1stOncology™: Cancer Intelligence Service – Page 15469 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

AVEO Announces First Patient Dosed in Phase 1/2 TiNivo Trial of Tivozanib and Opdivo® (nivolumab) in Advanced RCC

On March 22, 2017 AVEO Oncology (NASDAQ:AVEO) reported that the first patient has been dosed in the Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo (nivolumab), in advanced renal cell carcinoma (RCC) (Press release, AVEO, MAR 22, 2017, View Source [SID1234518233]). The study, which will be led by the Institut Gustave Roussy in Paris, is under the direction of Professor Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. The Phase 1 trial will evaluate the safety of tivozanib in combination with nivolumab at escalating doses of tivozanib and, assuming favorable results, is expected to be followed by an expansion Phase 2 cohort at the established combination dose.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"There is compelling scientific rationale for combining the antiangiogenic activity of VEGF inhibition with the immunologic activity of PD-1 inhibitors. Yet, to date, the tolerability of these combinations have been a challenge with currently approved VEGF TKIs and PD-1s," said Professor Escudier. "Tivozanib has been demonstrated to be the most selective VEGF inhibitor, delivering a uniquely favorable tolerability profile in past single agent and combination studies, and has the potential for minimal overlapping toxicities with immunotherapies. I look forward to understanding the clinical potential of combining tivozanib and nivolumab in the TiNivo study, and to the prospect of further improving outcomes in this very dynamic treatment area."

"VEGF-PD-1 combinations have yielded promising tumor response outcomes in renal cell cancer, yet the data presented to date point to challenging or prohibitive toxicity," said Michael Bailey, president and chief executive officer of AVEO. "We believe tivozanib offers a unique opportunity to potentially overcome this barrier, and look forward to initial results from the Phase 1 portion of the TiNivo trial in the first half of 2017."

About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

OXIS BIOTECH SCIENTIFIC ADVISORY BOARD MEMBER TO ADDRESS CANCER IMMUNOTHERAPY CONFERENCE IN CHINA

On March 21, 2017 Oxis International Inc. (OTCQB: OXIS) (Euronext Paris OXI.PA) reported that Dr. Daniel Vallera, a member of the Scientific Advisory Board of its wholly owned subsidiary, Oxis Biotech Inc., has been invited to speak at the 15th National Conference of Tumor Immunotherapy on June 22, 2017, in Hefei, China (Press release, OXIS International, MAR 21, 2017, View Source [SID1234539556]).

Dr. Vallera, Director of the section on Molecular Cancer Therapeutics at the University of Minnesota Masonic Cancer Center, said he will discuss two immunotherapy cancer treatments that he helped develop — Trispecific Killer Engager (TriKE) and Bispecific Killer Engager (BiKE). Both platforms have been licensed by Oxis.

The treatments empower the body’s immune system to identify and selectively kill cancer cells, while leaving healthy cells alone.

Dr. Vallera was instrumental in the development of Oxis’ promising cancer therapy, OXS-1550, which is currently in an FDA Phase 1/Phase 2 clinical trial in Minnesota.

The National Conference of Tumor Immunotherapy focuses on research, technology, clinical practice and government policy related to tumor immunology and immunotherapy. About 500 people are expected to attend.

Anthony Cataldo, Chairman and Chief Executive Officer of Oxis, said Dr. Vallera’s invitation is an indication that his work is widely recognized by his peers.

"We have received many requests for more information about the BiKE and TriKE platforms we have licensed from the University Of Minnesota," Mr. Cataldo said. "The biotech community realizes the potential for this technology and how it addresses the future of ‘Targeted Immunotherapy.’"

Dr. Vallera has spent 35 years with the University of Minnesota’s cancer center, where he oversees a laboratory specializing in the development of biological recombinant drugs focusing on bispecific antibody therapies that directly deliver toxic signals to cancer cells.

Final Results for the year ended 30 September 2016

On March 21, 2017 Redx (AIM: REDX) reported its results for the year ended 30 September 2016 (Press release, Redx Pharma, MAR 21, 2017, View Source [SID1234524746]):

Discovery engine delivers two assets to progress into clinical stage from extensive pipeline
Strategic refocus — Redx restructures to become a research and development focused company
£12 million gross raised post the period end and £10 million gross raised in March 2016
Pipeline produces first development assets
RXC004 — our best-in-class Porcupine inhibitor
Development candidate nominated for pancreatic, biliary and gastric cancer
Shown to have the potential to be used in combination with other immune-oncology products such as immune checkpoint inhibitors (anti-PD-1), with data presented at EORTC-AACR meeting in November 2016
Scheduled to enter first-in-human studies post clinical trial application (CTA) submission in Q2
Potential to treat fibrotic disease being investigated
RXC005 — our best-in-class reversible BTK inhibitor
In vivo proof of concept achieved for the reversible BTK program
Development candidate nominated for drug resistant chronic lymphocytic leukaemia (CLL) post -period
Pre-clinical profile presented at ASH (Free ASH Whitepaper) meeting in December 2016
Investigational new drug (IND) application and CTA to be filed around the end of 2017
Strategic Refocus
Redx will refocus its business to concentrate on its key assets in oncology and immunology, namely Porcupine and BTK
Anti-infectives research proposed to continue only under external collaborations
Redx remains committed to discovery research, but at a reduced investment level
Head count will be significantly reduced by around 86 positions. This equates to an approximately 60% reduction in staff
Key Financials
Net cash at 30 September 2016: £5.8m (2015: £9.4m)
Other operating income: £2.4m (2015: £2.6m)
Changes to the Board of Redx Pharma
The Board has received notifications from two directors, Dr Frank M. Armstrong, Chairman of the Board of Directors and Mr Peter McPartland, Non-Executive Director, have decided not to stand for re-election at the upcoming Annual General Meeting for shareholders. Dr Peter Jackson, Non-Executive Director, co-founder of Redx and Executive Chairman up to August 2014, will be stepping down from the Board on 31 March 2017.

Neil Murray, Chief Executive of Redx Pharma Plc, commented, Redx has created a world-class capability in small molecule drug discovery in oncology and immunology. We have a strong research engine that continues to deliver an innovative pipeline, but we must now shift our focus towards developing our key portfolio assets, specifically our Porcupine and BTK programs for hard to treat diseases. To reflect this new focus, we are reorganizing our business, including plans to reduce headcount.

On behalf of the Board of Redx I would like to thank Dr Frank M. Armstrong, Dr Peter Jackson and Mr Peter McPartland for their immense contributions to the success of Redx, both as a private and as a public company. Dr Peter Jackson has worked tirelessly for Redx since he helped found the business. I would also like to extend my personal thanks to Frank, Pete and Peter for the support they have given me and for the highly professional way in which they have carried out their roles.

Dr Frank M. Armstrong, Chairman of Redx Pharma Plc, added, I am pleased to have been a part of Redx, guiding the Company through the transition from private to public markets. Redx has made substantial progress with the portfolio since the IPO and I look forward to the Company’s continued progress as it makes this critical transition to clinical development and wish the Management, staff and shareholders every success for the future.

Lin BioScience Licenses Novel Therapeutic Program for Brain Cancer from the University of Sydney

On March 21, 2017 Lin BioScience, a drug development company specializing in innovative therapies for oncology, ophthalmology, and cardiology, reported an exclusive licensing agreement with the University of Sydney for a microtubule-targeting agent to treat brain cancers (Press release, Lin Bioscience, MAR 21, 2017, View Source [SID1234520604]).

The therapeutic candidate, LBS-002, is a small molecule that disrupts the division of cancer cells by preventing the formation of microtubules (the cell structures responsible for the segregation of chromosomes in cell division).

LBS-002’s ability to cross the blood-brain barrier shows promise for treating both primary and metastatic brain cancers

"To date, treating primary glioblastomas and metastatic brain cancers has been challenging because the blood-brain barrier prevents effective drugs from reaching their targets," stated Dr. Tom Lin, CEO of Lin Bioscience. "LBS-002’s ability to cross the blood-brain barrier enables it to overcome the permeability limitations experienced by traditional treatments, making it a promising therapeutic candidate. We’re excited to work with the expertise of Dr. Munoz, Dr. Kassiou and their teams at the University of Sydney to bring new cancer therapies to the clinic."

Under the terms of the agreement, Lin BioScience will gain exclusive global rights to the development and commercialization of intellectual property developed at University of Sydney by Drs. Lenka Munoz and Michael Kassiou. Further terms of the agreement are not disclosed.

"Our research has passed the discovery stage and now our goal is to progress into clinical testing," stated Drs. Munoz and Kassiou. "LBS-002 provides an exciting basis for a program that will lead to new treatments for brain tumors and we are very excited to be working with an innovative biotech like Lin BioScience in translating our fundamental research into clinical studies," said Drs. Munoz and Kassiou.

4SC-202 – a promising combination partner for cancer treatment

On 21 March 2017 4SC AG (4SC, FSE Prime Standard: VSC) reported that it will present two posters supporting the continued development of its product candidate 4SC-202, an epigenetic modulator with a unique mechanism of action that inhibits both the lysine-specific demethylase (LSD1) protein and class I histone deacetylase proteins (HDAC1, 2, 3), at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held on 1-5 April 2017 in Washington, D.C., USA (Press release, 4SC, MAR 21, 2017, View Source [SID1234518599]).

Both posters will be published on 4SC’s website on 3 and 4 April 2017, respectively.
4SC-202 plus checkpoint inhibition – boosting the immune system to fight cancer

"In the first set of experiments, we investigated the anti-tumor activity and mode of action of 4SC-202, both as single agent and in combination with anti-PD1 and anti-PD-L1 antibodies, both checkpoint inhibitors, in immunocompetent and immunocompromised mice. 4SC-202 showed anti-tumor activity alone and synergized with checkpoint inhibition by stimulating the immune system and increasing the number of cancer-killing cytotoxic T cells in the tumor microenvironment. Most importantly, this was achieved without harming the viability of the anti-tumor T cells, which differentiates 4SC-202 from other HDAC inhibitors," summarized Frank Hermann, M.D., Chief Development Officer of 4SC.

"These promising preclinical results build a rationale for further clinical development of 4SC-202. As we see highly synergistic effects of 4SC-202 in combination with checkpoint inhibitors, we should investigate the addition of 4SC-202 in cancer patients who are not responding to treatment with checkpoint inhibitors alone. In these patients, 4SC-202 might help to reactivate the immune system to fight the cancer."

Abstract #2632 / Poster #21: 4SC-202 induces inflamed tumor microenvironment, strongly enhances tumor infiltration with cytotoxic T cells and primes tumors for anti-PD-1/PD-L1 therapy
Date: Monday, 3 April 2017
Time: 1 – 5 p.m. EDT
Location: Section 25
4SC-202 – a potentially interesting player in acute myeloid leukemia (AML)

"In the second set of experiments we investigated a different capability of 4SC-202: the ability to induce differentiation in acute myeloid leukemia (AML) cells, which is a therapeutic approach already in use to treat that disease. We evaluated the anti-tumor activity of 4SC-202 alone and in combination with various cytokines to identify a suitable combination," said Roland Baumgartner, Ph.D., Chief Scientific Officer of 4SC.

"Treatment with 4SC-202 alone induced differentiation in AML cells. In combination with the cytokine interferon-γ (IFN-γ), 4SC-202 induced an enhanced tumor-specific T-cell response that can act against residual malignant AML cells which additionally highlights the potential of 4SC-202 to boost anti-tumor immunity."

Abstract #3088 / Poster #5: Combination of 4SC-202 and IFN-γ restores mature APC phenotype in AML cells
Date: Tuesday, 4 April 2017
Time: 8 a.m. – 12 p.m. EDT
Location: Section 3
Related articles

2 June 2016, 4SC at ASCO (Free ASCO Whitepaper): 4SC 202 and checkpoint inhibitors – strong partners in cancer treatment

21 March 2016, Epigenetic compound 4SC-202 strengthens endogenous immune response to cancer
Further information

About 4SC-202

4SC-202 is an orally administered small molecule for the treatment of cancer. 4SC-202 is an epigenetic modulator with a unique mechanism of action that inhibits both the lysine-specific demethylase (LSD1) protein and class I histone deacetylase proteins (HDAC1, 2, 3), which play significant roles in the regulation of signaling pathways in degenerated cancer cells.

4SC-202 has been investigated in a Phase I study with 24 intensively pretreated patients with several types of highly advanced hematologic cancers, and has proven to be tolerated. Positive signs of anti-tumor efficacy were observed with one complete remission for 28 months and one partial responder for 8 months.

Data from preclinical investigations showed that 4SC-202 strengthens the anti-tumor immune response. Treatment with 4SC-202 alters the tumor microenvironment and increases infiltration of immune cells into the tumor. In June 2016, further preclinical investigations showed that the combination of 4SC-202 with checkpoint inhibitors resulted in better anti-tumor activity than treatment with checkpoint inhibitors alone, suggesting a very promising clinical development path for 4SC-202 in both refractory and non-responding patients to treatment with checkpoint inhibitors.

About checkpoint inhibitors

The human immune system is capable of self-regulation via a wide variety of mechanisms to prevent excessive or misdirected defensive reactions. Tumors exploit these immune system "checkpoints" to switch off the immune response that specifically targets them. This is where checkpoint inhibitors are effective: they inhibit the signaling pathways to "release the brakes" on the immune cells and enable them to attack the cancerous tissue again.

Examples of checkpoint inhibitors that have returned promising data after investigation in clinical trials worldwide include drugs that block the PD-1 (Programmed Death-1) receptor on the surface of immune cells. The PD-1 receptor interacts with its ligands PD-L1 or PD-L2 on the surface of cancer cells to prevent the immune cells from attacking the tumor. With the PD-1 receptor or its ligand PD-L1 blocked, cancer cells can no longer escape the immune response.