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Anagnostics as industry partner of CD-Laboratory for sepsis
"On 25 January 2013 the new 'Christian Doppler Laboratory (CD-Laboratory) for Innovative Therapeutical Approaches in Sepsis' will be opened in Krems (Austria). Under the auspices of the Danube-University Krems and led by Univ.-Prof. DI Dr. Viktoria Weber new approaches in the diagnosis and supportive treatment of sepsis will be explored and tested together with two industry partners, namely Fresenius Medical Care and Anagnostics.
Emphasis is put on the development of new extracorporal appproaches for supportive sepsis therapy as well as the development of accompanying diagnostic procedures."
http://an000309.host.inode.at/index.php?id=26
Improving Safety and Efficacy of Red Blood Cells for Transfusion
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $200,000 for 6 months; Phase II: $1,500,000 for 2 years
Number of anticipated awards: 3
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.
Summary
Red blood cell (RBC) products for transfusion undergo metabolic and physical changes in both the cellular and plasma fractions during storage (RBCs can be stored up to 42 days currently) which may be associated with non-infectious risks and reduced tissue oxygenation capacity. The changes that occur during storage have been referred to in the literature as the RBCs “storage lesion”. Many of these changes have been characterized and include increasing levels of microparticles and potassium; free hemoglobin release; decrease in pH, adenosine triphosphate, and 2,3-diphosphoglycerate; loss of RBC membrane flexibility; and changes in enzymatic functionality resulting in a loss of nitric oxide (NO) signaling. Current research suggests that the storage lesion may result in extravascular hemolysis and inflammation, vasoconstriction, and potentially suboptimal tissue oxygenation. Many retrospective and prospective studies, including a recent meta-analysis of 21 studies, have demonstrated that the transfusion of RBC units which have been stored for longer periods (up to 42 days) appears to be associated with increased recipient morbidity and mortality; but these associations may be confounded by severity of illness. Two large blinded, multi-center randomized trials are currently underway in the United States and in Canada to determine if “younger” vs. “older” or “standard age” blood is equally safe and effective in complex cardiovascular surgery and ICU patients, respectively, but the results of these studies will not be known for several years.
While it is unclear at this stage whether the RBC storage lesion results in serious adverse clinical outcomes in transfusion recipients, it would seem biologically plausible that a reduction in the number of potentially toxic elements in RBC supernatants, as well as an increase in the concentration of well-preserved RBCs, would be beneficial in many ways. These potential benefits could include 1) improved effectiveness of RBC products; 2) markedly reduced adverse events; and 3) optimal tissue oxygenation by fully functioning RBCs. Developing improved blood bank storage and transfusion processes and practices to mitigate the RBCs Òstorage lesionÓ, improve the effectiveness of transfusion, and safely maintain the shelf-life of RBC components at or near the current FDA mandated maximal storage limit of 42 days, will be important to assuring blood availability for future public health needs.
There is scientific evidence that some of the RBC storage lesion changes might be reduced, restored or mitigated by changes in blood storage conditions and/or through manipulation prior to transfusion with processes such as washing, filtration and/or renitrosylation. Multiple strategies may be needed because targeting any single parameter may be insufficient to markedly improve RBC product quality.
The National Blood Collection and Utilization Survey Report estimates that a total of 17.3 million blood units were collected and 14.6 million RBCs units were transfused in the United States in 2008. Except for pediatric transfusions, blood banks always deliver the oldest available RBC units when a RBC transfusion is requested to optimize their inventory management. It is anticipated that a product and/or process developed for this contract topic could be utilized by all, or a portion of, the patients needing a transfusion in the U.S. and internationally. Depending on the product, the market may be any or all of the following: blood centers, blood banks, and hospitals as these are the facilities that collect, produce and/or transfuse RBC component units.
Applicants are encouraged to explore utilization of the NHLBI SMARTT program (https://www.nhlbismartt.org/ ) to assist with the preclinical and early clinical study planning and regulatory support for IND/IDE applications associated with this contract topic.
Project Goals
The purpose of this SBIR contract solicitation is to develop new additive solutions, storage bags and/or new processes to enhance RBCs function and survival after storage and transfusion and/or reduce non-infectious complications associated with allogeneic RBC component transfusions.
Accepted products, devices or technologies for the contract topic include, but are not limited to:
•New additive solutions for RBC component storage,
•Novel RBC component storage bags or modification of current storage bags,
•Small footprint cell washer and associated disposables for use in hospital blood banks and transfusion services,
•Pre- or post-storage processes and systems that will deliver a more therapeutic, less toxic transfused RBC component,
•Development of kits, including combinatorial approaches such as devices and technologies, to achieve the project goals.
Development of products and/or procedures for the sole purpose of leukoreduction will not be considered responsive to this solicitation.
Phase I Activities and Expected Deliverables
In Phase I, the investigator(s) are expected to complete proof-of-concept, become knowledgeable of regulatory requirements for required IND/IDE approval, and present the Phase I results and the development plan to NHLBI staff. The Phase I research plan must contain specific, quantifiable, and testable feasibility milestones along with alternate approaches if unexpected data are generated. The new technology needs to result in a demonstrable reduction in the development of the RBC storage lesion such as a decrease in the number of red blood cell microparticles and/or better preserved RBC rheology.
Phase II Activities and Expected Deliverables
Phase II should follow the development plan laid out in the Phase I if the FDA has approved the approach and feasibility has been demonstrated. Phase II studies should focus on developing the required technologies and working towards the initiation of clinical testing.
Deliverables include the provision of evidence of having initiated the process leading to IND/IDE submission (and hopefully approval), and the documentation that the plan is feasible and that there are alternate approaches if any contradictory data are generated. When appropriate, it must be documented that production of sufficient amount of clinical grade material suitable for an early clinical trial can occur. The Phase II research plan must contain specific, quantifiable, and testable feasibility milestones.
Scientific and Technical Merit Review: February-April 2013
Anticipated Award Date: July-September 2013
http://www.nhlbi.nih.gov/funding/sbir/funding/contract_topics/contracttopic_FY2013_074.htm
A reminder that CTSO is doing a scaled down version portable sepsis/trauma device in the SBIR grant that they received called "Investigation of CytoSorb cytokine and myoglobin removal in the treatment of trauma."
http://www.sbir.gov/sbirsearch/detail/398431
All DARPA DLT component developers are expected to work with the DLT integrators. Two integrator awards were given out this month: Harvard/Wyss (approx 9 million) and Battelle (approx 20 million). Battelle has been lead integrator before on another DARPA project sometime back, Immune Building program.
I think you are confused between a company sponsored study (where the company is actually paying for it) and an investigator-initiated study (the investigator funds the study). CTSO has had investigator-initiated studies already, many of them done by the University of Pittsburgh. These studies are not paid for by the company but funded by the university from grants that they received. One of the larger multi-year one is called "Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS)" to study the use of adsorbent polymer technology in the treatment of severe sepsis, a $7 Million dollar grant from NIH.
http://www.labome.org/grant/r01/hl/systems/engineering/systems-engineering-of-pheresis-intervention-for-sepsis-7682885.html
http://www.mcgowan.pitt.edu/medicaldevices/projects/projects7.asp
I do not share your concern because the German Ethics Committee approved the study protocol and the sites involved in the study. The company has to ensure that proper training is in place. In order to collect scientific data they would want to ensure that all are following the procedures.
Whirlybird, to clarify:
The dosing study is currently underway. This is a company sponsored study containing a total of 7 leading hospitals in Germany. All their sites were approved by the German Ethnics Committee and the company has to ensure that the procedures, training, data collection, patient safety etc are in place.
This is not the same as the studies that will be conducted by the other investigators. The corporate update from Nov 21 states, "Active discussion and planning of at least 6 new investigator-initiated human pilot studies in a growing list of critical care applications" and from the last PR about the ISICEM conference hints to the type of investigator-initiated studies, "We are pleased at the growing recognition and usage of CytoSorb® by leading experts in the field of critical care medicine in many different applications. We have already seen exciting cases in such areas as sepsis, burn injury, trauma, lung injury, cardiac surgery, liver failure, pancreatitis, influenza, and other indications. Users have confirmed the simplicity and ease of use of the CytoSorb® therapy. As we expand our commercialization efforts, we look forward to beginning a number of investigator-initiated studies this year in many different areas that may help drive future adoption and awareness for our technologies."
Why are you so concern with standardization? There is very little chance that a study is not standardized but that very little chance % of it in your mind is stronger. What's up with this?
I think one area where they can improve on is to not say that they are submitting for these grants, awards, etc and then just surprise everyone when they get it.
It doesn't appear professional when it doesn't turn out and the company puts out a PR to tell shareholders that they didn't get the contract.
There still looks to be time left on the BCRP, "Awards will be made no later than September 30, 2013." - page 18.
http://cdmrp.army.mil/funding/pa/12bcrpctra_pa.pdf
You must have missed the H1N1 influenza case study on slide 33/34 in the March presentation. The patient had multi-organ failure. He was discharged from the ICU 11 days after the 7-day CytoSorb treatment. Patient was alive and well at 60 day follow up.
His case study is the same one that showed up in the Jan 2012 SHL:
"Given this background, we believe that CytoSorb™ is in the right place at the right time, representing a potentially fundamental and revolutionary advance in the treatment of life-threatening illnesses. We have seen CytoSorb™ work in a number of different scenarios. For example, an extremely-ill middle aged man with documented H1N1 influenza infection developed septic shock requiring vasopressors, severe lung injury necessitating mechanical ventilation, and renal failure requiring hemodialysis. His IL-6 level was more than 8,000 pg/mL. This occurred despite treatment with Tamiflu, the standard of care anti-viral treatment for influenza. While undergoing a full 7-day treatment course with CytoSorb™ and additional Tamiflu therapy, his blood pressure stabilized and vasopressor therapy was discontinued. Within days of completing CytoSorb™ therapy, he was weaned from mechanical ventilation, left the ICU, and eventually made a full recovery. A second example was a patient with severe acute pancreatitis. The pancreas is an important digestive organ. It produces bicarbonate to neutralize stomach acid and numerous digestive enzymes that help break down fats, sugars, and proteins. When the duct that carries these enzymes and digestive juices to the small intestine becomes blocked, these agents can begin to auto-digest the pancreas and surrounding tissues, leading to massive abdominal inflammation and severe pain, while causing a systemic inflammatory response and frequently organ failure. Despite having a high expected mortality rate, the extent of treatment is typically limited to pain control and hydration. This seriously ill patient was in hemodynamic shock with severe lung injury on mechanical ventilation, and had a high predicted mortality of approximately 40%. His IL-6 level was greater than 900 pg/mL. The patient, whose physicians initially commented that they thought might not survive, recovered following treatment with CytoSorb, and was discharged from the ICU in about 2 weeks. A third example was during the food-borne enterohemorrhagic E. coli (EHEC) outbreak in Germany earlier in 2011 that infected thousands and killed 45 people. CytoSorb™ was used to treat a very ill woman infected with EHEC in a near coma with severe bloody diarrhea, and hemolytic uremic syndrome with renal failure. When treated multiple times with CytoSorb™ after plasmapheresis, she survived and eventually made a full recovery. These 3 individual cases are anecdotal, and should be considered in that context, but provide an early example of the variety of critical-care illnesses that CytoSorb may potentially have a positive effect on. "
And lets not forget some more recent examples from the recent Jan 2013 SHL:
"Outside of the trial, in every day clinical practice, physicians have had generally encouraging results with CytoSorb®. For example, there have been a number of cases of septic shock and multiple organ failure where CytoSorb® was used in patients with extremely high cytokine levels (e.g. IL-6 greater than 20,000 pg/ml). These patients were extremely sick with a variety of infections ranging from a Streptococcal limb infection to suspected gram negative sepsis following complications from a gynecologic procedure. In each of these cases, the prognosis was reportedly grim by the treating physicians. With CytoSorb® treatment, IL-6 levels dropped dramatically over the course of several days, with an eventual resolution of organ failure, and patient recovery. Based upon feedback from these physicians, they are interested in documenting these surprising results for potential publication."
Success stories would be more credible when attached with scientific data. I don't think Dr Chan will reveal much more until the dosing study or more data comes out.
Also this from the last conference news, "CytoSorbents to Exhibit at the ISICEM 2013 Critical Care Conference"
"Dr. Phillip Chan, Chief Executive Officer of CytoSorbents, stated, "We are pleased at the growing recognition and usage of CytoSorb® by leading experts in the field of critical care medicine in many different applications. We have already seen exciting cases in such areas as sepsis, burn injury, trauma, lung injury, cardiac surgery, liver failure, pancreatitis, influenza, and other indications. Users have confirmed the simplicity and ease of use of the CytoSorb® therapy. As we expand our commercialization efforts, we look forward to beginning a number of investigator-initiated studies this year in many different areas that may help drive future adoption and awareness for our technologies.""
Whirlybird, there has been interest outside sepsis. Dr Chan has touched on this last year. They are progressing further than you think.
Some of what Dr Chan has stated already:
"We are also beginning to see some unsolicited interest from physicians who have heard about our technology. "Sepsis continues to drive the most interest and usage in the technology, but as expected, other indications such as lung injury, cardiac surgery, trauma, liver failure, pancreatitis, and transplant surgery have also been generating additional interest. "
"With many key opinion leaders enthusiastic about working with us, our focus in the near future will be to harness this interest to drive broader awareness and usage amongst like-minded colleagues at their institutions. We are grateful for the continued positive reception of CytoSorb® amongst an increasing number of critical care physicians, as well as new studies that many of them are proposing. In addition, we are encouraged by positive CytoSorb® treatment case reports demonstrating benefit in patients with a number of different critical illnesses such as sepsis, pancreatitis, liver disease, lung injury, and others."
Investigation of CytoSorb usage in both cardiac surgery and protection of organ transplants could be something that Dr Quintel is leading on. It seems like it is something that is up his alley. He is a supporter of the device, being the current lead investigator on the dosing studies.
http://www.herzzentrum-goettingen.de/en/content/medicalcare/91.html
"Anesthesiology
The Department of Anesthesiology is represented by its director Prof. Michael Quintel. Our close cooperation with other departments of the Heart Center Göttingen, particularly with the Department of Thoracic Cardiovascular Surgery ensures effective and patient-oriented care.
Cardioanesthesia
Our cardioanesthesia division provides a full range of anesthesiological services: preoperative patient assessment, anesthetic management of cardiac, thoracic or vascular surgical patients, including neonatal and pediatric cardiac surgery, in four operating rooms, and anesthesiological care of patients undergoing interventional treatment of cardiac arrhythmias. Our services also include sedation or anesthesia for pediatric patients undergoing cardiac catheterization.
By standardizing our methods and procedures we are able to provide a high degree of safety for our patients, even for complicated operations. By combining selected drugs and procedures we can provide fast-track anesthesia and shorten the duration of stay in the intensive care unit.
Surgical intensive care medicine
Our department is provided with 42 beds in two surgical intensive care units where thirteen anesthesists and eighteen residents in specialist training care for the patients. We treat 4,000 patients per year - 1,500 of which have undergone thoracic, cardiac or vascular surgery as for instance a heart transplant.
With our state-of-the-art equipment we can provide bedside monitoring of global and regional cardiovascular function (pulmonary artery catheter, PiCCO, VoLEF, LIMON, gastric tonometry). Our services also include transthoracic and transesophageal echocardiography.
In addition to conventional therapy, we have outstanding expertise with mechanical organ support and assist devices. These include cardiac support with intra-aortic balloon pump counterpulsation (IABP) or various ventricular assist devices (Impella®, Berlin Heart®, Medos®), as well as veno-arterial extracorporeal membrane oxygenation (ECMO).
Extracorporeal CO2 elimination (ILA: interventional lung assist) and veno-venous ECMO are employed in patients with acute lung failure. Acute renal failure is treated with modern continuous renal replacement therapy.
Research and teaching of medical students are further important areas of our department."
http://www.herzzentrum-goettingen.de/en/content/medicalcare/88.html
"Thoracic Cardiovascular Surgery
The Department of Thoracic Cardiovascular Surgery and its outpatient department are headed by Prof. Dr. med Friedrich Schöndube. Heart surgery, thoracic surgery, lung surgery, and vascular surgery are represented here. Six senior physicians and 17 residents carry out around 2,100 surgical procedures per year including 1,200 heart surgeries.
Our department runs 3 wards for general care with 64 beds. For patients who need intensive care we closely cooperate with the Department of Anesthesiology II – Surgical Intensive Care headed by Prof Dr. med. Quintel. Here, 14 beds for intensive care equipped with lung ventilators are available.
In our outpatients department patients suffering from vascular or pulmonary diseases are treated. Patients with symptoms of severe therapy-refractory heart failure as well as post-operative heart-transplant patients are attended in cooperation with the Department of Cardiology and Pneumology.
Headed by Prof. Dr. med. Wolfgang Ruschewski, a professorship focused on pediatric cardiac surgery ensures competent care for our young heart patients in the Heart Center Göttingen. Here, more than 150 surgical procedures per year are performed in children. Pre- and post-operative care is ensured by the Department of Pediatric Cardiology and Intensive Care.
A main focus of the Heart Center Göttingen is supporting and treating young adults with congenital heart defects. Their portion of pediatric cardiac interventions sums up to about 20 percent. As with babies and children, pre- and post-operative diagnostic and therapy is carried out in the Department of Pediatric Cardiology and Intensive Care.
Range of surgical procedures
Surgery of acquired heart diseases
Coronary bypass surgery (conventional, minimal-invasive, without heart-lung machine, completely arterial, re-operation, high-risk intervention), cardiac valve surgery (reconstruction, valve replacement, biologic valves, homografts) minimal-invasive transapical aditus, thoracic aorta surgery (aneurysms, aortic injuries, acute and risk surgery), resection of ventricular aneurysms, implantation of ventricular assist devices (artificial hearts), heart transplants, heart tumors
Surgery of diseases of the pericardium and the mediastinum
Surgery of arrythmias
Interventions for the treatment of arrythmias (Maze surgery, ventricular tachycardia), pacemakers, intracardiac defibrillators for children and adults
Surgery of the lung and the chest (thoracic surgery)
Lung resections (open, video-assisted thoracoscopy), pleura interventions, chestwall interventions, mediastinoscopies, surgery of the trachea and bronchia
Vascular surgery
Aorta surgery (thoracic and abdominal, conventional, with stent), carotid artery surgery, surgery of peripheral vessels, surgery of venous vessels (removal of varicose veins, thrombosis of the leg and the pelvis)
Surgery of congenital heart defects (from newborns to adults)
Total correction of the whole range of congenital heart defects with or without heart-lung machine, palliation and primary correction of complex congenital heart defects in newborns (e.g. Norwood procedure), surgery of congenital heart defects in adolescents and adults, extracorporeal membrane oxygenation (ECMO), implantation of ventricular assist devices (artificial hearts, e.g. from Medos and Berlin Heart), heart transplants, special expertise in treating patients with diseased aortic valve (pulmonary autograft procedure) as well as patients with tetralogy of Fallot with pulmonary atresia and multifocal blood circulation in the lung (unifokalisation, total correction), long-standing experience since 1956 with in part multiple revision surgeries after cardiac surgical interventions.
In our department, we care for outpatients at the highest stage pursuing a consistent internal and external quality assurance. The department is intimately involved in interdisciplinary conferences and consultations in the Heart Center Göttingen.
"
No, I do not think they will be a subcontractor for DLT integrator phase. All DLT component developers are expected to work with the integrator thou.
From past history, AEMD does not acknowledge or send out news when they don't get a contract that they applied for. From what has been stated, AEMD teamed up with a large govt contractor and a major dialysis company for the DLT Integrator phase (12-30). There are no budget caps for this phase from DARPA and multiple awardees are expected. If a proposer goes after the Technology Investment (TIA) option, then DARPA will match it up to $25 Million.
From the meeting, Battelle fits the large govt contractor and Fresenius fits the dialysis company.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=79079544
Everyone from the DLT Component Development phase (11-30) is expected to work with the DLT integrator. I don't see AEMD as an integrator. They are a small company with limited resources. Battelle is large company with rich resources, they received approx $22 Million for the DLT systems integration. They have received DARPA contracts in the past; one was an approx $20 Million, two-year contract to serve as the lead systems integrator for the Demonstration Phase of the Immune Building program.
http://www.prnewswire.com/news-releases/battelle-named-lead-systems-integrator-for-final-phase-of-darpa-immune-building-project-75104712.html
It is also no surprise that Wyss/Harvard received the contract as well. They get lots of money from DARPA because their research is so cutting edge.
$37 million this past summer for organ on a chip.
http://wyss.harvard.edu/viewpressrelease/91/
I think this hinted that Wyss/Harvard would be getting some of the DLT Integration money:
http://www.darpa.mil/NewsEvents/Releases/2012/08/30a.aspx
"DARPA performers at the University of Washington and Wyss Institute at Harvard University will analyze the results. The most promising reagent designs may be manufactured for testing at Wyss."
My feeling is that based on the recent announcements and my research, I do not see opportunities for a small company to get this phase of the DLT. There could be another announcement but it would be for an integrator that has highly specialized skill sets that no other can offer that is unique to them.
Here is Dr Chan's response to my question: " The increase in authorized shares is a necessary but important housekeeping item to implement our strategy this year and relates to our up-listing intentions."
I'll also include email responses to V-Boy(Yahoo) from 2-3 years ago:
"Dear XXXXXX,
Thank you for your email. With the Series A shares, there is a redemption provision that would enable us to purchase back the shares at $1.25 per share. For the Series B shares, there is no such redemption option for the company. Our goal with the remaining preferred shares is to eventually force their conversion into common stock when we are ready to uplist to a national exchange. We absolutely understand that the 10% dividend represents ongoing dilution. So the sooner we can uplist, the better for all shareholders. Uplisting will improve our visibility, which should in turn translate into greater trading volume and liquidity for investors, and if our business is progressing well, hopefully future stock appreciation. We also have no interest to issue more preferred shares or shares with an indefinite coupon if we can possibly help it. Depending on our financial picture moving forward, specifically positive earnings and strong positive cash flow, we would consider a potential share buyback.
Hopefully this helps to answer your question. Thank you again for your ongoing support as a valued shareholder.
Best,
Phillip"
Dear XXXXXX
To meet the minimum share price requirements of an uplisting, we would likely need to do a reverse split - the ratio of which depends on what our stock is trading at. Recall, however, that a reverse split does not inherently change the enterprise value of the company. That being said, one of our main goals is to NOT do a reverse split prematurely. We are looking to create and bolster the underlying value in the company to ensure that the stock price is stable following a reverse split. If we can achieve this, then the increased universe of insititutional investors has the potential to provide the buying power to further support our stock.
Hopefully this helps answer your question.
Best,
Phillip
Take into consideration that they have CE Mark approval. They can be successful alone with just Germany.
154,000 annual cases of severe sepsis/stock in Germany = $500-800 Million total addressable German market
If they are successful in EU, then we should be alright. Europe is similar in size opportunity to the US. FDA approval is not for another 3-4 years.
For now let's wait and see. There's some kind of significant event/happening that will come out before the up-listing.
Having both parties work together in achieving the goals necessary with milestone payments make sense. It's not only on getting approval together, it can be things such as having certified manufacturing in place or specific labeling on the device approved by the FDA. I think right now a partner is smart enough to recognize opportunity when they see it. If milestones are not achieved, they don't have to pay out and just walk away. Don't underestimate people in the industry. Fresenius sees the potential in sorbent technology having invested in research for over 20 years and recently setup a center in Krems ( http://www.lifesciencesdirectory.at/index.php?file=show.php&ref=4 ; http://www.donau-uni.ac.at/en/aktuell/news/archiv/15581/index.php). They partnered with CTSO for BetaSorb way back and allowed CTSO to delay BetaSorb so that they could get CytoSorb on the market.
I maybe wrong to think this, different studies serve different purposes. They already have CE Mark approval, why would they focus on running a study with sufficient power? Stopping or cutting back on the dosing study because they don't have enough money is dumb. They should cut back in other areas. The more data they have the better off they will be.
The dosing study is not financed by the various KOLs. It is a company sponsored study. You can expect "standardization". Recall that the company are the ones adding the trial sites to the study: "We have had a unique opportunity to include some very important sites in our trial. This has slowed us down a bit, because getting them on board takes quite a bit of time (contract signing, ethics committee review, training, site initiation and preparation, etc), but the group that we now have participating in this trial are some of the top KOLs in Germany and their involvement in our trial is very significant. As I mentioned in the shareholder letter, the trial is ongoing, and we continue to recruit patients. In order to accommodate extra sites and reduce the risk of bias due to each site only doing a few patients, we anticipate the trial will be larger than initially planned, but not significantly so."
Indeed the dosing study is necessary before conducting the FDA trial because Dr Chan has already stated that the trial will be done in one of the high risk groups. They only need the interim data from the dosing study to submit with the application. In order to have a well designed and conducted FDA study, they would want to optimize the dosage. "The data from this study will be important to expand the knowledge base of how to best use the device, and will be useful when we design a future US pivotal study."
They are investigating or expecting fast track process for their FDA trial. From Dec's Medical Device Daily, “In the U.S. we’re looking at a 2016 or a 2017 timeframe in terms of getting a pivotal trial done, moving through what should be an accelerated approval process, and hopefully getting CytoSorb to the market,” he said." And if I am not mistaken, you had sent an email to Dr Chan about this, his response, "Yes, we have and are continuing to investigate the Fast Track pathway for accelerated review and approvals. It is something that could potentially work for us, given the major unmet medical need we are trying to address." I don't think announcement on starting FDA trial will have much impact on PPS. Having a partner to do the FDA trial with will.
The logic does not make sense to me. The interim dosing study data is required for the FDA trial application. In addition, the dosing study would be helpful in marketing CytoSorb in the EU. Where are you getting the impression that the studies are not standardized?
Are they focused on having sufficient power for the dosing study? I dont' think so because they are not comparing treated and non-treated patients. I think all the patients are treated with CytoSorb. They are comparing the 6 hour/7 day arm to the various treatment durations. They are investigating the effect of longer and more aggressive cytokine reduction on clinical outcome. This is intended to give clinicians the dosing flexibility to use CytoSorb in a variety of clinical situations. Don't you think this would be helpful in marketing the product?
The further test Dr Chan is referring to is the FDA study.
It surprises me that Dr Chan is talking about expanding beyond EU at this early stage. From the OneMed presention, the company is currently in discussions with distributors and corporate partners to expand to other parts of Europe and other countries outside the EU that accept the CE Mark. The slide has images of Europe, Canada, Asia, Middle East and India. IMO, a logical next step outside EU is to get to Japan, China and India. Japanese are believers in blood purification to treat disease. To sell in China, the product must be manufactured where it received approval, in this case in the EU.
So with this rapid expansion planned, they would require some partners with infrastructure and global distribution networks in place, in particular one that takes care of manufacturing in the EU because the NJ manufacturing can only handle up to the initial first 2 years. So I expect that the partnership announcement(s) will come this year for marketing of CytoSorb in the EU/Non EU countries that accept CE Mark. (Their revenue model would be combined with direct selling and independent distributors as well). I think we could see one for FDA study too. In the past Dr Chan did say, they would like to do it preferably with a partner. I think the appeal of US to a partner is that it is similar in size to all the combined countries in Europe without dealing with regulations and reimbursements of each.
Having partnership(s) could get them to their up-listing goal, especially a deal that has a significant upfront payment along with the milestone payments.
Dr Low, based on your comment here, would you say you think the company will not be successful in selling much of the product during this time until we see the US study complete? Are you in or out of the stock for now?
And upon thinking about this further: All 43 patients in the trial had multiple organ failure. It seems that the families that consented to enrollment of their loved ones in the clinical trial did it as a last resort.
There's nothing new in this abstract.
The EU trial was designed to demonstrate safety and achieve statistically significant reduction of IL-6 of which was the primary endpoint. The trial was not designed to demonstrate statistical significance in secondary endpoints. All 43 patients in the trial had multiple organ failure. Roughly half were age 65+ (13-fold risk of death). Roughly one third had very high cytokine levels. The dosage was not optimized for specific sub-groups. Based on the study protocol, the treatment stops at Day 7. I had email Dr Chan about the clinical data when it came out, this was what he said, "We believe the better strategy and use of resources is to prospectively design and conduct an appropriately powered trial in patients greater than age 65, with longer treatment, whose treatment effect is not diluted by the much lower mortality in patients < age 65, that has the chance to show a statistically significant greater absolute reduction in 28-day mortality, rather than try to enroll more patients under the existing protocol that has these treatment limitations and has no chance of showing statistical significance of a 5% benefit. Our dosing study is a prelude to this."
Considering that the EU trial was the first done on humans (with results from the last 43 patients of the trial only), it is reasonable that further research is suggested. This is where the sub-groups come in and ensuring that the dosage are optimized for them. Remember that when they looked at the group with high cytokine levels, the survival rate was 100% at day 28 (0% vs 63%) and the group with patients age 65+ had 100% survival at day 14 (0% vs 36%) . In addition to the dosing study, there will be 6 investigator-initiated human pilot studies for CytoSorb. CTSO has roughly 60 KOLs wanting to try or evaluate CytoSorb, so I don't see an adoption issue just yet.
As for running out of funds or unfavorable financing terms, I would not worry just yet. I would like to see why they have an uplisting goal for this year.
First Quarter 2013 - Dud or Fireworks?
First quarter of 2013 seems very low-keyed so far with exception of the sales of the NOL. Two upcoming exhibitor events mid-March that are very close together. Last year they hosted a symposium at the ISICEM. Considering that the ISICEM is a major conference, could there be news on that day or before? It would make sense that a PR firm would advise them to release some significant news before Q1 ends. If they have some kind of data (ie. dosing study, published data, new developments, etc), it would make sense to release it on day of the Westdeutsche Anasthesietage conference on March 15-16. (Their marketing materials would reflect the updates) Or if they achieved a major milestone, it would an excellent opportunity to include it in this quarter so that it sets the tone for the (exciting) 2013 year. Some kind of fireworks this quarter is needed for sure, IMO. Will Dr Chan surprise us like he did end of 2011 Q1?
2013 Q1
* OneMedForum presentation, Jan 7-9
* Received $391,562 from the Sale of Net Operating Loss carryovers from the Technology Business Tax Certificate Transfer Program sponsored by the New Jersey Economic Development Authority
* Resignation of Thomas Bocchino, CFO, Feb 8
* Exhibitor at Symposium Intensivmedizin + Intensivpflege Bremen, Feb 13-15, 2013
* Exhibitor at Westdeutsche Anasthesietage 2013, Germany, March 15-16, 2013
* Exhibitor at 33rd International Symposium on Intensive Care and Emergency Medicine, Brussels, March 19-22, 2013
------------------------
* Publication of European Sepsis Trial
* DARPA DLT Systems Intregration award (*unconfirmed if CTSO submitted)
* CytoSorb dosing study at 7 leading university hospitals in Germany, ongoing
* Results of interim PHII dosing study, was expected end of 2012
* Top line results from dosing study, was expected in 2013 H1
* Active discussion and planning of at least 6 new investigator-initiated human pilot studies in a growing list of critical care applications
* R&D - U.S. Army Phase II SBIR for trauma and burn injury research, ongoing
* R&D - DARPA multi-year agreement for the treatment of sepsis
* Other new products under development (R&D pipeline has expanded to include positive proof-of-concept data in several promising new applications that addresses areas of significant medical need), ongoing
* Intellectual property - multiple patent applications pending
* Discussions with critical care distributors and potential partners, ongoing
* Website re-vamp, English & German marketing materials, social and print media
* Discussion with FDA regarding modification of existing IDE application to a pivotal trial in one of the high risk groups
* Exhibitor at the Berlin Congress of Anaesthesiology and Intensive Care Medicine" (HAI), Sept 19-21
* Exhibitor at AABB 2013, Oct 12-15, Denver, CO
* Uplisting to national stock exchange
* Start of FDA trial
Upcoming events
* Westdeutsche Anasthesietage 2013, Germany - Exhibitor
March 15-16, 2013
* 33rd International Symposium on Intensive Care and Emergency Medicine, Brussels - Exhibitor
March 19-22, 2013
* Filing of 10-K (10-Q included), expected March 31, 2013
* In addition from the last SHL, the re-vamped website was expected to come out in the next several months. In the past he said it will be in two languages (English & German) and will be more product focused. This makes me think the dosing study will be ready to be included to the CytoSorb section and the full marketing is expected to take place. (Dr Chan talked that if things go well, FDA trial will start late 2013/early 2014, if I were to guess at timeline, the turnaround for the last IDE approval was approx 3 months, and assume additional 6-9 months to sign up and initialized the 2-3 sites for the trial, then expect interim dosing study to be release sometime in H1).
The dosing study is being done in two high risk groups that has high mortality. Because of this, the study is expected to be small. Additionally, Dr Chan stated the US trial will be smaller than originally thought. There is statistical significance achieved with a smaller size without having to conduct a large 300-500 patient study.
We already know that sub-optimal dosing has lead to deaths from the first EU sepsis study and probably from the current study with patients in the 6 hours/7 days treatment arms (SHL Jan 2013). The interim results from the dosing study will be submitted to the FDA in place of conducting a pilot study in the US. The FDA requires two studies: pilot and pivotal.
CytoSorb is a new product. The more the device is used, the more doctors can better understand how it works on the patient. CTSO can decide to end the dosing study or continue on. If you look at another company, Toray, there are doctors interested in the affects of using their device.
Toray has a endotoxin removal device, Toraymyxin. Besides conducting a US study in partnership with Spectral, there is an ongoing study in Italy about Toraymyxin usage. The study is called EUPHAS 2.
You can read about the protocol, etc at this link by going to the Download section.
http://li145-137.members.linode.com/en/
The goal of the study:
I think the PPS probably has people feeling that something is wrong fundamentally. They hired both an IR and a PR firm. They are serious about uplisting this year. Dr Chan bought this up in the Money TV interview in December. Why brother doing this, if the results are bad? There are working on more than one papers. Although I maybe wrong, the paper come out after the data is presented. From Dr Chan's past comments , I get the impression the results and testimontials will be very good. In order to be competitive in the market, a smart partner would know the opportunity in sepsis and would want their foot in early. I don't think there is any problem in finding a partner to help them. I think Dr Chan will probably provide an update about their marketing/sales activities later. (ie. distributors, expansion, reimbursement, etc)
HAI, Sept 19 - 21, 2013
CytoSorbents as exhibitor
http://www.hai2013.de/aussteller.php
Westdeutsche Anasthesietage 2013
March 15-16, 2013
CytoSorbents as exhibitor
http://www.mcn-nuernberg.de/externeseiten/wat_2013/ausstellerverzeichnis.html
The up-listing will occur when the fundamentals are in place. Most likely there will be a reverse split, Dr Chan has repeatedly stated it will only happen when the fundamentals are in place so that the PPS does not fall back to the pre split levels. It appears that substantial news will be announced this year, perhaps over the next several months as they get their story out. That's also when their revamped website will be up.
From SHL 2013:
"Expanding our investor relations efforts fits with our longer term goal of leaving the OTCBB and up-listing to a national stock exchange. This requires significant preparation, and clearly must be done at the appropriate time when our fundamentals justify it. However, the advantages are many, including a higher profile and greater access to the broader investment community, particularly institutional investors."
About the dosing study
- Dr Quintel is Principle Investigator of the dosing studies
- total of 7 leading university hospitals in Germany
- 28-day mortality is the primary endpoint
- broken up into two groups; 1. patients with high cytokine levels 2. patients aged 65+
- intended to obtain more data in these high risk groups and optimize treatment parameters
- High cytokine levels group: "theranostics" study using high cytokine levels (either IL-6 or IL-1ra) as inclusion criteria
- High cytokine levels group: inclusion criteria of IL-6 = 1,000 pg/mL or IL-1ra = 16,000 pg/mL.
- Age 65+ group: treat for 6 hours a day for more than 7 days or treat for more than 6 hours a day ; advisors view this similarly to the treatment with antibiotics where critically-ill patients typically receive more than 7 days of treatment. From the R&R conference, Dr Chan mentioned that antibiotics are typically given for 10-14 days in the hospital which they is the same way they feel they should treat the immune system, the second part of sepsis
- According to Brean Murray, "The CytoSorb arms for this trial include a 24 hour continuous usage arm that lasts for 7 days, and a 6-hour per day arm that continues until the patient experiences improvement in organ function."
- In our ongoing dosing study, CytoSorb has been successfully used with continuous treatment (each cartridge used for 24 hours) for 7 days with no serious device related events.
- With these data, we plan to meet with the FDA to modify our existing IDE application to a pivotal trial in one of these high risk groups
Dosing study
I sent an email to Dr Chan this morning. I asked about study size and if they were behind in enrollment. Not a direct answer but a close enough response. The things to remember is that they still plan to do an interim result, if the KOLs do not believe that something works, they would not get involve in the study, if it is a high profile KOL such as Dr Konrad Reinhart, this would be worth waiting for and if some of these KOLs are "World Sepsis Day" members, it is wonderful that they are open to helping out. The aim of the "World Sepsis Day" movement is to reduce the incidence and mortality of sepsis by 20% by 2020.
"Thank you for your email. I wrote this to another shareholder yesterday, and expands a little bit more upon what I had emailed you.
“We have had a unique opportunity to include some very important sites in our trial. This has slowed us down a bit, because getting them on board takes quite a bit of time (contract signing, ethics committee review, training, site initiation and preparation, etc), but the group that we now have participating in this trial are some of the top KOLs in Germany and their involvement in our trial is very significant.”
As I mentioned in the shareholder letter, the trial is ongoing, and we continue to recruit patients. In order to accommodate extra sites and reduce the risk of bias due to each site only doing a few patients, we anticipate the trial will be larger than initially planned, but not significantly so."
Blood Purification on Severe Sepsis: New Insights
10:10 Thursday, 7th February 2013
Moderators: A. Artigas, MD (Sabadell, Spain)
M. Antonelli, MD (Rome, Italy)
Expert Panel: JL. Vincent, MD (Brussels, Belgium)
D. Payen, MD (Paris, France)
R. Ferrer, MD (Terrassa, Spain)
M. Antonelli, MD (Rome, Italy)
11:10 Literature Review: Sepsis in 2013
JL. Vincent, MD (Brussels, Belgium)
Plus other sepsis topics here:
http://www.infections-online.es/program.pdf
33rd International Symposium on Intensive Care and Emergency Medicine
Dates : from 19/3/2013 to 22/3/2013
Location : Square - Brussels Meeting Center
CytoSorbents as exhibitor.
http://www.intensive.org/1/m4I2_5.asp?L1=4&L2=2&L3=5&ety=1
Scientific program
http://www.intensive.org/1/m2I1_2.asp?L1=2&L2=1&L3=2&ety=1
Dr Kellum has some interesting topics for his presentations:
- Reversing sepsis-induced immune suppression
- Can goal-directed therapy work for brain-dead organ donors?
Dosing study and published paper
Dr Chan's responded to my email about the two:
"Thank you for your email. In terms of the paper, this is still in process. This is a priority for the company and if it were just up to us, it would have been published already.
In terms of the dosing trial, we have a unique opportunity to bring in some additional very high profile sites and KOLs to the trial. To get them up and running is not a short process. We believe their addition will be worth the wait. We still plan on an interim analysis."
OneMedForum webcast, Jan 8, 2013
CytoSorbents:
http://www.onemedplace.com/onemedtv/play.php?vid=2218
OneMedForum 2013 - links to webcasts, schedule and conference book
Reminder: CytoSorbents to present 10:40 AM on Tues, Jan 8.
Webcasts:
http://onemedplace.com/forum/webcast/#page=page-a
Jan 7 - 9 Full schedule:
http://www.onemedplace.com/forum/wp-content/uploads/2012/12/December27-Full-Schedule.pdf
2013 Conference Book:
http://www.onemedplace.com/forum/wp-content/uploads/2012/12/OMFSF13-Conference-Book.pdf
------------------------
A company you may want to see a webcast of is ExThera Medical.
ExThera Medical’s CEO Bob Ward to Present at ‘OneMedForum 2013’ Next Week in San Francisco
Presentation set for Tuesday, Jan. 8, at 2:40 p.m. PST
Click here for 12/13/12 feature story in The Sentinel, featuring the company’s Seraph™ device designed to reduce the duration of bacteremia to prevent sepsis, a top-10 cause of death in the U.S.
BERKELEY, Calif.--(BUSINESS WIRE)--ExThera Medical announced today that its President and CEO, Bob Ward, will present ExThera Medical’s opportunity at ‘OneMedForum 2013.’ Dr. Ward’s presentation will be at The Sir Francis Drake Hotel beginning at 2:40 p.m. PST on Tuesday, Jan. 8th.
ExThera’s Seraph™ (Selective Removal by Apheresis) Microbind™ Affinity Blood Filter has received enthusiastic scientific scrutiny for its potential to bind a wide range of pathogens, toxins and pro-inflammatory cytokines to thwart bacteremia and viremia in the prevention of sepsis.
While other medical treatments of bacteremia caused by S. aureus or MRSA (Methicillin-Resistant S. Aureus) rely on antibiotics with failure rates up to 40%, the Seraph™ apheresis device capitalizes on the affinity of the bacteria in an infected patient’s blood to attach to immobilized heparin—a natural anticoagulant, with many other biological attributes. Seraph™ is designed to be a biomimetic adjunct to antibiotic therapy that reduces bacterial load and duration of bacteremia while lowering levels of pro-inflammatory cytokines in a patient’s blood, thereby preventing complications such as endocarditis, osteomyelitis, and sepsis.
Although presently aimed at its prevention, another critically important application of Seraph™ is expected to be the treatment of sepsis within intensive care units (ICU). Seraph™ consists of a specially designed cartridge packed with a novel bioactive polymer substrate that acts as a hemofilter. By incorporating immobilized heparin, and supplemental ligands the cartridge’s high-surface-area may safely and selectively reduce pro-inflammatory cytokines such as TNF-alpha and remove many toxins and pathogens such as S. aureus including MRSA, from a patient’s blood before the blood is (re)infused.
About ExThera Medical
Privately held ExThera Medical, based in Berkeley, Calif., is targeting the clinical treatment of blood-borne diseases including bacteremia and sepsis, as well as the removal of harmful substances present in banked human blood.
CAUTION: ExThera Medical’s products are for investigational use only.
http://www.businesswire.com/news/home/20130103005832/en/ExThera-Medical%E2%80%99s-CEO-Bob-Ward-Present-%E2%80%98OneMedForum
2012 Recap
2012 Q1
* SBIR PH I research grant from army, $100,000
* OneMedForum presentation
* Raised $1,000,000 through LPC
* During February 2012 the Company issued 12-month Promissory Notes in the aggregate principal amount of $700,000, which accrue interest at the rate of 8% per annum.
* Exhibit and host research symposium at International Symposium on Intensive Care and Emergency Medicine (ISICEM) - March 21
* DARPA systems intregrator meeting - March
* Revenue of $16,893 for Q1 ($52,971 running since 2011)
2012 Q2
* Establishment of European subsidiary
* Trademark for CytoSorb
* Frankfurt MedTech Investor Forum, Germany - May 15
* Raised $650,000 in Apr/May through LPC
* Analyst coverage initiation from Zacks Small Cap Research
* Marcum MicroCap Conference, New York - June 20
* Dr Chan - Finalist for Ernst & Young Entrepreneur of the Year 2012 Award - June 27
* CytoSorb product launch in Germany
* Hire of Dr Christian Steiner + 3 sales hires for direct selling in Germany - training and start of sales
* Key opinion leaders at nearly 20 different German hospitals have agreed to evaluate CytoSorb with about 10 more outside of Germany
* Revenue of $33,042 for Q2, $49,935 for H1
2012 Q3
* Departure of David Lamadrid
* Raised $450,000 through LPC in Jul/Aug
* DARPA DLT Systems Intregration grant - application deadline July 13
* Analyst coverage initiation from Brean Murray
* Sucessful completion of the PHI SBIR. SBIR PHII army grant submission
* Military Health System Research Symposium, Aug 13-16, data presentation and exhibit
* More than 40 key opinion leaders at different German hospitals have now agreed to evaluate CytoSorb with many more outside of Germany
* Opened accounts in the neighboring DACH (Austria and Switzerland)
* DARPA DLT grant - awarded a five year technology development contract for 3.8 million (removal of cytokines, toxins and certain biowarfare agents from blood)
* MoneyTV interviews
* Dr Chan purchases 190,000 shares, Sept 4
* Rodman & Renshaw Conference, New York - Sept 9 - 11
* Introduction of new product, ContrastSorb, IV contrast removal in blood
* Became sponsor and member of the German Sepsis Society
* Sponsor of Sepsis Heroes in Honor of World Sepsis Day, Sept 13
* Exhibited at the 14th Capital City Conference of the DGAI Congress of Anesthesiology and Intensive Care Medicine HAI 2012 with nursing symposium, Sept 13-15
* Increase of 2 new patents bringing total to 31 issued US patents and multiple applications pending
* SBIR US Army and US Air Force grant award - trauma, burn and smoke injury
* As of August 8, 2012 there were 202,962,314 shares of the issuer’s common stock outstanding.
2012 Q4
* Employment renewal for key executives
* Appoints Thomas Bocchino as CFO
* MoneyTV interview
* Reimbursement for CytoSorb in Germany and Austria
* Expansion to more than 60 key opinion leaders throughout Germany, Austria and Switzerland who are interested in using or are currently using CytoSorb
* Active discussion and planning of at least 6 new investigator-initiated human pilot studies
* $1 million U.S. Army Phase II SBIR award, granted and is currently under contract negotiations.
* Exhibit at Bayerische Anasthesietage, Germany, October 5 & 6 2012
* Exhibit and poster at AABB Conference CTTXPO Exhibition Oct 6-9 in Boston
* Exhibit at the DIVI 2012 Congress, Germany, Dec 5-7
* Increase of two assigned patents bringing total to 33 issued US patents and multiple applications pending
* Selected for Business Tax Certificate Transfer program by the New Jersey Economic Development Authority (EDA) for fiscal year 2013
* Revenue of $605K in Q3 2012 consisting predominantly of first DARPA milestone payment, with product sales of 13K
* As of Nov 21, Q4 2012 product sales are nearly $70K to date
* During October and November, the Company received approximately $250,000 as proceeds from the sale of shares with LPC
* As of November 5, 2012 there were 211,912,915 shares of the issuer's common stock outstanding.
2013
* OneMedForum presentation, Jan 7-9
* Publication of European Sepsis Trial
* DARPA DLT Systems Intregration award (*unconfirmed if CTSO submitted)
* CytoSorb dosing study + small studies for CytoSorb uses in other areas
* Results of interim PHII dosing study
* New products under development, ongoing
* Discussions with distributors/partners for other EU countries, ongoing
* Website revamp, English & German marketing materials, social and print media
* Discussion with FDA regarding modification of existing IDE application to a pivotal trial in one of the high risk groups
* Exhibit at Symposium Intensivmedizin + Intensivpflege Bremen, Feb 13-15, 2013
* Top line results from dosing study, H1
* Uplisting to national stock exchange
* Start of FDA trial
New Jersey Economic Development Authority (EDA) funding for CytoSorbents.
TRENTON, N.J. (Nov. 27, 2012) – In support of the Christie Administration's commitment to nurturing the growth of emerging technology and biotechnology businesses, the New Jersey Economic Development Authority (EDA) announced that 65 companies have been
approved to share the $60 million allocation available through the State’s Technology Business Tax Certificate Transfer Program in Fiscal Year 2013.
http://www.njeda.com/web/pdf/NOLApprovals2012.pdf
OneMedForum, Jan 7-9 2013, San Francisco
CytoSorbents to present at the OneMedForum:
http://www.businesswire.com/news/home/20121210006108/en/OneMedPlace-Announces-Presenting-Companies-%E2%80%98OneMedForum-2013%E2%80%99-San
There was a webcast at this event last year. Put it in your calendar to tune in.
2012's webcast:
http://www.onemedplace.com/onemedtv/play.php?vid=1821
CTSO received their award a few months ago. I don't think this particular document is up to date.