On April 3, 2019 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that data from pre-clinical studies supporting the potential of BP1003, a novel liposome-incorporated STAT3 oligodeoxynucleotide inhibitor, for the treatment of pancreatic cancer, non-small cell lung cancer (NSCLC) and acute myelogenous leukemia (AML) were presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 today in Atlanta, GA (Press release, Bio-Path Holdings, APR 3, 2019, View Source [SID1234535001]).

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The poster, entitled "BP1003, a Novel Liposome-Incorporated STAT3 Antisense Oligodeoxynucleotide Inhibitor," was presented by Ana Tari Ashizawa, Ph.D., Vice President of Research and Development at Bio-Path.

The poster highlights four antisense oligo sequences directed against STAT3 mRNA identified by Bio-Path and manufactured using DNAbilize antisense RNAi nanoparticle technology. Cell viability tests and Western blots were conducted to determine the inhibitory effects of liposome-incorporated STAT3 antisense oligo on NSCLC and AML cells. An ex vivo live tissue sensitivity assay (LTSA) was performed with a panel of 20 pancreatic ductal adenocarcinoma (PDAC) patient-derived xenografts (PDX) to study the overall activity of BP1003 alone, and in combination with gemcitabine. Using previously defined criteria, tissue slice viability inhibition greater than 30% and with a p<0.05 was considered to be a response. For validation of ex vivo results, PDAC PDX tumor bearing mice were administered BP1003 and gemcitabine twice a week for 28 days. Tumor volumes were monitored for up to 49 days.

The most potent liposome-incorporated STAT3 antisense sequence in decreasing NSCLC cell viability was selected as the drug candidate BP1003. Further validation in AML cells demonstrated that BP1003 inhibited cell viability and STAT3 protein expression. In the ex vivo LTSA assay, BP1003 at a dose of 10 µM significantly inhibited the tissue slice viability in 9 out of 18 PDAC PDXs by more than 30% (p<0.05). The combination of BP1003 and gemcitabine further enhanced ex vivo efficacy of BP1003 in a subset of PDXs. In the in vivo study with PDAC PDX models, a combination of BP1003 and gemcitabine caused tumor regression during the 28-day drug treatment period. This anti-cancer activity was maintained for another 21 days, even when drug treatment had ceased.

Preclinical pancreatic cancer models demonstrated that BP1003 successfully penetrated the stroma into pancreatic tumors. As previously reported, Bio-Path’s lead drug candidate, prexigebersen, has been tested in the above-described ex vivo pancreatic cancer preclinical model, and the results also demonstrated that prexigebersen penetrated the pancreatic tumors. Finally, the results in pancreatic cancer showed that BP1003 inhibited tumor slice viability in 9 of 18 PDAC PDXs.

"We believe these data suggest that between our two drug candidates, BP1003 and prexigebersen, Bio-Path will be able to treat human pancreatic tumors. The Company expects to initiate a Phase I study of prexigebersen for the treatment of solid tumors in 2019, including a cohort of metastatic pancreatic cancer patients. We plan to complete Investigational New Drug (IND) enabling studies in 2019 and to file an IND application for a Phase I study of BP1003 for the treatment of pancreatic cancer in 2020," stated Peter Nielsen, Chief Executive Officer of Bio-Path.

"We developed BP1003, a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide, as a specific inhibitor of STAT3 as it is thought to be one of the most important genes involved with a variety of cancers. STAT3 is considered to be an undruggable target, which has hampered the development of a therapy for it. Inhibition of STAT3 requires a systemic RNAi solution, such as DNAbilize, in order to exert its anti-cancer activity," noted Dr. Tari Ashizawa.

"These data are very encouraging and suggest that our two drug candidates, BP1003 and prexigebersen, are active against pancreatic cancer which is often treatment refractory and lethal. As with prexigebersen, studies to date have shown BP1003 to be generally safe and well-tolerated in preclinical models. We believe there is a great potential for the additional development of BP1003 as a treatment for NSCLC, AML and a variety of metastatic cancers," added Mr. Nielsen.

About Signal Transducer and Activator of Transcription 3 (STAT3)

Signal Transduction and Activator of Transcription-3 (STAT3), though typically inactive in normal cells, is aberrantly active in cancer cells. The abilities of tumor cells to proliferate uncontrollably, resist apoptosis, induce vasculature formation, and invade distant organs are well-recognized hallmarks of cancer. STAT3 is a regulator of the genes involved in these cancer processes. More recently, the capability of tumors to evade immune surveillance and avoid destruction by the immune system has also gained significant acceptance in the cancer research field. STAT3, which is a point of convergence for many oncogenic pathways, has emerged as a critical mediator of tumor immune evasion at multiple levels.

Activation of STAT3 has been found in many types of cancers, including NSCLC, AML, and PDAC. Activation of STAT3 correlates with poor clinical outcome, high grade disease and metastasis, and has been linked with resistance to chemotherapy, including gemcitabine, considered a standard-of-care agent for advanced PDAC. Therefore, inhibition of STAT3 in combination with chemotherapy is expected to produce enhanced clinical benefit.

On April 3, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported data on JTX-8064, its first tumor-associated macrophage program, at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Jounce Therapeutics, APR 3, 2019, View Source [SID1234535370]). The poster presentation includes preclinical data demonstrating the immunotherapeutic properties of JTX-8064 to reprogram immune-suppressive macrophages within the tumor microenvironment.

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"Today, we presented the characterization of JTX-8064 and the preclinical data for this novel product candidate, demonstrating its potential in re-programming tumor-associated macrophages within the tumor microenvironment to enhance anti-tumor immunity. We believe that LILRB2 functions as an immune checkpoint for macrophages and have demonstrated differentiation from other macrophage-directed approaches," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "New insights from our Translational Science Platform continue to inform JTX-8064 development and we expect to file an Investigational New Drug application and initiate a Phase 1 clinical trial later this year."

In a poster titled "Preclinical evaluation of JTX-8064, an anti-LILRB2 antagonist antibody, for reprogramming tumor-associated macrophages," Jounce researchers describe the preclinical evaluation of JTX-8064 including:

JTX-8064 is a specific and potent antagonist antibody of LILRB2 (leukocyte immunoglobulin like receptor B2; ILT4)
LILRB2 binds to its ligands (classical MHC I molecules [e.g. HLA-A, HLA-B] and non-classical MHC I molecules [e.g. HLA-G]) and maintains an immuno-suppressive state in macrophages. JTX-8064 blocks ligand binding to LILRB2 and induces an immune activating state in macrophages that may lead to enhancement of the anti-tumor immune response
Inhibiting LILRB2 induces pro-inflammatory cytokine secretion and a unique transcriptional profile suggestive of an M1-like shift in human macrophages, which is distinct from macrophage-targeted mAbs CSF1R and TIM-3
The poster is available on the "Our Approach" section of the Jounce Therapeutics website at www.jouncetx.com.

About JTX-8064
JTX-8064 is an anti-Leukocyte Immunoglobulin Like Receptor B2 (LILRB2) antibody and is the first candidate to emerge from Jounce’s Translational Science Platform efforts that focuses on tumor-associated macrophages. Preclinical data presented at the 2019 AACR (Free AACR Whitepaper) Annual Meeting supports the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. JTX-8064 is currently in IND-enabling activities and Jounce anticipates filing an IND and initiating a Phase 1 clinical trial for JTX-8064 in 2019.

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 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting pre-clinical data from ongoing research of RGX-019, a monoclonal antibody that targets MERTK, for the treatment of advanced cancer (Press release, Rgenix, APR 3, 2019, View Source [SID1234534968]). In a presentation of a late-breaking abstract, "Characterization of the anti-cancer and immunologic activity of RGX-019, a novel pre-clinical stage humanized monoclonal antibody targeting the MERTK receptor," which was accepted for the 2019 American Association of Cancer Research Annual Meeting, Isabel Kurth Ph.D., Rgenix VP of Research, discussed data showing RGX-019 to be a potent and selective inhibitor of MERTK signaling, resulting in suppression of cancer growth and activation of the innate immune response.

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RGX-019 is a humanized monoclonal antibody that selectively targets MERTK, a receptor tyrosine kinase of the TYRO3/AXL/MERTK (TAM) family. MERTK is expressed in immune cells such as macrophages, dendritic cells and NK cells, and is also overexpressed in a wide variety of liquid and solid cancers.

Activation of MERTK on cancer cells via ligand binding activates several tumor-promoting signaling pathways, stimulating tumor proliferation, migration and angiogenesis, and decreasing apoptosis and chemosensitivity. When activated on macrophages, MERTK promotes an immune-suppressive M2 phenotype.

RGX-019 binds to human MERTK with high affinity and selectivity, without detectible binding to other related TAM kinases. RGX-019 has a unique mechanism of action that not only leads to blockade of ligand binding, but also to MERTK degradation via receptor internalization.

This novel mechanism of action leads to inhibition of cancer growth in vitro and in vivo as well as activation of M1 (pro-inflammatory) cytokine release from immune-suppressive M2 macrophages.

Masoud Tavazoie, MD, PhD, and Chief Executive Officer of Rgenix, said, "We are excited to have an opportunity to reveal the pre-clinical data that demonstrates the positive progress we are making with the development of RGX-019, our third proprietary program. The ability of RGX-019 to selectivity degrade MERTK in cancers cells and M2 macrophages provides a distinct advantages over current small-molecule approaches to targeting MERTK which are hampered by off-target binding to other related kinases. This data provides a strong foundation for IND enabling studies."

Sohail Tavazoie, MD, PhD, and Chair of Rgenix’s Scientific Advisory Board, said, "RGX-019 shows great potential as a cancer therapeutic and its ability to selectively modulate both cancer growth and innate immune activation is illustrative of that possibility. We look forward to continuing our research on this antibody and its impact on various MERTK expressing cancers."

On April 3, 2019 Aileron Therapeutics (NASDAQ: ALRN), the clinical-stage leader in the field of stabilized cell-permeating peptides to treat cancer and other diseases, reported the closing of its previously announced private placement of Aileron common stock and warrants, resulting in gross proceeds of $26 million, before deducting placement agent fees and offering expenses, and excluding the exercise of any warrants (Press release, Aileron Therapeutics, APR 3, 2019, View Source [SID1234535002]).

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The private placement was led by Satter Medical Technology Partners, L.P. Additional participants included Jennison Associates (on behalf of certain clients) and an undisclosed institutional investor, in addition to other new and existing investors.

In connection with this financing, Aileron also announced that Dr. Nolan Sigal, a Partner at Satter, has joined Aileron’s Board of Directors.

Dr. Sigal has served as a partner at Satter Management, a private investment firm, since January 2018. From March 2008 to December 2017, Dr. Sigal was the president and chief executive officer of Tunitas Therapeutics, Inc., a private biopharmaceutical company. Prior to 2008, Dr. Sigal held various leadership positions with several public and private pharmaceutical and biotechnology companies, including Merck & Company, Trellis, Cytokinetics, and Pharmacopeia. Dr. Sigal received an A.B. from Princeton University and an M.D. and Ph.D. from the University of Pennsylvania School of Medicine.

"I believe that the application of Aileron’s proprietary peptide drug, ALRN-6924, in the indications of MDM2-amplified tumors (with Pfizer’s Ibrance) and myelopreservation represent compelling opportunities. As a member of the Board of Directors, I look forward to helping the Company as it seeks to create value for its shareholders through the advancement of these programs," stated Nolan Sigal, M.D., Ph.D.

"We expect that the proceeds from this closing will enable Aileron to achieve key clinical data readouts" said Dr. Manuel Aivado, M.D, Ph.D., CEO & President of Aileron. "We expect the addition of Dr. Sigal to our Board of Directors to play an important role in our success. His extensive research experience as an executive in the biotech industry makes him a welcome addition to the Aileron team."

In the private placement the Company sold 11,838,582 units, consisting of 11,838,582 shares of common stock and associated warrants to purchase 11,838,582 shares of common stock, for a combined price of $2.01 per unit. In addition, the Company also sold 1,096,741 units, consisting of pre-funded warrants to purchase 1,096,741 shares of common stock and associated warrants to purchase 1,096,741 shares of common stock, for a combined price of $2.01 per unit.

William Blair & Company, L.L.C. acted as sole placement agent in connection with the financing.

Aileron expects to use the net proceeds from the financing to fund the further advancement of its ALRN-6924 clinical trials and research programs, including its ongoing clinical trial collaboration with Pfizer testing ALRN-6924 in combination with palbociclib in MDM2-amplified cancers and its planned Phase 1b/2 clinical trial to evaluate ALRN-6924 as a myelopreservative agent to protect against chemotherapy-induced toxicity. This use of proceeds reflects Aileron’s decision to cease enrollment and clinical development in AML/MDS in light of the Company’s resources and its re-assessment of the commercial opportunities in AML/MDS considering the rapidly evolving competitive landscape in this field.

The securities sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or applicable state securities laws, and accordingly may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. Aileron has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in the private placement and the shares of common stock issuable upon the exercise of the warrants issued in the private placement.

This release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be by means of a prospectus.