the Cancer Research UK Centre for Drug Development, led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. (ClinicalTrials.gov identifiers: NCT02797977 and NCT02797964).

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Under the terms of the agreement, ProNAi will pay the CRT Pioneer Fund an upfront payment of US$7.0 million. ProNAi will take on sponsorship and management of the clinical development of the agent from Cancer Research UK’s Centre for Drug Development and pay a fee of up to $2.0 million upon the successful transfer of the two ongoing Phase 1 clinical trials to the Company. Additional payments in the aggregate amount of up to US$319.5 million may become payable upon achievement of certain development, regulatory and commercial milestones. ProNAi will also owe CRT Pioneer Fund high single to low double digit royalties on net sales.

"This transaction adds another high-quality asset to our pipeline. PNT737 targets the DNA Damage Response (DDR) network, a promising approach to treating cancer based on recent leading-edge discoveries in cancer biology," said Dr. Nick Glover, President and CEO of ProNAi. "Cancer cells often depend on activated Chk1, a central cell cycle checkpoint regulator in the DDR network, as a strategy to survive and replicate despite accumulating extensive DNA damage due to replicative stress or in response to chemotherapeutic intervention. PNT737 is a potent and selective inhibitor of Chk1 that targets a potential Achilles’ heel of cancer cell proliferation and survival."

PNT737 was discovered and initially developed by scientists in the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research (ICR) in collaboration with Sareum Holdings plc (LSE AIM: SAR), with funding provided by Cancer Research UK, the ICR and Sareum. The program was licensed in September 2013 to the CRT Pioneer Fund, a specialist cancer investment fund established by Sixth Element Capital LLP (6EC), Cancer Research Technology (CRT) and the European Investment Fund (EIF) and managed by 6EC.

"This is another significant milestone on the development path for this promising Chk1 inhibitor. We recently initiated a Phase 1 single agent monotherapy study and a Phase 1 study of PNT737 in combination with DNA-targeting chemotherapies. ProNAi has a world-class oncology development team and is well-capitalized, and we believe these studies and the ongoing development strategy for this drug are in excellent hands," added Robert James, Managing Partner of 6EC.

Dr. Udai Banerji, Cancer Research UK Reader in Molecular Cancer Pharmacology at the ICR and Consultant at The Royal Marsden, stated: "This is an exciting opportunity to investigate a novel anticancer agent targeting the aberrant tumor DDR pathway. Two PNT737 clinical trials are now underway and, as Principal Investigator of these studies, I look forward to working closely with ProNAi to optimize the development path for this promising drug candidate."

Professor Paul Workman, Chief Executive and President of The Institute of Cancer Research, London, said: "I’m very pleased that ProNAi has secured the licence to take forward development of PNT737. This drug – which was discovered here at the ICR – represents an exciting new approach to targeting Chk1 and one that holds significant potential for treating several tumor types. I anticipate this agreement will help accelerate development of PNT737 and lead to an expanded program of clinical trials, to maximize the chances of patient benefit as quickly as possible."

Clinical development is currently taking place in facilities funded by Cancer Research UK, the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden and ICR, and the Experimental Cancer Medicine Centre Network. ProNAi anticipates expanding on the current clinical program underway for PNT737, including into the United States, with the expectation of filing an Investigational New Drug application in the second half of 2017. To support broader studies, ProNAi plans to conduct research designed to explore markers of sensitivity to PNT737 that may facilitate patient selection and to identify additional therapeutic combination strategies.

"The ICR and The Royal Marsden are world renowned for their work together in cancer research and this is a great opportunity for our team to collaborate on the early clinical development of a promising anti-cancer agent, where we can potentially employ innovative development strategies and leverage emerging science," said Dr. Barbara Klencke, Chief Development Officer of ProNAi. "A possible development path for PNT737 is the treatment of tumors carrying mutations in genes known to contribute to DNA damage and genomic instability – a key hallmark of cancer. The significant and persistent DNA damage caused by these mutations, coupled with Chk1 inhibition, may result in death of the cancer cells, a synergistic effect referred to as ‘synthetic lethality’. Similarly, excessive DNA damage can be induced with certain chemotherapies or radiation, highlighting the potential for synergies between these modalities and Chk1 inhibition."

"ProNAi is also advancing PNT141, a Cdc7 inhibitor that regulates DNA replication and the DDR network in a different, potentially complementary way to PNT737. Inhibiting both Chk1 and Cdc7 simultaneously may be advantageous and presents the potential for novel combination strategies for PNT737 and PNT141," added Dr. Christian Hassig, Senior Vice President, Research at ProNAi.

About PNT737 and Chk1
PNT737 is a highly selective, orally available, small molecule inhibitor of Checkpoint kinase 1 (Chk1).
DNA is continuously subject to damage through a variety of endogenous and exogenous mechanisms and, in turn, cells have developed complex processes to resolve this DNA damage. Chk1 is a central regulator in the DDR network of cellular pathways that detect and repair DNA damage. Chk1 impacts multiple cell cycle checkpoints, temporarily inhibiting the progression of cell replication and division in order for DNA repair processes to be undertaken.

Malignant cells tolerate substantially greater levels of DNA damage than would be acceptable in healthy cells. Cancer cells survive and replicate, despite accumulating DNA damage due to replicative stress, via an over-reliance on select components of the DDR network, including Chk1. As such, inhibition of Chk1 by PNT737 may be synthetically lethal to cancer cells and of potential benefit in the treatment of certain cancers.

Certain standard chemotherapeutic agents and radiotherapy also induce DNA damage in order to kill cancer cells. There exists potential for synergy between these standard therapies and Chk1 inhibitors such as PNT737.

Daiichi Sankyo to Present at ESMO 2016 Late-Breaking Clinical Data for Novel HER2-Targeting Antibody Drug Conjugate in T-DM1 Pre-Treated Breast Cancer

On September 27, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that safety and preliminary efficacy phase 1 data evaluating DS-8201a, a novel HER2-targeting antibody drug conjugate, will be presented during a late-breaking poster discussion session during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress from October 7 -11 in Copenhagen, Denmark (Press release, Daiichi Sankyo, SEP 27, 2016, View Source [SID:SID1234515463]).

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"We are looking forward to presenting these results for DS-8201a to the scientific community at ESMO (Free ESMO Whitepaper)," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Additionally, for the first time we will be showcasing our innovative in-house antibody drug conjugate technology that was used to develop DS-8201a."

LBA17: Single Agent Activity of DS-8201a, a HER2-Targeting Antibody-Drug Conjugate, in Breast Cancer Patients Previously Treated with T-DM1: Phase 1 Dose Escalation
Results from part 1 (dose escalation) of a two-part phase 1 study of DS-8201a by Kenji Tamura, MD, PhD, Chairman, Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo will be presented on Sunday, October 9 at 4:30 pm CEST. The primary objective of the dose escalation part of the study was to examine the safety and tolerability of DS-8201a along with determining the maximum tolerated dose. Secondary objectives include evaluating the pharmacokinetics and efficacy of DS-8201a. Additional sub-group analyses of preliminary efficacy of DS-8201a in advanced or metastatic breast cancer patients previously treated with ado-trastuzumab emtansine (T-DM1) will be presented.

About DS-8201a
DS-8201a is an investigational antibody drug conjugate comprised of a humanized anti-HER2 antibody attached by a peptide linker to a novel topoisomerase I inhibitor, utilizing Daiichi Sankyo’s proprietary payload and linker-payload technology. It is currently in phase 1 clinical development for HER2 expressing advanced or metastatic breast cancer or gastric cancer and other HER2 expressing solid cancers.

The second part (dose expansion) of the phase 1 clinical trial evaluating the safety and efficacy of DS-8201a is currently underway, and will enroll patients in the United States and Japan into one of four treatment cohorts: patients with HER2+ breast cancer previously treated with T-DM1; patients with HER2+ gastric or gastroesphageal junction adenocarcinoma previously treated with trastuzumab; patients with HER2-low expressing breast cancer; and, patients with other solid cancers that express HER2. For more information about the study visit ClinicalTrials.gov.