On April 3, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that it will announce its first-quarter 2019 financial results on Thursday, April 25 before the market opens (Press release, AbbVie, APR 3, 2019, View Source [SID1234534956]). AbbVie will host a live webcast of the earnings conference call at 8 a.m. Central time (9 a.m. Eastern). It will be accessible through AbbVie’s Investor Relations website investors.abbvie.com. An archived edition of the session will be available later that day.

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On April 3, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology corporation, reported that preclinical research presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 demonstrated how the mechanism of action (MOA) of IMV’s proprietary DPX technology can enhance a broad spectrum of immune cell infiltration into tumors, which included T cells, Natural Killer (NK) cells, and macrophages (Press release, IMV, APR 3, 2019, View Source [SID1234534955]). Analyses also revealed the differentiated characteristics of the immune cell responses and the potential implications for enhanced anti-tumor efficacy.

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"The new preclinical data shared at this year’s AACR (Free AACR Whitepaper) Annual Meeting provides greater insight into the unique mechanism of our immunotherapy programs," said Marianne Stanford, Vice President, Research at IMV. "These data demonstrate our commitment to fully understanding how our platform impacts our product candidates, which in turn informs our clinical program designs and ability to identify patient needs that are more likely to benefit from our approach."

In the poster titled, T-distributed stochastic neighbor embedding (t-SNE) analysis of tumor infiltrating lymphocytes after treatment with a T cell activating therapy identifies a unique population of recruited CD8+ T cells and novel options for combination immunotherapy, IMV researchers used specialized data analytics to examine how DPX-based agents, when combined with cyclophosphamide (CPA), induced T cells to infiltrate tumors and attack cancerous cells. The study closely examined the types of immune cell responses and how and why they were able to affect disease.

The data indicated that this approach stimulated the infiltration of a broad base of immune cells into tumors, including T cells, NK cells, and macrophages. The specific T cell population that moved into tumors could be grouped based on the co-expression of different checkpoint molecules such as PD-1 and Tim-3. However, those stimulated to infiltrate tumors generally did not express CTLA-4 (a protein found on T cells that inhibits the immune response).

Researchers also found that combining DPX/CPA treatments with a CTLA-4-blocking antibody increased efficacy in controlling tumor growth in the animal models. The data suggested that this result was due to the antibodies acting on T cells present in the tumors, rather than those induced by treatment. This finding contrasts previously published studies with anti-PD-1 combinations in which treatment directly enhanced DPX-induced T cell responses.

"We believe there is a need for more targeted immunotherapy approaches and this work is another important step for us toward achieving this goal," said Frederic Ors, Chief Executive Officer, at IMV. "This is a new frontier in immuno-oncology drug development, and I’m proud of the work our team has done and the potential it represents to, ultimately, improve treatments for patients."

IMV’s current clinical program includes multiple phase 2 studies assessing the safety and efficacy of its lead candidate, DPX-Survivac, in combination with mCPA and Merck’s checkpoint inhibitor, Keytruda.

On April 3, 2019 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported the University of Texas MD Anderson Cancer Center’s (MDACC) Institutional Review Board (IRB) has approved a trial protocol amendment to expand DelMar’s ongoing Phase 2 clinical trial of VAL-083 in patients with MGMT-unmethylated glioblastoma (GBM) (Press release, DelMar Pharmaceuticals, APR 3, 2019, https://ir.delmarpharma.com/news/detail/891/delmar-pharmaceuticals-receives-approval-from-md-anderson-cancer-centers-irb-for-protocol-expansion-to-include-maintenance-stage-mgmt-unmethylated-gbm-patients-in-ongoing-phase-2-trial-of-val-083 [SID1234534949]). The biomarker driven trial, which was originally designed as a single arm study evaluating VAL-083 in patients with MGMT-unmethylated bevacizumab (Avastin)-naïve recurrent GBM, has been expanded to include an additional maintenance-stage (adjuvant therapy) treatment group.

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This protocol amendment, in addition to the Company’s ongoing Phase 2 trial in newly diagnosed patients with MGMT-unmethylated GBM being conducted at Sun Yat-sen University Cancer Center (SYSUCC), expands DelMar’s evaluation range of VAL-083 as a potential treatment for unmethylated GBM patients to include newly-diagnosed, maintenance-stage, and recurrent patients. Maintenance-stage GBM provides the greatest opportunity to control disease progression after radiation therapy, and represents the largest addressable GBM market opportunity for VAL-083 given patients are typically healthier and as such, are able to optimally benefit therapeutically from increased treatment cycles compared to the recurrent treatment setting. Maintenance GBM patients may be able to receive 12+ cycles of VAL-083 versus 5 or 6 cycles for recurrent GBM patients.

"VAL-083 offers a unique therapeutic approach that is independent of MGMT promoter status, has been shown to be safe, and may provide a valuable treatment option for the over 60% of patients with MGMT promoter unmethylated GBM who do not currently have strong chemotherapy options. As such, we are excited to expand the ongoing clinical trial at MD Anderson Cancer Center to include up to 24 maintenance (adjuvant) stage patients in the new treatment arm. This provides trial patients with VAL-083 much earlier than in the recurrent setting, and in lieu of adjuvant therapy with TMZ, which is acknowledged to be of limited value in this patient population," commented Principal Investigator Dr. Barbara O’Brian, Assistant Professor, Department of Neuro-Oncology, MD Anderson Cancer Center.

"The MGMT-unmethylated GBM patient population represents a significant unmet medical need and in fact, the 2017 NCCN guidelines highlight the inadequacy of currently approved therapies for these patients, who represent the majority of GBM cases. As the only company with late stage clinical assets focused on this underserved patient population, we are extremely pleased with the MDACC’s IRB approval to expand the Phase 2 trial to include the MGMT-unmethylated patients in the maintenance-stage setting," commented Saiid Zarrabian, President and Chief Executive Officer of DelMar Pharmaceuticals. "Moving forward, we will continue to maintain our clinical development focus on this biomarker-enriched patient population while leveraging our fast track status with the FDA to optimize the path to a potential regulatory approval."

The additional maintenance-stage treatment group is expected to enroll up to 24 newly diagnosed GBM patients who have completed chemo-radiation treatment with temozolomide (TMZ) without the continued TMZ maintenance therapy as provided for on the label. The trial will determine if intervention prior to TMZ maintenance therapy offers clinical benefit and extends the time to recurrence as compared to TMZ maintenance. In addition, the protocol amendment provides for enrollment of up to 35 additional patients for the ongoing recurrent patient trial arm to enable the trial arm to maintain the originally planned statistical powering.

About VAL-083

VAL-083 (Dianhydrogalactitol) is a novel bi-functional DNA targeting agent that rapidly induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083’s unique cytotoxic mechanism circumvents MGMT mediated chemoresistance and differentiates it from other therapies used in the treatment of GBM, including TMZ. This makes VAL-083 an ideal candidate to explore treating patients who are unlikely to respond to TMZ due to MGMT expression in their GBM as per the 2017 National Comprehensive Cancer Network guidelines (NCCN).

VAL-083 has been granted orphan drug designations 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 3, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported that preclinical data supporting activity of its STAT3-inhibiting Immune/Transcription Modulators was presented by Dr. Waldemar Priebe, Founder and Chair of the Scientific Advisory Board of Moleculin, Inc. at the 2019 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") in Atlanta, GA (Press release, Moleculin, APR 3, 2019, View Source [SID1234534948]).

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Please click the link below to view the Abstract for WP1066 and WP1732.

AACR Abstract:
View Source

The presentation included data resulting from preclinical evaluation in pancreatic cancer models of STAT3 inhibitors WP1066 and WP1732, both discovered at The University of Texas MD Anderson Cancer Center and licensed by Moleculin. WP1066 is an orally bioavailable drug with significant brain uptake that is currently in Phase I clinical studies in patients with brain tumors. Complementary to WP1066, STAT3 inhibitor WP1732 is suitable for IV administration and demonstrates high uptake by the pancreas without uptake to the brain. In vitro efficacy of both inhibitors was assessed using proliferation and apoptosis induction assays in a panel of patient-derived and commercially-available Pancreatic Ductal Adenocarcinoma ("PDAC") cell lines. Both WP1066 and WP1732 were similarly potent and shown to induce apoptosis and inhibit p-STAT3 and its nuclear localization in all tested PDAC cell lines. Observed IC50 values ranged from 0.5 to 2 μM. WP1732 was well tolerated by mice (LD50 85 mg/kg given IV). Pharmacokinetic and biodistribution studies revealed very high uptake of WP1732 in the pancreas of mice and rats exceeding up to ~30 fold more than the drug levels in plasma. Importantly, both agents show in-vivo efficacy in preliminary experiments when tested alone or in combination with T cell immune checkpoint inhibitors.

The presentation concluded that WP1066 and WP1732 are inhibitors of p-STAT3 with demonstrated in vitro and in-vivo activity against PDAC tumor models, and that preliminary data warrant the further pre-clinical and clinical evaluation of these oncology agents alone and in combination with immunotherapy as promising new therapeutics for pancreatic cancer.

"The scientific community has been increasingly focused on inhibition of p-STAT3 as a new area for developing cancer therapies," commented Walter Klemp, Moleculin’s Chairman and CEO. "Our Immune/Transcription Modulators have a unique ability to both inhibit p-STAT3 and other key oncogenic transcription factors and to stimulate a natural immune response. We believe available preclinical data and the data presented at this AACR (Free AACR Whitepaper) Conference form a solid basis to pursue translational efforts for pancreatic cancer as one of our primary indications."

On April 3, 2019 Aprea Therapeutics reported the results of studies with APR-246 in combination with immune checkpoint blockade presented by researchers from Memorial Sloan Kettering Cancer Center at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in Atlanta (Press release, Aprea, APR 3, 2019, View Source [SID1234534946]). The studies collectively support a role for p53 activity in the tumor microenvironment and suggest that stabilization of the tumor suppressor protein, p53, by APR-246 can enhance anti-tumor immune response, particularly when combined with immuno-oncology agents.

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The studies characterized changes in the tumor immune microenvironment in melanoma and colorectal cancer in vivo models when treated with APR-246 and immuno-oncology agents, either alone or in combination. APR-246 monotherapy treatment of melanoma tumors induced a pro-inflammatory tumor microenvironment. The analysis of tumor infiltrating immune cells demonstrated a pattern of gene expression suggesting that stabilization of p53 by APR-246 alters the immune tumor microenvironment and enables the immune system to target tumor cells more effectively. Anti-tumor activity was observed with APR-246 monotherapy; the combination treatment with APR-246 and anti-PD-1 enhanced the effects of PD-1 blockade in a T cell-dependent manner, as assessed by reduced tumor growth and improved survival. Also, the administration of APR-246 together with anti-PD-1 and anti-CTLA-4 dual immune checkpoint blockade significantly augmented anti-tumor control.

Abstract: 4843

Poster Title: TP53-stabilization with APR-246 enhances antitumor effects of immune checkpoint blockade in preclinical models.

Session Title: Targeted Therapies and Immunological/Tumor Microenvironment Effects

Poster Presentation Date and Time: Wednesday April 3, 2019, 8:00 am – 12:00 pm EDT

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 has been shown to reactivate mutant and inactivated p53 protein – by restoring wild-type p53 conformation and function – and thereby induce programmed cell death in human cancer cells. APR-246 has demonstrated pre-clinical anti-tumor activity in a wide variety of solid and hematological (blood) tumors, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase I/II clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.