Pediatric septic shock

I could not find this as one of the weekly case studies that have been published this year. Since January, the company has published 46 case studies. The last pediatric case that the company formally presented was back in November of 2015 during the Q3 earnings call. It was a 4 year old girl who had developed toxic shock syndrome after an insect bite. She had extensive capillary leak syndrome, was progressing towards scalded skin syndrome, which is akin to having a massive burn injury all over the body. She made a complete recovery after three weeks and CytoSorb was credited with helping to save for the life and helping to prevent an amputation for leg. The case was later presented at the Hungarian Pediatric Congress.

The use of Cytosorb in treating pediatric patients is an area I would think the company definitely has an interest in and is studying as some of the board members and officers have a background in this area. Dr. Paul Checchia, who is on the company's Cardiac Surgery Board, is the Medical Director of the Pediatric Cardiovascular ICU at Texas Children's Hospital in Houston.  He is also Professor of Pediatric Critical Care Medicine and Pediatric Cardiology at Baylor College of Medicine.  Also Gregory Di Russo whom the company hired as Senior VP of Clinical Development, is an accomplished pediatric cardiothoracic surgeon specializing in congenital cardiac surgery, and was Vice Chairman of Cardiothoracic Surgery at the Children's National Medical Center in Washington, D.C.

Google Scholar http://downloads.hindawi.com/journals/cricc/aip/6987167.pdf
or just search for keywords "cytosorb pediatric"

Hemoadsorption with CytoSorb - Pediatric Case

This paper has not yet been published but will most likely be appearing as another 'case of the week'.

Hemoadsorption with Adult CytoSorb® in a Low Weight Pediatric
Case - A Worldwide Premiere Procedure

Authors:
Catalin Gabriel Cirstoveanu1,2
Ileana Barascu2
Samantha Mc Kenzie Stancu1

Affiliations:
“Carol Davila” University of Medicine & Pharmacy, Bucharest
37 Dionisie Lupu Street, District 1, Bucharest, Romania 020021

“Marie S. Curie Children’s Emergency Hospital” Bucharest 2
Neonatal Intensive Care Unit
20 Constantin Brancoveanu Street, District 4, Bucharest, Romania
041451

ABSTRACT
Cytokine adsorber (CytoSorb®) has been used successfully as adjunctive treatment for adult patients with elevated cytokine levels in the setting with severe sepsis, septic shock and to reduce blood myoglobin, unconjugated bilirubin and conjugated bilirubin. In this article we present the case of a nine-month male infant who was admitted to the NICU due to sepsis post cardiac surgery - Fallot tetralogy, and multisystem organ failure (MSOF) including liver failure, renal failure which was successfully treated by a combination of continuous hemodiafiltration (HDF) and hemoadsorption with CytoSorb®. HDF was safe and effective from the first day for urea removal, but the patient’s bilirubin levels kept increasing gradually, culminating on the 9th day with a maximum value of 54 mg/dl of total bilirubin and 31.67 mg/dl of direct bilirubin when we performed hemoadsorption with CytoSorb®. Over the 49-hours period of hemoadsorption, the total bilirubin value decreased from 54 to 14 mg/dl, the patient’s general status improved considerably accompanied by a rapid drop of
aminotransferases. Hemodynamic status has been improved as well and inotropes dropped rapidly. The patient’s ventilation settings improved during CytoSorb® treatment permitting to wean the patient from mechanical ventilation after five days of hemoadsorption. The patient was discharged home after 34 days of hospitalization, in a good general status.

Cardiac surgery trial updates are available
in the 2013 Q4 call transcript as well as the most recent 2014 Q2 call transcript. Below is an excerpt from an analyst report that summarizes it probably best:


"The company's previous game-plan relative to the U.S. market was to use the European sepsis dosing trial data as support for FDA approval to run a sepsis trial in the U.S. On the 2013 Q4 call, however, the company said that they are now focused on running a pivotal trial in the U.S. for cardiac surgery. The reasons for focusing on cardiac surgery include the demand (and clinical successes) that CytoSorb has had in that application in Europe and the company believes cardiac surgery represents a faster regulatory approval timeline and will be lower cost and have less risk of failure than a sepsis related trial. For one, the company noted that outcomes are more predictable with cardiac surgery than with sepsis. Also, mortality will not be an endpoint in cardiac surgery whereby it is with sepsis and is a relatively high hurdle. The cardiac surgery focus for the U.S. makes sense in that it is a relatively lower-risk endeavor and can get CytoSorbs foot in the domestic door the company can then focus on expanding the label to encompass additional indications. It also likely puts the device on the U.S. market and generating revenue here earlier than would have been the case if the company had pursued sepsis as the initial indication.

In addition, while there are currently blood -filtration products on the market that a re used during cardiac surgery to reduce inflammatory substances, they do not target cytokines which offers CytoSorb a wide-open market opportunity. While cardiac surgery was barely mentioned just 18 months ago, this seems to have quickly become a major driver of demand and interest in CytoSorb with the company noting that 22 cardiac surgery centers have either used the device or expressed interest in doing so this is up from just 10 in 2013. The company also indicated that based on interest that they have seen for the cardiac surgery application that specifically changed some of their sales efforts to dedicate more focus on cardiac surgery.

And while the market for cardiac surgery, at approximately $ 500M in the U.S.(per the company's estimates), is likely significantly smaller than for sepsis (potentially 1+billion dollars), it still represents a relatively large target market. And, again, the company would likely look to expand the label in the U.S. beyond just cardiac surgery."

Updates are also available in the recent 2014 Q2 call transcript which detail where they are at with the regulatory pathway research and the company did note that they will be hiring a Chief Scientific Officer to manage the U.S. trial (as well as European studies). They just recently recruited a Cardiac Surgery Advisory Board and began drafting the protocol for the study. The cardiac surgery clinical data generated overseas might be used as support to petition U.S. regulators to initiate a clinical study in this country.

Thanks Ping, that was in line with exactly why I was asking. Trying to get a sense where they are at with their studies, so this is very exciting to see them presenting at this conference.

It is also interesting that the CMCR (Centers for Medical Countermeasures Against Radiation) is a program of the U.S. Department of Health and Human Services, Office of Public Health Emergency Medical Countermeasures, and the National Institutes of Health.

Between the company's inroads with the various grants by the ARMY and Airforce through the DARPA and SBIR programs as well as the NHLBI grant for Hemodefend, it shows the potential that the government can have in validation of the technology as well as opening up other opportunities down the road - all in parallel with what is going on with the commercialization of the product overseas.

Google "ADMINISTRATION OF AN ADSORBENT POLYMER FOR TREATMENT OF SYSTEMIC INFLAMMATION" patent publication "US 20110212172 A1"

Abstract:

The invention provides a method of ameliorating systemic inflammation in a patient involving administering to the patient a therapeutically effective dose of composition including polystyrene divinyl benzene copolymer and a polyvinyl pyrrolidone polymer. More particularly, the method relates to using these polymers as an enteral sorbent preparation to remove inflammatory mediators, such as cytokines, from the intestinal lumen. The polymers can be in the form of a preparation of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinyl pyrrolidone polymer coating.

The keyword here is "enteral" as in involving or passing through the intestine, either naturally via the mouth and esophagus.

EntericSorb QTDP grant

Ping, thanks for this information. Do you know if the company has received any additional funding since their original Qualifying Therapeutic Discovery Project grant back in 2010? From my recollection the original grant was for around $245k.

I would assume that some of the data that they will be presenting at this conference will be as a result of having received this funding.

I haven't posted much if any on this board so I hope you don't mind if I put something here that investors in the company may find useful. Yahoo's limitations on the number of characters and other recent changes almost make it unusable and very frustrating - that plus the crazies have once again taken over the board for the short term price swing and I can barely stand it over there.

I have looked hard for an example of an OTC company that had gone through the process of RS and uplisting in order to shed some light and dispel concerns if it is done properly. This company happens to be in the same industry, had a similar share structure, and was just beginning commercialization. Now granted there will be some differences that I am sure some will point out but this is about as close as an example I believe you will find. The main points I would hope someone could take away from this example are that the RS was 43:1 (vs. a suggested 10:1 on the conference call), this company had operating losses at the time of the uplisting, and a major partnership/licensing agreement was the catalyst that propelled the stock after the RS through uplisting. I will keep this brief:

Alliqua, Inc. (ALQA) is a biomedical company that focuses on the development, manufacture, and distribution of proprietary transdermal wound care and drug delivery technologies. The company also develops HepaMate, an extracorporeal temporary liver support system designed to provide whole liver function to patients with acute or severe liver failure.

11/18/13 - the company announced and effected a 43.75:1 reverse split the same day (reduced OS from 310,993,023 to approximately 7,108,412) - pps was $.08 (pre-split) and closed at $3.93 (post-split)

11/19/13 - the day after the RS went into effect they announced a licensing along with a share purchase agreement with Celgene to sell to Celgene common stock and a five year warrant to purchase an additional shares of common stock at an exercise price of $5.69, in exchange for $6.0 million. In connection with this agreement to invest in Alliqua’s securities, Celgene received a right to appoint a director to Alliqua’s Board of Directors. The pps hit a high of $8.00 after 2 days of heavy volume.

1/27/14 - 2 months after the intention to uplist was announced and RS went into effect, they received approval from NASDAQ’s Listing Qualifications Department to list its common stock on the NASDAQ Capital Market. A few days prior to this the stock had traded as high as $10.00 (post-split) or $.23 (pre-split). The stock began trading on 1/28.

From 11/18/13 when the RS was effective until trading began on NASDAQ on 1/28 of this year, the stock price appreciated 142%. The stock has pulled back since then due to a variety of operational issues and currently trades at $5.60 (post-split).

For those individual who have been complaining about the CTSO revenue numbers for the quarter, this company just reported their Q2 results and the CEO was proud that they had their first $1M quarter and this included contract manufacturing fees - the total PRODUCT revenue for the quarter was only $549,008 and $661,313 YTD! In fact at the time they announced their RS and subsequent licensing deal with Celgene back in 2013 they had a NET LOSS of $2,236,045 for the quarter and $7,029,224 loss YTD!

In this scenario the company announced and effected a RS in the same day and used that new share structure as part of the deal struck with Celgene, and by announcing the license agreement the next day, counteracted any negative impact that the RS would have had on the pps going into uplisting. I am not saying this is how things will play out with CTSO but it is a scenario to entertain. If there are other examples of OTC companies with successful uplisting (with or without a RS), I believe it would be beneficial to share them.

Patient case report-80 yr old with kidney failure & sepsis

For those interested, a patient case report was recently published (July 31, 2013) "Improvement of Hemodynamic and Inflammatory Parameters by Combined Hemoadsorption and Hemodiafiltraion in Septic Shock: A Case Report". From the Divisions of Nephrology and Pulmonology and Internal Intensive Care at University of Rostock, Rostock Germany. (Mitzner, Gloger, Henschel and Koball).

I did not want to pay for the full report but have included the first page of it below.

"Dear Editor, we report the case of an 80-year old male who was stable on chronic hemodialysis for more than 12 months. Past history included coronary artery disease with myocardial infarction 14 months ago, end-stage renal disease due to nephrosclerosis, arterial hypertension, and diabetes mellitus type 2. The patient was admitted to the emergency department after he collapsed at the end of a regular dialysis session. After regaining consciousness he reported shortness of breath, frequent coughing, physical weakness, and dizziness over the last few days. On examination, the patient had fever (39.2 C), moist rales in bilateral lungs, O2 saturation 79%, BP 126/60 mm Hg, HR 130 beats/min, lactic acidosis with pH 7.1, Apache II 33 and SAPS II 48. Later blood cultures remained negative; however, bronchoalveolar lavage was positive for Staphylococcus aureus. Upon further deterioration of the circulatory situation, the patient was diagnosed as having pneumogenic septic shock, intubated for mechanical ventilation, and moved to the ICU.

He was immediately started on ceftriaxone and clarithromycin as well as 0.2 ug/kg/min norepinephrine (NE). On day 3 of the ICU stay the patient was in clinical need for renal replacement therapy and therefore started on citrate anticoagulated continuous venovenous hemodiafiltration (CVVHD, Multifiltrate, FMC, Bad Homburg, Germany). As the interleukin-6 (IL-6) level was elevated to 665 pg/ml (normal range 5.4 pg/ml), a hemoadsorption column (CYTOSORB, Cytosorbents GmbH, Berlin Germany) was added in a predialyzer position for 24 hours. The hemoadsorber was then removed while CVVHD continued. NE and laboratory values during this combined treatment are depicted in figure 1. The treatment was well tolerated. NE could be reduced from a maximum of 3.0-0.4 ug/kg/min while MAP remained stable. Values of IL-6, C-reactive protein (CRP), creatinine, procalcitonin, and leukocytes decreased during treatment and continued to decrease in the following days. The cumulative vasopressor dose in septic patients is correlated with ICU mortality [1]. The CYTOSORB hemoadsorber was shown to remove various proinflammatory cytokines in vitro and in animal models of sepsis [2, 3]. To the best of our knowledge, this is the first clinical case report in a patient with acute on chronic kidney failure and septic shock. The treatment appeared to be safe and was well tolerated by the patient. A decrease in plasmatic IL-6 and other markers of inflammation along with a marked decrease in NE need were the major results of this treatment. Further studies are necessary to clarify to what extent these favorable results were due to the hemoadsorbent or the CVVHD, respectively."

This report can be found on Karger web site under Article-FullText-351206.