On March 30, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the fourth quarter and full year ended December 31, 2019 and provided a corporate update (Press release, TCR2 Therapeutics, MAR 30, 2020, View Source [SID1234555984]).

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"The past twelve months represent an exciting period for TCR2 as we advanced two programs into clinical trials. Last year we began using TC-210 to treat patients with mesothelin-positive solid tumors and, more recently, we initiated a Phase 1/2 trial of TC-110 in patients with CD19-positive hematological malignancies because we believe that TRuC-T cells alone can improve on the benefit provided by approved CAR-Ts," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "Looking ahead, 2020 is a pivotal year for the Company with interim Phase 1 data for both TC-210 and TC-110 as well as updates on new targets, our platform enhancements and allogeneic TRuC-T cells. With a year-end 2019 cash balance of $158.1 million, we are in a strong financial position to maintain runway into 2022 and execute on our strategic priorities."

"Commercially available CD19 CAR-Ts provide durable benefit in fewer than half of patients with lymphoma and their approval in acute lymphoblastic leukemia (ALL) remains limited to pediatric patients because they result in excessive toxicity in adult patients, as I witnessed while developing Kymriah," said Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics. "Our TRuC T-cells are more effective at trafficking in solid tumor models, which lymphoma tumors resemble, and are metabolically fitter than CAR-Ts, which enhances their ability to persist longer within the immunosuppressive solid tumor microenvironment. This gives us confidence that TC-110 may be more effective in treating patients with lymphoma and could allow us to salvage those who have previously failed CD19-directed CAR-Ts. In addition, we have shown that TRuC-T cells consistently release lower levels of cytokines in preclinical experiments, which could translate into a more favorable toxicity profile that would allow us to treat adult patients with ALL more safely."

Recent Developments

The U.S. Food and Drug Administration cleared the investigational new drug (IND) application for TC-110. TCR2 initiated its Phase 1/2 trial to treat patients with CD19-positive B-cell hematological malignancies, including adult acute lymphoblastic leukemia (aALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other non-Hodgkin lymphoma (NHL) subtypes.

TCR2 established operational capabilities at its manufacturing facility in Stevenage, UK and expects to use the facility to manufacture and supply clinical material after approval by the UK Medicines and Healthcare Regulatory Agency (MHRA).

TCR2 presented a poster at the 2020 Keystone Symposia Conference on Emerging Cellular Therapies: Cancer and Beyond highlighting allogeneic (off-the-shelf) T Cell Receptor Fusion Constructs (TRuC) T cells that lack alloreactivity and upregulate activation markers, secrete cytokines and kill tumor cells in an antigen-specific manner.

COVID-19 has significantly impacted the global healthcare system, including the conduct of clinical trials as medical institutions prioritize the treatment of those afflicted with COVID-19. As we balance the commitment to treat our cancer patients while mitigating the risk of viral spread to patients, employees and their families, we have instituted protective policies consistent with guidelines provided by the Centers for Disease Control and Prevention at all TCR2 facilities. While we are committed to providing an interim update of the Phase 1 portion of the TC-210 Phase 1/2 clinical trial in the second quarter of 2020 and the Phase 1 portion of the TC-110 Phase 1/2 clinical trial in the second half of 2020, the effect of the COVID-19 pandemic may impact the exact timing or content of these interim updates.

TC-110 Clinical Trial Design

The Phase 1/2 clinical trial is evaluating the safety and efficacy of TC-110, TCR2’s TRuC-T cell targeting CD19. The trial is enrolling patients with CD19-positive B-cell hematological malignancies including aALL, DLBCL, FL and other NHL subtypes.

In the Phase 1 portion of the clinical trial, patients will receive increasing TC-110 T cell doses following lymphodepleting chemotherapy. The primary objective of the Phase 1 portion of the study is to assess safety with a key secondary objective to determine the recommended Phase 2 dose (RP2D).

In the Phase 2 portion of the clinical trial, approximately 60 patients are planned to receive TC-110 at the RP2D and will be stratified according to their cancer diagnosis in three distinct cohorts: aggressive NHL, indolent NHL and aALL. Approximately 20 patients per indication will be infused with TC-110 T cells.

In addition to standard assessments of safety and efficacy, a panel of translational assays will be performed on patient samples throughout both phases of the study to assess, among others, cytokine production as well as expansion, trafficking, persistence, and changes in immunophenotype of TC-110 T cells.

TC-110 Patient Opportunity

Adult ALL

In 2019, there were an estimated 5,900 cases of ALL and over 1,500 related deaths in the United States. Adults comprise approximately 45% of all ALL cases but make up more than 85% of ALL-related deaths. CD19 directed CAR-Ts are not approved for patients with aALL.

DLBCL

In 2019 there were an estimated 74,000 new cases of NHL and 20,000 related deaths in the United States. Approximately two-thirds of patients with DLBCL are cured of their disease with frontline chemoimmunotherapy (R-CHOP). However, refractory patients have a median overall survival of only 6.3 months.

CD19-directed CAR-T cell therapy has shown activity in heavily pre-treated patients with CD19-positive DLBCL and two CAR-T cell therapies, Kymriah and Yescarta, have been approved for that indication. However, the response rate six months post-infusion ranges from 37% to 41% and both therapies are associated with high rates of severe CRS (13% to 23%) and neurotoxicity (12% to 28%).

Follicular Lymphoma

Approximately 15,000 patients were diagnosed in the United States with FL in 2019. The clinical course of patients with FL is generally indolent. However, 20% of patients with FL relapse within two years of R-CHOP therapy and have a median five-year survival rate of only 50% compared to 90% for the remaining 80% of

patients with a longer response duration. The experience with CAR-T cell therapy in FL is much more limited than in ALL or DLBCL.

Anticipated Milestones

TCR2 anticipates an interim update from the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for patients with mesothelin-expressing solid tumors in 2Q20.

TCR2 anticipates an interim update from the Phase 1 portion of the TC-110 Phase 1/2 clinical trial for patients with CD19+ non-Hodgkin lymphoma or adult acute lymphoblastic leukemia in 2H20.

TCR2 anticipates clinical production of TRuC-T cells at its manufacturing facility in Stevenage, UK, in 2H20.

TCR2 anticipates advancing a third mono TRuC-T cell therapy in 2Q20 with a target IND filing in 1H21.

Financial Highlights

Cash Position: TCR2 ended 2019 with $158.1 million in cash, cash equivalents, and investments compared to $123.2 million as of December 31, 2018. Net cash used in operations was $41.4 million for 2019 compared to $18.7 million for 2018. TCR2 projects net cash use of $60-70 million for 2020.

R&D Expenses: Research and development expenses were $37.5 million for 2019 compared to $19.7 million for 2018. The increase in R&D expenses is primarily related to increase in headcount, activities related to the Phase 1/2 clinical trial of the Company’s lead solid tumor product candidate, TC-210, and activities related to the IND submission of the Company’s lead hematologic cancer product candidate, TC-110.

G&A Expenses: General and administrative expenses were $13.9 million for 2019 compared to $6.8 million for 2018. The increase in general and administrative expenses was primarily due to an increase in personnel costs and costs associated with operations as a public company.

Net loss: Net loss was $47.6 million for 2019 compared to $24.3 million for 2018, driven predominantly by increased R&D expense for 2019.

Upcoming Events

TCR2 Therapeutics management are scheduled to participate at the following upcoming conferences.

Goldman Sachs Cell Therapy Day: Alfonso Quintás Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics, will present using a virtual platform on Monday, April 6, 2020 at 2:00pm ET

On March 30, 2020 Euronext Growth: ALIMM), the specialist drug discovery and development company, is reported that subscriptions to raise £1.5 million (the "Subscriptions") through the issue of 15,000,000 new ordinary share of 10 pence each in the Company ("Ordinary Shares") (the "Subscription Shares") at a price of 10p per Ordinary Share ("Issue Price") (Press release, ImmuPharma, MAR 30, 2020, View Source [SID1234555982]). The Subscriptions comprise a £200,000 subscription from Dr Robert Zimmer, (Director, President & Chief Scientific Officer of ImmuPharma) through Luca and Associates AG ("Luca")( a company to which he is connected) and a £1.3 million subscription with Lanstead Capital Investors L.P. ("Lanstead"), an institutional investor and substantial shareholder, together with a related sharing agreement, to raise in aggregate £1.5 million before expenses.

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Highlights

Subscription for 2,000,000 new Ordinary Shares (the "Luca Subscription") by Luca and Associates AG at an issue price of 10 pence per Subscription Share to raise gross proceeds of £200,000 (the "Luca Subscription").
Subscription for 13,000,000 new Ordinary Shares (the "Lanstead Subscription Shares") by Lanstead at an issue price of 10 pence per Subscription Share to raise gross proceeds of £1.3 million (the "Lanstead Subscription").
Further supportive investment in the Company by Lanstead following the £4.43 million investment and sharing agreement in February 2016, from which ImmuPharma ultimately received just over £5.0 million from Lanstead, and the £2.66 million investment in June 2019 which was invested in an ongoing sharing agreement with Lanstead, which is also currently ahead on cumulative settlements to date.
The Issue Price represents a 6.45 per cent. discount to the closing price (of 10.69p) of the Ordinary Shares on 27 March 2020, the latest business date prior to the Subscription.
The £1.3 million gross proceeds of the Lanstead Subscription will be pledged by the Company pursuant to a sharing agreement with Lanstead (the "Sharing Agreement"). The Sharing Agreement, details of which are set out below, entitle the Company to receive back those proceeds on a pro rata monthly basis over a period of 24 months, subject to adjustment upwards or downwards each month depending on the Company’s share price at the time. The Sharing Agreement provides the opportunity for the Company to benefit from positive future share price performance.
The Company has also agreed to issue to Lanstead 650,000 new Ordinary Shares (the "Value Payment Shares") in connection with the Sharing Agreement.
The proceeds of the Subscriptions receivable by the Company, of £1.5 million, of which £1.3m is subject to the Sharing Agreement, will be used primarily to fund:
– Expansion of the Company’s R&D programmes (see below); and
– General working capital.
Update on R&D Programmes

ImmuPharma’s pipeline will now comprise four therapy areas, which are Autoimmunity; Anti-Infectives; Metabolism and Cancer.

Highlights:

Strengthened advisory team for Lupuzor international Phase III trial;
Proof of Concept study planned for Lupuzor in CIDP patients;
3 new Anti-Infective programmes; and
New BioGlucagon product, with a potential market launch date in 2022.
Autoimmunity | Lupuzor for Lupus and CIDP

Lupus

The Company continues positively with its collaboration with our exclusive US partner Avion Pharmaceuticals LLC ("Avion"), who is fully funding the new optimised international Phase III trial for Lupuzor in lupus.

Recently, Avion has strengthened its team of advisors for the Phase III trial, entering into a collaboration with a leading lupus patient group and the formation of a Board of Key Opinion Leaders ("KOLs"), all of whom are senior respected consultants within the lupus and autoimmune community in the US and Europe.

In consultation with these advisors, a number of key decisions will now be made and next steps agreed in advance to meeting with the Food & Drug Administration (FDA). These will include:

Agreeing the structure of the optimised international Phase III Lupuzor trial;
Agreeing on the demographics and patient inclusion criteria; and
Guidance on key territories where the trial will be conducted
Once the Phase III trial has commenced, these advisors will together provide:

The support and expedition to identify and recruit the most appropriate lupus patients for the trial and;
Promotion to patient steering groups to raise awareness of Lupuzor to lupus patients and their clinicians throughout the duration of the trial.
Discussions continue with potential partners for Lupuzor outside of the US.

Chronic Inflammatory Demyelinating Polyneuropathy ("CIDP")

Outside of lupus the unique mechanism of action of Lupuzor (also known as Forigerimod or P140) has demonstrated in a number of pre-clinical trials that it has the potential to also be effective within other auto-immune diseases. One disease of key interest to ImmuPharma’s team is Chronic Inflammatory Demyelinating Polyneuropathy ("CIDP") where compelling pre-clinical data* has been generated. CIDP could potentially be granted ‘Orphan Drug Designation’ due to the unmet clinical need and with around 50,000 to 100,000 confirmed cases in the US and Europe, which would provide a fast approval process. The sales potential however could be greater than $500 million annually, with currently no effective approved drug on the market.

ImmuPharma is planning to commence a Proof of Concept study in CIDP patients based on the strong data already gained within the Company’s lupus dossier.

*Results were published in 2018 in the ‘Journal of Autoimmunity’ entitled: "An autophagy-targeting peptide to treat chronic inflammatory demyelinating polyneuropathies". This paper is available to review on line at the Journal of Autoimmunity: click here

Anti-Infectives

Why Anti-Infectives?

There is growing resistance to antibiotics and antifungal agents, and more recently the Covid-19 outbreak has highlighted mankind’s unpreparedness and susceptibility to more aggressive infectious microorganisms, not only from a health perspective but also from an economic and social impact. Surviving cancer and other fatal diseases is undoubtedly vital but without sufficient ammunition against bugs (viral, fungal or bacterial, ) we survive to face a bigger problem.

The World Health Organisation has stated that resistance to antibiotics is one of the biggest threats to global health, costs and mortality. Pandemic disease events could cost the global economy over $6 trillion in the 21st century (National Academy of Medicine: 2016).

However, despite the obvious threats to the health and wellbeing of the world’s population, anti-infectives is a therapy area that attracts one of the lowest R&D spends in the biopharma industry. For example, there are three trials in oncology for one in anti-infectives, even though anti-infective drug development is faster and less expensive. Trials are generally much shorter for anti-infection versus chronic disease. So, this is an attractive therapy area for speed to market and lower cost of trials.

Antiviral opportunity

The Company through its subsidiary UREkA Pharma has recently become a partner in a consortium dedicated to the development of novel peptides intended to block the fusion of COVID-19 and other viruses to the target cell, an approach similar to Fuzeon (enfuvirtide) by Roche.

Drugs that target viral entry into the host cell have been proven effective against a wide range of viral diseases. The aim is to apply the results of fundamental research to the development of novel inhibitors of SARS-CoV-2 entry into target cells using the Urelix patented technology of UREkA Pharma together with contributions from the other members of the consortium. The strategy is based on inhibiting viral entry, using peptides specific for the viral fusion protein.

Anti-fungal opportunity | ‘BioAMP-B’

ImmuPharma has recently developed BioAMP-B, a novel peptide-based drug that offers a potential improvement on Amphotericin-B ("Amp-B"). Amp-B is one of the few effective treatments for many serious and life threatening fungal infections such as aspergillosis (lung infection). However, the leading AMP-B, ‘Ambisome’ is known to cause serious kidney toxicity in 14-15% of patients. ImmuPharma’s BioAMP-B’s target profile has a superior safety profile to Ambisome. Sales of Ambisome in 2019 were $407 million. Next step is lead candidate optimisation.

Anti-bacterial opportunity | ‘IPP-203101’

IPP-203101 is ImmuPharma’s novel peptide-based antibiotic for the treatment of MRSA ("methicillin-resistant Staphylococcus aureus" or "superbug") and other severe and hospital acquired multi-resistant infections. MRSA infections are increasingly resistant to even the last lines of drug defence such as ‘vancomycin’ and ‘teicoplanin’, which are two commonly used antibiotics. IPP-203101 causes bacterial cell death by a two-step mechanism involving interaction with the lipid component of the membrane followed by membrane breakdown. IPP-203101’s target profile is to be as efficacious as vancomycin, but with a better safety profile, weekly administration, less susceptible resistance and a better efficacy profile for certain strains. Next step is lead candidate optimisation.

Metabolism | BioGlucagon

ImmuPharma has developed its product, BioGlucagon, as a potential new rescue therapy for low sugar events in diabetes. Existing glucagon products have poor solubility and are inconvenient with variable dosing due to poor solubility creating risks for patients. BioGlucagon has 100% solubility, can be formulated in pre-filled syringe pens and could be used in insulin pumps. The next step will be to progress towards a bio equivalence study for BioGlucgagon, which if successful could result with a potential market launch date in 2022.

On March 30, 2020 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a clinical-stage biopharmaceutical company specialized in the development of novel therapeutic and prophylactic vaccines, including one for coronavirus COVID-19, reported that financial, clinical and operational updates for the year ended December 31, 2019 (Press release, Heat Biologics, MAR 30, 2020, View Source [SID1234555981]).

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Jeff Wolf, Chief Executive Officer of Heat Biologics, commented, "2019 was an exciting year for Heat, as we advanced our therapeutic pipeline. This past November, we presented additional positive top line Phase 2 data of HS-110 plus BMS checkpoint inhibitor nivolumab (Opdivo) in advanced NSCLC lung cancer patients at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Tumor Immunology and Immunotherapy. We are highly encouraged by the data as we advance partnership and collaboration discussions. Earlier this year, we announced dosing the first patient in a Phase 1 clinical trial of our co-stimulatory HS-130, in combination with HS-110, for patients with advanced solid tumors refractory to standard of care, which marks a key milestone for Heat."

"We recently announced plans to develop a vaccine for preventing infection from the SARS-CoV-2 coronavirus that causes COVID-19 utilizing our robust gp-96 vaccine platform in collaboration with the University of Miami. Heat’s gp96 platform has undergone rigorous testing as a vaccine against SIV/HIV, malaria, zika and other infectious diseases in numerous National Institutes of Health (NIH) and Department of Defense (DOD)-funded mice and primate trials and has been tested in over 300 patients in multiple NIH and Heat-funded oncology trials. We believe this platform has the potential to provide broad protection against COVID-19, and possible future mutations of COVID-19 or other coronaviruses. We are encouraged by the prospects for this program and are moving forward with our partners to advance this vaccine as quickly as possible."

"Earlier this month we also announced a collaboration with the University of Miami to develop a proprietary COVID-19 point-of-care diagnostic test. The new paper-based test is being designed to provide a read-out in a fraction of the time required for most other tests, have no technical hardware requirements, have low cost of goods, be easily manufactured at scale, and provide binary readout if the patient is positive for a disease within 30 minutes. Unfortunately, current diagnostic tests, are in short supply and often take days for results. This diagnostic is being designed for early detection to provide critical and time-sensitive information to help curb the spread of the disease."

Mr. Wolf concluded, "We share our sympathies to those individuals and families impacted by COVID-19 and are committed to helping find solutions to this global pandemic. I’d like to thank all of the Heat and University of Miami professionals that have worked tirelessly to advance our therapeutic and diagnostic platforms. Importantly, we have over $25 million of cash and short-term investments as of March 23, 2020, which should put us on a solid financial footing as we advance our programs. Moreover, we believe that upcoming catalysts and milestones have the potential to drive significant shareholder value."

2019 Financial Results

Research and development expenses decreased by 20% to $13.0 million for the year ended December 31, 2019 compared to $16.2 million for the year ended December 31, 2018. The variance of approximately $3.2 million is primarily due to reduced clinical trial expenses related to HS-110 patient enrollment completion.

General and administrative expense increased approximately 36% to $9.5 million for the year ended December 31, 2019 compared to $7.0 million for the year ended December 31, 2018. The variance of $2.5 million is primarily due to the increase in personnel and stock compensation expense.

Net loss attributable to Heat Biologics was approximately $20.0 million, or ($0.60) per basic and diluted share for the year ended December 31, 2019 compared to a net loss of approximately $15.7 million, or ($0.90) per basic and diluted share for the year ended December 31, 2018.

As of December 31, 2019, the Company had approximately $14.8 million in cash, cash equivalents and short-term investments.

On March 30, 2020 Eagle Pharmaceuticals, Inc. ("Eagle" or the "Company") (NASDAQ: EGRX) reported that its marketing partner SymBio Pharmaceuticals Limited ("SymBio") has completed patient enrollment in a clinical trial for TREAKISYM rapid infusion ("RI"), a liquid bendamustine injection with a 10-minute administration time, in Japan (Press release, Eagle Pharmaceuticals, MAR 30, 2020, View Source [SID1234555980]). The study’s primary objective is to confirm the safety of the RI product. SymBio expects to obtain regulatory approval in the second half of 2022.

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SymBio intends to submit a New Drug Application ("NDA") for the RI product for all indications for which TREAKISYM is currently approved (low-grade non-Hodgkin’s lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia). As previously disclosed, SymBio filed an NDA for its TREAKISYM ready-to-dilute ("RTD") product in October 2019.

In September 2017, Eagle licensed to SymBio intellectual property necessary to develop, market and sell RTD and RI formulations of TREAKISYM in Japan. As part of the agreement, SymBio assumed responsibility for securing regulatory approval of the TREAKISYM RTD and RI injection products using the licensed technology in Japan.

Pursuant to the terms of the license with SymBio, Eagle received a $12.5 million upfront milestone payment in 2017, and is entitled to additional milestone payments, including $5 million upon approval of an NDA for either TREAKISYM RTD or RI, and other amounts upon achievement of cumulative sales thresholds. Eagle will also receive royalties on future net sales of the licensed bendamustine products.

According to SymBio, sales in Japan for TREAKISYM were $78 million in 2019.

"SymBio continues to make excellent progress in advancing TREAKISYM RTD and RI for approval in Japan as evidenced by the completion of enrollment of the safety study for the RI product. With anticipated future approvals for both the TREAKISYM RTD and RI products, we look forward to SymBio’s successful commercialization in Japan, allowing patients to benefit from these products’ key advantages," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

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.