Hack cyber Daily News – 2020-09-24 – STATOPERATOR
How to write a (toy) JVM In this article - Serge Zaitsev creates a toy (and incomplete) JVM to show the core principles behind it and hopefully sparkle some interest for you to learn more about the Java Virtual Machine. Cyberwar Is Harder Than It Looks – Reason.com. SoCPhysics: A Stream-of-Commerce Physics-Based Data Generation. Harmony and religious tolerance, who by his power of pious devotion and deep faith in Lord Shiva, acquired the boon of eternal life by defeating the invincible Yamraja), MM(DU) began with the establishment of MM Engineering College at Mullana in 1995.
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Usage ideas & examples get redirected here. Single Tick when Depressing the Accelerator - 2020 5.3L. By Kate Bradbury 18 Nov 2020, 2: 19pm The Government's green revolution is a fine ambition, but how will it work in practice? Directorate Plan 2020/24.
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INVGEN-34389: Resolved issue where invisible intersect points incorrectly impact the Degree of Freedom value. Multicore systems, and fault tolerance - 36 - Department of Computer Science and Engineering. Brain-inspired computing is an emerging field, which aims to extend the capabilities of information technology beyond digital logic. I need unlock code for Tolerance Data If this is your first visit, be sure to check out the FAQ by clicking the link above.
1 FT-CNN: Algorithm-Based Fault Tolerance for
The modifications to the existing text of the draft Regulation (see EDR-DSSAD-01-03) are marked in bold for new or strikethrough for deleted characters. In Situ TEM of Two-Phase Lithiation of Amorphous Silicon. Commonly adopted PE array-based deep neural network accelerator architecture and the observation of diminishing dynamic timing margin from a single PE unit to a large PE array.
NIH Guide: All Active Funding Opportunities (RFAs & PAs)
The libraries are organized in order to expose the variable precision kernels as compatible replacements of their usual counterparts in the BLAS and solver libraries. Officially, the video content which makes the link between 5G and COVID-19 does not actually break community guidelines, but it will be removed from recommendation engines as it has been deemed as borderline content. OHCS Statewide Housing Plan Milestone 4 Update July 2020. And also all the chip select (CS) pins are connected together.
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Compression in this release is optimized for cold data or write-once objects and files. Conference Program - American Coatings Show. In the pre- and post-crash EDRs, data such as vehicle speed, engine speed (rpm), accelerator angle and brake application (whether the brake pedal was applied or not) is also recorded. We apologise to the patron affected by the incident and we would like to assure our customers that their safety is paramount to us. It is our.
Key biogas Plants: New Challenges need New Solutions
The solution automatically accepts prices that are returned within a client-defined tolerance with note-rate detail, to individually approve prices outside of those parameters. Proposal for amendments to document EDR-DSSAD-01-03 https://ya-pilot.ru/download/?file=1416. Published Mon, Oct 5 2020 2: 40 PM EDT Updated Mon, Oct 5 2020 2: 43 PM EDT Michelle Fox @MFoxCNBC Melissa Bradley founded 1863 Ventures to help women and people of color jump start their businesses. Canyons School District.
Activity code steven Marcus - Lead Product Engineer
Congress (2020-2020): John S. McCain National Defense Authorization Act for Fiscal Year 2020. Download Autodesk Multi-Sheet Plot for Inventor 2020. Aadit Patel - Defense Innovation Accelerator Entrepeneuer. President, Students' Union.
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Phoenix V-Belt Pulley - 5/8in. Even though the system shows a 96 Mb/s receiving speed after calculation it was really only 1.5 Mb/s. Get answers fast from Autodesk support staff and product experts in the forums. Tolerance data 2020.2 keygen accelerator.
Pooja Bedi invited to next Kumbh by Mahant Giri
Making rapid progress in a short span of 25 years, it has developed into a vast campus comprising the institutions of high– profile. I search in forum, but i did't find this problem! Search among more than user manuals and view them online [HOST]. Noramay Cadena is the Co-founder of an early stage hardware accelerator in Los Angeles, with a strong history of helping to bring digital knowledge and entrepreneurship to women and the latin community.
While You Were Distracted by the Riots
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Literally 1984:Executive order set to make social media platforms liable for their users posts. Get ready for a whole new wave of censorship. You ain't seen nothing yet.
Minnesota is now using contact tracing to track protestors, as demonstrations escalate
The Long, Ugly History of How Police Have Tracked Protesters
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The "Pandemic" is bullshit:Protests could set off second wave of coronavirus infections — Recent protests across the country are likely to cause a spike in coronavirus cases as the pandemic continues to impact the United States. Dr. Dave Campbell discusses when and where the country could see spikes.
Top HIV scientist says he wouldn't count on a vaccine for coronavirus soon
The first human trial of a COVID-19 vaccine finds that it is safe, well-tolerated, and induces a rapid immune response: “These results represent an important milestone.”
Governments and WHO changed Covid-19 policy based on suspect data from tiny US company
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In Other News:Spain approves national minimum income
Sixth mass extinction of wildlife accelerating, scientists warn
Artificial intelligence begins to show signs of human-like creativity
‘Collapse of civilisation is the most likely outcome’: top climate scientists
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War is Coming:Un-identified military personnel extend perimeter around the White House
The U.S. Will Exit The Open Skies Treaty and It’s Unclear Why
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Voting and Trump:Will he go? A law professor fears a meltdown this November.
U.S. states see major challenge in delivering record mail ballots in November
Revealed: conservative group fighting to restrict voting tied to powerful dark money network
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Other People's Opinions:COVID-19 and the riots could possibly be the greatest attempt at division among the common people induced by media disinformation.
George Floyd’s murder was exactly what the MSM needed to get out of the COVID corner they painted themselves into
This is all fucking exhausting. And I think that’s just how they want it to be.
Maybe they wanted civil unrest the whole time
It’s too late. The protests are orchestrated. It’s all planned. It’s part of their game plan. And people don’t care. We are walking right into it. And it’s exactly what we’re supposed to do.
A New Chapter Begins - BofA Analyst Greg Harrison Begins Covering Athersys
I also think Richard's purchase says a lot about the upcoming prospects for Athersys. A lot of things are coming together.
BofA Securities Starts Athersys (ATHX) at Buy; 'More than a COVID-19 Story'
More than a COVID-19 Story; Initiate at Buy, $5 PO Initiating Coverage: BUY | PO: 5.00 USD | Price: 2.22 USD Core respiratory distress program provides foundation We initiate coverage on Athersys with a Buy rating and $5 PO. Athersys is a clinicalstage cell therapy company developing a stem cell therapy, MultiStem, for a variety of acute regenerative medicine applications. The lead program in Acute Respiratory Distress Syndrome (ARDS) has compelling phase 2 data showing meaningful reductions in mortality and ventilator- and ICU-free days. Given Athersys’ use of Multipotent Adult Progenitor Cells (MAPCs), which do not require tissue matching and can be acquired and expanded from a single adult donor, MultiStem is positioned for rapid administration in indications where time to treatment is critical. Athersys’ program is timely, given the potential to treat ARDS from all causes, including COVID-19, which could lead to an accelerated path to market and government funding and purchases. While the programs are not without risk, we see blockbuster sales potential (ARDS $2.8B peak, stroke $2.9B peak, unadjusted), and meaningful 2020 catalysts in data from partner Healios in Japan and BARDA funding. We value the ARDS program at $4/sh, stroke at $1/sh, and net cash at $0/sh, making up our $5 PO. COVID-19 program could speed market entry With ARDS being the leading cause of death among COVID-19 patients, MultiStem could make an impact for patients with severe disease. While we see COVID as a short-lived opportunity, the program could provide Athersys with government funding (discussions with BARDA are ongoing) and ongoing purchases for emergency stockpiles, given MultiStem’s potential application to ARDS from a variety of viral infections. Stroke and trauma programs provide upside optionality The MultiStem stroke program is high-potential but high-risk, in our view, after missing the primary endpoint in phase 2. Changes in entry criteria for the ongoing phase 3 trial could result in more positive data, though we ascribe minimal value to the program until we see derisking data. The DoD-funded phase 2 trauma trial could provide an interesting follow-on indication given the similar proposed mechanism of action. We think the stroke trial could derisk trauma but do not assign value due to earlier stage. MultiStem technology The MultiStem product is a donor-derived, universal stem cell therapy intended to work through multiple mechanisms to heal and repair tissue via inflammation reduction, immunomodulation, neuroprotection, cytoprotection, and angio/vasculogenesis. In contrast to traditional immunology/inflammation assets which are limited to dampening immune responses, MultiStem’s cells secrete anti-inflammatory factors as well as cytokines associated with tissue healing like VEGF and other factors that stimulate the growth of new blood cells in the effected tissues. Given that MultiStem is derived from bone marrow of healthy adult donors, ethical concerns associated with embryonic stem cells are avoided. Athersys’ technology allows for expansion from a single donor bank into millions of doses, allowing for significant scalability. In addition, MultiStem can be administered quickly as an off-the-shelf product, allowing for rapid treatment in acute settings like stroke and ARDS. MultiStem uses a class of stem cells called Multipotent Adult Progenitor Cells (MAPC). These cells differ from other stem cells like hematopoietic stem cells and mesenchymal cells in that MAPCs: 1) do not require tissue matching, 2) do not engraft into the body and are eventually removed via natural cell recycling processes, and 3) do not require immunosuppression during administration. MultiStem Programs Athersys is developing MultiStem for several acute care indications where the regenerative approach has shown promise. Acute Respiratory Distress Syndrome (ARDS) The primary driver of our valuation is the ARDS program. ARDS encompasses respiratory distress from a variety of causes, including influenza viruses, coronaviruses, trauma, and aspiration, and has specifically been associated with SARS, MERS, H1N1, and SARSCOV-2. The burden from ARDS is significant, with annual incidence of ~500,000 patients in the U.S., Europe, and Japan combined. When a patient has ARDS, a pulmonary hyperinflammatory response occurs which creates morbidity beyond the impact of the initial cause. MultiStem cells secrete factors intended to reduce the excessive inflammatory response as well as simulate healing of damaged tissues. Big unmet need with limited treatment available ARDS has a high mortality rate of 30-50%, with patients typically put in a medically induced coma while on a ventilator and spending a median of 25 days in the ICU. There are no ARDS treatments currently approved, though the COVID-19 epidemic has increased research in the area and the steroid dexamethasone recently showed a mortality benefit in COVID-19 patients. Dexamethasone is also currently used in ARDS from other causes. With ventilator support being the only option for ARDS patients currently, the unmet need is significant for a treatment that can affect the course of ARDS. Ventilators, while capable of supporting patients’ recoveries, create high costs and often require lengthy recovery periods after leaving the ICU. Phase 2 data bodes well for upcoming pivotal trial The phase 2 MUST-ARDS trial for patients with ARDS met its two primary safety endpoints of safety and tolerability within 4 hours of MultiStem administration and no Suspected Unexpected Serious Adverse Reactions (SUSARs) within 24 hours of MultiStem administration. Ventilator and ICU usage decreased in MultiStem patients Notably, the trial also showed efficacy, which if replicated in a larger trial, would be highly meaningful in our view. Through the 28-day clinical assessment, patients receiving MultiStem had 12.9 days free of the ventilator, compared with 9.2 days for the placebo group. On a median basis, the difference was greater, with 18.5 ventilator-free days for the MultiStem arm vs. 6.5 days for placebo. Considering the disability associated with time spent on ventilators, we think it is likely that a significant increase in ventilator-free days would result in improved longer-term patient outcomes. Time spent in the ICU was also lower in the MultiStem arm, with mean ICU-free days of 10.3 (12.5 median) compared with a mean of 8.1 (4.5 median) in the placebo arm. Beyond the faster recovery of these patients, we would also argue that the reduction in the cost associated with ICU usage makes for a more straightforward economic argument for any agent that can reduce time spent. Mortality benefit seen, more patients needed to confirm Most importantly, treatment with MultiStem resulted in a mortality benefit at 28 days, with a 25% mortality rate in the MultiStem arm, compared with 40% in the placebo arm. While numbers were small in the trial (n=20 in the MultiStem arm, n=10 placebo), a mortality benefit approaching this magnitude in a pivotal trial would be an excellent outcome in our view. More severe subgroup shows more profound benefit In a prospectively defined analysis of patients with more severe ARDS, the benefit from MultiStem was even more apparent. On the ventilator-free days endpoint, MultiStem had a mean benefit of 6.6 days, while showing a mean 5.5 day benefit on ICU days. The 28-day mortality benefit within this subgroup was even higher than in the overall population, with 25% for MultiStem and 50% in the placebo arm. The benefit from MultiStem in this severe patient group was quite strong, though we would caution that the patient numbers were even smaller here, with 8 patients in each arm. MultiStem patients recovered faster and had better long-term outcomes In addition to the endpoints discussed above, patients treated with MultiStem also had faster recoveries, with 45% of MultiStem patients off of ventilators at day 7 compared with only 20% of patients on placebo. At 1 year of follow up, 80% of surviving MultiStem patients had achieved complete independence in self-care, vs. only 40% in the placebo group. Pivotal ARDS trial likely to start later this year In our conversations with management, we learned that the pivotal trial is currently in the design stage, which should be completed in the next few months. As the MACoVIA phase 2/3 study in COVID-19-induced ARDS recently began enrolling, Athersys will apply lessons from this program to the ARDS pivotal trial. The trial will be comparably sized to the MACoVIA trial and designed for a broad approval in ARDS, with the potential to support use in future pandemics. Management views the hurdle for a positive trial as any statistically significant decrease in ventilator-free days, noting that this endpoint does include mortality within the 28-day period, as any patient death would have a ventilatorfree days result of 0. COVID-19 ARDS program provides nearer-term optionality Separate from the general ARDS program, Athersys recently began enrolling a phase 2/3 trial in patients with COVID-19 induced ARDS. The MACoVIA trial is a randomized, double blind, placebo controlled trial enrolling ~400 patients with acute onset moderate to severe ARDS and a diagnosis of COVID-19. The trial will test MultiStem on top of standard of care and assess efficacy with a primary endpoint of ventilator days at day 28. Secondary endpoints include mortality, ICU-free days, proportion of patients achieving ventilator independence at Day 7, and biomarker analysis. In addition, a oneyear follow up will evaluate functional independence, self-care, and quality of life. With the first patient having enrolled on May 4, we estimate enrollment will take 12-18 months, likely putting data in 2H21. Given the intense need for COVID-19 treatments, particularly in the severe end of the spectrum, we would anticipate that MultiStem 6 Athersys Inc | 25 June 2020 would make it to market quickly if the data show a meaningful treatment benefit. Still, we see the COVID-19 program as likely to have a shorter period of significant uptake as COVID-19 incidence is likely to decline in coming years as a result of a combination of potential vaccines, other treatments, and herd immunity. Stroke Program is high-risk but could be transformational Athersys’ stroke program is another opportunity in an area of high unmet medical need. With limited success across the industry in developing treatments for stroke, treatments are typically limited to tissue plasminogen activator (tPA), which must be administered between 3-4.5 hours of the stroke and mechanical thrombectomy (within 6-16 hours). Less than 10% of patients are treated within this timeframe and receive supportive care. MultiStem has the potential to extend the treatment window to 36 hours, which would allow 90-95% of patients to be treated. With ~2.2 million strokes annually between the U.S., EU, and Japan, ischemic stroke is a meaningful opportunity, and MultiStem’s ease of administration and wide treatment window could allow for the treatment of a large number of these patients. With a strong rationale for MultiStem’s mechanism to affect the pathology of ischemic stroke (see Exhibit 3 below), the program has potential to be a transformational treatment, though we still view the program as high risk due to the difficulty in developing stroke treatments generally, as well as questions around the data from the phase 2 trial. Phase 2 MASTERS-1 trial The phase 2 study of MultiStem in ischemic stroke did not meet statistical significance on its primary outcome of percentage of patients achieving an excellent outcome at 90 days, though MultiStem-treated patients did have a numeric advantage. Among all patients, at day 90 there was an 8.8% delta between the MultiStem arm (15.4% having excellent outcomes) and the placebo arm (6.6%), though the p-value was only 0.10. In contrast, the delta increased throughout the year, as the MultiStem arm had 23.1% of patients achieving excellent outcomes compared with 8.2% of placebo patients (p=0.02). In addition, patients receiving early MultiStem treatment within 36 hours of the stroke showed an increased benefit beyond the trial population as a whole, with 16.1% achieving excellent outcome vs 6.6 in the placebo group (9.5% difference, not stat sig, Athersys Inc | 25 June 2020 7 p=0.14). At day 365, the data was stronger, with a 20.8% improvement over placebo (p<0.01). Caveats to MASTERS-1 While the MASTERS-1 trial did not meet its primary outcome, we list below several factors that increase the likelihood of success in phase 3. 1. Treatment window was extended in phase 2 – in contrast to the original protocol calling for treatment within 36 hours, the window was extended to 48 hours due to logistical constraints with having MultiStem available. Since rapid treatment is necessary for the best possible stroke outcome, any treatment delay would be expected to reduce the chance for success. In phase 3, the treatment window will be returned to 36 hours post-stroke. 2. Primary endpoint was composite combining 3 scales – With an excellent outcome in the trial defined as positive scores on the NIHSS, mRS, and Barthel Index, they were not common and it was harder to statistically prove significant. In phase 3, the primary endpoint will be the modified Rankin Scale (mRS) alon3. Proportion of patients achieving excellent outcomes will be collected as secondary endpoint. 3. Larger phase 3 sample size to increase power – The phase 3 MASTERS-2 study will recruit 300 subjects, compared with 136 in Masters-1, giving the trial more opportunity to show statistical significance. We expect MASTERS-2 to complete enrollment in 2021. Although the stroke market presents an attractive opportunity, we remain cautious on the outlook for phase 3 given the historical difficulty of the indication as well as the lack of clear phase 2 data. Still, we see signs of activity in the phase 2 dataset and do include value in our model for MultiStem in stroke (~$1/sh). Healios collaboration Athersys has a partnership with Healios where Healios will develop and commercialize MultiStem in Japan. Healios is currently running trials in stroke (phase 3 TREASURE study) and pneumonia-induced ARDS (phase 2 ONE-BRIDGE). We expect pivotal stroke data at the end of 2020 and data from the ARDS study in early 2021. In our view, positive data from these trials would significantly derisk the MultiStem program and could lead to upside in shares. We model royalties from the partnership at $126M peak. Trauma Beyond the core ARDS and stroke indications, Athersys is developing MultiStem in trauma indications as well. With similarities to stroke in that excessive inflammation creates secondary damage after the initial injury, any success in the stroke program could have read-throughs to the potential in trauma. Athersys recently got authorization to begin a double blind, placebo controlled phase 2 MATRICS-1 study in trauma evaluating systemic inflammatory response syndrome (SIRS), which occurs in ~2/3 trauma patients and can lead to ARDS, sepsis, and organ failure. In addition, the trial will look at all-cause mortality at 30 days. As the leading cause of death in the 1-45 age group in the U.S., trauma could make for a sizable franchise, though we await derisking data before assigning value to the program. Competitive Landscape Given the unique approach utilizing MAPCs, Athersys doesn’t have direction competitors with a similar product. While there are a number of product candidates in development for each of MultiStem’s proposed indications, we would argue that due to the difficulty of the indications and the likely need for combination therapy to get the best outcomes, that MultiStem’s success is more likely to be determined by its success in trials than in the marketplace versus competitors. We forecast a MultiStem launch in 2022 in COVID-19 induced ARDS. Assuming a net price of $30k per treatment in the U.S. with a 40% discount in the EU, we model peak unadjusted revenues of $202M in 2023 (see Exhibit 4 below). We note however, that this indication is highly unknown and the epidemiological estimates are subject to constant change. We are more confident in the non-COVID-19 induced ARDS program (launch expected 2023), peak unadjusted revenues of $2.8B, and highlight potential upside from the higher-risk stroke program (peak unadjusted sales of $2.9B). We assume continued growth in R&D and SG&A expenses and losses continuing until MultiStem is into its launch. Still, we estimate profitability starting in 2023, with the MultiStem launch driving significant EPS growth on a non-probability adjusted basis. Additional capital needed, but potential for external funding sources With ~$97M cash on hand, Athersys has guided to having sufficient cash to fund operations through 2021. We would anticipate additional capital raises to fund latestage development before MultiStem begins generating cash flows, though funding from BARDA or milestones from Healios could provide capital as well. Valuation and Risks We use a sum-of-the-parts NPV model to value Athersys based on our risk-adjusted revenue forecasts and estimated margins. NPV Sum-of-the-Parts Analysis Our 12-month price objective for Athersys of $5/sh is based on our NPV analysis summarized below in Exhibit 7. We forecast sales for MultiStem through 2030. We assume a WACC of 15%, in line with peer companies of similar size and risk and a terminal growth rate of 0%. We assume a 25% probability of success for the ARDS program and 5% probability for stroke. Given these assumptions, we estimate a value of $1/sh for the stroke program, $4/sh for the ARDS program, and $0/sh net cash. This underlies our $5/sh price objective and our Buy rating Blue sky scenario of $32/sh Given our conservative estimates of probability of success, positive trial data and eventual approvals could meaningfully increase valuation. Our blue sky valuation scenario, shown below in Exhibit 8, assumes 100% probability of success in the two primary indications, stroke and ARDS. This results in a value of $32 per share, which in our view is a compelling demonstration of the low expectations for these programs. While we understand the questions around the stroke program, and only assign the program 5% probability of success, we think the ARDS programs are quite underappreciated given the strong data from phase 2 and the lack of other treatment options for this urgent need. Even in a scenario where the stroke program failed and ARDS was approved, our model would suggest a value of $15/sh, which is >6x the current stock price. Price objective basis & risk Athersys Inc (ATHX) Our sum-of-the-parts NPV valuation of ATHX includes $4/share for MultiStem for ARDS, $1/sh for the stroke program, and $0/sh in net cash. We use a 15% WACC, in line with other biotech companies of similar size and risk. We assume a 0% terminal growth rate. Risks to our price objective are 1) clinical trial failures, 2) lack of uptake in the market, 3) unexpected safety signals, and 4) pricing pushback from payers. Analyst Certification I, Greg Harrison, CFA, hereby certify that the views expressed in this research report accurately reflect my personal views about the subject securities and issuers. I also certify that no part of my compensation was, is, or will be, directly or indirectly, related to the specific recommendations or view expressed in this research report.