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OCTIMET partners OMO-1 and OMO-2 with Shanghai Allist Pharmaceuticals Co., Ltd. for Greater China

On September 16, 2020 OCTIMET Oncology NV, a clinical-stage Belgian life science company with a focus on the development of highly selective, differentiated MET kinase inhibitors, reported the licensing of the Greater China rights for its lead clinical compound OMO-1 and a second preclinical asset exclusively to Shanghai Allist Pharmaceuticals Co., Ltd (Press release, Octimet Oncology, SEP 16, 2020, View Source [SID1234565266]).

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OMO-1 is an oral, highly selective small molecule MET kinase inhibitor, that has demonstrated potent single agent and combination activity in a range of preclinical cancer models.

OMO-1 has been evaluated in a monotherapy setting as well as in combination with small molecule EGFR tyrosine kinase inhibitors (TKIs) in Europe, showing a favorable safety profile and early signs of efficacy in MET-selected cancer patients. Allist will drive the clinical development of this compound in China, initially focusing on expanding the combination data with Allist’s third generation EGFR TKI Furmonertinib (AST2818). In China, more than 38% of NSCLC patients harbor activating EGFR mutations, making the region ideal for completing expanded clinical efficacy studies more rapidly whilst addressing a large potential market.

"We are proud to have Shanghai Allist Pharmaceuticals Co., Ltd. as a partner in developing this exciting therapeutic agent," said Shelley Margetson, Chief Executive Officer of OCTIMET. "Development in China is strategically important for OMO-1 and we look forward to seeing the results of the combination studies with Allist’s EGFR TKI compound, thereby making a difference for cancer patients in need of efficacious targeted therapies."

"MET amplification is known to be a key driver of resistance to EGFR TKIs. We are excited to explore further the combination of OMO-1, a differentiated selective MET kinase inhibitor, with our innovative third generation EGFR TKI Furmonertinib and look forward to generating significant efficacy data that will aim to meet clinical unmet need in providing further treatment for seriously ill cancer patients who have few other therapy options," said Ms. Sandy Mou, the CEO from Allist Pharmaceuticals.

About OMO-1

OMO-1 is a small molecule inhibitor of the enzymatic activity of the MET receptor tyrosine kinase (RTK). The MET gene has been shown to be responsible for some hereditary types of cancer. In addition, inappropriate MET activation has been shown in most types of solid tumors, often correlating with poor prognosis (Trusolino et al 2010, Gheradi et al 2012).

About EGFR Tyrosine Kinase Inhibitors

Lung cancer is the leading cause of cancer-related mortality worldwide. Of all lung cancer cases, 80–85% are non-small-cell lung cancers (NSCLC), and the majority of these cases are in advanced or metastatic stage (III or IV) at the time of diagnosis. Among these patients with NSCLC, a substantial number are harboring activating EGFR mutations, ranging from 10% in Europe to 38.4% in Asia. During the past years, EGFR tyrosine kinase inhibitors (TKIs) have been developed and have become standard first-line treatment for patients with EGFR mutation-positive NSCLC. Various trials showed higher response rates and improved progression-free survival (PFS) for first-line treatment with the EGFR TKIs afatinib, erlotinib, and gefitinib compared to platinum-based doublet therapy in patients with activating EGFR-mutated NSCLC.

Kanazawa University research: Potential drug treatment for particular type of lung-cancer

On September 16, 2020 Kanazawa University reported in Nature Communications the mechanism making some lung-cancer patients resistant to the drug osimertinib (Press release, Kanazawa University, SEP 16, 2020, View Source [SID1234565264]). In addition, they suggest a combined drug treatment resolving osimertinib resistance in the case of cancer cells expressing low amounts of AXL, a protein belonging to the class of receptor tyrosine kinases.

The effectiveness of cancer treatment is often hampered by cancer cells being heterogeneous. This is the case for EGFR-mutated lung cancer: drugs based on biomolecules of a type known as tyrosine kinase inhibitor (TKI) have been used to treat the disease, but with various levels of efficacy. (EGFR stands for "epidermal growth factor receptor", a protein playing an important role in signaling processes from the extracellular environment to a cell.) Sometimes, tumor cells are simply resistant to the drug. Now, Seiji Yano from Kanazawa University and colleagues have investigated the efficacy of the TKI osimertinib for treating EGFR-mutated lung cancer, and how it relates to the expression in tumor cells of a particular protein called AXL. They found that both AXL-high and -low expressing tumor cells showed tolerance (acquired resistance) to osimertinib, but that the mechanisms involved are different for the two situations. Moreover, the researchers suggest a way to enhance the success of osimertinib treatment for the case of AXL-low expressing tumors.

First, the scientists compared the susceptibility to osimertinib in both AXL-high and -low expressing tumor cells in in vitro experiments. They observed that osimertinib inhibited the viability of the cancer cells in both cases, but that the sensitivity to the drug was higher for AXL-low expressing EGFR-mutated lung cancer cells. They also noticed that a small number of tumor cells survived the procedure — an indication of osimertinib tolerance. These findings were consistent with results from the clinical study of the drug performed earlier on 29 patients with EGFR-mutated non-small cell lung cancer.

Through experiments aiming to understand the mechanism behind osimertinib tolerance, Yano and colleagues discovered that phosphorylation of IGF-1R was increased in AXL-low-expressing tumor cell lines, but not in AXL-high expressing tumors. (IGF-1R stands for ‘insulin-like growth factor 1 receptor’; it is a protein located on the surface of human cells. Phosphorylation is the chemical process of adding a phosphoryl group.) The researchers then found that phosphorylated IGF-1R supported the survival of AXL-low expressing tumors after exposure to osimertinib.

The scientists then tested whether the observed osimertinib resistance could be resolved by administering linsitinib, a substance known to inhibit the phosphorylation of IGF-1R. Encouraged by the positive outcome of the experiment, Yano and colleagues went further and evaluated the combination of osimertinib and linsitinib. Their conclusion was that the transient combination of linsitinib with continuous osimertinib treatment could cure or at least dramatically delay tumor recurrence in AXL-low-expressing EGFR-mutated lung cancer. More investigating needs to be done, though. Quoting the researchers: "… the safety and efficacy of the transient combination of IGF-1R inhibitor and osimertinib should be evaluated in the clinical trials."

Background

Tyrosine kinase inhibitors

A tyrosine kinase inhibitor is a drug inhibiting (that is, preventing or reducing the activity of) a specific tyrosine kinase. A tyrosine kinase is a protein (enzyme) involved in the activation of other proteins by signaling cascades. The activation happens by the addition of a phosphate group to the protein (phosphorylation); it is this step that a tyrosine kinase inhibitor inhibits. Tyrosine kinase inhibitors are used as anticancer drugs. One such drug is osimertinib, used to treat EGFR-mutated lung cancer.

AXL

AXL is a receptor tyrosine kinase — a tyrosine kinase consisting of an extracellular part, a transmembrane part (‘sitting’ within a cell membrane) and an intracellular part. AXL regulates various important cellular processes, including proliferation, survival and motility.

In recent years, it has become clear that AXL is a key facilitator of drug tolerance by cancer cells. Seiji Yano from Kanazawa University and colleagues have found that this is also the case for EGFR-mutated lung cancer. While a high expression of AXL correlates with resistance to osimertinib, such tolerance also occurs in AXL-low-expressing cancer cells. Yano and colleagues have now found that for the latter case, phosphorylation of IGF-1R (insulin-like growth factor 1 receptor) is responsible for the resistance to osimertinib.

Reference

Rong Wang, Tadaaki Yamada, Kenji Kita, Hirokazu Taniguchi, Sachiko Arai, Koji Fukuda, Minoru Terashima, Akihiko Ishimura, Akihiro Nishiyama, Azusa Tanimoto, Shinji Takeuchi, Koshiro Ohtsubo, Kaname Yamashita, Tomoyoshi Yamano, Akihiro Yoshimura, Koichi Takayama, Kyoichi Kaira, Yoshihiko Taniguchi, Shinji Atagi, Hisanori Uehara, Rikinari Hanayama, Isao Matsumoto, Xujun Han, Kunio Matsumoto, Wei Wang, Takeshi Suzuki, and Seiji Yano. Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer, Nature Communications 11, XX (2020).

DOI: 10.1038/s41467-020-18442-4

Bausch Health Provides Company Update At 18th Annual Morgan Stanley Global Healthcare Conference

On September 16, 2020 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health" or the "Company") reported it has published a presentation that Joseph C. Papa, chairman and CEO, and Paul S. Herendeen, executive vice president and chief financial officer, are scheduled to present at the virtual 18th Annual Morgan Stanley Global Healthcare Conference today, Sept. 16, 2020, at 1:15 p.m. ET (Press release, Bausch Health, SEP 16, 2020, View Source [SID1234565263]).

The presentation provides an update on Bausch Health’s current business recovery in the wake of the COVID-19 pandemic, as well as an update and progress report regarding the Company’s previously disclosed intention to spin off its eye health business.

The presentation is available on the Investor Relations page of the Bausch Health Companies Inc. web site at: View Source A live webcast and audio archive of the event will be also be available for 90 days.

Genelux to Present Data from Phase 2 Trial of Olvi-Vec in Heavily Pre-treated Platinum-Resistant/Refractory Ovarian Cancer at ESMO Virtual Congress 2020

On September 16, 2020 Genelux Corporation, a privately-held biopharmaceutical company, reported that data from the Phase 2 VIRO-15 study evaluating its lead oncolytic virus, Olvi-Vec-primed immunochemotherapy in platinum-resistant/refractory ovarian cancer (PRROC) (NCT02759588), will be presented at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020, being held September 19-21 (Press release, Genelux, SEP 16, 2020, View Source [SID1234565262]).

"The Phase 2 data in PRROC patients demonstrated remarkable overall survival in combination with a platinum-based regimen, especially in the difficult-to-treat platinum-refractory disease population, considering these patients were heavily pretreated and largely at pre-hospice stage," said Robert Holloway, MD, principal investigator for VIRO-15 and Chair of Genelux’s Clinical Advisory Board on gynecologic cancers.

"Genelux is pleased with the promising data out of the Phase 2 VIRO-15 study, and we are optimistic about the potential of Olvi-Vec-primed immunochemotherapy to extend the life expectancy and improve the quality of life of patients who currently lack effective treatment options," said Thomas Zindrick, J.D., President and CEO of Genelux. "A registration trial of Olvi-Vec-primed immunochemotherapy is being planned."

Data from the Phase 2 VIRO-15 trial are outlined below.

Abstract Number: 2982

Abstract Title: Phase 2 Trial of Oncolytic Vaccinia Virus Olvi-Vec-Primed Immunochemotherapy in Heavily Treated Platinum-Resistant/Refractory Ovarian Cancer (PRROC)

Abstract Authors: Robert W. Hollowaya, Alberto A. Mendivilb, James E. Kendricka, Lisa N. Abaidb, John V. Brownb, Christine K. Fitzsimmonsa, Jessica A. Kennarda, Monica Kingb, Jane LeBlanca, Katrina Lopezb, Madhavi Manyama, Nathalie D. McKenziea, Kristina M. Morib, Amanda J. Stephensa, Sarfraz Ahmada. aAdventHealth Cancer Institute, Orlando, FL 32804, USA, bGynecologic Oncology Associates, Newport Beach, CA 92663, USA

Session Title/Date: ESMO (Free ESMO Whitepaper) Virtual Congress 2020, Science Weekend, September 19-21, 2020

Abstract Highlights:

Background: Intraperitoneal infusion of Olvi-Vec virus followed by IV carboplatin-doublet (CD) ± bevacizumab (Bev) in heavily pretreated patients with PRROC was evaluated. Primary objectives were RECIST overall response rate (ORR) and progression-free survival (PFS). Secondary objectives included overall survival (OS), CA-125 response, safety and translational studies.

Methods: Patients who progressed on most recent therapies received 2 consecutive days of Olvi-Vec followed by CD ± Bev, and then maintenance single agent ± Bev. Pre- & post-virotherapy tumor biopsies and blood were obtained for analyses.

Key results: 27 patients (median 4 prior lines, 52% platinum-refractory, 48% platinum-resistant) enrolled. Median OS was 15.7 mos (95% CI: 12.3 – 23.5) for all patients. 9/27 (33.3%) patients have survival > 18 months, with 4 of these patients still alive beyond 3-4 years. In patients with platinum-refractory disease, median OS was 15.2 months (95% CI: 10.8 – 33.6).

Conclusions: Despite having PRROC and documented disease progression at enrollment, most patients responded to CD therapies after oncolytic virotherapy, with OS exceeding historical comparisons in heavily pretreated PRROC patients. Virus-induced changes in the tumor microenvironment may explain the apparent reversal of platinum resistance.

About Olvimulogene Nanivacirepvec (Olvi-Vec)
Olvi-Vec is a proprietary, non-pathogenic oncolytic vaccinia virus, modified to increase its safety, tumor selectivity and anti-tumor activity. Virus-mediated oncolysis results in immunogenic cell death and triggers immune activation and memory for long-term immunotherapy against cancer. Clinical results in more than 150 subjects have shown Olvi-Vec is well tolerated with documented clinical benefits.

Ashion Analytics announces innovative cancer treatment partnership with Elevation Oncology

On September 16, 2020 Ashion Analytics LLC reported a partnership with Elevation Oncology, a clinical stage biopharmaceutical company, focused on the matching of patients with tumors harboring an NRG1 gene fusion identified using Ashion’s proprietary GEM ExTra test with CRESTONE, a registration-directed Phase 2 study sponsored by Elevation Oncology (Press release, Ashion Analytics, SEP 16, 2020, View Source [SID1234565261]).

NRG1 gene fusions are a rare genomic alteration implicated as a driver of tumorigenesis and growth across many types of solid tumors, including lung, breast, pancreatic, ovarian, and colorectal cancers. CRESTONE — or Clinical study of REsponse to Seribantumab in TumOrs with NEuregulin 1 (NRG1) fusions — provides an investigational treatment opportunity for patients with any advanced solid tumor who have not responded or are no longer responding to standard cancer treatment, and whose tumor has tested positive for an NRG1 fusion.

This partnership creates a new dynamic in the way cancer patients can be matched to precision medicine therapeutics. By first identifying a genetic driver that has an available targeted therapy option, in this case an NRG1 fusion and the investigational therapy seribantumab, the diagnostic technology, data insights, and network reach at Ashion Analytics can be leveraged to efficiently identify and directly match eligible patients to the CRESTONE trial using test results that are already available today, while also maximizing the value of every additional test.

"The comprehensive nature of the GEM ExTra test means that its value grows directly with each new genomic driver that is identified and each new precision therapy under development," said Laurie Goodman, Ph.D., Ashion Analytics Director of Business Development and Medical Affairs. "Partnerships like this enable us to continuously facilitate the ability for our patients to receive the most up-to-date information about the emerging treatment opportunities available to them today."

Ashion Analytics recently announced that Medicare has approved coverage of its proprietary cancer profiling test, GEM ExTra, one of the nation’s most comprehensive genomic cancer analysis tests. Medicare coverage enables potentially 44 million more patients to afford this test, which aims to match patients with best available treatments for their disease.

GEM ExTra detects tumor-specific mutations in both DNA and RNA, allowing physicians to make the best-available treatment recommendations for patients with advanced solid tumors. An Ashion study poster presented at the 2020 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) details the importance of using RNA as part of the analysis to give cancer physicians the best possible options for treating their patients: Employing RNA Sequencing to Enhance Treatment Options for Cancer Patients.

This leading-edge test provides treating physicians with vital interpreted information needed to understand changes to a patient’s genomic profile. It outlines a therapeutic treatment plan best suited for each patient. Conditions that may benefit from this approach include treatment of refractory, rare or aggressive cancers.

"We are partnering with Ashion Analytics because we recognize the sensitivity and continuing potential of their GEM ExTra cancer profiling test," said Shawn Leland, PharmD, RPh, Founder and Chief Business Officer of Elevation Oncology. "Elevation Oncology is committed to expanding the benefit of precision medicine to all patients with cancer by developing therapies that make results from tests like GEM ExTra clinically actionable, no matter how rare the finding. Close collaboration between diagnostic and therapeutic developers is critical to re-thinking our approach to clinical trial enrollment as an industry and finding more efficient ways to bring the right treatment opportunities to the patients that need them."