On April 5, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the presentation of preclinical data for KO-947, its development candidate targeting the ERK1/2 kinases, and KO-539, its development candidate targeting the menin-MLL interaction, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 (Press release, Kura Oncology, APR 5, 2017, View Source [SID1234518488]).

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"We are progressing multiple programs aimed at addressing the urgent needs of cancer patients facing a poor prognosis and limited treatment options," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "The data presented today illustrate that KO-947 and KO-539 demonstrate significant anti-tumor activity in preclinical models, supporting their continued advancement as potential therapeutics."

About KO-947

KO-947 is a potent and selective inhibitor of ERK1/2 kinases, which are critical components of the MAPK pathway. Aberrant signaling caused by mutations or dysregulation of the MAPK pathway are frequent contributors to the development of cancer and are associated with numerous tumor types, including lung, colorectal and pancreatic adenocarcinomas and squamous cell carcinomas. Although small molecule inhibitors of BRAF and MEK have demonstrated clinical activity in selected patients, duration of response has been limited, and resistance is often associated with reactivation of the MAPK signaling pathway. In preclinical studies presented at AACR (Free AACR Whitepaper), KO-947 demonstrated prolonged inhibition of the MAPK pathway. Durable tumor regression was observed in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations, when KO-947 was administered on schedules ranging from daily to once weekly. Kura anticipates initiating a Phase 1 clinical trial for KO-947 in 1H 2017.

About KO-539

KO-539 is a potent and selective inhibitor of the interaction between the menin protein and the MLL fusion proteins, which characterize MLL leukemias. MLL-rearranged leukemia patients typically have a poor prognosis with a 5-year survival rate estimated to be 40%. As the leukemogenic activity of MLL fusion proteins has been shown to be dependent on their direct interaction with menin, the development of small molecules that block the menin-MLL interaction is a promising therapeutic strategy for the treatment of this disease. In preclinical studies presented at AACR (Free AACR Whitepaper), KO-539 demonstrated robust, sustained tumor regressions in multiple aggressive models of MLL-rearranged leukemias that correlated with modulation of target gene expression. KO-539 has been nominated as a development candidate, and further efforts are currently underway to assess potential utility of menin-MLL inhibitors in additional hematological malignancies and solid tumor indications.

On April 5, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported additional clinical translational and pre-clinical data from its ongoing intratumoral IMO-2125 development program at the AACR (Free AACR Whitepaper) 2017 Annual Meeting being held in Washington, DC (Press release, Idera Pharmaceuticals, APR 5, 2017, View Source [SID1234518486]).

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In the poster presentation entitled, "Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase 1/2 study in patients with anti-PD-1 refractory metastatic melanoma," Cara Haymaker, Ph.D. from the University of Texas, MD Anderson Cancer Center, presented an update on the translational findings from the ongoing Phase 1/2 trial of intratumoral IMO-2125 in combination with ipilimumab in patients with anti-PD-1 refractory metastatic melanoma.

The key findings in Dr. Haymaker’s presentation were that intratumoral IMO-2125 monotherapy in the injected lesions results in activation and maturation of dendritic cells, and the induction of type-1 interferon gene signature by 24 hours after first dose. After 8 weeks of therapy with intratumoral IMO-2125 and ipilimumab, increased immune infiltration has been observed in distant lesions of responding patients, suggesting an abscopal effect. Dr. Haymaker concludes that activation of intratumoral dendritic cells and induction of the associated downstream immune cascade enhances T-cell priming. In combination with checkpoint blockade, this mechanism may be an important key in treating patients who have been refractory to prior immune oncology approaches.

"We are excited to be examining the significant amounts of data emerging from this trial, which goes far beyond merely conducting clinical outcome analysis and to our knowledge has not been done to this depth before," stated Sri Chunduru, Ph.D., Idera’s Vice President, Translational Research. "The data emerging from the serial biopsies in these patients is highly informative to the guidance of our ongoing development program with IMO-2125 and leads us to a significantly greater understanding of tumor microenvironment before, during, and after immune therapy. We look forward to continuing to build upon this body of data as our study continues to enroll further patients. Importantly, we are very pleased that the data that has been generated validates our understanding of IMO-2125’s mechanism of action correlated with clinical results also generated to date."

A second poster presentation entitled, "Local treatment with novel TLR9 agonist IMO-2125 demonstrates anti-tumor activity in preclinical models of pancreatic cancer," presented by Daqing Wang, Ph.D., Principal Scientist & Group Leader, Idera Pharmaceuticals, demonstrated that intratumoral IMO-2125 showed dose-dependent antitumor responses associated with the increased tumor-infiltrating lymphocytes (TILs) in treated tumors of the Panc02 pancreatic cancer model. These antitumor responses and TILs were also observed in the distant, untreated tumors. In this study, treated mice, which remained tumor-free, showed lack of tumor growth upon rechallenge with the same tumor cells, suggesting an antitumor memory response.

Furthermore, a local treatment of IMO-2125 was evaluated by administering intraperitoneally in a peritoneal metastasis Panc02 model. Mice treated with intraperitoneal IMO-2125 showed increased survival compared to mice treated with placebo, control oligo compound or subcutaneous IMO-2125. Histological analysis showed significant reduction of tumor growth in the peritoneal cavity. This illustrates that while local treatment is necessary, routes of administration other than i.t. may also be effective to generate an antitumor response in pancreatic cancer. Overall, we believe these data demonstrate that treatment with IMO-2125 modulates the tumor microenvironment and increases infiltration by TILs and that these changes are associated with antitumor activity in pancreatic cancer models, and indicate that IMO-2125 may potentiate checkpoint inhibitor therapy for the treatment of pancreatic cancer.

A copy of the poster presentations are currently available on Idera’s corporate website at View Source

About IMO-2125
Toll-like receptors (TLRs) play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD-1) are designed to enable the immune system to recognize tumor cells. In this setting, intratumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs), and thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

Idera’s TLR9 agonist, IMO-2125 has been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was generally well tolerated in about 80 patients with hepatitis C. Idera has conducted further preclinical and clinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data being presented at several medical conferences during the past two years. The posters from these presentations can be found at View Source

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths. The American Cancer Society estimates that in 2017, there will be 87,110 new cases of melanoma in the U.S., and about 9,730 will die of this disease.

On April 5, 2017 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported results of preclinical in vitro and in vivo studies supporting the potential of BP1002 in the treatment of aggressive non-Hodgkin’s lymphoma (NHL) (Press release, Bio-Path Holdings, APR 5, 2017, View Source [SID1234518485]). These results are being presented at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place in Washington, DC.

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The poster titled, "Activity of Bcl-2 antisense therapeutic in aggressive non-Hodgkin’s lymphoma," summarizes results from two studies: an in vitro study in which 15 cells lines of aggressive NHL subtypes were incubated with BP1002; and two in vivo studies in which mice with follicular lymphoma xenografts were treated with BP1002. BP1002 was shown to have strong anti-NHL activity in each of these studies.

"Survival for patients with aggressive NHL has improved with the use of certain chemotherapy regimens, but the prognosis remains poor for the 30% of patients who relapse after treatment," said Peter Nielsen, chief executive officer of Bio-Path Holdings. "Aggressive NHL is associated with high levels of Bcl-2 expression, making it an ideal candidate for treatment with BP1002, a potent and targeted inhibitor of Bcl-2. While these results are early, we believe they indicate a potential for BP1002 to provide a survival benefit to patients with aggressive NHL. We look forward to initiating a clinical study later this year to assess this candidate in patients with NHL."

In the in vitro study, cell lines of germinal center B-cell lymphoma diffuse large B-cell lymphoma (DLBCL), activated B-cell DLBCL, mantle cell lymphoma and Burkitt’s lymphoma were incubated with BP1002. After four days, it was determined that BP1002 induced greater than 50% inhibition in 11 of the 15 cell lines tested. In the two animal studies, none of the untreated or control (empty liposome) mice survived beyond 39 days. In the BP1002 arms, a combined 87% of treated mice survived until the end of the 5-week studies.

About BP1002
BP1002 (Liposomal Bcl-2 antisense), Bio-Path’s second product candidate, is a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Bcl-2, a protein that promotes cellular survival and inhibits apoptosis. Bcl-2 is overexpressed in a majority of non-Hodgkin’s lymphoma subtypes, including follicular lymphoma and diffuse large B cell lymphoma, as well as in a wide variety of solid tumors. Bio-Path is preparing to submit an investigational new drug (IND) application for BP1002, and is planning to initiate a Phase 1 clinical trial for lymphoma in 2017.

On April 5, 2017 Heat Biologics, Inc. (Nasdaq:HTBX), a leader in the development of immunotherapies designed to activate a patient’s immune system against cancer, reported that it presented new preclinical data from its collaboration with OncoSec Medical Incorporated (Nasdaq:ONCS), focused on evaluating the combination of Heat’s immunotherapy platforms with intratumoral electroporation (EP), at the AACR (Free AACR Whitepaper) Annual Meeting (Press release, Heat Biologics, APR 5, 2017, View Source [SID1234518484]). In the poster entitled "Combined Intratumoral Electroporation and Allogenic Vaccination of Gp96-Ig/Fc-OX40L Stimulates CD8+ T cell Cross Priming to Tumor-Specific Neoantigens and Enhances Anti-Tumor Response," (abstract #5617) researchers combined EP of ComPACT DNA (expressing Gp96-Ig and FC-OX40L) directly into a tumor, with cell-based ComPACT vaccination, to explore the effects of an intratumoral plus vaccination approach in a preclinical mouse model of melanoma. Results confirmed that this combination approach led to increased antigen-specific CD8+ T cells, enhanced anti-tumor response and improved overall survival compared to individual treatments.

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"This proof-of-principal study shows there may be benefit in combining our vaccines with an intratumoral approach to deliver the vaccine directly into the tumor to increase the coverage of tumor-specific shared- and neo-antigen presentation," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "It opens up the possibility of pairing our ImPACT and ComPACT platform technologies with intratumoral approaches, which aligns with our strategy to advance new, synergistic immuno-oncology combinations to improve patient outcomes."

A copy of the abstract is available and can be viewed online through the AACR (Free AACR Whitepaper) website at www.aacr.org. The poster will be made available in the Publications section of Heat’s corporate website

About Heat Biologics, Inc.
Heat Biologics, Inc. (Nasdaq:HTBX) is an immuno-oncology company developing novel therapies that are designed to activate a patient’s immune system against cancer utilizing an engineered form of gp96, a protein that robustly activates the immune system. Heat’s highly specific T cell-stimulating therapeutic vaccine platform technologies, ImPACT and ComPACT, in combination with other therapies, such as checkpoint inhibitors, are designed to address three distinct but synergistic mechanisms of action: robust activation of CD8+ "killer" T cells (one of the human immune system’s most potent weapons against cancer); reversal of tumor-induced immune suppression; and T cell co-stimulation to further enhance patients’ immune response. Currently, Heat is conducting a Phase 2 trial with HS-110 (viagenpumatucel-L) in combination with an anti-PD-1 checkpoint inhibitor to treat patients with non-small cell lung cancer (NSCLC) and a Phase 2 trial with HS-410 (vesigenurtacel-L) in patients with non-muscle invasive bladder cancer (NMIBC).

Heat’s wholly-owned subsidiary, Zolovax, Inc., is developing therapeutic and preventative vaccines to treat infectious diseases based on Heat’s gp96 vaccine technology, with a current focus on the development of a Zika vaccine in conjunction with the University of Miami.

For more information, please visit www.heatbio.com.

On April 5, 2017 Geron Corporation (Nasdaq:GERN) reported a poster presentation by Janssen Research & Development, LLC describing non-clinical data on the telomerase inhibitor imetelstat at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held in Washington, D.C. from April 1-5, 2017 (Press release, Geron, APR 5, 2017, View Source [SID1234518483]). The poster presentation is available on Geron’s website at www.geron.com/presentations.

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"These data from preclinical studies presented at AACR (Free AACR Whitepaper) this year provide further insight into the mechanisms by which inhibiting telomerase with imetelstat may impact cancer cells," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "These studies also build on previously published reports that suggest the potential application of imetelstat in the treatment of multiple hematologic myeloid malignancies, including acute myeloid leukemia, and reflect the ongoing work by our colleagues at Janssen to advance the imetelstat program for patients in need of new therapies."

Poster Presentation

Title: Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia (Abstract #1101)

Prior research by others has shown that telomerase and BCL-2 are overexpressed in acute myeloid leukemia (AML) cells and are involved in blocking apoptotic signals. Therefore, Janssen designed preclinical studies to test whether inhibiting telomerase expression and/or activity and BCL-2 could enhance cell killing and result in a greater anti-tumor effect in AML through the combined administration of imetelstat and venetoclax, a selective BCL-2 inhibitor, as compared to either treatment alone.

Janssen presented data of imetelstat’s activity in combination with venetoclax in AML cell lines, patient samples and a mouse xenograft model. In AML cell lines, telomerase expression and activity were decreased by imetelstat and further reduced in combination with venetoclax. In addition, imetelstat enhanced apoptosis induced by venetoclax in AML cell lines and AML patient samples. Combining imetelstat with venetoclax in an AML mouse model prolonged survival, with four of ten mice alive approximately 80 days after treatment was stopped.

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting malignant progenitor cell clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms and cytopenias. Patients in these studies also experienced elevated liver enzymes, which resolved to normal or baseline in the majority of patients followed after imetelstat treatment was withdrawn. Imetelstat has not been approved for marketing by any regulatory authority.

About the Collaboration with Janssen

On November 13, 2014, Geron entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc., to develop and commercialize imetelstat for oncology, including hematologic myeloid malignancies, and all other human therapeutics uses. Under the terms of the agreement, Geron received an upfront payment of $35 million and is eligible to receive additional payments up to a potential total of $900 million for the achievement of development, regulatory and commercial milestones, as well as royalties on worldwide net sales. All regulatory, development, manufacturing and promotional activities related to imetelstat are being managed through a joint governance structure, with Janssen responsible for these activities.