On January 13, 2020 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition") reported an update on its Nu Q Clinical Assays which use a magnetic particle-based assay format (Press release, VolitionRX, JAN 13, 2020, View Source [SID1234553125]). Volition has completely re-engineered its Nu.Q assays leading to a step-change improvement in analytical performance. Volition expects this enhanced analytical performance to translate into improved clinical performance in the studies to be carried out and reported in the coming months.

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Relative to Volition’s ELISA plate Nu.Q assay format, the magnetic particle-based assay format demonstrates:

A 10-20-fold improvement in analytical sensitivity of the assays.
Typical within-day reproducibility of quantitative test results below 3% (previously <10%).
Decrease in test result turnaround time from 6 hours to approximately 1 hour and 20 minutes, allowing much higher throughput.
The ability to be developed and processed on fully-automated Random-Access platforms (allowing the use of a wide range of commercial automated platforms).
Commenting on the assay transfer program Dr. Gaetan Michel, Chief Executive Officer of Belgian Volition said, "I am incredibly proud of the effort the whole team has made in the assay development program over the last two years and in particular, I would like to thank Mhammed Bougoussa, our recently appointed Assay Validation Expert for his significant contribution to the project. We now plan to finalize blood plasma sample pre-analytics with these assays and are excited to utilize these automated magnetic chemiluminescent assays in our clinical studies and aim to start reporting data during this quarter, and throughout 2020."

Volition has continued to create assets by:

Developing recombinant nucleosomes as calibrants which provide for assay specificity and reliable quantitation. Volition developed synthetic nucleosomes with its partners but has now brought this expertise in-house with the recent acquisition of Octamer, Gmbh announced January 10.
Internalizing key processes such as chemiluminescent antibody labeling and coating of magnetic beads. This secures our supply chain and provides flexibility to speed up our assay development work.
Moving from a microtiter plate format to a magnetic particle-based assay format. This improves assay kinetics and hence assay sensitivity and reduces assay time and increases assay throughput.
Moving from a traditional colorimetric endpoint format to a chemiluminescent endpoint. This further reduces background, leading to further improvements in assay sensitivity as well as greatly extending the usable range of the assays. Moreover, the combination of a chemiluminescent endpoint with a magnetic particle-based assay format greatly improved the specificity of Nu.Q assays.
Moving all these improvements onto an FDA-approved automated immunoassay analyzer which is currently in clinical use across USA and Europe. This further decreases assay processing time and greatly increases the reproducibility and reliability of assay results so that the same correct result is produced for any patient sample regardless of where or when the test is done or who operates the instrument.
Moving from blood serum to blood plasma as the test sample which reduces assay interference.

On January 13, 2020 John Theurer Cancer Center at Hackensack University Medical Center in New Jersey were part of the CANDOR global phase III clinical trial for patients with refractory (persistent) multiple myeloma (Press release, John Theurer Cancer Center, JAN 13, 2020, View Source [SID1234553124]). The study was selected as the prestigious plenary presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the world’s leading conference for hematologic cancers and blood disorders, held in Orlando in December.

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The CANDOR study showed that the addition of the anti-CD38 monoclonal antibody daratumumab to treatment with carfilzomib and dexamethasone was more effective than conventional carfilzomib and dexamethasone. Patients receiving the three-drug regimen experienced a 37% reduction in the risk of disease progression or death, establishing a new standard of care. Patients in the CANDOR trial had been heavily pretreated and most had failed to respond to lenalidomide, an immunomodulating drug that forms the backbone of most multiple myeloma treatment regimens.

"In this population, we have had limited choices. This study shows that we can safely combine what are arguably the most active drugs for the treatment of myeloma," explained David Siegel, M.D., Ph.D., founding director of John Theurer Cancer Center’s Multiple Myeloma Institute, who led John Theurer Cancer Center’s involvement in the study. "Treatment with daratumumab, carfilzomib, and dexamethasone represents a new effective regimen for patients with recurrent or persistent multiple myeloma, especially those whose disease came back or continues to grow after lenalidomide therapy."

The phase III CANDOR study included 466 patients with multiple myeloma that persisted despite one to three prior regimens of therapy. Patients were randomly assigned 2:1 to receive either daratumumab, carfilzomib, and dexamethasone or carfilzomib and dexamethasone. After a median follow-up of 17 months, the median progression-free survival was not yet reached in the three-drug combination group, versus 16 months in patients receiving the standard therapy. Patients receiving three drugs had a better overall response rate (84.3% versus 74.7%) and a better rate of complete response or better (28.5% versus 10.4%), and the achievement of undetectable disease was nearly ten times higher (12.5% versus 1.3%). It was too early to detect any differences in overall survival.

On January 13, 2020 Amgen (NASDAQ: AMGN) reported strategic collaborations with leading diagnostic companies Guardant Health, Inc. and QIAGEN N.V. to develop blood- and tissue-based companion diagnostics (CDx), respectively, for investigational cancer treatment AMG 510 (Press release, Amgen, JAN 13, 2020, View Source [SID1234553123]). AMG 510 is the first KRASG12C inhibitor to advance to the clinic for investigation in treatment of multiple tumor types. KRAS G12C is one of the most frequently mutated oncogenes in human cancers. The agreements with both companies will initially focus on CDx tests for non-small cell lung cancer (NSCLC) but allow for further development of the diagnostic tests for Amgen’s other oncology clinical development programs.

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"Amgen is committed to driving broad accessibility to biomarker testing in order to select appropriate patients who will directly benefit from targeted treatments," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "With one in eight patients with NSCLC having KRAS G12C, there’s a critical need to improve access to high quality diagnostics and more routine screening. Collaborating with QIAGEN and Guardant Health to have both tissue- and blood-based diagnostic tests available will help to identify patients with NSCLC who may benefit from AMG 510."

Amgen will work with QIAGEN to develop a tissue-based diagnostic test utilizing its therascreen platform to identify patients whose cancers have the KRAS G12C mutation. QIAGEN will also pursue global regulatory approvals, including Pre-Market Approval (PMA) from the U.S. Food and Drug Administration (FDA). To enable biomarker testing in patients for whom insufficient tissue remains a challenge, Amgen is also collaborating with Guardant Health to develop a liquid biopsy CDx. Guardant360 CDx is a multi-tumor comprehensive NGS (Next Generation Sequencing) test that is being developed to identify patients with actionable alterations, in this instance with the KRAS G12C mutation in NSCLC. Guardant Health will seek global regulatory approvals for the test, including a PMA from the FDA.

AMG 510 is currently enrolling patients in a potentially registrational Phase 2 study (CodeBreak 100). The FDA granted Orphan Drug Designation to AMG 510 for previously treated metastatic NSCLC and colorectal cancer with KRAS G12C mutation and Fast Track Designation for previously treated metastatic NSCLC with KRAS G12C mutation.

Amgen established RAS as the first actionable biomarker in metastatic colorectal cancer and is now pioneering the development of KRAS mutation specific inhibitors in lung cancer and other solid tumors with AMG 510.

About KRAS
The subject of almost four decades of research, the RAS gene family are the most frequently mutated oncogenes in human cancers.1,2 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors.2 A specific mutation known as KRAS G12C is found in approximately 13% of non-small cell lung cancers, three to five percent of colorectal cancers and one to two percent of numerous other solid tumors.3 KRASG12C has been considered "undruggable" due to a lack of traditional small molecule binding pockets on the protein.4 Amgen is exploring the potential of KRASG12C inhibition across a broad variety of tumor types.

On January 13, 2020 Innovent Biologics, Inc. ("Innovent" or the "Company") (HKEX: 01801), a biopharmaceutical company that develops and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported that the Company has entered into an out-license agreement with Coherus BioSciences, Inc. ("Coherus",Nasdaq: CHRS), a leading biosimilar company that develops and commercializes its own high-quality therapeutics as well as those of others seeking capable access to the United States market, to commercialize Innovent’s biosimilar candidate to Avastin (bevacizumab) (IBI305) in the United States and Canada (Press release, Innovent Biologics, JAN 13, 2020, View Source [SID1234553122]).

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Coherus plans to file a Biologics License Application ("BLA") with the U.S. Food and Drug Administration ("FDA") in late 2020 or early 2021 depending on FDA interaction timing, and to launch directly upon approval. IBI305 successfully completed a large Phase 3 safety and efficacy study in China, and the application was filed for approval and was accepted by the National Medical Products Administration ("NMPA") in China in January 2019, and subsequently granted priority review status. Also, under the terms of the agreement, Coherus has a non-exclusive option to license Innovent’s biosimilar to Rituxan (rituximab) (IBI301) for development and commercialization in the United States and Canada. IBI301 was filed for approval and accepted by the NMPA in China in June 2019 with priority review status.

"The clinical efficacy and safety results of IBI305 compared with bevacizumab in advanced, first-line, non-squamous NSCLC patients were presented at the 55th Annual Meeting of the ASCO (Free ASCO Whitepaper) in 2019. With the encouraging results, IBI305 is expected to be high-quality and effective therapy for patients with solid tumors," said Michael Yu, Ph.D., Founder, Chairman and CEO of Innovent. "UDENYCA, has been the most successful biosimilar launch in the United States, and made Coherus the obvious partner of choice. Coherus and Innovent share a very similar mission, vision and set of values. We are pleased to be working together to expand the products’ presence in the U.S. and benefit more patients globally."

"We are excited to enter into a strategic collaboration with one of the premier Chinese biologics companies," said Denny Lanfear, Chairman and CEO of Coherus. "Innovent is an impressive fully-integrated organization delivering substantial benefits to the healthcare system and patients in China with their first approved and successfully commercialized PD-1. Its oncology therapeutics complement UDENYCA and advance our core mission to expand choice, improve patient access and lower healthcare costs in the United States."

According to the terms of the agreement, Coherus will pay up to US$45 million for upfront and milestones payments for IBI305. In addition, Coherus will also pay double-digit percent of royalty payments based on future sales of IBI305. Financial terms for IBI301 will be the same when optioned.

On January 13, 2020 Genome & Company (KONEX: 314130) is reported that it has entered into a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc. to evaluate the safety, tolerability, biological and clinical activities of GEN-001 therapy in combination with avelumab, a human anti-PD-L1 therapy, in multiple cancer indications (Press release, Genome & Company, JAN 13, 2020, View Source;company-announces-a-clinical-trial-collaboration-and-supply-agreement-with-merck-kgaa-darmstadt-germany-and-pfizer-300985435.html [SID1234553121]).

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Under the terms of this agreement, Genome & Company will be the sponsor of the study, and Merck KGaA, Darmstadt, Germany and Pfizer will supply avelumab for the phase 1/1b clinical trial that is expected to be commenced in 2020 in the U.S. Both parties will have access to the clinical data.

The combination trial is designed to be a first-in-human (FIH) study including dose escalation and expansion cohorts to evaluate the safety and preliminary efficacy.

"GEN-001 has been developed as the backbone of Genome & Company’s immuno-oncology pipeline, and we are delighted to collaborate with the global leaders in oncology such as Merck KGaA, Darmstadt, Germany and Pfizer on this phase 1/1b clinical trial for this combination of GEN-001 and avelumab. We are excited to investigate how the preclinical data of this combination will be translated to humans. We look forward to initiating this clinical trial in the coming months," said Dr. Jisoo Pae, CEO of Genome & Company.

Avelumab Approved Indications

Avelumab (BAVENCIO) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

The US Food and Drug Administration (FDA) also granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity, major adverse cardiovascular events (MACE) [which can be severe and have included fatal cases], and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 clinical chemistry and hematology laboratory value abnormalities reported in at least 10% of patients treated with BAVENCIO monotherapy include hyponatremia, lymphopenia, GGT increased; in patients receiving BAVENCIO in combination with axitinib, grade 3-4 clinical chemistry and hematology laboratory value abnormalities included blood triglyceride increased and lipase increased.

For full Prescribing Information and Medication Guide for BAVENCIO, please see www.BAVENCIO.com.

About GEN-001

GEN-001 is an oral microbiome therapeutic candidate developed to have immune modulating activities, resulting in potential partnership with immune checkpoint inhibitors. GEN-001 consists a single strain bacteria isolated from gut of healthy human volunteers that has been shown to activate dendritic cells, macrophages and T cell response. In preclinical studies, GEN-001 has shown optimal safety margin and synergistic effects in combination with immune checkpoint inhibitors by enhancing the effect of suppressing the growth of both immune checkpoint inhibitor sensitive and resistant tumor models.