The digital press release with multimedia content can be accessed here:

Basel, August 20, 2020 Novartis today announced that the US Food and Drug Administration (FDA) has approved Kesimpta (ofatumumab, formerly OMB157) as an injection for subcutaneous use for the treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that has shown superior efficacy with a similar safety profile compared with teriflunomide and is a first-choice treatment option for RMS patients1. Kesimpta is the first B-cell therapy that can be self-administered once monthly at home via the Sensoready autoinjector pen3.

This approval is wonderful news for patients with relapsing multiple sclerosis. In the key clinical studies, this breakthrough treatment produced a profound reduction in new brain lesions, reducing relapses and slowing underlying disease progression1, said Professor Stephen L. Hauser, Director of the UCSF Weill Institute for Neurosciences and co-chair of the steering committee for the ASCLEPIOS I and II studies. Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center1.

One of the goals when managing RMS is to preserve neurological function to slow down the worsening of disability4. Despite the availability of several disease-modifying therapies (DMTs) for the treatment of RMS, the majority of individuals with RMS continue to experience disease activity5. Evidence suggests early initiation of high-efficacy treatment can improve long-term outcomes for patients with RMS6.

Multiple sclerosis (MS) is a complex disease, and response to disease modifying treatment will vary among individuals, said Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. This makes it important to have a range of treatments available with different mechanisms of action and routes of administration. We are pleased to have an additional option approved for the treatment of relapsing forms of MS.

Traditionally, B-cell treatments, which bind to and deplete B-cells associated with disease activity in MS, have predominantly been available in hospitals or infusion treatment centers, which can add costs to the healthcare system and present a lifestyle burden for some patients7,8. Kesimpta provides patients the flexibility of self-administering via once-monthly subcutaneous dosing requiring no premedication, eliminating the need to travel to an infusion center. The positive results from the APLIOS studyan open-label Phase II study to determine the bioequivalence of subcutaneous delivery of Kesimpta via a prefilled syringe and a Sensoready pen in patients with RMSand the ASCLEPIOS studies show Kesimpta to be a highly effective B-cell therapy that can be easily self-administered at home1,3.

At Novartis, we challenge treatment paradigms and strive to offer the best treatment choice for patients, said Marie-France Tschudin, President, Novartis Pharmaceuticals. When treating patients with RMS, Kesimpta is a meaningful treatment option that delivers both high efficacy and safety with the ability for patients to have more freedom in managing their disease. The development of Kesimpta is a great example of our commitment, knowledge and understanding of multiple sclerosis, which enabled us to identify a targeted treatment that can significantly improve patient outcomes and experience.

Ofatumumab was first approved by the FDA in 2009 for the treatment of chronic lymphocytic leukemia (CLL) as an intravenous infusion with a high dose, administered by a healthcare provider. Ofatumumab was then investigated in an entirely new development program in RMS, as B-cells are known to play a critical role in the development of autoimmune diseases, such as MS7. The clinical development program for ofatumumab in RMS took 10 years and has involved more than 2,300 patients around the world as part of rigorous studies that were reflective of the broad patient population. Kesimpta was found to work through a distinct mode of action, and the treatment regimen (dosing)which was specifically designed for RMSplays a critical role in the outcome9. This is a different dosing regimen and route of administration than was previously approved for the CLL indication.

The approval of Kesimpta is based on results from the Phase III ASCLEPIOS I and II studies, in which Kesimpta demonstrated superiority versus teriflunomide in significantly reducing the annualized relapse rate (ARR, primary endpoint), 3-month confirmed disability progression (CDP), and the number of gadolinium-enhancing (Gd+) T1 and new or enlarging T2 lesions1. Results from these two studies were recently published in the August 6, 2020 issue of The New England Journal of Medicine.

Kesimpta is expected to be available in the United States in early September.* Additional regulatory filings are currently underway across the world, and regulatory approval for Kesimpta in Europe is expected by Q2 2021.

*Time of availability may vary as healthcare providers integrate Kesimpta into their practices.

About ASCLEPIOS I and II studiesThe ASCLEPIOS I and II studies are twin, identical design, flexible duration (up to 30 months), double-blind, randomized, multi-center Phase III studies evaluating the safety and efficacy of Kesimpta 20 mg monthly subcutaneous injections versus teriflunomide 14 mg oral tablets taken once daily in adults with RMS. The ASCLEPIOS I and II studies enrolled 1,882 patients with MS, between the ages of 18 and 55 years, with an Expanded Disability Status Scale (EDSS) score between 0 and 5.51. The studies were conducted in over 350 sites in 37 countries10. Kesimpta demonstrated a significant reduction in ARR by 51% (0.11 vs 0.22) and 59% (0.10 vs 0.25) compared with teriflunomide (P<.001 in both studies) in ASCLEPIOS I and II, respectively (primary endpoint). Kesimpta also showed a relative risk reduction of 34.4% (P=.002) in 3-month CDP compared with teriflunomide in pre-specified meta-analysis, as defined in ASCLEPIOS1.

Kesimpta showed significant reduction of both Gd+ T1 lesions and new or enlarging T2 lesions. It significantly reduced the mean number of both Gd+ T1 lesions (98% and 94% relative reduction in ASCLEPIOS I and II, respectively, both P<.001) and new or enlarging T2 lesions (82% and 85% relative reduction in ASCLEPIOS I and II, respectively, both P<.001) vs teriflunomide1.

Kesimpta had a similar safety profile to teriflunomide, with the frequency of serious infections and malignancies also being similar across both treatment groups1. Upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions were the most commonly observed adverse reactions with Kesimpta (incidence greater than 10%)1.

A separate post hoc analysis demonstrated Kesimpta may halt new disease activityin RMS patients. It showed the odds of achieving no evidence of disease activity (NEDA-3; no relapses, no MRI lesions, and no disability worsening combined) with ofatumumab versus teriflunomide were >3-fold higher at Months 012 (47.0% vs 24.5% of patients; P<.001) and >8-fold higher at Months 1224 (87.8% vs 48.2% of patients; P<.001)2.

Overall Kesimpta, an antibody targeting CD20 positive B-cells, delivered superior efficacy and demonstrated a safety profile with infection rates similar to teriflunomide1.

About APLIOS studyThe APLIOS study is a 12-week, open-label, Phase II bioequivalence study to determine the onset of B-cell depletion with Kesimpta subcutaneous monthly injections and the bioequivalence of subcutaneous administration of Kesimpta via a prefilled syringeas used in ASCLEPIOS I and IIand a Sensoready pen in patients with RMS. Patients were randomized according to injection device and site including the abdomen and the thigh. B-cell depletion was measured nine times over 12 weeks and Gd+ lesion counts were assessed at baseline and at Weeks 4, 8 and 12. Regardless of injection device or site, Kesimpta 20 mg subcutaneous monthly injections resulted in rapid, close to complete and sustained B-cell depletion; the proportion of patients with B-cell concentrations of <10 cells/L was >65% after the first injection by Day 7, 94% by Week 4, and sustained >95% at all following injections. Kesimpta treatment reduced the mean number of Gd+ lesions from baseline (1.5) to 0.8, 0.3 and 0.1 by Weeks 4, 8 and 12, respectively; the proportion of patients free from Gd+ lesions at the corresponding time points were 66.5%, 86.7% and 94.1%, respectively3.

About Kesimpta (ofatumumab, formerly OMB157)Kesimpta is a targeted, precisely dosed and delivered B-cell therapy that provides the flexibility of self-administration for adults with RMS. It is an anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly injection, delivered subcutaneously1,3. Initial loading doses of Kesimpta are given at Weeks 0, 1 and 2, with the first injection performed under the guidance of a healthcare professional. As shown in preclinical studies, Kesimpta is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion9. The selective mechanism of action and subcutaneous administration of Kesimpta allows precise delivery to the lymph nodes, where B-cell depletion in MS is needed, and preclinical studies have shown that it may preserve the B-cells in the spleen11. Once-monthly dosing of Kesimpta also allows faster repletion of B-cells and offers more flexibility12. Ofatumumab was originally developed by Genmab and licensed to GlaxoSmithKline. Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 201513.

About Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by myelin destruction and axonal damage in the brain, optic nerves and spinal cord14. MS, which affects approximately 2.3 million people worldwide15, can be characterized into four main types of MS: clinically isolated syndrome (CIS), relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS)16. The various forms of MS can be distinguished based on whether a patient experiences relapses (clearly defined acute inflammatory attacks of worsening neurological function), and/or whether they experience progression of neurologic damage and disability from the onset of the disease14.

Novartis in NeuroscienceNovartis has a strong ongoing commitment to neuroscience and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. We are committed to supporting patients and physicians in multiple disease areas, including MS, migraine, Alzheimer's disease, Parkinson's disease, epilepsy and attention deficit hyperactivity disorder, and have a promising pipeline in MS, Alzheimer's disease, spinal muscular atrophy and specialty neurology.

DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as potential, can, will, may, could, expected, committed, commitment, promising, pipeline, addressing, underway, to include, or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Kesimpta, or regarding the timing of availability of Kesimpta in the United States, or regarding regulatory approval of Kesimpta in Europe, or regarding potential future revenues from Kesimpta. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Kesimpta will be submitted or approved for sale or for any additional indications or labeling in Europe or in any other markets, or at any particular time. Neither can there be any guarantee that Kesimpta will be available in early September, or in any other time frame, in the United States. Nor can there be any guarantee that Kesimpta will be commercially successful in the future. In particular, our expectations regarding Kesimpta could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally, including European regulatory authorities not approving Kesimpta in the expected time frame, or at all; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AGs current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

Dr. Hausers statements reflect his professional opinion and not necessarily the views of The Regents of the University of California. Nothing in his statements shall be construed to imply any support or endorsement of Novartis, or any of its products, by The Regents of the University of California.

About NovartisNovartis is reimagining medicine to improve and extend peoples lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the worlds top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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References1. Kesimpta Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2020.2. Hauser S, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis: analysis of no evidence of disease activity (NEDA-3) from ASCLEPIOS I and II trials. Eur J Neurol. 2020;27(S1).3. Bar-Or A, Fox E, Goodyear A, et al. Onset of B-cell depletion with subcutaneous administration of ofatumumab in relapsing multiple sclerosis: results from the APLIOS bioequivalence study. Poster presentation at: ACTRIMS; February 2020; West Palm Beach, FL.4. Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016;(4):217-33.5. The Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. Accessed August 12, 2020. http://ms-coalition.org/the-use-of-disease-modifying-therapies-in-multiple-sclerosis-updated/6. Cree BA, Mares J, Hartung HP. Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm. Curr Opin Neurol. 2019;32(3):365-377.7. Lehmann-Horn K, Kronsbein HC, Weber MS. Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges. Ther Adv Neurol Disord. 2013;6(3):161-173.8. Dieguez G, Engel T, Jacobson N. Site of service and cost dispersion of infused drugs. Accessed August 12, 2020. https://www.milliman.com/insight/2019/Site-of-Service-and-Cost-Dispersion-of-Infused-Drugs/9. Smith P, Kakarieka A, Wallstroem E. Ofatumumab is a fully human anti-CD20 antibody achieving potent B-cell depletion through binding a distinct epitope. Poster presentation at: ECTRIMS; September 2016; London, UK.10. Kappos L, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in relapsing multiple sclerosis: baseline characteristics of two pivotal phase 3 trials (ASCLEPIOS I and ASCLEPIOS II). Poster presentation at: ECTRIMS; October 2018; Berlin, Germany.11. Smith P, Huck C, Wegert V, et al. Low-dose, subcutaneous anti-CD20 therapy effectively depletes B-cells and ameliorates CNS autoimmunity. Poster presentation at: ECTRIMS; September 2016; London, UK.12. Savelieva M, Kahn J, Bagger M, et al. Comparison of the B-cell recovery time following discontinuation of anti-CD20 therapies. ePoster presentation at: ECTRIMS; October 2017; Paris, FR.13. Genmab Press Release: Genmab announces completion of agreement to transfer remaining ofatumumab rights. December 21, 2015. Accessed August 12, 2020. https://ir.genmab.com/static-files/9d491b72-bb0b-4e46-a792-dee6c29aaf7d14. Guthrie E. Multiple sclerosis: a primer and update. Adv Studies Pharm. 2007;4(11):313-317.15. Multiple Sclerosis International Federation. Atlas of MS 2013-Mapping Multiple Sclerosis Around the World. Accessed August 12, 2020. http://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf 16. National MS Society. Types of MS. Accessed August 12, 2020. https://www.nationalmssociety.org/What-is-MS/Types-of-MS

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FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple...

23 August 2020 9min read

News moves entire markets and stocks within a market, both up and down. Today that core investing assumption is arguably more apparent than ever as any positive news on a potential vaccine for COVID 19 can send an entire index into an upward trend.

However, it is equally true that current market conditions have produced some stunning reactions to negative economic news with market prices ignoring what seem to some to be objective facts and maintaining or quickly resuming an upward trajectory.

The signal to noise ratio has been extracted from its origins in the field of electrical engineering and applied to stock market movements in the face of news. Market experts warn investors that not all news is created equal, with some announcements evidence of relevant information, or signal. Other announcements should be viewed as noise containing irrelevant information.

The argument is helpful in highlighting the inherently subjective nature of share market investing. The definition of relevance versus irrelevance is often a matter of perception. Some seemingly objective news such as positive financial results, new product launches, contract signings, and acquisitions fail to excite investor interest since markets are about the future, not the past or even the present.

The question that muddles the validity of the signal to noise characterization of market news is how market participants see the future not the present impact of the news.

On 17 August Hydrix Limited (HYD), a small cap product design, engineering, and technology commercialisation company with applications for multiple sectors made the news, sending the share price up more than 250% on that day.

The companys Hydrix Medical subsidiary announced the successful implementation of a monitor capable of providing early warnings of heart attacks and other suspicious cardiovascular activity. The hi-tech implantable AngelMed Guardian was developed by Angel Medical Systems, a US based company, using artificial intelligence machine learning algorithms.

In March of this year Hydrix acquired a seven-year exclusive distribution rights agreement for the AngelMed Guardian monitor in Asia Pacific Region countries, including Japan, Singapore, Hong Kong, Indonesia, Malaysia, Thailand, Australia, and New Zealand. The agreement was with equity firm Jaspar Capital, the original acquirer for the rights from Angel Medical.

Hydrix is making plans to offer the AngelMed Guardian cardia monitor here in Australia in Q4 of 2020 under the TGAs (Therapeutic Goods Administration) Special Access Scheme.

Within the top four Asia Pacific countries Hydrix is initially targeting, approximately 500,000 people experience an acute coronary event each year. The company estimates as little as a 1% market share would generate $35 million dollars in annual revenue.

Hydrix Medical designs and distributes other cardiovascular high-technology devices in the Asia Pacific Region and serves the industrial, defense, mining, and aerospace markets through its other operating companies, Hydrix Services and Hydrix Ventures. In March, the company withdrew its guidance prior to the COVID 19 Pandemic calling for a 15% revenue growth and an operating profit for the full year 2020.

On 24 October of 2011 high profile regenerative medicine company Mesoblast Limited (MSB) hit an all-time high of $9.89 at the open back in the day when the stem cell sector was all the rage in share markets around the world. The share price has been in steady decline since as the potential of stem cell medical treatments failed to live up to their promise quickly enough to satisfy the rapid appetites of investors. Mesoblast shareholders were again and again exposed to the optimistic phrase an exciting potential pipeline for future revenue and profit growth. They are still waiting for a profit.

The company has a widely acclaimed proprietary cell technology and an impressive list of treatments in Phase 3 Clinical Trials:

Remestemcel-L is the latest candidate to reignite the dreams of ten-bagger status for MSB. The treatment proved successful in its Phase 3 clinical trial for aGVHD (an inflammatory condition that can affect multiple organs following bone marrow or organ transplants). The trial was for steroid-refractory acute graft versus host disease in children. The inflammatory condition was similar enough to a serious immune system condition seen in COVID 19 to lead the US FDA (Food & Drug Administration) to clear Remestemcel-L for treatment of acute respiratory distress syndrome in COVID 19 treatments back on 6 April.

In advance of a scheduled review meeting with the Oncologic Drugs Advisory Committee (ODAC) of the FDA to consider how effective the trials had shown Remestemcel-L in treating pediatric patients with steroid-refractory acute graft versus host disease (SR-aGVHD), nervous investors began to panic sell the stock driving down the price more than 30% in a matter of days.

Following a trading halt, investors were elated to learn the ODAC had voted to recommend approval of the treatment to the FDA. A majority of market participants treated the news as signal, driving up the price. Others may have seen the announcement as noise and await what they will believe will be the real signal a final FDA approval vote scheduled for 30 September.

Regeneus Limited (RGS) is another clinical stage regenerative company whose share price got a big boost from recent news interpreted by most investors as signal.

The company entered into a licensing and collaboration agreement with Japans Kyocera Corporation to develop and commercialise its lead stem cell platform technology Progenza for the treatment of knee osteoarthritis in the Japanese market.

Kyocera will fund the effort from development to initial clinical trials to regulatory filing costs to manufacturing. Regeneus received an initial payment of $13 million dollars with an additional $13 million in milestone payments as well as single to high double-digit royalties on all future Progenza product sales in Japan based on future reimbursement prices.

For investors who drove up the stock price this news stands as a signal. Certainly, the confidence expressed by a multi-national conglomerate like Kyocera is relevant information. But for others, this is noise in the absence of completed clinical trials and regulatory approvals.

CardieX Limited (CDX) changed its name from AtCor Medical Holdings back in May of 2018 to reflect an expanded focus in medical technology devices for cardiovascular disease to include wearable smart health monitors and telehealth.

Although still in start-up stages for some of its planned products, reports are that CardieX is close to introducing new devices and software solutions for cardiovascular disease into the consumer health market in late 2020 or 2021.

The companys reimaged focus targets three high growth sectors in medical technology, through three operating companies.

AtCor Medical has manufacturing and research and development operations here in Australia with a subsidiary company in the US. This operating company offers non-invasive early detection technologies for cardiovascular and renal disease. The AtCor SphygmoCor technology allows medical professionals to non-invasively measure the central arterial pressure waveform, central aortic pressures, and pulse wave velocity, factors considered critical for managing hypertension and other cardiovascular issues.

The SphygmoCor Xcel device has an impressive list of customers, including the Mayo Clinic and Cleveland Clinic in the US and Novartis and AstraZeneca, and is the only FDA approved alternative to the invasive procedures using stents.

CardieX is a minority owner and 50/50 joint venture partner with Silicon Valley based Blumio to develop a non-invasive cuff less wearable blood pressure sensor, the first of its kind in the world.

CardieX took a 50.5% ownership in US based inHealth Medical Services, a provider of a wide array of telehealth programs. inHealth partners with major US health technology providers including Anthem, American Well, Blue Cross Blue Shield, and Kaiser Permanente.

The companys share price was already trending upward following a 12 March update on changes to existing contracts with both Bayer and AstraZeneca for clinical trials of the CardieX Xcel Systems.

In addition, the CardieX announced the company now has a successful wearable cardiac monitoring system and would be presenting its findings to an official Google partner, China-based artificial intelligence and consumer electronics company Mobvoi Information Technology Co, a company assisting CardieX to bring the wearable sensor to market.

The announcement on 19 August that sent the share price higher related to an extension of two existing trials ongoing with Bayer, Avanti, and Concord. The Avanti trial lease has been extended through June of 2021. Avant trial is being conducted at 70 sites across 9 European countries.

The following table includes price movement information for these four healthcare stocks making news.

See the rest here:
Healthcare Stocks in the News - TheBull.com.au

In an interview with Medical News Today, James Hindley, Ph.D., from Indoor Biotechnologies explains how his company is developing a new T cell test during the COVID-19 pandemic. He also reveals why this test is a much-needed tool for those designing new vaccines and studying immune responses to the new coronavirus.

Since the COVID-19 pandemic began, scientists across disciplines and geographical locations have collaborated in unprecedented ways.

The speed at which diagnostic tests went from conception to reality was astounding, as were the global efforts to test new and repurposed drugs to find treatments for those with the disease.

However, effective treatments are only tentatively emerging. Diagnostic testing capabilities have been slow to ramp up to the scales needed to keep the pandemic at bay.

Many questions remain about how the virus causes catastrophic deterioration in some but leaves many others relatively unscathed.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Undeterred, investigators continue to research and develop new arsenals in this global fight.

Medical News Today spoke to one such scientist, who recently began a new project with a grant from the British governments Innovate UK fund.

James Hindley, Ph.D., is the Executive Director at Indoor Biotechnologies in Cardiff in Wales, and the work is underway in collaboration with Martin Scurr, Ph.D., a research associate at Cardiff Universitys School of Medicine.

Working with the team at Indoor Biotechnologies, Dr. Hindley and Dr. Scurr are developing a new type of test that can show if someone has developed specific T cells to SARS-CoV-2.

T cells are a type of white blood cell. They play a key role in how our bodies fight off viral pathogens, such as SARS-CoV-2, the new coronavirus.

MNT: Why is there a need to develop a new T cell test?

Dr. James Hindley: The current focus for testing immunity to the SARS-CoV-2 virus is based on the assessment of antibodies.

These are an undoubtedly important part of our memory immune response to viruses. However, another critical component of our immune response to viruses is the T cell. These also provide memory immune responses and may even be more sensitive than antibodies.

The challenge with T cells is that, unlike antibodies, measuring them is not simple.

As such, there is a need for a simple T cell test, that could enable testing for virus-specific T cells to be done routinely.

MNT: What will the test results show?

Dr. Hindley: The test we have developed can provide quantitative results measuring the magnitude of an individuals T cell response to the SARS-CoV-2 virus.

We can also run in parallel the same test for other human coronaviruses and viruses, such as influenza. This allows us to establish a persons immune status. Like antibodies, whether a positive T cell test is protective against future infection remains to be determined.

MNT: Who will benefit from your test, and who can administer it?

Dr. Hindley: At first, we believe the primary use of this test will be for vaccine development, to determine whether a T cell response to the vaccine has been generated and whether that is adequate to be protective from infection.

Such testing would be done in laboratories, alongside other tests needed for the vaccine trial.

We also believe this test will enable public health bodies to perform much wider screenings of the population. Again, this would be carried out by laboratories in conjunction with antibody testing to determine what constitutes protective immunity.

Once this is proven, the assessment could then be made available to the wider public, but it is likely to remain as a test performed in a laboratory.

MNT: Are there other tests available, and how is yours different from these?

Dr. Hindley: At present, there are no tests for measuring T cells to SARS-CoV-2 in a high throughput manner.

Any T cell testing for SARS-CoV-2 has been performed as part of a research study in a handful of specialist laboratories. These laboratories use specialist techniques, most commonly techniques called flow cytometry or ELISpot, which require highly trained staff and relatively expensive equipment.

The main drawbacks of these techniques are that they are relatively long, laborious, and therefore do not have high throughput. They are also difficult to standardize.

Where we were innovative was looking at the minimum requirements to perform this test, to get the necessary data to answer the question of whether a person has specific T cell responses.

By providing just these elements without the added complexity, we made this test much easier to perform in almost any lab, using routine laboratory equipment. Our test also uses whole blood, rather than a population of precursor cells, which require an additional step to purify.

The test uses specific parts of the virus to stimulate virus-specific memory T cells within the blood to release cytokines. Were able to detect these cytokines within hours of them after production.

MNT: Given that we are currently in a pandemic, how has the way you develop your technology changed compared to how you would normally design a new test?

Dr. Hindley: The main change has been the speed at which we have operated, both internally and externally.

The initial funding from Innovate UK was turned around within 30 days. We were given fast-track approval for our research and ethics committee application. In addition, participants have been keen to make themselves available for testing.

It feels like everyone is coming together and working around the clock to try to tackle this pandemic.

MNT: How did your collaboration come about?

Dr. Hindley: Martin and I did our Ph.Ds. at the same institute and are longstanding colleagues and friends.

The collaboration on this project came about as we were in close contact throughout the start of the pandemic, primarily watching from afar and debating the science.

Then when we heard about the call for funding from Innovate UK to support the development of innovations for tackling COVID-19, we put in an application as we felt like we had a great idea which could genuinely help in the fight against this virus.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

Continue reading here:
COVID-19: How a new blood test could help speed up vaccine development and population screening - Medical News Today

Large processes sometimes occur on a small scale. "Microfluidics is the world in which entire processes conducted in the laboratory are miniaturized into tiny containers," explains Prof. Doron Gerber. In chemistry, biology and other fields, the processes take place in a liquid environment, even when working with miniature dimensions, hence the name 'microfluidics.'

'Laboratory-on-a-chip,' that is based on microfluidics, enables us to simultaneously conduct multiple and complex sets of experiments that generate a high data output such as a survey of biochemical, physical and cell data, with a tremendous saving in the number of samples required and the duration of the experiment.

Prof. Doron Gerber is a researcher in the Nanotechnology Center and Faculty of Life Sciences at Bar Ilan University. "My background is in biology," he says. "After a doctorate that examined membranal proteins, I decided to do something of a more technological nature. I completed a post doctorate with Prof. Stephen Quake at Stanford a researcher who introduced me to the whole field of controlled microfluidics. Prof. Quake invented a new type of microfluidics that enables us to conduct extremely complex experiments and to develop applications in the fields of biology, chemistry, and physics by using flexible switches that enable complete control of whatever happens inside the chip. In other words, the technology allows smart management of small nano-liter quantities of fluids.

"How does it all work? Let's say that we want to conduct 1,000 simultaneous experiments. First, we need a sample of the substance we are studying such as, a drop of blood. In regular experiments, we only have a limited number of available samples, either because they are taken from a single person or because they are very expensive.

"Microfluidics allows us to perform complex procedures with tiny amounts of samples. Let's imagine that I had an endless quantity of blood to examine: I would take 1,000 test tubes and attempt to perform one experiment using different substances on a blood sample in each one according to the parameter I wanted to test.

"Here, we miniaturize the experiment set so that we have 64 micro-cavities instead of test tubes. Each of these cavities contains only one-thousandth of a drop of the patient's blood. Each cavity is one quarter of a square millimeter and is 20 microns high, so its volume is only a few nano-liters (1 nano-liter is one millionth of a liter). The passages between the micro-cavities are canals, each up to a hairbreadth wide, through which the substances required for the different experiments move. Multiply this set by 64 levels and you can conduct thousands of experiments at the same time.

"To make it work, we need each experiment to remain separate from the others, so we created a 'door' that in addition to separation also allows us to insert and extract things. This door is an elastic switch that opens and closes according to instructions given from a computer software.

"In other words, our microfluidic chips are set of extremely small cavities and a system of fully controlled switches ('doors') capable of timed insertion and extraction of substances from the cavities. An experiment set like this can be used in a wide range of scientific experiments such as searching for substances in the blood like antibodies, pieces of DNA or RNA from a viral source, indicators of cancer etc. A small volume of a patient's blood can be used as a sample, inserted into the chip so that each of the chip's many cavities contains a small drop of blood and can 'host' a test to locate the substance under examination, enable its quantification, or a qualitative analysis that indicates its presence in the blood.

"In other experiments, such as those that check the connection between proteins of different viruses and human proteins, we can start from the level of the genetic material of a person or a virus, translate it into proteins that are given fluorescent markers (fluorophores) in the chip's cavities, and evaluate the degree and strength of the connection created between these proteins. Information such as this is extremely valuable in studying viruses' operating mechanisms and the way they influence human cells. Finding a strong connection between a viral protein and a human protein hints to the involvement of these proteins in the way the virus infects or spreads and can therefore constitute a target site for the development of a treatment for that virus.

"In addition to working with different molecules, the microfluidic platform also enables us to work with whole cells.

"In the field of cancer research, there is a good correlation between the results of the laboratory experiment and clinical results. Nevertheless, the main problem is that a sample taken from a cancer patient contains many cancer cells and there is no way to cultivate them in such a way as to be able to conduct dozens of experiments and analyze their influence on a range of possible treatments. In an attempt to overcome this obstacle, scientists are trying to grow the tumor cells in the lab and increase their number and only then expose them to different treatments, but this is a race against time.

"We have developed a microfluidic chip for culturing the cells. Each of the chip's cavities can accommodate a tiny quantity of cancer cells taken from a specific patient and allows us to expose each group of cells to a different pharmaceutical treatment and check their reaction to it. This method enables us to know which treatment the cancer cells are resistant or sensitive to and how they respond, all within just a couple of days.

"Although there are currently many drugs for treating cancer, it's not clear how each patient will respond to each of them. A specific drug may cause harsh side effects and be ineffective in treating the disease so the window of opportunity for treating these patients is extremely limited. The results of an experiment using our chip can help direct the patient's physician to choose the most efficient treatment for him, thereby saving precious time and unnecessary suffering.

"A year ago, we published an initial paper in which we proved the theory and presented the system's capabilities. We have now begun checking patient samples. The paper gained considerable interest, and many have expressed a wish to examine samples using our system.

"We recently began collaborating with Dr. Amir Onn, Head of the Institute of Pulmonary Oncology at the Sheba Medical Center and Dr. Limor Broday from Tel Aviv University. The time limit with lung cancer is especially short. From the moment the patient stops responding to treatment, a doctor needs to receive the relevant knowledge and make a very quick informed decision regarding alternative treatment. In our joint study, we attempt to assess whether our method can facilitate a swift and accurate decision, thereby enhancing the results of the treatment administered to the patient.

"There is a tremendous need in this field, and we are attempting to get financing from scientific grants that will enable us to survey about 300 patients over the next two years. This will, in turn, allow us to characterize the system in relation to a set of lung cancer medications while simultaneously upgrading the system that checks the vitality and mortality data following exposure to the medication. In the future, we hope to add a further capability to the system that will facilitate the measurement of metabolic indices which report on processes within the cells such as glucose and energy levels, and that provide more in-depth information.

"The device's complexity means that the need for large-scale investment is a fundamental issue in the chips' production processes. Our dream is to enable biologists to take an idea and bring it to engineering implementation: lab production of a chip. This for me is the essence of Bio-convergence a biologist using sophisticated engineering to create innovative solutions.

"We built a factory at Bar Ilan University for producing microfluidic chips, not only for my laboratory but also for additional labs at Bar Ilan and other institutions as well as for Israeli industry, but we belong to academia and it's only a small factory with limited human and financial resources. As of now, our largest challenge is to enable industry to utilize the potential of the infrastructure we have constructed, he said.

Prof. Gerber predicts a rosy future for the tiny chips: "It's happening all around the world microfluidics is entering the world of diagnostics and the field of developing tools for scanning medications and substance synthesis e.g., therapeutic antibodies or antibodies for genetic engineering of viruses etc.

"The industry needs microfluidic chips to produce therapeutic antibodies and to market them as drugs and increasingly more microfluidic tools are appearing in manufacturing or development processes. As of now, this kind of research only exists on a small scale in Israel, primarily in academia, with large-scale microfluidic centers needed to integrate the technology into the industry. If, for instance, we assume that a startup company receiving a limited initial sum of money wants to use a microfluidic tool, its chances of success are slight. Among the reasons for this is the lack of appropriate infrastructures production of a simple microfluidic chip requires a manufacturing plant with clean rooms, equipment for creating molds by lithographic processes, equipment for coating molds, and equipment for producing the chips.

"Today, when it is obvious to everyone that there is a need to connect biology and high-tech, it is also clear that most of the major tools for doing so actually exist in academia far more than in industry. On the other hand, academia lacks the large-scale infrastructures required to transform technology into an off-the-shelf product like production of a chip prototype. Since entering academia, I have established, and am still establishing, a microfluidic chip center capable of producing different kinds of chips and providing support to new researchers seeking to make use of microfluidic technology, all subject to the limitations of the existing support in academia.

"There is no doubt that large-scale investment and significant financial incentives directed at the development of basic infrastructures are required for the field of microfluidics to transcend the walls of academia and penetrate industrial realms. In contrast to biology for example, where you can buy a robot to perform large quantity tasks, microfluidics is characterized by a scarcity of companies that develop these tools for others. Investment in this infrastructure will enable companies to make use of off-the-shelf products and to integrate these innovative technologies into their applications. Young industry must also be connected to academic capabilities.

"Many companies who come to our nanotechnology center for example, use our equipment and at the same time, receive good counseling. But this happens at an academic pace. We must invest a little more in this infrastructure so that it serves industry better, for example, in the establishment of a consortium which we aspire to be a member of."

Dr. Itai Kela, Scientific Director of the Bio-Convergence Program:

"The integration of microfluidics used for discovering new medicines and 'lab-on-a-chip' systems creates an amazing technology that enables to dramatically reduce the use of lab animals when developing drugs and constitutes an engineering technological platform for the scanning and more rapid and efficient detection of new medicines and treatments."

The Sensors that Discover Why Medications Fail

When discussing Bio-convergence and the combination of industry and academia, it is important to learn about the work of Prof. Yaakov "Koby" Nahmias. Prof. Nahmias, Founding Director of the Bioengineering Center at the Hebrew University in Jerusalem, is a serial entrepreneur and Chief Scientist of the Tissue Dynamics corporation which he founded a year ago.

"Bio-convergence the structured combination of engineering biology and medicine is a very important part of projects' technological maturity and enables amazing breakthroughs," he says. "In practice, one of the main reasons behind the establishment of the Bioengineering Center at the Hebrew University was the desire to provide an academic response to the growing need for engineers who understand biology and vice versa."

As an example of the importance of Bio-convergence, Prof. Nahmias relates to the coronavirus: "When the 'Hepatitis C' virus was discovered in the year 2000, it took 3-4 years to sequence it and then an entire year to grow it. The first medication arrived only several years later. In other words, it took about a decade to develop molecules capable of contending with 'Hepatitis C'.

"In contrast, the new coronavirus was only discovered in November and was more or less sequenced already in December. Its first tissue cultures were ready in January-February with the first molecules being introduced to clinical research around March. What took years with 'Hepatitis C' is being done in just weeks and a few short months with Covid-19. This is much more than an exponential increase it's a quantum leap.

"Today's world moves extremely fast and investors need to take into account that the pharma industry is going to reverse itself. The 1970s and 1980s were characterized by a lot of mediocre pharma companies, most of which were swallowed up by a small number of pharma giants that are the only ones with the massive resources necessary to bring a new drug to the market. The next technological revolution will enable an entire community of small pharma companies to compete with the giants.

"I am a member of the Innovation Authority's Bio-convergence Committee that will lead a dramatic breakthrough in Israel's technological capabilities. The Authority helps the academic world penetrate industry, receive necessary resources, and transform theoretical solutions into practical applications. If until 15 years ago the world of academia was extremely theoretical and did not view the connection with industry as something positive, I believe that this view has changed over the last decade. Today, both the universities and their academic staff are very interested in industry and are working closely with the Authority. The attitude has changed even more in recent years during which young faculty members are themselves beginning to lead startup companies to the market and I hope that this trend will continue, he said.

Tissue Dynamics operates in the 'organ-on-a-chip' field and seeks to change the world of pharma development.

"Drug development is a long and high-risk process," Prof. Nahmias explains. "2.6 billion dollars and 10-12 years are required to bring a new drug to the market. For each molecule that reaches the medical market, there are 90 others that fail despite the huge resources invested in them. Every molecule that fails at the animal testing stage or in clinical trials costs hundreds of millions of dollars. Drugs sometimes fail even after FDA approval, release to the market, or administration to patients.

"This is the reason that although there are hundreds of companies developing pharmaceuticals in Israel, none of them has the resources to reach the market. These companies will eventually be sold to a pharma giant which will then conduct the final clinical trials. This reality limits Israel's ability to compete with other countries.

"One of the main reasons that drugs fail is that we develop them on animals. We have drugs that work well in mice but not in humans. Another problem is that we don't understand precisely why a drug fails clinical trials. It's a kind of black box that means we can't just change the molecule and move forward we have to start again from the beginning. That's why pharmaceutical development is such a Sisyphean, costly and long process.

"The 'organ-on-a-chip' story began more than a decade ago when an entrepreneur approached my lab at Harvard to ask for help with developing the technology. The idea is to take human cells with human genetics and metabolism and place them on a microfluidic chip that simulates human physiology in order to grow tissues of different organs. The microfluidic chip is made of plastic and is about the size of a 5-shekel coin. Instead of conducting an experiment on a rat or a mouse, we use a microfluidic chip containing tiny tissues of human organs.

"I am very interested in this field and I developed the first 'organ-on-a-chip' technology that was commercialized for an American company called HuREL. Although the technology met the need for human trials, it didn't solve the second problem attaining a clear understanding of why a drug doesn't work.

"When I returned to Israel to set up the bioengineering center, I focused on the attempt to solve both problems simultaneously. For five years, we developed a technology that enables us to take human cells, use them to create human liver, heart, brain and kidney tissues, and to insert into them sensors that allow us to measure the tissues' activity in real time. This in turn gives us the ability to discover what happens to human tissue when we give it a drug or during a disease.

"The sensors operate exactly as they do in a motor vehicle: if the vehicle shuts down, the oil warning light flashes and we understand the problem. When I administer a drug to healthy tissue that suddenly stops working, I know precisely where that molecule has hit. If I insert a molecule into a heart in which I identify a disease and it restores the regular heartbeat, the sensors show me why it works.

"This technology enables us to completely alter the world of pharmaceuticals. It can reduce development costs up to 80% which means that it will be possible to develop a drug from scratch and bring it to the market for the cost of a few hundred million dollars. This has tremendous significance for the Israeli economy. Hundreds of Israeli pharma companies may not be sold but rather, reach the market by themselves."

The Road to Decentralizing Drug Development

Tissue Dynamics was founded two years ago. As Prof. Nahmias explains: "we started out as a small company, without any external funding. We gave giant companies like L'Oral, Merck, and Teva access to our technology so that they would understand its potential. Several months ago, just before the Corona crisis, we embarked on a funding round for initial investments.

"We are currently at the stage of slowly moving out of the university. We have independently developed new molecules for treating arthritis and cancer and are now taking our platform in the direction of a new model of drug development. This is Tissue Dynamics' second and more mature corporate stage.

"Our overall vision is of a decentralized drug development structure: a cloud-based smart learning program that has access to several Tissue Dynamics systems distributed between leading labs around the world. The primary platform is situated at our company where we are developing new biological and molecular models but also forging contacts with leading labs worldwide and assimilating our technologies there. These contacts allow us to create biological and chemical data and information that are not just ours, and to include information from other groups worldwide. Our first collaboration in the US is with ATCC (American Type Culture Collection), the world's largest cell and tissue database. ATCC has about 4,500 human tissues from healthy and sick people and access to such information allows us a much deeper understanding of the different mechanisms.

"Six months ago, we developed a new model of the human kidney that enables us to observe a drug's activity and toxicity in the kidney. One of the drugs we examined is called cyclosporine and is given to patients who received organ transplants or who suffer from arthritis. Cyclosporine generates global sales revenues of approximately 4 billion dollars a year despite the known fact that it causes kidney damage.

"When we inserted the drug into a kidney, the sensors were activated and provided us with an energy map of how the drug behaves in a human kidney. Strangely, it turns out that it activates the same mechanism as that in a fatty liver. Nobody knew about this mechanism previously and it was impossible to see without our sensors. This breakthrough meant that we could perform a quick reformulation of the drug and reduce its toxicity. We believe that this constitutes a revolutionary breakthrough in drug development."

The article was written in collaboration with the Israel Innovation Authority, responsible for the countrys innovation policy. Its role is to nurture and develop Israeli innovation resources, while creating and strengthening the infrastructure and framework needed to support the entire knowledge industry.

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A quantum leap In the drug development world - CTech