On June 25, 2020 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported the publication of a study in JCI Insight, a peer-reviewed journal dedicated to biomedical research from preclinical to clinical studies (Press release, NantHealth, JUN 25, 2020, View Source [SID1234561468]). This research looked into the discordance between genomic sequencing and transcriptome analysis, and how this may reflect a mechanism of resistance to therapy in tumors that has previously been under-recognized and should be subject to further investigation.

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Next-generation sequencing (NGS) of DNA has not revealed all the mechanisms underlying resistance to genomically matched drugs. This study was designed to discover another potential mechanism. Researchers evaluated data from 1,417 tumors whole-exome tumor (somatic)/normal (germline) NGS and whole-transcriptome sequencing in order to examine transcriptomic silencing of putative driver alterations. Drivers are significant in this context, compared to passenger mutations, which are not linked to targeted drug therapies. Thus the data is particularly clinically relevant because it pertains to mutations that are commonly used to prescribe drug therapies. In this large-scale study, they also determined the frequency of tumor mutations being germline, rather than somatic, in these and an additional 462 tumors with tumor and normal exomes. They found there was a high risk of germline mutations being falsely reported as somatic. In that event, clinicians may prescribe a treatment that would actually target the normal healthy germline cells in addition to tumor cells and result in greater toxicity. In examination of a set of 50 genes highly associated with cancer and targeted therapies, at least 13% of variants detected in DNA were unexpectedly not expressed.

The research confirmed that both the frequency of silenced variant transcription and the risk of falsely identifying germline mutations as somatic are important. Therefore, transcriptomics is critical in conjunction with genomics when interrogating patient tumors for actionable alterations, and to ultimately reduce the risk of therapeutic resistance.

"Exploring another mechanism of resistance to therapy and thus helping bring about a deeper understanding around the interrogation of patients’ tumors brings with it hope and excitement for the success of future therapeutics," said Dr. Sandeep "Bobby" Reddy, Chief Medical Officer, NantHealth. "NantHealth is dedicated to the fight against cancer, devoting much time to finding effective personalized cancer treatments. The recognition of transcriptomic silencing means that we may be giving targeted therapies to up to 13% of patients in whom the target is actually missing."

JCI Insight publishes well-executed, high-quality, insightful research in all biomedical specialties, including autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, vascular biology and many others. JCI Insight builds on the editorial leadership of the JCI, one of the oldest and most respected biomedical research journals, and is self-published by the American Society for Clinical Investigation (ASCI). JCI Insight serves to fulfill the ASCI’s objective to advance medical science through the publication of clinically relevant research reports.

NantHealth is focused on using data to close the loop – connecting payers, providers, and patients. Through its software, it facilitates the delivery of precise and timely data for creating efficiency, personalized treatment, and collaboration across healthcare.

On June 25, 2020 NeoImmuneTech, Inc., a clinical-stage T cell-focused biopharmaceutical company, reported the first patient has been dosed at The University of Texas MD Anderson Cancer Center in the Phase 1b/2a clinical trial of NT-I7 (efineptakin alfa) in combination with KEYTRUDA, a leading checkpoint inhibitor (CPI), for the treatment of patients with relapsed/refractory advanced solid tumors (Press release, NeoImmuneTech, JUN 25, 2020, View Source [SID1234561486]).

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"We’re very pleased to further progress this critically important clinical program quickly, despite the challenges due to the COVID-19 pandemic. Dosing the first patient in this study marks a major milestone in the development of NT-I7 for the treatment of patients with advanced solid tumors," said NgocDiep Le, M.D., Ph.D., Executive VP and Chief Medical Officer of NeoImmuneTech. "We will investigate clinically NT-I7’s potential to augment the already proven anti-tumor activity of pembrolizumab in CPI-responsive tumors. Additionally, we will also explore whether the combination can overcome CPI resistance. We hope that NT-I7 in combination with KEYTRUDA can improve the lives of cancer patients with various solid tumors."

The goal of the Phase 1b portion of the study, which will enroll up to 18 patients, is to establish a recommended dosing regimen. The Phase 2a portion will enroll up to 150 patients and will explore the preliminary anti-tumor activity of the combination therapy both in patients who have been treated with a CPI and patients who are CPI-naïve. The results of this study will be used to guide further clinical development of this combination in select tumor types.

More information can be found at www.neoimmunetech.com or www.clinicaltrials.gov, identifier: NCT04332653

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.

About NT-I7

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On June 25, 2020 TAE Technologies Inc. of Foothill Ranch races to solve the world’s energy problems via nuclear fusion,reported that its 3-year-old biologically-targeted radiation therapy offshoot is inching closer to its own world-changing target: treating and curing cancer patients (Press release, TAE Life Sciences, JUN 25, 2020, View Source [SID1234561517]).

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TAE Life Sciences LLC recently announced a $30 million investment to support its drug development program, which when combined with its neutron beam accelerator technology could unlock a new generation of targeted cancer therapy.

The Series B initial funding is among the largest in Orange County in the first half of the year.

The amount of funding is indicative of the company’s high expectations, officials tell the Business Journal.

"TAE Technologies doesn’t shy away from some pretty ambitious goals. We have the same culture at our company," said Bruce Bauer, chief executive of TAE Life Sciences, or TLS.

"We believe we have a technology that is going to change the world of cancer therapy. That’s an ambitious goal and a challenging area, but we have a culture of solving big problems. We’re not shying away from the magnitude of it."

Tumors Targeted

TLS publicly launched in March 2018 with some $40 million in funding at a $100 million valuation. Its combined $70 million of reported investments to date is a relatively small amount of funding compared to the $700 million its parent company has raised over the past 18 years; TAE Technologies backers have included Google and the late Paul Allen, co-founder of Microsoft Corp.

The PhD-heavy parent company, which is aiming to commercialize its space-age fusion technologies in the next three years or so, is reported to have a $3 billion valuation.

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TLS exclusively licensed its parent company’s accelerator technology, built on more than two decades of research that originated at the University of California-Irvine. The parent company’s goals are to provide an abundant source of energy that produces fewer pollutants.

TLS is using that same base of technology for medical applications: it aims to build a neutron delivery system for an emerging type of radiation therapy called Boron Neutron Capture Therapy or BNCT. BNCT is a radiation therapy technique that offers noninvasive treatment options for cancers of the head and neck, brain tumors and other aggressive and recurrent cancers.

TLS’ delivery system, called the AlphaBeam, produces low-energy neutrons that neutralize tumors containing accumulated boron-10, a nontoxic type of isotope that when given to a patient via a drug collects in tumor cells.

The radiation therapy is designed to spare healthy tissue. Because the boron-10 carrier drug is highly targeted to accumulate cancer cells, a patient could in theory be treated in just one or two treatment sessions, without many of the side effects of traditional radiation therapy.

Testing Underway

The technology is still in the testing phase.

The company’s first commercial system is currently on its way to a site in China, where its partner Neuboron Medtech Ltd. plans to launch Phase II clinical trials with TLS’ accelerator-based neutron system and a boron-10 target drug called BPA, which has been used to treat about 2,000 patients to date.

In the meantime, TLS is finalizing construction plans with an Italian-based partner, which will kick off clinical trials for CE markings in 2022. U.S. clinical trials will follow with at least three or more clinical sites.

On the drug development side, Bauer said research will continue for several years before clinical trials can begin.

"We’re bringing together everything from particle acceleration technology to pharmaceutical development. It takes time and perseverance, and that’s what we’re bringing to the table."

$100M Mission

TLS announced the $30 million initial close of its Series B round of financing on June 2.

More’s in store. Bauer—whose résumé includes stints in the private equity and medical imaging industries—said TLS ultimately wants to raise $100 million in its Series B round.

San Francisco-based Artis Ventures, which led TLS’ $40 million Series A round in 2018, participated in the deal.

R&D

Funds from the latest funding round will support drug development, which takes place at the company’s new R&D facility in Santa Monica. The building was previously occupied by Japan’s Stella Pharma Corp., which has experience in creating boron compounds for BNCT.

TLS subleased the 16,000-square-foot lab and recruited a core team of researchers from Stella, Bauer said.

The new round of funding will also support growing teams in R&D, manufacturing, quality control, software and systems engineering in Foothill Ranch.

TLS currently has 30 employees, though more than 70 people including contractors and TAE Technologies employees are working on the project, Bauer said.

Bauer declined to comment on future job openings, saying the subsidiary is "performing very well" occupying one of the four buildings at TAE Technologies’ Foothill Ranch headquarters.

Bright Future

Amid COVID-19, Bauer said TLS has transitioned to work from home and, he joked, "given everyone a chance to catch up on their paperwork, given the regulatory environment we operate in."

Joking aside, "we’ve had very productive continuity on the device side and drug development side."

The biggest challenge for the business has been maintaining its international partnerships amid travel restrictions, which have prevented teams from traveling to sites in Russia and China.

"The good news is we have strong partnerships in these locations and we’ve been relying on local assets to continue our work. It’s slowed us down a bit, but we’re working it out. Our teams will travel when they can."

Bauer is no stranger to patience and persistence, and he’s keeping his ambitions high.

"OC has a history of companies that have undertaken big challenges in healthcare, and succeeded, and really made an impact.

On June 25, 2020 Varian Medical Systems reported that Long-term results of the Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) study published June 2, 2020 in the Journal of Clinical Oncology showed positive increases in overall survival for patients with multiple sites of metastasis when treated with stereotactic ablative radiotherapy (SABR) versus standard-of-care (Press release, Varian Medical Systems, JUN 25, 2020, View Source [SID1234561469]).1 Through the extended follow-up, the impact of SABR on overall survival was larger in magnitude than in the study’s initial analysis published last year in The Lancet.2

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"The durability of the randomized data indicates a paradigm shift in our approach to the treatment of patients with low burden metastatic disease," commented senior study author Suresh Senan, MRCP, FRCR, PhD, Professor of Radiation Oncology at the Amsterdam University Medical Centres in Amsterdam, the Netherlands. "These data add to a growing body of evidence that supports the use of SABR as an ablative therapy for oligometastatic cancers."

As outlined in the latest study results, patients in the international randomized phase II trial who received SABR demonstrated a 22-month improvement in 5-year median overall survival compared with patients who received a standard-of-care approach alone, corresponding to an absolute survival benefit of 24.6%.3 This is a marked improvement from the results of the initial analysis2 in which the patients receiving SABR demonstrated a 13-month improvement in median overall survival over the control group.

"The size of the effect on long-term survival in this seminal study marks a step-change in the way clinicians should treat metastases from the highest incidence cancers," said Ricky Sharma, MD, PhD, vice president of Clinical Affairs at Varian (NYSE: VAR). "With over one million stereotactic body radiotherapy cases treated on TrueBeam alone, Varian continues to invest heavily to incorporate artificial intelligence, extraordinary precision, and unrivalled patient workflow into our industry leading delivery platforms for radiosurgery. We believe our continued pursuit of innovation and investment will ultimately help change the trajectory of cancer outcomes for all patients."

While systemic therapy, including chemotherapy, has been offered to patients with multiple metastases, the SABR-COMET data add to the growing body of evidence that suggests the addition of non-invasive treatments such as SABR can improve long-term outcomes for patients. Phase III randomized trials are ongoing to confirm the magnitude of the survival benefit for patients with a variety of metastatic cancers, including the international, multi-center SABR-COMET-3 clinical trial funded by Varian.

Mirroring the most common cancers treated across the world, primary tumor types in the study were breast, lung, colorectal and prostate. All patients enrolled had one to five new metastatic lesions. Although patients treated with radiotherapy were 20% more likely to suffer adverse events, there was no long-term impairment of quality of life. The study further showed that even with SABR, patients may progress with new metastases, likely due to the presence of micrometastatic disease, but that some can receive salvage therapy with repeat SABR.

On June 25, 2020 KIYATEC, Inc. reported that the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences (UAMS) has joined the growing roster of institutions participating in its 3D-PREDICT clinical study to validate the company’s test as a patient-specific predictor of response to recommended drug therapies for patients with ovarian cancer (Press release, KIYATEC, JUN 25, 2020, View Source [SID1234561487]).

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"Ovarian cancer patients and clinicians do not have the luxury of time to experiment with drug therapies they don’t know will work, so we developed our investigational ovarian cancer drug response profile to help optimize therapeutic decision-making over the course of the disease," said Matthew Gevaert, CEO of KIYATEC. "We are delighted to welcome UAMS to the 3D-PREDICT study as we endeavor to deliver on the promise of pre-treatment, patient-specific drug response profiling for ovarian cancer."

3D-PREDICT is a prospective, open-label, non-interventional study to validate KIYATEC’s ovarian cancer drug response profile, which leverages the company’s ex vivo 3D cell culture technology platform to assess pre-treatment, patient-specific response to a panel of 11 drugs most commonly used to treat patients with newly diagnosed or recurrent ovarian cancer. Details on the study can be found at View Source

"The Winthrop P. Rockefeller Cancer Institute is proud to offer 3D-PREDICT to our ovarian cancer patients. It is our hope that this trial will help develop a method to assist us in determining which drugs will most benefit individual patients and get them on the most effective treatment as quickly as possible," said Michael Birrer, M.D., Ph.D., vice chancellor and director of the Cancer Institute.