On April 16, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, today provided highlights from its Research Reception held on Sunday, April 15, 2018, during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018.

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The Research Reception was organized to provide industry experts gathered at the AACR (Free AACR Whitepaper) with a comprehensive overview of OncoSec’s ongoing and anticipated clinical programs involving ImmunoPulse IL-12 (or Intratumoral tavo-EP) in metastatic melanoma and triple-negative breast cancer (TNBC), including an overview of a poster presented at AACR (Free AACR Whitepaper) regarding a Phase 1 pilot study of ImmunoPulse IL-12 in TNBC ("Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC)" – Poster 055 / Abstract CT022).

ImmunoPulse IL-12 is currently being used in several ongoing clinical trials, with the technology demonstrating evidence of anti-tumor activity in the treatment of various solid tumors, the potential to initiate a systemic immune response, and a favorable safety profile. ImmunoPulse IL-12 combines intratumoral plasmid IL-12 with electroporation to produce a controlled, localized expression of IL-12 in the tumor microenvironment, which in turn, enables the immune system to target and attack tumors throughout the body.
The full webcast and presentation slides from the Research Reception can be accessed via OncoSec’s website: View Source

The following is a recap of key highlights from the event:
Melanoma Data Update: OMS-I100 Monotherapy Study & OMS-I102 Pembrolizumab Combination Study
Led by Alain Algazi, MD of the UCSF Helen Diller Family Comprehensive Cancer Center, the first presentation provided data from the OMS-I100 Phase 2 clinical trial, which demonstrated that ImmunoPulse IL-12 delivered as a monotherapy promoted innate and adaptive immune responses, importantly driving increased CD8+ TIL frequency.
Updated clinical data from the OMS-I100 study demonstrated that, in addition to peripheral immune responses, regression of distal, non-treated lesions were observed on average in 45% of the patients
Also, the treatment-related reshaping of the tumor microenvironment points to amplification of the IFN-γ/IL-12 feedforward loop, which in addition to supporting anti-tumor immunity, triggers adaptive immune resistance (PD-L1 expression) and provides the basis for a combination with IL-12 and anti-PD-1 therapy
Updated data from the OMS-I102 Phase 2 clinical trial (ImmunoPulse IL-12 in combination with pembrolizumab) demonstrated a 57% progression free survival (PFS) rate at 21 months with 100% (11/11) duration of response and median PFS/OS not yet reached

OMS-I140 Protocol; Review of Intratumoral IL-12 Data in TNBC Presented at AACR (Free AACR Whitepaper)
Led by Melinda Telli, MD of the Stanford University Medical Center, the following presentation provided a review of the OMS-I140 Phase 1 pilot study of ImmunoPulse IL-12 in TNBC, including an analysis of initial findings from the study, which were presented as a poster during AACR (Free AACR Whitepaper). The Phase 1 pilot study was designed to determine whether intratumoral plasmid IL-12 with electroporation (ImmunoPulse IL-12) would elicit a pro-inflammatory molecular and histological signature in treated as well untreated sites. Following administration of ImmunoPulse IL-12 on Days 1, 5 and 8 of a single 28-day cycle, data was obtained from five patients of the 10-patient study.
Treatment-related increase in CD8+ TIL density was observed by intratumoral chromogenic staining in 2 of 5 patient tumors (1 treated /1 untreated tumor)
NanoString analysis suggests that 1 cycle of Intratumoral tavo-EP did not globally impact intratumoral immune-related gene expression
Evidence of a treatment-related productive systemic immune response was seen in reduced gMDSCs and increased SLECs in the peripheral blood
Reported treatment-related adverse events included transient pain associated with electroporation and fatigue (both grade 1)

These results suggest that Intratumoral tavo-EP is a safe and tolerable TIL-stimulating therapy of skin and subcutaneous TNBC tumors

Further study of this therapy in combination with anti-PD-1 antibody therapy is warranted
OMS-I141 Protocol; Upcoming Anti-PD-1 Combination Clinical Trial in TNBC
A presentation given by Pamela Munster, MD of the UCSF Helen Diller Family Comprehensive Cancer Center, provided a review of OncoSec’s proposed Phase 2 trial in TNBC involving a combination of ImmunoPulse IL-12 (intratumoral tavo-EP) and an anti-PD-1 antibody therapy. The future Phase 2 trial will be a Simon 2-stage minimax design, non-comparative, open-label, single-arm, multicenter study of ImmunoPulse IL-12 plus an anti-PD-1 antibody therapy.
The study is expected to enroll approximately 25 patients (15 in Stage 1, and, if appropriate, 10 in Stage 2) with TNBC and electroporation accessible cutaneous / subcutaneous tumors

The proposed primary endpoint is to assess efficacy as measured by objective response rate (ORR) by independent central review (ICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 of intratumoral tavo-EP in combination with an anti-PD-1 antibody therapy in subjects with inoperable locally advanced or metastatic TNBC
OncoSec expects to initiate this proposed study in 2018

PISCES/KEYNOTE-695 Operational Update
Led by OncoSec’s Chief Clinical and Regulatory Officer, Sharron Gargosky, PhD, the final presentation offered an operational assessment of PISCES/KEYNOTE-695, a global, multicenter Phase 2b, open-label trial of ImmunoPulse IL-12 in combination with pembrolizumab in patients with stage III/IV melanoma who have progressed or are progressing on either pembrolizumab or nivolumab treatment. OncoSec expects to report preliminary data at an upcoming medical meeting in 2018.

On April 16, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported four poster presentations being delivered at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") annual meeting (Press release, DelMar Pharmaceuticals, APR 16, 2018, View Source [SID1234525448]).

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On Sunday, April 15, 2018, DelMar presented a poster showing preclinical data demonstrating that VAL-083, a first-in-class small molecule chemotherapeutic, may be beneficial, either as a single-agent, or as part of combination therapy regimens, for difficult-to-treat, or resistant, pediatric high-grade gliomas, including diffuse intrinsic pontine glioma ("DIPG"). DIPG is a rare, inoperable childhood brain tumor with very poor prognosis and a bleak survival outlook. In a poster entitled, "Dianhydrogalactitol (VAL-083) has the potential to overcome major challenges in the treatment of DIPG," VAL-083 is shown to be active as a single-agent and synergistic with AZD1775, a Wee1 inhibitor, against DIPG cell lines with varying genetic profiles, including p53 and H3.3/H3.1 K27M mutations.

Today, DelMar will be presenting a poster showing preclinical data demonstrating that the combination of VAL-083 and PARP inhibitors may be an effective therapeutic approach for the treatment of cancer. The data show that VAL-083 can synergize PARP inhibitors in both a BRACA-proficient and –deficient setting. Multiple PARP inhibitors are currently approved for the treatment of recurrent breast and ovarian cancer. DelMar also presented data in this poster further demonstrating that VAL-083 is active as a single-agent against platinum-resistant ovarian cancer.
"These important data continue to support the broad potential of VAL-083 to provide a new treatment option against a range of cancers," said Saiid Zarrabian, DelMar’s interim president and chief executive officer. "Our ongoing clinical trials in MGMT-unmethylated GBM and planned trial in platinum-resistant ovarian cancer continue to leverage insights gained through more than 40 Phase 1 and Phase 2 clinical trials sponsored by the U.S. National Cancer Institute."

DelMar will present an update on two ongoing clinical trials for MGMT-unmethylated GBM tomorrow, Tuesday April 17, 2018:
A Phase 2 clinical trial of VAL-083 in patients with MGMT-unmethylated, bevacizumab (Avastin)-naïve recurrent glioblastoma, currently being conducted in collaboration with the University of Texas MD Anderson Cancer Center; and
A Phase 1-2 clinical trial of VAL-083 in combination with radiotherapy in patients with newly diagnosed MGMT-unmethylated GBM, currently being conducted in collaboration with Sun Yat-sen University Cancer Center.
DelMar’s poster presentations can be viewed on the company’s website at:
View Source
About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class," DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute ("NCI"). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at:
View Source.
VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On April 16, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the presentation of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the Company’s broad spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, APR 16, 2018, View Source [SID1234525340]). Filip Janku, M.D., Ph.D., Assistant Professor, The University of Texas MD Anderson Cancer Center presented the poster titled "Pharmacokinetic (PK), safety, and tolerability profile of DCC-2618 in a phase 1 trial supports 150 mg QD (once daily) selected for a pivotal phase 3 trial in gastrointestinal stromal tumors (GIST)" at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL. The poster includes an assessment of the safety and tolerability profile of DCC-2618 in 100 GIST patients treated at the recommended Phase 2 dose (RP2D) of 150 mg QD, which supports the selection of this dose for the ongoing pivotal, randomized Phase 3 INVICTUS study (NCT03353753).

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"The data presented at AACR (Free AACR Whitepaper) provides a robust assessment of the safety and tolerability profile of DCC-2618 in GIST patients at the 150 mg QD dose selected for the INVICTUS pivotal Phase 3 study in fourth-line and fourth line plus GIST, which we initiated in January 2018," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "If successful, the INVICTUS study could serve as the basis for a New Drug Application (NDA), providing a much-needed therapeutic option for these patients for whom there are no approved treatment options. We also plan to initiate a second Phase 3 registration study later this year, evaluating DCC-2618 in second-line GIST patients who have progressed, or are intolerant to front-line therapy with imatinib."

The poster presentation includes the following highlights:
Safety and tolerability of DCC-2618 on 100 GIST patients treated at the 150 mg QD dose out of the total of 169 patients treated with DCC-2618, as of the cut-off date of January 18, 2018.
As of March 19, 2018, 81 of 137 GIST patients enrolled at the cut-off date and treated at 100 mg or more per day, remained on study treatment. In addition, 46 patients were treated for more than 6 months, including 10 patients who were treated for more than 12 months.
Employing a population pharmacokinetic (PK) model based on steady state exposure to DCC-2618 and the active metabolite, DP-5439, increasing doses of DCC-2618 resulted in dose proportional increases in the combined exposure.

Preliminary data from the 12 GIST patients dose escalated from 150 mg QD to 150 mg BID following progression by RECIST (Response Evaluation Criteria in Solid Tumors) are immature and do not currently support a conclusion regarding a benefit from intra-patient dose escalation.
Based on the 100 GIST patients treated at the RP2D dose of 150 mg QD, DCC-2618 was well-tolerated, supporting the use of this dose in the pivotal, randomized Phase 3 trial, INVICTUS (NCT03353753).

About DCC-2618
DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, systemic mastocytosis and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

On April 16, 2018 Personalis, Inc., a provider of advanced genomic sequencing and analytics for immuno-oncology, reported that the company will present four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held this year in Chicago, Illinois from April 14-18, 2018 (Press release, Personalis, APR 16, 2018, View Source [SID1234525356]).

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Following is a list of abstracts that will be presented at the meeting.

Session ID / Poster Number

Title & Presenter
Day & Time
Location
PO.BSB01.01
1292
Methods of improving accuracy of neoantigen identification for therapeutic and diagnostic use in immuno-oncology
Presenter: Sean Michael Boyle
April 16
8am-12pm
Poster section
12
PO.BSB01.02
2245
Deconvolution of diverse immune cell populations within tumors using ACE Transcriptome
Presenter: Eric Levy
April 16
1-5pm
Poster section
12
PO.MCB09.08
5385
Supporting neoantigen discovery and monitoring in plasma through analytical validation of a deep Augmented Content Enhanced (ACE) exome
Presenter: Ravi Alla
April 18
8am-12pm
Poster section
17
PO.IM02.04
5710
Molecular profiling of anti-PD-1 treated melanoma patients reveals importance of assessing neoantigen burden and tumor escape mechanisms for clinical treatment
Presenter: Sean Michael Boyle

On April 16, 2018 Galera Therapeutics, Inc., a clinical-stage biotechnology company developing drugs targeting oxygen metabolic pathways with the potential to transform cancer radiotherapy, reported that preclinical data on GC4419, a highly selective and potent small molecule dismutase mimetic, were presented during poster sessions at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago (Press release, Galera Therapeutics, APR 16, 2018, View Source [SID1234525450]).

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/EIN News/ — "New therapies that enhance the efficacy of radiation on cancer cells while actually decreasing toxicity to normal tissue are desperately needed to improve therapeutic outcomes in cancer. We are encouraged that the data presented at AACR (Free AACR Whitepaper) demonstrate our lead candidate, GC4419, has these properties, underscoring its potential to become an important part of cancer radiotherapy," said Mel Sorensen, M.D., President and CEO of Galera. "We look forward to building upon positive results from our Phase 2b clinical trial of GC4419 in head and neck cancer with data like this, and with the Phase 1/2 trial of GC4419 in combination with stereotactic body radiation therapy in patients with locally advanced pancreatic cancer, which is underway at The University of Texas MD Anderson Cancer Center."
The radioprotector GC4419 ameliorates radiation induced lung fibrosis while enhancing the response of non-small cell lung cancer tumors to high dose per fraction radiation exposures

The studies from The University of Texas Southwestern Medical Center covered in this poster highlight that GC4419 can both significantly reduce the normal tissue toxicity of even high-dose radiation and increase tumor response to radiotherapy. Specifically, either pretreatment or mitigation with GC4419 significantly reduced pulmonary fibrosis in focally irradiated (54 Gy single dose) mice, similar to the reduction in severe oral mucositis seen in Galera’s clinical and pre-clinical studies. Separately, mice with H1299, A549, and HCC827 lung tumor xenografts were treated with GC4419 prior to irradiating the tumors with a single 18 Gy dose. Tumor growth in all three tumor types was significantly delayed (p = 0.0022), with the majority of mice apparently tumor-free at study end. Similar enhancements in tumor radiation response were seen with syngeneic lung (LLC) and breast (4T1) tumor models. Subsequent Tumor Cure Dose (TCD50) assays demonstrated that GC4419 enhanced the efficacy of radiation by a factor of 1.67.

GC4419 enhances the response of non-small cell lung carcinoma cell lines to cisplatin and cisplatin plus radiation through a ROS-mediated pathway
These studies from The University of Texas Southwestern Medical Center report that GC4419 synergistically decreased clonogenic survival in H460 and H1299 cells treated with either cisplatin or cisplatin plus radiation. Consistent with the mechanism in combination with radiation alone, GC4419 was found to reduce intracellular superoxide, increase intracellular hydrogen peroxide, and induce early apoptosis. H1299CAT cells were used to demonstrate that this enhancement of cisplatin and cisplatin plus radiation cancer cell killing is also due to elevation of H2O2. The results are particularly intriguing given that the combination of cisplatin and radiotherapy is the primary treatment modality in GC4419’s phase 2b trial in patients with head and neck cancer.

About GC4419
GC4419 is a highly selective and potent small molecule dismutase mimetic that closely mimics the activity of human superoxide dismutase enzymes. GC4419 works to reduce elevated levels of superoxide caused by radiation therapy by rapidly converting superoxide to hydrogen peroxide and oxygen. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the anti-tumor efficacy of radiation therapy. Conversion of elevated superoxide to hydrogen peroxide, which is selectively more toxic to cancer cells, can also enhance the effect of radiation on tumors, particularly with stereotactic body radiation therapy (SBRT), which produces high levels of superoxide.
GC4419 has been studied in patients with head and neck cancer, GC4419’s lead indication, for its ability to reduce the duration, incidence and severity of radiation-induced severe oral mucositis (SOM). Results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrated GC4419’s ability to dramatically reduce the duration of SOM from 19 days to 1.5 days (92 percent), the incidence of SOM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, while demonstrating acceptable safety when added to a standard radiotherapy regimen. In addition, in multiple preclinical studies, GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.
The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to GC4419 for the reduction of the duration, incidence and severity of SOM induced by radiation therapy with or without systemic therapy. The FDA also granted Fast Track designation to GC4419 for the reduction of the severity and incidence of radiation and chemotherapy-induced OM.