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.

On November 15, 2018 MorphoSys and I-Mab Sign Strategic Partnering Agreement for MorphoSys’s Novel Immuno-Oncology Agent MOR210 (Press release, MorphoSys, NOV 15, 2018, View Source [SID1234531391])

MorphoSys AG (FSE: MOR; Prime Standard Segment, MDAX & TecDAX; NASDAQ: MOR) and I-Mab Biopharma ("I-Mab"), a biotech company focusing exclusively on innovative biologics in immuno-oncology and autoimmune diseases, jointly announced today that they have entered into an exclusive strategic collaboration and regional licensing agreement for MOR210. MOR210 is MorphoSys’s proprietary, preclinical-stage antibody directed against C5aR, which has potential to be developed as an immuno-oncology agent. I-Mab will have exclusive rights to develop and commercialize MOR210 in China, Hong Kong, Macao, Taiwan and South Korea, while MorphoSys will retain rights in the rest of the world. The agreement deepens the existing partnership between the two companies, building upon the ongoing collaboration on MorphoSys’s anti-CD38 antibody MOR202.

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Under the terms of the agreement, I-Mab will exercise its exclusive license rights for development and commercialization of MOR210 in its territories. With support from MorphoSys, I-Mab will perform and fund all global development activities for MOR210, including clinical trials in China and the U.S., towards clinical proof-of-concept (PoC) in oncology.

MorphoSys will receive an upfront payment of USD 3.5 million from I-Mab and will be eligible for development and commercial milestone payments of up to USD 101.5 million, as well as tiered, mid-single-digit royalties on net sales of MOR210 in I-Mab’s territories. In return for the execution of a successful clinical proof-of-concept study, I-Mab is eligible to receive low-single-digit royalties on net sales generated with MOR210 outside its territories and a tiered percentage of sub-licensing revenue.

"This deal builds on our excellent existing relationship with I-Mab for MOR202. We are delighted to grant rights for MOR210 in the Chinese region to I-Mab and enable them to conduct clinical proof-of-concept studies while we focus on other priorities", said Dr. Simon Moroney, Chief Executive Officer of MorphoSys. "The deal takes advantage of our very close working relationship to the benefit of both companies".

"The release of immune checkpoint blockades within the tumor has become a successful strategy to fight cancers. MOR210 is a novel immuno-oncology asset directed against C5aR made by MorphoSys. By adressing this target molecule, we seek to modulate the tumor microenvironment. We look forward to seeing I-Mab drive this interesting program forward into clinical studies, while we retain rights to continue development of MOR210 outside of I-Mab’s territories after clinical proof of concept," commented Dr. Markus Enzelberger, Chief Scientific Officer of MorphoSys AG.

"This agreement is part of our continued efforts to develop innovative biologics with First-in-Class and Best-in-Class potentials," said Dr. Jingwu Zang, Chief Executive Officer of I-Mab. "Through partnership with global innovative companies such as MorphoSys, we expand our innovative oncology portfolio to address unmet medical needs in China and jointly develop drug candidates for the world."

"We look forward to deepening our productive partnership with MorphoSys. We are thrilled to pursue the therapeutic potential of MOR210 with the ultimate goal of translating it into a new treatment option for patients in immuno-oncology," Zang added.

About MOR210 and C5aR
MOR210 is a preclinical-stage human antibody directed against C5aR derived from MorphoSys’s HuCAL Platinum(R) technology. C5aR, the receptor of the complement factor C5a, is investigated as a potential new drug target in the field of immuno-oncology and autoimmune diseases. Tumors have been shown to produce high amounts of C5a which, by recruiting and activating myeloid-derived suppressor cells (MDSCs), is assumed to contribute to an immune-suppressive pro-tumorigenic microenvironment. MOR210 is intended to block the interaction between C5a and its receptor, thereby being expected to neutralize the immune suppressive function of the MDSCs and to enable immune cells to attack the tumor.