On March 30, 2020 Bio-Techne Corporation (NASDAQ:TECH) reported researchers from its Munich-based laboratory, Exosome Diagnostics, in a paper published in the scientific Journal of Extracellular Vesicles (JEV) (link), showed that tumor- derived RNA was not detected in thrombocytes in samples where the tumor RNA was readily detected in exosomes (Press release, Bio-Techne, MAR 30, 2020, View Source [SID1234555979]). This finding holds significant implications for developers of liquid biopsies for cancer.

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The results from this study raise doubts about the commonly held belief that platelets include abundant tumor RNA that can be used for tumor specific RNA analysis, a process named Tumor Educated Platelets (TEPs). This has important implications for the use of platelets as a potential technology platform for liquid biopsies that aim to detect or monitor molecules of tumor origin in a biofluid sample. Such platelet-based strategies have recently been proposed by other companies and academic labs in the field.

"We wanted to find the most sensitive way to detect tumor specific RNA and were looking for ways to increase our clinical sensitivity. In light of previous publications on TEPs, we isolated RNA from exosomes as well as platelets from the same samples in hopes of improving the detection. We learned that combining the sample gave more RNA, but actually decreased the sensitivity for mutation assays," said Dr. Johan Skog, Chief Scientific Officer at Exosome Diagnostics, a Bio-Techne brand. "This finding led to this study quantifying the amount of tumor specific RNA in the platelets, if any, compared to other normal RNA". The researchers in this study applied a sensitive mutation assay but were unable to detect any tumor RNA in the platelet fraction, even when it was readily detected in the exosome fraction from the same sample. This casts doubt that keeping the platelet fraction adds value when looking at single nucleotide mutations on RNA. "There is plenty of RNA in platelets," continued Dr. Skog, "far more than in exosomes… but it does not come from the tumor."

In this carefully executed study, involving prospective collection of blood samples from patients with melanoma, whose tumor tissue had been confirmed to carry the BRAF V600E mutation, the researchers directly compared the RNA mutation signals detectable in exosomes to platelets isolated from the same blood sample. Using an exceptionally sensitive assay for detection of the BRAF V600E RNA, the mutation could be detected in 10 out of 12 exosome fractions, but not in a single platelet preparation. The researchers conclude in the article, that based on their findings, the differences in platelet RNA expression, previously published between cancer patients and normal healthy controls are unlikely to be of tumor origin. The researchers further conclude that as a consequence of their findings, it is recommended for most cases to remove platelets from a blood specimen for optimal detection of tumor-derived RNA in extracellular vesicles.

On March 30, 2020 BerGenBio, a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported that Richard Godfrey, Chief Executive Officer, will present at the upcoming Solebury Trout Virtual Investor Conference (Press release, BerGenBio, MAR 30, 2020, View Source [SID1234555978]). The 25 minute presentation includes an interactive Q&A with participants prompted to submit questions electronically. Details are as follows:

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Date/Time: Tuesday March 31, at 11am EDT

Access: https://78449.themediaframe.com/dataconf/productusers/solebury/mediaframe/36522/indexl.html

Webcast archive: 24 hours following the presentation an archive copy of the presentation will be available on the Company’s website at View Source

On March 30, 2020 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported recent business highlights and full year 2019 financial results (Press release, Beam Therapeutics, MAR 30, 2020, View Source [SID1234555977]).

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"So far in 2020, we have made strides across all aspects of our business, and despite the many uncertainties we face today amid the COVID-19 pandemic, we remain committed to moving our programs forward for patients," said John Evans, chief executive officer of Beam. "Following the successful completion of our initial public offering and the recent additions to our team, we have the resources needed to steadily advance a broad and deep portfolio of base editing programs addressing a wide range of disease areas and to invest in the science of base editing, illustrated by the recent platform technology publications. As we look ahead, we are planning for additional scientific publications throughout the year and remain on track to file an initial wave of IND applications beginning in 2021, in an effort to bring a new class of precision genetic medicines to the clinic and, ultimately, to patients."

Recent Business Highlights

Leadership Team Strengthened with Key Appointments: Since the beginning of 2020, Beam has named several appointments and promotions aimed at further supporting advancement of its pipeline and expanding its business operations. These include the promotion of Giuseppe "Pino" Ciaramella, Ph.D., to president and chief scientific officer, the promotion of Manmohan Singh, Ph.D., to senior vice president of pharmaceutical sciences and delivery technologies, and the appointment of Christine Swenson as senior vice president of regulatory affairs.

Advancements in Base Editing Technology Platforms Highlighted in Scientific Publications: New research on Beam’s novel adenine base editor (ABE) and cytosine base editor (CBE) technologies were reported in multiple scientific publications. Data from these internal and collaborator publications further support that Beam’s continued evolution of ABEs and CBEs can enhance the precision of targeted A-to-G and C-to-T DNA base changes, potentially improving the range of therapeutic applications.

In a paper entitled, "ABE8: Superior adenine base editors with expanded targeting range, higher activity, and therapeutic application", accepted for publication in Nature Biotechnology, Gaudelli, et al., highlight continued evolution of Beam’s adenine base editors. These proprietary, next-generation "ABE8 variants" demonstrated improved therapeutic potential compared to previously published versions, including increased on-target activity while maintaining low-levels of off-target editing across a number of cell types, including transformed and human primary cells.

In a paper entitled, "Next-generation cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity," accepted for publication in Nature Communications by Yu, et al., highlighted proprietary next-generation versions of CBEs. Off-target editing rates with the first published version of CBEs, known as BE3, are low and within mutation rates that naturally occur with no consequence in somatic cells. These next-generation CBEs display comparable on-target editing to BE3 while further reducing the low levels of off-target editing seen with BE3.

Two papers published in Nature Biotechnology by Beam co-founder Dr. David Liu, highlight novel CBEs that diminish or eliminate the low levels of off-target editing observed with BE3s, and novel variants of base editors that are able to bind a wider range of genetic targets, expanding their therapeutic potential.

Oversubscribed $207M Initial Public Offering Completed: On February 11, 2020, Beam announced the closing of its initial public offering of 12,176,471 shares of common stock, including the exercise in full by the underwriters of their option to purchase up to 1,588,235 additional shares of common stock, at a public offering price of $17.00 per share. The net proceeds to Beam Therapeutics from the offering were approximately $188.3 million, after deducting underwriting discounts and commissions and estimated offering expenses.

Business Continuity: Beam is executing its business objectives for 2020 and beyond, while closely monitoring the impact of the COVID-19 situation. The company has established a remote operating model while prioritizing the most critical research and development activities needed to advance its portfolio of novel base editing programs.

Full Year 2019 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $91.8 million as of December 31, 2019, which does not include the $188.3 million in net proceeds from the company’s IPO completed in February 2020. In addition, cash used to fund our operations was $72.0 million for the year ended December 31, 2019.

R&D Expenses: Research and development (R&D) expenses were $54.6 million for the full year ended December 31, 2019.

G&A Expenses: General and administrative (G&A) expenses were $20.6 million for the full year ended December 31, 2019.
Net Loss: Net loss was $78.3 million for the full year ended December 31, 2019.

On March 30, 2020 ImaginAb Inc., a leading clinical stage immuno-oncology imaging company, reported it has signed a multi-year non-exclusive license agreement with AstraZeneca (Press release, ImaginAb, MAR 30, 2020, View Source;utm_medium=rss&utm_campaign=imaginab-announces-licensing-deal-with-astrazeneca-for-cd8-immunopet-technology [SID1234555974]).

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Under the terms of the agreement, ImaginAb’s CD8 ImmunoPET technology will be used in AstraZeneca’s clinical trials in North America and Europe to facilitate clinical development of AstraZeneca’s novel immunotherapies and to advance the clinical utility of ImaginAb’s CD8 ImmunoPET.

The deal is an opportunity for ImaginAb to support AstraZeneca’s project teams on imaging CD8 cells in patients and both teams will be committed to analysing and interpreting the data for their respective research and development activities.

ImaginAb will receive license fees and other contingent payments.

This agreement follows the recently signed pre-competitive alliance between AstraZeneca, ImaginAb and other global pharmaceutical companies, announced on October 14, 2019.

Commenting on the news, Ian Wilson, Chief Executive Officer of ImaginAb said: "We are very pleased that AstraZeneca is expanding our relationship. Under the new agreement, ImaginAb will provide AstraZeneca with clinical doses of ImaginAb’s CD8 ImmunoPET minibody, as well as technical support, to AstraZeneca clinical trials involving novel immunotherapies. ImaginAb’s CD8 ImmunoPET technology is the clinically most advanced CD8 PET tracer. It is a powerful diagnostic approach for measuring non-invasively the effect of immunotherapies, which we believe will ultimately be used to predict therapeutic efficacy."

On March 30, 2020 ISA Pharmaceuticals reported that Just weeks after International Human Papilloma Virus (HPV) Awareness Day, new results from two long-time Cancer Research Institute (CRI) scientists highlighted the promise of immunotherapy against HPV-associated cervical cancer (Press release, ISA Pharmaceuticals, MAR 30, 2020, View Source [SID1234555973]).

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In a phase 1/2 study, women with advanced, recurrent, or metastatic cervical cancer were treated with the combination of an HPV-targeting vaccine and standard-of-care chemotherapy. Of 72 evaluable patients, 43 percent had their tumors shrink.

Led by Cornelis J. M. Melief, M.D, Ph.D., and Sjoerd H. van der Burg, Ph.D., this clinical breakthrough was the latest fruit borne by the duo, both of whom have been supported by CRI during their time at Leiden University Medical Center in the Netherlands. In addition to being a member of the CRI Scientific Advisory Council, Melief was the recipient of the 2019 AACR (Free AACR Whitepaper)-CRI Lloyd J. Old Award in Cancer Immunology and is currently the chief scientific officer at ISA Pharmaceuticals. Van der Burg, who earned his doctorate in Melief’s lab in 1998, is also affiliated with ISA as a member of their Scientific Advisory Board, as well as the Oncode Institute.

In 2002, CRI-funded preclinical work by Melief and van der Burg provided an early proof of principle that therapeutic HPV vaccines could eliminate HPV-associated cancers. To do so, they used synthetic long peptide (SLP) vaccines to target the E6/E7 oncoproteins produced by the HPV16 strain.

Next, they demonstrated that HPV-targeting vaccines could clear pre-malignant lesions. However, vaccination wasn’t effective against advanced cancers because of the presence of immunosuppressive myeloid cells. By adding chemotherapy to the treatment regimen, the current study sought to decrease the number of myeloid cells and thereby enable more potent anti-tumor immune responses after vaccination, especially by the immune system’s "killer" T cells.

In many patients, the combination appears to have done just that.

Two weeks after chemotherapy, when patients’ myeloid cells were at their lowest point, varying doses of the ISA-101 vaccine were administered. Half of them also received a molecule called pegylated type 1 interferon that may help boost adaptive immune responses. Overall, about one-third of patients analyzed had low levels of HPV-targeting T cells after chemotherapy alone and prior to vaccination. Post-vaccination, HPV-specific T cell responses were detected at all dose levels, and "the patients with higher than median strength responses survived the best," Melief told CRI.

"These results, provided they are validated in larger trials, could lead to significantly improved care for patients with cervical cancer."

In another ongoing study, this vaccine paired well with checkpoint blockade immunotherapy in patients with advanced head and neck cancer—another cancer linked to HPV infection. A similar trial will soon be testing that approach in cervical cancer, according to Melief, who believes we might benefit from going even further with vaccine combinations.

"Last year, we demonstrated the synergy between vaccination and anti-PD-1 checkpoint immunotherapy in patients with recurrent or metastatic HPV+ head and neck cancer. It is therefore tempting to combine all three therapeutic measures—anti-PD-1, vaccination, and chemotherapy—for additional synergy because chemotherapy and anti-PD-1 act by non-overlapping mechanisms. This chemotherapy combination also pinches in nicely with other types of immunotherapy because many types of late-stage cancer induce this kind of myeloid cell-mediated immunosuppression in patients."