On November 15, 2018 Aradigm Corporation (NASDAQ: ARDM) (the "Company") reported financial results for the third quarter and nine months ended September 30, 2018 (Press release, Aradigm, NOV 15, 2018, View Source [SID1234531428]).

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Third Quarter 2018 Financial Results

The Company recorded $282,000 in revenue in the third quarter of 2018 compared with $2.7 million in revenue in the third quarter of 2017. The Company recognized $170,000 in contract revenue-related party, $52,000 in government contract revenue and $60,000 in government grant revenue for the third quarter of 2018, as compared to $2.7 million in contract revenue-related party, $6,000 in government contract revenue and $13,000 in government grant revenue for the third quarter of 2017.

Total operating expenses for the third quarter of 2018 were $2.8 million, compared with total operating expenses of $5.7 million for the third quarter of 2017. The decrease in research and development expenses of $2.0 million was due to a lower regulatory spend in support of Linhaliq during the ongoing EMA review process of the validated MAA submission and our ongoing interaction with the FDA to address the issues raised in their complete response letter dated 26 January 2018. The decrease in research and development expenses for the quarter was also due to lower employee related expenses from a reduction in headcount. The decrease in general and administrative expenses of $0.9 million was primarily related to lower legal expenses, lower consulting expenses and lower employee-related expenses due to a reduction in headcount.

Net loss for the third quarter of 2018 was $3.6 million or $(0.24) per share, compared with a net loss of $3.9 million or $(0.26) per share in the third quarter of 2017. For the quarter ended September 30, 2018, the net loss decreased by $0.3 million primarily from a decrease in operating expenses of $2.9 million offset by a decrease in revenue of $2.4 million and an increase of $0.2 million in other interest expense.

Liquidity and Capital Resources and Related Matters

As of September 30, 2018, the Company reported cash and cash equivalents of $2.9 million. During the second and third quarters of 2018 Aradigm raised an aggregate of approximately $7.0 million through the issuance and sale of promissory notes. In October 2018, Aradigm entered into an additional note purchase agreement for the issuance and sale of approximately $4 million in promissory notes, of which $2.0 million of promissory notes were issued and sold on October 25,

2018. Subject to the satisfaction of certain conditions, the Company anticipates that an additional closing for the issuance and sale of $2.0 million of promissory notes will occur prior to December 31, 2018. The Company believes that the $2.0 million received in October along with the cash balance of $2.9 million will be sufficient to fund operations through the fourth quarter of 2018. Aradigm is pursuing potential alternatives to resolve our cash position in the short-term as well as developing strategic options that would provide for our long-term viability. However, no assurance can be given that we will be successful in raising such additional capital on favorable terms or at all. Not achieving such funding on a timely basis would materially harm our business, financial condition and results of operations and could require us to delay or reduce the scope of all or a portion of our development programs, dispose of our assets or technology or to cease operations entirely.

About Non-Cystic Fibrosis Bronchiectasis

NCFBE is a severe, chronic and rare disease characterized by abnormal dilatation of the bronchi and bronchioles, frequently associated with chronic lung infections. It is often a consequence of a vicious cycle of inflammation, recurrent lung infections, and bronchial wall damage. NCFBE represents an unmet medical need with high morbidity and mortality that affects more than 150,000 people in the US. and over 200,000 people in Europe. There is currently no drug approved for the treatment of this condition

On November 15, 2018 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported the presentation of clinical and preclinical data supporting the development of TP-0903 for the treatment of patients with solid tumors (Press release, Tolero Pharmaceuticals, NOV 15, 2018, View Source [SID1234531405]). TP-0903 is an oral, small molecule inhibitor of the AXL receptor tyrosine kinase. Key findings from syngeneic mouse models suggest that TP-0903 has immune activating potential leading to enhanced host immune responses in tumor models.

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The data will be presented at the 2018 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Dublin. Posters will be on display from 10:00 a.m. to 2:00 p.m. GMT on Nov. 16 in the Exhibition Hall of the Convention Centre Dublin.

"There is a significant need to develop new cancer therapeutic solutions aimed at strengthening the body’s own immune response," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "AXL kinase is an important oncolytic target; we are encouraged by the findings of TP-0903 showing the inhibition of AXL kinase, demonstrating enhanced host immunity. We look forward to further developments of TP-0903 in counteracting AXL-mediated effects."

The data show that TP-0903 treatment alters tumors by suppressing the mesenchymal phenotype of the cancer cells and favoring a tumor microenvironment amenable to an immune response. Preclinical models in immune competent animals show modulation of immune cell populations, including neutrophils, regulatory T-cells, and dendritic cells, in the tumors. Additionally, the predictive power of soluble AXL levels in the serum of cancer patients as a biomarker to select patients likely to benefit from TP-0903 treatment will be presented.

Recent data suggest that AXL kinase is involved in tumor cell proliferation and development of resistance to chemotherapeutics. TP-0903 is an AXL receptor tyrosine kinase inhibitor, which has showed nanomolar activity in biochemical assays. In this preclinical study, the immune modulating capabilities were assessed using immunohistochemical and real-time PCR techniques in syngeneic mouse models of solid tumors.

The associated abstract #413, PB-076, is available on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) meeting program website.

About TP-0903
TP-0903 is an investigational oral, small molecule inhibitor of the AXL receptor tyrosine kinase (RTK), which has demonstrated effectiveness in cell-based and animal models of human cancers. The first-in-human Phase 1/1b study is underway identifying the safety and tolerability profile of TP-0903. In addition, the study is analyzing the pharmacodynamics of TP-0903 by assessing biomarkers in patients’ samples before and after treatment with TP-0903, including markers of immune suppression.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers. It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.1,2

On November 15, 2018 DNAtrix, a leader in oncolytic virus immunotherapies for cancer, reported that it will present interim results from the ongoing Phase 2 trial of its oncolytic virus DNX-2401 (tasadenoturev) with pembrolizumab for patients with recurrent glioblastoma at the upcoming 2018 Annual Meeting of the Society for Neuro-Oncology (SNO) which is being held in New Orleans, Louisiana from November 15th – 18th (Press release, DNAtrix, NOV 15, 2018, View Source [SID1234531404]).

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CAPTIVE / KEYNOTE-192 is a Phase 2 multicenter, dose escalation study evaluating a single intratumoral injection of DNX-2401 followed by standard dosing with pembrolizumab every three weeks to determine the optimal dose, safety, and efficacy in patients with recurrent glioblastoma. Preliminary results demonstrate that DNX-2401 with pembrolizumab is well tolerated, and associated with promising survival.

"I am excited by the early results of the trial. We have had some very remarkable responses. If I had not done the case myself, I would not have believed the complete response we have seen in one of our patients," said Gelareh Zadeh, MD, Associate Professor at the Department of Surgery University of Toronto, and presenting author for the CAPTIVE / KEYNOTE-192 study.

"There are limited treatment options for patients with this devastating disease, and we are encouraged by the initial data showing safety and disease control with the combination of DNX-2401 and pembrolizumab," added Frank Tufaro, PhD, CEO of DNAtrix. "We are pleased that enrollment is nearly complete and we are looking forward to maturation of the survival data."

DNAtrix collaborators will present additional results from studies of DNX-2401 (a.k.a. Delta-24-RGD) and murine DNX-2440 (a.k.a. Delta-24-RGDOX), an oncolytic adenovirus expressing the immune modulator OX40 ligand. Details of the presentations are as follows:

Interim results of a phase II multicenter study of the conditionally replicative oncolytic adenovirus DNX-2401 with pembrolizumab (Keytruda) for recurrent glioblastoma; CAPTIVE Study (KEYNOTE-192)
Date: Saturday, November 17
Abstract Number: ATIM-24
Presenter: Gelareh Zadeh, MD, University Health Network, University of Toronto, Toronto, ON, Canada
To access the abstract, click here >

Inflammatory reprogramming of gliomas using Delta-24-RGDOX and immunometabolic adjuvants
Date: Friday, November 16
Abstract Number: EXTH-27
Presenter: Teresa Nguyen, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
To access the abstract, click here >

Local oncolytic adenovirus treatment affects both the innate and adaptive arms of the immune system and provides an avenue for enhancing immunotherapies for GBM
Date: Friday, November 16
Abstract Number: EXTH-03
Presenter: Martine Lamfers, PhD, Erasmus Medical Center, Rotterdam, Netherlands
To access the abstract, click here >

In Situ Autovaccination Mediated by Oncolytic Adenovirus Delta-24-RGDOX Induces Efficacious Immunity Against Metastatic Melanoma
Date: Saturday, November 17
Abstract Number: EXTH-30
Presenter: Hong Jiang, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
To access the abstract, click here >

Delta-24-RGD in combination with positive regulators of the immune synapsis for gliomas in adults and children
Date: Sunday, November 18
Oral Presentation: Juan Fueyo, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

For more information about ongoing DNAtrix clinical studies, visit the ClinicalTrials.gov website: NCT02798406 (DNX-2401 + pembrolizumab for recurrent glioblastoma), NCT03178032 (DNX-2401 for newly diagnosed pediatric diffuse intrinsic pontine glioma, DIPG), and NCT03714334 (DNX-2440 for recurrent glioblastoma).

About DNX-2401 (Tasadenoturev)
DNX-2401 is an investigational oncolytic immunotherapy designed to treat cancer. DNX-2401 sets off a chain reaction of tumor cell killing by selectively replicating within cancer cells (but not normal cells), causing tumor destruction and further spread of the oncolytic virus to adjacent tumor cells. This process then triggers an immune response directed against the tumor. Previous studies demonstrated that DNX-2401 was well tolerated, provided clinical benefit, and extended survival for patients with recurrent glioblastoma.

On November 15, 2018 PsiOxus Therapeutics, Ltd. (PsiOxus) and the Parker Institute for Cancer Immunotherapy (Parker Institute) reported a research project to investigate the use of PsiOxus’ virus-based gene therapy for treating solid tumors that have been historically resistant to immunotherapy (Press release, PsiOxus Therapeutics, NOV 15, 2018, View Source [SID1234531403]).

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This pre-clinical immuno-oncology research will utilize PsiOxus’ proprietary T-SIGn platform. The platform uses the enadenotucirev oncolytic virus as a vector to deliver combinations of therapeutic transgenes to carcinomas to fight cancer.

In effect, the T-SIGn viruses work by turning tumor cells into "drug factories" to express gene therapy products, such as cytokines or antibodies, designed to engage the immune system to attack cancer cells.

The viruses first selectively infect and replicate only in tumor cells. The tumor cells then express the encoded genes, producing biologic therapies to alter the tumor microenvironment. Changing the tumor microenvironment is believed to enhance the activation of cancer-fighting immune cells so they can eradicate the tumor.

Working together, PsiOxus and the Parker Institute aim to build and test viruses carrying different combinations of genes.

"One of the challenges in treating solid tumors with immunotherapy is the tumor microenvironment, which is very suppressive and effectively prevents the immune system from attacking the tumor," said Fred Ramsdell, Ph.D., vice president of research at the Parker Institute. "What is promising about the PsiOxus approach is its potential to overcome this suppression using a novel virus platform to deliver gene therapy."

Unlike other oncolytic viruses that require direct injections to the tumor, which can be costly and complicated to administer, PsiOxus’ platform can be delivered to patients intravenously.

"Given the potential of PsiOxus’ IV-delivered cancer gene therapy platform, establishing strategic relationships with world leaders in immuno-oncology will accelerate our ability to bring gene therapy treatment to cancer patients," said Brian Champion, Ph.D., Chief Scientific Officer of PsiOxus. "The Parker Institute is a leader in building strategic relationships between leading immuno-oncology academic and industry partners. We are thrilled to collaborate with the Parker Institute to jointly accelerate research on innovative cancer immuno-oncology therapy."

On November 15, 2018 Sophiris Bio Inc. (NASDAQ: SPHS) (the "Company" or "Sophiris"), a biopharmaceutical company studying topsalysin (PRX302), a first-in-class, pore-forming protein, in late-stage clinical trials for the treatment of patients with urological diseases, reported that Randall E. Woods, president and chief executive officer, will present a corporate overview at the Piper Jaffray Healthcare Conference on Tuesday, November 27, 2018 at 2:00 p.m. ET in New York, NY (Press release, Sophiris Bio, NOV 15, 2018, View Source [SID1234531402]).

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The discussion will be webcast live and can be accessed through the Investor Relations page at www.sophirisbio.com. A replay of the presentation will be available on the Company’s website for 90 days.