On November 17, 2020 Bristol Myers Squibb reported cold water on Celgene shareholders who have been hoping to see a payout related to the merger of the two companies (Press release, BioSpace, NOV 17, 2020, View Source [SID1234571461]). This morning, the pharma giant signaled it will fail to meet a deadline related to $9 per share Contingent Value Rights (CVR) tickets, essentially killing that payment.

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When BMS and Celgene merged, CVR payouts hinged on the approval of three drugs. The first of the three CVR medicines, Celgene’s multiple sclerosis drug Zeposia (ozanimod), was approved in March. The other drugs related to the CVR are cancer treatments, ide-cel and liso-cel (lisocabtagene maraleucel). Under terms of the deal, ide-cel, an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, must be approved by the U.S. Food and Drug Administration by March 31, 2021. The FDA accepted the Biologics License Application for ide-cel under priority review in September.

Liso-cel, though, is another matter. The deadline to meet the CVR milestone for this cancer drug is Dec. 31. BMS had a Prescription Drug User Fee Act (PDUFA) action date of Nov. 16, but COVID-19 threw a spanner into the works, pushing back the timeline for its review.

Liso-cel is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. BMS is seeking approval of the drug as a treatment for adults with relapsed or refractory (R/R) large B-cell lymphoma after at least two prior therapies.

The BLA is based on the safety and efficacy results from the TRANSCEND NHL 001 trial, evaluating liso-cel in 268 patients with R/R large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade lymphoma, primary mediastinal B-cell lymphoma and Grade 3B follicular lymphoma. TRANSCEND NHL 001 is the largest study of CD19-directed CAR T cells to support a BLA to date.

In its announcement this morning, BMS said the delay is due to COVID-19-related travel restrictions at the FDA. The travel restrictions prevented the FDA from conducting an inspection of a third-party manufacturing facility in Texas before the PDUFA date. Because the regulatory agency could not ensure that the manufacturing facility meets its standards, it has deferred potential approval of liso-cel until the inspection can be completed. The FDA has not provided a new anticipated date for approval, BMS said.

Samit Hirawat, chief medical officer of Global Drug Development at BMS, said the company will continue to work with the FDA to support the ongoing review of the liso-cel BLA. Hirawat said the company is "committed to bringing liso-cel to patients with relapsed or refractory large B-cell lymphoma who still have significant unmet need."

This isn’t the first delay for liso-cel that jeopardized potential approval. Earlier this year, the FDA delayed review of the BLA for liso-cel by three months, which gave it the Nov. 16 PDUFA date.

On November 17, 2020 NantHealth, Inc. (NASDAQ: NH), a provider of enterprise solutions that help businesses transform complex data into actionable insights, reported the publication of a study that revealed RNA sequencing is not only viable but may also provide significant clinical value in analyzing a cancer patient’s specific disease biology to enable an optimized treatment decision with a higher likelihood of success (Press release, NantHealth, NOV 17, 2020, View Source [SID1234571228]). The study was published in Nature’s Scientific Reports, an open access, peer-reviewed journal dedicated to original research from across all areas of the natural and clinical sciences.

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Prepared in collaboration with NantOmics, LLC and ImmunityBio, Inc., the study was designed to explore the potential use of formalin-fixed paraffin-embedded (FFPE)-derived RNA transcriptome profiling for clinical decision-making. This technique was previously not considered to yield significant clinical value due to the lower quality, degraded samples typically produced by the formalin fixation process. FFPE is the most common method used in clinical settings for storing tumor biopsies.

The study revealed an overall sequencing success rate of 81% with highly consistent coverage in direct FFPE and fresh-frozen (FF) replicates (98% agreement). The results provide strong rationale for the use of FFPE-derived RNA sequencing in clinical decision-making based on the reproducibility, robustness, and consistency of whole transcriptome profiling. This research enables the comparison of clinical samples to research studies, which generally differ in both data collection and sequencing methods, and which may unlock highly valuable insights that would not be possible with DNA sequencing techniques alone.

"This is an important step to advancing towards molecularly informed medicine, both from the perspective of diagnostics to precise therapeutic intervention," said Dr. Patrick Soon-Shiong, CEO of NantHealth, NantOmics and ImmunityBio. "Genomic reporting capabilities could be enhanced through clinical applications resulting from this technology, including identifying cancers of unknown primary (CUP), prevalence of immune cell infiltrates in the tumor microenvironment (immunome), and expression analysis of checkpoint markers including those targeted by commercial and investigational immunotherapies," he continued.

The study also demonstrates that RNA sequencing is not only clinically viable but valuable and can provide a more thorough understanding of what genes are driving each individual patient’s tumor to better inform personalized treatment decisions.

To achieve this, researchers performed ribo-deplete RNA extractions on more than 3,200 FFPE slide samples to measure the expression of clinically significant genes that help identify treatments with the highest likelihood of response. The study included a comprehensive evaluation of RNA extraction methods (Poly-A and ribo-depletion) by comparing transcriptomes from The Cancer Genome Atlas (TCGA) cohort and 3,116 FFPE samples. Findings showed minimal differences between the two approaches within clinically important genes, while establishing a computational framework for comparing the expression of FFPE clinical samples to the growing database of research samples generated by academic studies.

"These are very exciting results from a robust scientific study of a high caliber," said Shahrooz Rabizadeh, Ph.D., Chief Scientific Officer, ImmunityBio. "The implication of using RNA sequencing to molecularly define a patient’s cancer, identify the origin of cancers of unknown primary, and most importantly, optimize treatment plans for the highest chance of success, especially with immunotherapies, is profound."

"Through this research, we demonstrated the robustness of the RNA assay and the informatics techniques that help clinicians understand the transcriptional drivers of disease in their patients, allowing the further advancement of personalized medicine," said Dr. Sandeep "Bobby" Reddy, Chief Medical Officer, NantHealth. "NantHealth knows that high-quality data is the backbone of modern medicine. This study unlocks valuable insights through a method that allows the analysis of both academic research and clinical data for treatment optimization, further strengthening our fight against cancer."

Receiving widespread attention in policy documents and the media, Scientific Reports is the seventh most-cited journal in the world, with more than 350,000 citations. The publication has an extensive network of expert peer reviewers and an editorial team who provide rigorous and objective review. Scientific Reports is guided by the same ethical and editorial guidelines as other Nature Research publications to ensure that all the research is original, scientifically robust and of the highest quality. The journal is published through a number of different channels, including nature.com, where it receives approximately two million monthly visitors.

On November 17, 2020 Istari Oncology reported that UH Seidman Cancer Center became one of just six sites participating in a Phase II clinical trial to test the safety and efficacy of oncolytic polio/rhinovirus recombinant (PVSRIPO), a modified polio vaccine-based viral immunotherapeutic, in patients with recurrent malignant glioblastoma (rGBM) (NCT02986178) (Press release, Istari Oncology, NOV 17, 2020, View Source [SID1234571263]).

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The first-in-man Phase I trial, conducted at the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center, showed encouraging results. The study found that survival rates were significantly higher in rGBM patients who received an intratumoral infusion of PVSRIPO immunotherapy compared to similar patients receiving standard treatment at the same institution. Overall survival among patients who received PVSRIPO plateaued at 21 percent at 24 to 36 months and appeared to last for up to five years based on a publication of the interim trial results (Desjardins, et al., 2018 NEJM). The overall survival rate was sustained at 36 months in these patients.

"We’ve never seen survival rates like this before," says Andrew E. Sloan, MD, FACS, Director of the Brain Tumor & Neuro-Oncology Center and the Center of Excellence in Translational Neuro-Oncology at UH Seidman Cancer Center and UH Neurological Institute, and Professor and Vice Chairman, Department of Neurosurgery at Case Western Reserve University School of Medicine, who serves as principal investigator for the trial. "The long-term survival rate is very exciting. We are proud that University Hospitals was selected as one of a handful of top brain tumor centers, including the Stephen E. and Catherine Pappas Center for Neuro-Oncology at Massachusetts General Hospital and UCSF Brain Tumor Center, to participate in the Phase II clinical trial based on our expertise in immunotherapy and reputation for treating brain tumors."

To date, Dr. Sloan has treated seven patients with rGBM at UH Seidman Cancer Center according to the trial protocol, all of whom are surviving. Building on this experience, he is now seeking to enroll patients with rGBM into a new Phase I/II trial of PVSRIPO, but this time with a difference. This trial combines PVSRIPO with the immune checkpoint inhibitor pembrolizumab (Keytruda). The hypothesis is that the combination of the two therapies will be able to generate a potent and specific anti-tumor response in rGBM patients, given their different but complimentary mechanisms of action. This new trial is now open at UH Cleveland Medical Center. When it adapts to a Phase II trial in the coming weeks, it will be offered at approximately six total sites nationwide.

"The tumor we’re targeting is one of the most aggressive tumors known to man," Dr. Sloan says. "The virus can counteract some of that, but we want to test whether we can perhaps give it a little boost. PVSRIPO and pembrolizumab together may be more effective than either on its own."

That is, in fact, the working theory. According to Istari Oncology, Inc., which is sponsoring the new trial, "pre-clinical data and limited clinical use suggest that PVSRIPO followed by pembrolizumab may be associated with synergistic anti-tumor responses."

As in the first trials, patients in the new trial will receive PVSRIPO via a catheter into the tumor, a process known as convection enhanced delivery (CED). The infusion will be performed in the NeuroIntensive Care Unit at UH Cleveland Medical Center. The PVSRIPO infusion will be followed by intravenous pembrolizumab at approximately 14 days post-procedure, and then every three weeks thereafter, for up to 24 months, provided no toxicity or disease progression.

Dr. Sloan says he’s hopeful that the combination of PVSRIPO and pembrolizumab will prove successful for his patients with rGBM. In fact, he says, approaches that seem to hold the most promise for this intractable cancer are those that seek to increase expression of tumor-specific neo-antigens, coupled with checkpoint inhibition. This clinical trial fits that bill.

"That’s likely what’s necessary to overcome the profound immune blockade associated with this disease," he says.

On November 17, 2020 Dynavax Technologies Corporation (NASDAQ: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported that Ryan Spencer, Chief Executive Officer, will participate in a virtual fireside chat at the 3rd Annual Evercore virtual ISI HealthCONx Conference on Thursday, December 3, at 10:05 a. m. E.T (Press release, Dynavax Technologies, NOV 17, 2020, https://www.prnewswire.com/news-releases/dynavax-to-present-at-the-3rd-annual-evercore-virtual-isi-healthconx-conference-301175311.html [SID1234571290]).

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The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at www.dynavax.com. A replay of the webcast will be available for 30 days following the live event.

On November 17, 2020 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that the Company will host a Virtual Life Science Event for the investment community on Thursday, December 10 at 8:30 a.m. ET (Press release, PerkinElmer, NOV 17, 2020, View Source [SID1234571229]).

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This event is organized to serve as an in-depth breakdown of the Company’s business serving Life Science End Markets, including its portfolio, strategy, latest innovations and scientific advances. Speakers will include Jamey Mock, SVP and chief financial officer of PerkinElmer, Alan Fletcher, VP and GM of PerkinElmer Life Sciences, Kevin Willoe, VP and GM of PerkinElmer Informatics, and Gary Grecsek, VP and GM of PerkinElmer Enterprise Services.

A live audio webcast will be available on the Investors section of the Company’s website at www.perkinelmer.com. A replay of the presentation will be posted on the PerkinElmer website after the event and will be available for 90 days following.