On September 7, 2018 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that the first patient has been dosed in its Phase 1 clinical trial of COM701, a first-in-class cancer immunotherapy antibody targeting PVRIG (Press release, Compugen, SEP 7, 2018, View Source [SID1234529393]). PVRIG is a novel immune checkpoint identified by Compugen using its computational discovery capabilities.

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!

"Dosing the first patient with COM701, a first-in-class drug opportunity targeting a novel immune checkpoint we identified with our computational predictive platform, is a landmark event for us. We look forward to clinically testing it," stated Anat Cohen-Dayag, Ph.D., Compugen’s President and CEO. "It also serves as a proof of concept for our discovery capabilities and marks Compugen as a leader in the field of computational discovery. We will continue leveraging this core competency in expanding our therapeutic pipeline and achieving our corporate and business goals."

Drew W. Rasco, M.D., Associate Director of Clinical Research at the START Center for Cancer Care and a Principal Investigator in the Phase 1 COM701 study, said, "Immunotherapy has revolutionized the landscape for oncology treatments by providing a new treatment option leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can result in the development of new cancer immunotherapies for non-responsive and refractory patients. COM701 preclinical data suggest that the newly-discovered PVRIG pathway may be a dominant pathway in certain cancer subpopulations, including those that are unresponsive to PD‑1 or PDL-1 inhibitors. As such, it is important to evaluate COM701 in clinical trials with these patient populations who have exhausted available standard therapy."

Henry Adewoye, M.D., Chief Medical Officer of Compugen, said, "COM701 is a promising and differentiated asset in the crowded landscape of immuno-oncology trials. Our clinical and biomarker strategy for testing COM701 is premised on a robust biological rationale which suggests that targeting PVRIG may be necessary to induce a sufficient anti-tumor immune response in cancer patient subpopulations where both the PVRIG and TIGIT pathways are operative, thereby addressing the high unmet need of relapsed and refractory disease following treatment with existing immunotherapies. We look forward to exploring the full clinical potential of COM701."

This Phase 1 open-label clinical trial is designed to assess the safety and tolerability of administering escalating doses of COM701 monotherapy as well as combination administration with a PD-1 inhibitor in patients with advanced solid tumors. Additionally, the trial will evaluate evidence of preliminary antitumor activity of COM701 as a monotherapy as well as in combination with a PD-1 inhibitor in patients with selected tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. The study will be conducted in multiple leading oncology clinical centers in the United States, which are expected to enroll approximately 140 patients. Additional information will be available shortly at www.clinicaltrials.gov.

About COM701
COM701 is a humanized hybridoma antibody that binds with high affinity to PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen, blocking its interaction with its ligand, PVRL2. Blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. In addition, COM701 combined with antagonist anti-PD-1 antibodies has demonstrated synergistic effects on human T cell stimulation, indicating the potential of these combinations to further enhance immune response against tumors.

Preclinical data for COM701 suggest that PVRIG may be a dominant checkpoint in diverse patient populations with tumors that express elevated PVRL2 as compared to expression of the TIGIT ligand PVR. This include patients with breast, endometrial, and ovarian cancers. In addition, expression studies show that PVRIG and TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as those noted above, as well as lung, kidney, and head & neck cancers. In these tumors the blockade of both TIGIT and PVRIG may be required to sufficiently stimulate an anti-tumor immune response, with or without additional PD-1 pathway blockade.

On September 6, 2018 RedHill Biopharma Ltd. (NASDAQ: RDHL) (Tel-Aviv Stock Exchange: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on proprietary drugs for gastrointestinal diseases, reported that the ongoing single-arm Phase IIa study with orally-administered YELIVA (opaganib, ABC294640)1 for the treatment of advanced cholangiocarcinoma (bile duct cancer) has achieved its pre-specified efficacy goal for the first stage of the two-stage study design, and as a result, the study will continue to its second stage, enrolling the full cohort of 39 evaluable patients (Press release, RedHill Biopharma, SEP 6, 2018, View Source;LNGID=1&TMID=178&FID=1384&PID=0&IID=9184 [SID1234529317])

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!

The primary efficacy endpoint of the study is defined as either partial or complete response, or stable disease at four months treatment with YELIVA. Enrollment of all subjects is expected to be completed by mid-2019.

The single-arm Phase IIa study is evaluating the activity of YELIVA as a single agent in patients suffering from advanced, unresectable intrahepatic, perihilar and extrahepatic cholangiocarcinoma. All subjects enrolled in the study have received up to two lines of other systemic therapy for advanced disease. The study is being conducted at renowned clinical institutions in the U.S.

YELIVA was granted FDA Orphan Drug designation for the treatment of cholangiocarcinoma, providing various development incentives to develop YELIVA for this indication and, if approved, a seven-year marketing exclusivity period for the treatment of cholangiocarcinoma.

Complete Response Achieved in Patient treated under RedHill’s Expanded Access Program:
Additionally, a patient in the U.S. with advanced gallbladder carcinoma, a condition closely related to cholangiocarcinoma, who had progressed following standard-of-care chemotherapy, received treatment with YELIVA as part of RedHill’s Expanded Access Program, which allows compassionate use for eligible patients, and achieved a confirmed complete response, as measured by RECIST criteria (i.e. disappearance of all target lesions and all non-target lesions).

About cholangiocarcinoma:
Cholangiocarcinoma (bile duct cancer) is a highly lethal malignancy for which there is an urgent need for more effective treatments. Approximately 8,000 people are diagnosed with intrahepatic and extrahepatic bile duct cancers annually in the U.S.2, with recent studies showing an increased incidence of cholangiocarcinoma, mainly attributed to recent advancements in the diagnosis of this disease3. Surgery with complete resection remains the only curative therapy for cholangiocarcinoma; however, only a minority of patients are classified as having a resectable tumor at the time of diagnosis4. Additional treatment options include radiation therapy and chemotherapy. Still, the efficacy of these treatments in cholangiocarcinoma patients is also limited and the prognosis for relapse patients who have failed initial chemotherapy is very poor with an overall median survival of approximately one year5. The 5-year relative survival rates of intrahepatic and extrahepatic cholangiocarcinoma patients range between 2% to 30%, depending on the tumor type and stage at diagnosis6.

About YELIVA (opaganib, ABC294640):
YELIVA (ABC294640), a new chemical entity, is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting oncology, inflammatory and gastrointestinal indications. By inhibiting SK2, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid-signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. YELIVA received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute.

The Phase IIa study in cholangiocarcinoma was initiated following an extensive pre-clinical program, and a Phase I clinical study with YELIVA in patients with advanced solid tumors which successfully met its primary and secondary endpoints, demonstrating that the drug is well tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity. Of the three patients with cholangiocarcinoma treated in the Phase I study, all of whom had prior therapy, one subject achieved a sustained partial response (overall survival (OS) = 20.3 months) and the other two subjects had prolonged stable disease (OS = 17.6 and 16.3 months).

The ongoing studies with YELIVA (ABC294640) for cholangiocarcinoma, multiple myeloma and advanced hepatocellular carcinoma (HCC) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

On September 6, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from its broad clinical development programme across different types of lung cancer will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC), taking place from 23–26 September in Toronto, Canada (Press release, Hoffmann-La Roche, SEP 6, 2018, View Source [SID1234529353]). 10 abstracts have been accepted, including three ‘late breakers’ and five oral presentations.

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!

"We look forward to presenting new data from our comprehensive lung cancer programme, including new immunotherapy and targeted treatment strategies across different types of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are particularly pleased to be sharing positive TECENTRIQ data in extensive-stage small cell lung cancer, which has seen limited progress in treatment over the last two decades, as well as new pivotal data for our investigational therapy entrectinib for the treatment of ROS1 fusion-positive lung cancer."

Key presentations
Progression-free survival (PFS) and overall survival (OS) data from the Phase III IMpower133 study of TECENTRIQ plus chemotherapy (carboplatin and etoposide) for the initial (first-line) treatment of people with extensive-stage small cell lung cancer (ES-SCLC) will be presented in the Presidential Symposium. These are the first positive survival data from a Phase III study with an immunotherapy-based combination in the initial treatment of ES-SCLC.

PFS and OS data will be presented from the Phase III IMpower132 study investigating TECENTRIQ plus pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) in the initial treatment of people with advanced non-squamous NSCLC. The IMpower132 and IMpower133 data will be featured as part of WCLC’s official press programme on Monday 24th and Tuesday 25th of September, respectively.

Additionally, results from a Phase Ib study investigating Tarceva plus TECENTRIQ in tyrosine kinase inhibitor (TKI)-naïve people with EGFR mutation-positive NSCLC will also be presented.

New pivotal results of entrectinib, an investigational oral, CNS-active treatment for people with locally advanced or metastatic ROS1 fusion-positive NSCLC, from a pooled analysis including the global Phase II STARTRK-2 basket study will be presented. These data have also been selected to be featured in the WCLC press programme on Monday 24th of September.

Follow Roche on Twitter via @Roche and keep up to date with WCLC 2018 congress news and updates by using the hashtag #WCLC2018.

For more information on Roche’s approach to cancer, visit Roche.com.

Overview of key presentations featuring Roche medicines at WCLC 2018

About NSCLC and SCLC
Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85% of all cases,2 with SCLC accounting for approximately 15% of all lung cancer cases.2 Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis.3 The five-year relative survival rate for people with stage I SCLC is approximately 31%, however, at stage IV, the five-year relative survival rate declines to approximately 2%.4

About TECENTRIQ
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

About ROS1 fusion-positive non-small cell lung cancer (NSCLC)
ROS1 is a tyrosine kinase, which play a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, ‘healthy’ cell signalling malfunctions, causing cells to grow and proliferate in an uncontrolled manner – this results in cancer.

ROS1 gene fusions account for 1-2% of NSCLC. Lung cancer is the leading cause of cancer-related death across the world. Each year, 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 NSCLC is the most prevalent type of lung cancer, accounting for around 85% of all cases.2 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 fusions.

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK fusions. Entrectinib is being investigated across a range of solid tumour types, including NSCLC, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumours (GIST) and cancers of unknown primary (CUP).

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.

On August 6, 2018 Aileron Therapeutics (NASDAQ: ALRN), the clinical-stage leader in the field of stapled peptide therapeutics for cancers and other diseases, reported that Manuel Aivado, MD, PhD, has been named President and Chief Executive Officer and elected to its Board of Directors (Press release, Aileron Therapeutics, SEPT 6, 2018, View Source;p=irol-newsArticle&ID=2366358 [SID1234529414]). Since 2012, Dr. Aivado has served as Aileron’s Senior Vice President and Chief Medical and Scientific Officer. He succeeds John P. Longenecker, PhD, who was appointed interim CEO on May 15, 2018.

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!

"We are very pleased to announce this well-deserved promotion for Dr. Aivado," said Aileron Chairman Jeff Bailey. "Manuel clearly best exemplifies the skill set and talent needed to lead the company through its next stage of development."

"I am very excited to take on this new responsibility at Aileron as we further expand the clinical development of our lead product candidate, ALRN-6924, into combination therapies. ALRN-6924 represents the proof-of-concept for Aileron’s stapled peptide technology, which I believe to be capable of producing additional novel drug candidates that address previously undruggable targets," said Dr. Aivado. "In the future, we plan to broaden the applicability of our technology and expand our external collaborations. I am pleased with the external recognition that ALRN-6924 and our stapled peptide technology have earned in the scientific community, and I look forward to additional collaborations translating this recognition into therapeutic and commercial success."

Dr. Aivado brings more than 20 years of scientific, medical, and executive leadership to this position. Most recently, Dr. Aivado led Aileron’s clinical testing of stapled peptides against intracellular targets and designed and implemented the ALRN-6924 first-in-human trial. ALRN-6924 was selected for the "Best of ASCO (Free ASCO Whitepaper) Meetings," which highlights the most cutting-edge science and education from the world’s premier oncology event. Prior to joining Aileron, Dr. Aivado served as Vice President of Clinical Development and Pharmacovigilance at Taiho Oncology, Inc. He previously served as a Senior Medical Director in clinical development at GlaxoSmithKline. In addition, Dr. Aivado was an Instructor in Medicine at Beth Israel Deaconess Medical Center/Harvard Medical School. Prior to his industry experience, Dr. Aivado practiced clinical medicine in Germany for nearly ten years, during which he was awarded the Dr. Mildred Scheel cancer research scholarship award in 2002. Dr. Aivado is a German board-certified physician in internal medicine, hematology and medical oncology. He received his MD and PhD degrees from the Medical School of the University of Dusseldorf, Germany.

About ALRN-6924
ALRN-6924 is a first-in-class product candidate designed to reactivate wild-type p53 tumor suppression by disrupting the interactions between p53 and its two primary suppressor proteins, MDMX and MDM2. Aileron believes ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the interaction of MDMX and MDM2 with p53. Based on preclinical data and preliminary evidence of safety and anti-tumor activity in its ongoing clinical trials, the Company believes there may be a significant opportunity to develop ALRN-6924 as a monotherapy or combination therapy for a wide variety of solid and liquid tumors. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS) and peripheral T-cell lymphoma (PTCL). For information about its clinical trials, please visit www.clinicaltrials.gov.

On September 6, 2018 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immunotherapies derived from its Immulytic platform, reported the U.S. Food and Drug Administration (FDA) has accepted the Company’s investigational new drug (IND) application for its lead product candidate, RP1, for patients with solid tumors (Press release, Replimune, SEP 6, 2018, View Source [SID1234529738]). The Company intends to open its ongoing Phase 1/2 clinical trial in the U.S. and begin enrolling patients in the fourth quarter of 2018. The clinical trial is currently ongoing in the U.K., as previously announced.

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!

In part one of the Phase 1/2 clinical trial, Replimune is assessing the safety and tolerability of RP1 administered alone in patients with advanced solid tumors. Following this dose escalation phase, further patients will receive RP1 in combination with nivolumab anti-PD1 therapy. In part two of the Phase 1/2 clinical trial, expected to initiate in the first half of 2019, Replimune intends to study the safety and efficacy of RP1 in combination with nivolumab in approximately 120 patients with metastatic melanoma, metastatic bladder cancer, microsatelite instability high cancers, and non-melanoma skin cancers. For each of the tumor types other than melanoma, patients will be naïve to immune checkpoint blockade, whereas in melanoma, patients both previously treated and previously untreated with immune checkpoint blockade will be enrolled. This clinical trial is a collaboration with Bristol Myers Squibb, which is providing nivolumab for use in the study.

RP1 is Replimune’s first Immulytic product candidate to enter the clinic and is based on a proprietary new strain of herpes simplex virus engineered to maximize tumor killing potency. This is intended to result in highly immunogenic cell death and robust activation of a systemic anti-tumor immune response.

About Oncolytic Immunotherapy
Oncolytic immunotherapy is an emerging class of cancer therapy which exploits the ability of viruses to selectively replicate in and kill tumors, while at the same time inducing a potent, patient-specific, anti-tumor immune response. Oncolytic viruses have the ability to induce a robust immune response against a patient’s particular complement of tumor antigens, including neo-antigens, in situ in the patient in an off-the-shelf format. While clinically active alone, oncolytic immunotherapy may have synergy with certain other treatments and, in particular, with immune checkpoint blockade therapies.