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Tweet from Palex at ILTS 2018 Annual Congress
This picture was tweeted by Palex at the Cytosorbents booth at International Liver Transplantation Society yesterday. I translated it to English:
"Come visit us at the @CytoSorbents stand at the # ILTS2018 congress in #Lisboa and meet #Cytosorb, the bridge therapy for the elimination of #bilirubin, ammonium and bile acids and #cytokines!"
Nuestros compañeros de @PalexCuiCli están junto a @CytoSorbents en el #ILTS2018 de #Lisboa. ¡No olvidéis pasar a saludar por su stand! https://t.co/qZO25Mah30
— Palex España (@Palex_Espana) May 24, 2018
Capital raise coming?
There is an interesting discussion going on Yahoo Finance between Ping and CG - both of whom I feel have a solid understanding of the company but they have differing opinions regarding whether a capital raise is coming on the heels of this recent IR tour from Dr. Chan and subsequent investment firm upgrades.
I have pasted the context of the thread below but would be interested in opinions on this board. I think CG is coming from an analysis of the nuts and bolts of the recent financings and communications whereas Ping (who has been for the most part spot on in the past) is basing it on historical patterns from the company. The posts are in chronological order from most recent at the top.
I put weight to both of their positions, but my gut feel is 60/40 it does not happen this time. I would rather see the company out-license Hemodefend and get a large partner to fund the US trial, instead of the company trying to do that themselves like REFRESH.
Thoughts???
Thread
CG
12 hours ago
@Ping-Pow-Princess, They have raised ~$9.5M via the Cantor ATM since Q3 2017 with $6M+ of that coming in Q1 2018 -- all at 0% discount. Because they recently modified their Bridge Loan, principal payments are not due now until at least 2020 ($1.67M in 2020; $4M in each of 2021 and 2022; and $333K in 2023). They also can opt for the second tranche of the $5M. In short, given their cash position, their debt load, their product sales growth, their stock price, and the ~$15M remaining on the Cantor ATM, I see absolutely zero reason why they will raise the kind of money you're talking about at a discount by the end of June.
Ping-Pow-Princess
13 hours ago
@CG Yes, they were raising via the Cantor ATM as the opportunity presents itself. I think they want to raise significant cash through an offering. I should add Maxim Group on the list for this month that raised their price target...so 3 out of the 5 companies working on the next offering. When I first invested in CTSO (MSBT) at the time many years ago, they had 30 million outstanding shares and were running one trial. They are in a similar situation but with rapid growth. The timing of a cash raise is now, IMO. Maybe 10-25 million at a 15% discount.
CG
13 hours ago
@Ping-Pow-Princess, CTSO wants more institutional investors. I suspect at least some of the Cantor ATM sales probably have been going to institutional investors (institutional ownership is finally at 10-11% after being stuck around 8% for a while).
CG
21 hours ago
@Ping-Pow-Princess, They have been continuously raising via the Cantor ATM for the past couple quarters (through mid-April 2018). With the stock price breaking out to 3-year highs, I expect that to continue if they want to raise more funds. Recall that prior to the March 2017 raise at $4.50, CTSO last raised at $8.25 in January 2015.
Ping-Pow-Princess
yesterday
@Ping-Pow-Princess If you look at the March 31, 2017 PR regarding their last offering, these companies are working together, "Cowen and Company is acting as the sole book-running manager and representative of the underwriters for the offering. Aegis Capital Corp, H.C. Wainwright & Co., B. Riley & Co., Maxim Group LLC and Northland Capital Markets are acting as co-managers for the offering."
Ping-Pow-Princess
yesterday
Hi Mak, It's only 100 shares at $10 after hours. I wouldn't worry too much about this tomorrow. I just want to remind everyone that there will be cash raising coming. I've mentioned my reasons in my past posts. My estimate is that it will happen by end of June. Dr Chan is not enjoying a holiday in Santa Monica and in Europe with his recent conferences there. The B.Riley and HC Hainwright buy rating is a past strategy (by other companies involved in cash raising) in attracting more investors and lifting the price up.
Kathleen Bloch Comments:
“Lastly, let us take a look at our working capital position. As of March 31, 2018, we had a record approximately $21.1 million in cash, which provides a very solid foundation for the Company. Those shareholders who have been with us for a long time know that we have been historically very thoughtful and deliberate about financing this Company in a way that minimizes shareholder dilution with a combination of non-dilutive grants, monetization of our net operating losses, the use of debt, and of course, equity raises, while always striving to minimize shareholder dilution.
For example, in March 2018, the Company replaced its existing $10 million term loan with $10 million of new debt. This new debt facility is structured as a four-year term loan with monthly payments of interest- only for the first 18 months, and this has reduced our cash needs over that same period by approximately $6 million. Another $5 million in term loan debt is available by March 2019 to further extend our operating runway should we choose to take it.
Also, in the first quarter of 2018, we raised approximately $6 million through our at-the-market, or ATM, equity facility with Cantor Fitzgerald at an average price of $7.97. Using this ATM, we have been trying to strike a balance between having a strong balance sheet so that we can fund rapid growth while limiting shareholder dilution. The ATM provides an efficient and cost-effective way for us to raise funds for the Company's needs. Given our strong cash position and good working capital position, we have not utilized the ATM since mid-April 2018. We would like to remind our shareholders that we, the Company's Management, are shareholders as well, and we strive to do what is in our collective best interest. Finally, as of March 31, 2018, we had approximately 35 million common shares on a fully diluted basis.”
Busy week
Lot's of meetings and conferences going on this week where the company is present, in addition to the B. Riley Investor Conference and investor meetings today and tomorrow:
International Liver Transplantation Society Annual Congress 2018
5/23-26
Lisbon, Portugal
Booth # 9
https://ilts.org/meetings/ilts-2018-annual-congress/
EuroELSO 2018 (7th EuroELSO Congress on ECMO-ECLS)
5/23-26
Prague, Czech Republic
Booth # 5a
http://www.prague-euroelso2018.com/important-deadlines.page
ERA-EDTA 2018 (European Nephrologists)
5/24-27
Copenhagen, Denmark
Booth # 3.103
http://www.era-edta2018.org/programme_at_a_glance.pdf
Getting in front of the right people
For all those that were decrying Dr. Chan was doing too many conferences, I think we are starting to see the evidence of that starting to pay off. What I think may have evolved over time is that they have honed their IR strategy to focus on attracting their 'natural' investors which are those smaller institutions and individual, self-directed investors who are looking to become long-term owners of the company's stock. Small caps tend to fall in between the cracks and are a blind spot for most analysts at the larger firms. I think as the market cap increases we will start to show up on more radars IMO.
On the heels of the Cohen meetings last week and B. Riley meetings today, let's see how we end the week - if it is strong it bodes well for a continued trend next week.
Baxter is always out there are a potential suitor/partner
Below are a few snippets from an article written after Baxter's Q3 earnings:
Why Baxter is on the Prowl for Acquisitions
CEO Joe Almeida said M&A deals, particularly smaller tuck-in acquisitions, will continue to play a key role in Baxter's growth strategy. According to Seeking Alpha transcripts of the third-quarter earnings call, Almeida gave analysts reason to expect more acquisitions to fuel the company's growth going forward. "M&A deals like Claris will continue to play an important role in building out our portfolio and pipeline across our key growth categories and adjacencies," Almeida said. Baxter doesn't have an M&A strategy per se, he said, but M&A is coupled together with the strategy of each business at Baxter. As a company, Almeida said Baxter plans to expand inorganically across all regions, including the U.S., Europe, and Asia, particularly in China. "And we have the people being put in place to be able to scout those opportunities. We have an M&A team that is focused on bringing more deals," Almeida said. The company is more likely to pursue smaller tuck-in deals though, as Almeida said larger deals more difficult to integrate, and tend to have a marginal return on investment.
"So, we are focusing on molecule purchasing," he said. "We have a lot of those in process right now, tuck-ins, product lines from companies that are divesting, things such as this to augment our growth in the long-term, and augment our four pillars of growth in our business, which is the pharmaceutical business, the critical care, the surgical, as well as parts of our renal area, primarily areas that will be beneficial to us outside the U.S. in terms of buying clinics and things like that."
José Almeida the CEO has been on a roll at Baxter International. This is his third year as CEO and their stock is up nearly 70%, with strong earnings and profits. Even just recently he spoke with Fortune Magazine, and said he is ready to do more acquisitions this year and he’s interested in “any company that is within our area of business.” Almeida says his acquisition strategy has the support of Dan Loeb. The activist investor owns just under 7% of Baxter and the stock is one of the top holdings of his firm Third Point. Almeida says Loeb and Third Point have been “great owners of Baxter” adding, “I think what Dan wants at the end of the day is that you create value for your shareholders.”
I would think Baxter is well aware of Cytosorb through their own efforts to market and sell oXiris and the fact that Cytosorb has been used in in numerous cases in conjunction with Baxter CRRT machines (HF 19 Aquamax, BM11/BM14).
Dr. Chan on multiple occasions kind of held up the Fresenius acquisition of NxStage Medical as an example, e.g. what that deal went for, how it was valued, and what Fresenius was looking for in terms of how NxStage would fix into their market strategy. I think both Fresenius and Baxter see hemodialysis and critical care as huge growth opportunities that complement their current businesses and both companies have gone on record this year of publishing their growth strategies out past 2020 and a key component of them is acquisitions.
As you say, time will tell...
DIC apparently has long been associated with increased mortality in patients with sepsis, but I had to look it up to get a better understanding.
From my earlier post I meant 2015 Users Meeting - here is the official literature which is much more legible and professionally formatted. Those two case studies from Austria (Klaus Krenn) are on page 15.
http://cytosorbents.com/wp-content/uploads/2016/03/Proceedings%202nd%20Int%20Users%20Meeting%202015_EN.pdf
There was a specific Cytosorb case published for DIC but I was not able to get it to retrieve properly on the company's web site.
Successful treatment of severe sepsis with disseminated intravascular coagulopathy
http://cytosorb-therapy.com/infoitem/successful-treatment-severe-sepsis-disseminated-intravascular-coagulopathy/
I think what you have seen in the recent activity with the stock was from the announcement of the expansion for the EU approved indications to include myoglobin removal. Cytosorb has proven case studies in which demonstrate its excellent myoglobin binding properties.
There are numerous cases and information published on the company's web site involving rhabdomyolysis and the presence of myoglobin. I would encourage you to read some of these if you are new to the company or technology.
http://cytosorb-therapy.com/?s=myoglobin
FMC has exclusive distribution rights
Under the terms of the original agreement which was signed at the end of 2014, Fresenius Medical Care has exclusive rights to distribute CytoSorb for critical care applications in France, Poland, Sweden, Denmark, Norway, and Finland. At the beginning of 2017 the two companies expanded the terms of their partnership and added a co-marketing agreement for the CytoSorb blood adsorber in countries where the therapy is available. According to the 3-year agreement, CytoSorbents extended Fresenius’ exclusive distributorship of the device for critical care applications in France, Poland, Sweden, Denmark, Finland and Norway through 2019. In these countries, Fresenius will develop a CytoSorb CRRT kit that will include its compatible blood tubing set and it must meet minimum quarterly orders and payments. The co-marketing agreement mandates that the 2 companies will jointly market CytoSorb and Frensenius’ compatible blood tubing sets to FMC’s critical care customer base in the countries where Cytosorb is actively commercialized. Fresenius will be responsible for identifying new CytoSorb sales opportunities and will make customer introductions with CytoSorbents and its distributors. The companies said that they anticipate the co-marketing program will begin in the 2nd half of this year.
The exclusivity is intended to protect FMC from other distribution agreements for those countries. I have not seen anything that would indicate Cytosorbents desires to expand their direct sales footprint beyond the five countries they are currently focused on - Germany (Austria, Switzerland, Belgium, Luxembourg).
DIC is a recognized complication of Rhabdomyolysis
which is a condition in which damaged skeletal muscle breaks down rapidly. Rhabdomyolysis symptoms may include muscle pains, weakness, vomiting, and confusion, there may be tea-colored urine or an irregular heartbeat. In addition some of the muscle breakdown products, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure. The muscle damage is most often the result of a crush injury, strenuous exercise, medications, or drug abuse.
Rhabdomyolysis and it's associated complication disseminated intravascular coagulopathy(DIC), were actually on one of the first case study presentations done from the first Cytosorbents User Group in 2013 (see slide/page #5
http://cytosorb-therapie.de/wp-content/uploads/2015/04/5-Krenn_Cytosorb-case-report.pdf
New study Post-Cardiac Arrest Syndrome (CATCH)
Another new study staring in June. This study is being conducted out of Centre Hospitalier Universitaire Vaudois one of 5 university hospitals in Switzerland, 40 patients running through 2020.
Post Cardiac Arrest Syndrome (PCAS) describes the spectrum of organ dysfunction. The four key components of PCAS are:
- Post-cardiac arrest brain injury
- Post-cardiac arrest myocardial dysfunction
- Systemic ischaemia/reperfusion response
- Persistent precipitating pathology
In the US, in-hospital mortality rates after transfer to hospital are 60–70% for PCAS. The prognosis for postcardiac arrest patients remains very bleak, not only because of anoxic-ischemic neurological damage, but also because of the "postcardiac arrest syndrome," a phenomenon often severe enough to cause death before any neurological evaluation. This syndrome includes all clinical and biological manifestations related to the phenomenon of global ischemia-reperfusion triggered by cardiac arrest and return of spontaneous circulation. The main component of the postcardiac arrest syndrome is an early but severe cardiocirculatory dysfunction that may lead to multiple organ failure and death. Out-of-hospital cardiac arrest (OHCA) is a common initial presentation of cardiovascular disease, affecting up to 325 000 people in the United States each year.
I would imagine that the length of this trial and the small number of patients they are recruiting is indicative of the complexity of this type of study. There are numerous factors in the "chain of survival" from the procedures performed by the EMT's in the field to the hospital staff.
https://clinicaltrials.gov/ct2/show/NCT03523039?lupd_s=04%2F18%2F2018&lupd_d=30
CytoSorb - may fast replace complicated procedures/devices like Prometheus
This is from hofno2003 (who from what I recall has been in CTSO before and provides really good observations from a medical perspective). The comments are posted over on the Yahoo Finance board. I think his observations are valid albeit speculative at this point.
"Liver dialysis (bilirubin removal) with CytoSorb - will fast replace complicated procedures/devices like Prometheus (R) liver support system" https://en.wikipedia.org/wiki/Liver_dialysis
"Prometheus could become very fast obsolete and be replaced by CytoSorb - unfortunately (?) Prometheus is sold by Fresenius - what should Fresenius do in order to upheld its market share with liver support products / systems?
The established liver dialysis systems are very complicated - there are TWO filter steps associated with all available devices (e.g. Prometheus liver support system). The first filter step (pump system and filter device) includes the separation of the serum albumin-toxin complex (serum albumin binds lipophilic/hydrophobic toxins like bilirubin) and with a second filter step (pump system and adsorber device) the separation of albumin and its bound toxins (e.g. bilirubin) is organized. The "clean" albumin is then given back to the patient. In parallel normal hemodialysis has to be done to remove all other water soluble toxins. With CytoSorb all these procedures and devices are combined into ONE STEP - that is really a huge advantage and big deal!"
https://www.therapeutic-apheresis.com/en/products/prometheus/
Trauma/myoglobin market alone is > $1B
From the recent 10K:
"Cytokine and myoglobin reduction by CytoSorb and related technologies may have benefit in trauma, potentially improving clinical outcome. The total addressable market for CytoSorb for the treatment of trauma is estimated to be $1.5 billion to $2.0 billion in the U.S. and the EU."
In general, most extracorporeal therapies are not well-suited to remove myoglobin. CytoSorb reduces myoglobin, and other polymers under development, removes myoglobin without significant losses of albumin.
If you recall they had a long running FDA approved study with the Air Force a while back but ended up closing it down due to recruiting difficulties.
"In June 2013, we announced that the U.S. Air Force was funding a 30 patient, single site, randomized controlled human pilot study of CytoSorb to evaluate patients with severe trauma and rhabdomyolysis. The primary endpoint for this study was myoglobin removal. Though we did not expect to receive material direct funding from this $3.0 million budgeted program, it was hoped that the study would generate valuable data that could be used commercially by us or in our future trauma studies. However, because of the stringency of the inclusion criteria, and because of the patient mix seen at the single clinical trial site, the study experienced difficulty in enrolling patients. In an effort to increase enrollment, in 2015 we amended the applicable study protocol to modify the key inclusion criteria and expand the number of clinical trial sites. Unfortunately, these amendments did not result in increased enrollment. In December 2016, we contacted the Contracting Officer’s representative for the study to discuss potential options and alternatives, including closing the study. Due to the continued difficulty in enrolling patients in this study and likelihood this would continue without significant modification to the protocol, we determined, together with the U.S. Air Force, to close the study."
The “Hospital Universitario Marqués de Valdecillas” receives Cytosorb
Haven't seen or heard much about Spain and Portugal where Palex is the distributor. (http://cytosorbents.com/cytosorbents-and-palex-bring-cytosorb-to-spain-and-portugal/)
Ran across the following use from March:
http://www.palexmedical.com/en/news_item.cfm?id=not_cyto_2018#.WvjoCpdOkuU
"On March 7th, an excellent and complicated surgical intervention was carried out at the Cantabrian hospital, a national reference in cardiac surgery for more than 25 years.
It’s known between the health professionals the possible and serious surgical complications related to the storm of cytokines and the exposure of free hemoglobin, so on March 7th the HUMV’s team of perfusionists, cardiac surgery and anesthesia performed a spectacular Valvular replacement with endocarditis using Cytosorb® adjuvant technology.
The Cytosorb® adsorption technology is designed to help control the systemic inflammatory response and multiorgan failure. In cardiac surgery, it is especially indicated in cases of endocarditis, reoperations, aortic surgery with hypothermia, combined procedures (aortocoronary bypass with graft, repairs or valve replacement, ...) cardiac failure in need of inotropic, renal or hepatic dysfunction, need for LVAD or ECMO and extracorporeal for more than 120 min.
Cytosorb® hemoadsorbers modulate without completely eliminating mediators inflammatory and have a capacity of action of 24 hours, can be easily installed in BCP, ECMO, Hemoperfusion or combined with dialyzers of any platform."
Technology takes the lead in reducing sepsis
Susan Cantrell - Infection Prevention Editor
Healthcare Purchasing News
https://www.hpnonline.com/technology-takes-lead-reducing-sepsis/
This was an article published on Healthcare Purchasing News this month that discusses several diagnostic and treatment options for sepsis. There must not have been a strenuous editing process before publishing it as she only refers to Dr. Chan as 'Chan'.
REFRESH 2 announcement industry sites
It is good to see that in addition to the general press release of the recent first patient enrollment in REFRESH II, that the announcement made it also on an industry-specific web site/publication:
Cardiovascular Business
http://www.cardiovascularbusiness.com/topics/coronary-intervention-surgery/cytosorbents-enrolls-first-patient-pivotal-us-refresh-2-aki
Even though this trial has a long way to go the more the company can do to spread awareness here in the medical community the better it will be when it comes time to approval and commercialization.
The company will owe Bridge Bank a success fee
of 6.37% of $10M = $637K if the price stays above $8.00 for 5 successive business days. The company can opt to pay this in common shares instead of cash. Reference: https://www.sec.gov/Archives/edgar/data/1175151/000114420416111020/v443267_ex10-2.htm.
Paper: Cytosorb use for pneumococcal and meningococcal sepsis (5 cases)
This study was published this past week. .pdf can be downloaded from here: https://www.hindawi.com/journals/cricc/aip/1205613/
Effect of hemoadsorption for cytokine removal in pneumococcal and meningococcal sepsis
Bacterial meningitis and septicemia are invasive bacterial diseases, representing a significant cause of morbidity and mortality worldwide. Both conditions are characterized by an impressive inflammatory response, resulting rapidly to cerebral edema, infarction, hydrocephalus and septic shock with multiple organ failure.
Despite advances in critical care, outcome and prognosis remain critical. Available adjunctive treatments to control the inflammatory response have shown encouraging results in the evolution of patients with sepsis and systemic inflammation, but meningococcal or pneumococcal infection has not been investigated.
We herein report five patients with similar critical pathological conditions, characterized by pneumococcal or meningococcal sepsis and treated with hemoadsorption for cytokine removal. All patients showed a progressive stabilization in hemodynamics along with a rapid and marked reduction of catecholamine dosages, a stabilization in metabolic disorders, and less-than-expect ed loss of extremities. Therapy proved to be safe and well tolerated.
From this first experience, extracorporeal cytokine removal seems to be a valid and safe therapy in the management of meningococcal and pneumococcal diseases and may contribute to the patient stabilization and prevention of severe sequelae. Further studies are required to confirm efficacy in a larger context.
Continuing to bolster cash position
One of the primary reasons the company continues to hold these investor meetings is they are building a solid cash position which will help ensure they hit their value creation milestones these next two years for both the REFRESH and HemoDefend trials. This also enables them to avoid a less-than-optimal partnership deal when that time comes, and should they be strategizing about an exit strategy this will bring a much higher acquisition premium.
I think this is also substantiated from a post today from Ping via Yahoo Finance board:
"The recent PRs: today's, the Bridge Bank, and the Cowen conference seem to indicate they are currently in the process of getting more cash in. I think it will be significant amount. The amount is unknown but I expect it will be known before this quarter ends or the first week of July. This is a pattern based on past history."
Volunteer firefighter loses hands and feet
Another sepsis casualty from this years flu epidemic. This young healthy 19 year old volunteer fire fighter from NY lost both hands and feet from the resulting pneumonia and sepsis.
http://www.fox5ny.com/news/volunteer-firefighter-hospitalized
EY predicts big surge in M&A in 2018
The M&A environment has better potential now than the past several years for medical device companies. As I mentioned in a previous post Cytosorbents I believe is starting to peak at the right time, and it will be interesting to see if the meetings in Geneva that ranchhand surfaced, bring any interesting suitors to the table - at least for a partnership.
3 ways the medical device industry could evolve in 2018
January 8, 2018 By Chris Newmarker
Continued M&A, investment in long-term innovation, transforming business models – those are some of the ways the medical device industry could evolve this year, according to Jeff Greene, EY’s global life sciences transaction advisory services leader.
EY today released its 2017 M&A Firepower Report: Life sciences deals and data, which analyzes three life sciences subsectors: biopharma, biotechnology and medical devices. The report’s biggest overall prediction for 2018 involves a surge in mergers and acquisitions (M&A) by life sciences companies, with the total value of deals once again surpassing $200 billion.
Here’s are the three things that especially stuck out to Greene when it comes to the medical device industry:
1. M&A isn’t going away.
There have been so many huge medical device companies merging in recent years: Medtronic and Covidien, Abbott and St. Jude Medical, Zimmer and Biomet, to name a few. That means there isn’t a lot of fodder left for big deals, according to Greene. But the incentives for medtech M&A are still there, because hospitals are merging, healthcare payment models are changing, and there’s pricing pressure on medical device products.
“We look for continued M&A in the sector, including in the medium-sized space,” Greene said.
2. More investment in long-term R&D
The business-friendly environment – especially in the U.S. (e.g. the new tax laws, the Trump administration’s slashing of regulations and other business-friendly moves) – should give medical device companies more room financially to invest in research and boost innovation over the long-term, Greene said.
“Innovation is going to continue, even accelerate, as companies have more confidence and a positive outlook,” Greene said.
3. Continued evolution toward new business models
The shift, especially in the U.S., toward value-based healthcare means that medical device companies are increasingly seeking out service-based models. Expect that trend to continue in 2018, according to Greene.
Look out for some unexpected partnerships and acquisitions. In the same vein as CVS’s planned acquisition of Aetna or UnitedHealth’s plans to buy DaVita, medical device companies may seek to buy health providers, for example.
“We talk of biopharma companies needing to thing beyond the pill,” Greene said “I think medical device companies have been better at thinking about services beyond their products.”
https://www.medicaldesignandoutsourcing.com/ey-medtech-trends-2018/
I should mention, that
like a few others on the board this was the first time I have heard Dr. Chan mention a private equity investment during a presentation in the context he did, and I am a long time shareholder. It could have been the setting he was in but I believe this could be one of the reasons they have been laser-focused on achieving cash flow break even which makes them also an attractive acquisition target.
PE plus an industry partnership could be in the cards
A management buyout is something I would not want to see as a shareholder nor do I think it is what Dr. Chan was referring to. Under an MBO management can use its control of a company to manipulate the sale process to its own benefit and it's in management's best interest to get the lowest price possible. Plus they would have to come up with the financing. I think if a Growth PE firm gets involved it might be a first step to get the company sufficiently capitalized to finish these US trials (REFRESH and HEMO). They could get a huge chunk of change up front with potentially some large milestone payments in exchange for a minority stake using preferred securities along with some protective provisions and redemption rights upon certain triggering events. There is also the potential partnership from another large healthcare or device company and obviously an acquisition is not off the table. However I believe an acquisition would not come until after Phase 2 results at the earliest. From what I have read FDA clearance has been perceived as the primary milestone to trigger an acquisition for companies in this space.
One thing the company has going for it is that it is peaking at the right time. Operating history and their financial performance has demonstrated they can sustain this growth pattern and with the increasing margins exceeding what you typically see in medical device companies, they are on a great trajectory. This combined with the fact that the M&A activity for medical device companies is heating up again, especially with the recent tax act where billions of dollars are being re-patriated. The tax reform did away with U.S. taxes on corporations’ future foreign earnings – including repatriation of cash. The provision, according to S&P, represents a “permanent reduction in a company’s tax obligation and gives companies greater access to cash from profits generated overseas.” Medical device companies with billions of accumulated foreign earnings in their most recent fiscal year include Johnson & Johnson (NYSE: JNJ) ($66.2 billion), Medtronic ($31.8 billion), Abbott ($24 billion) and Danaher (NYSE: DHR) ($23 billion), S&P reports. JNJ and Medtronic are two of the most aggressive acquires of medical device companies.
I am not an expert in this area and this just speculation and my opinion of course.
Growth Equity 101
What about Summit Partners, JMI or TA Associates? Ever hear about those guys? They’re all growth PE firms.
Growth equity firms invest in quickly growing companies with proven ideas/business models to help support further growth. These firms will not only provide financial capital, but also strategic guidance and operational support, so they can help the company grow and achieve its full potential.
These PE firms will generally make minority equity investments and will let the current management team continue to run the business. The capital injection can be used to scale-up operations, to enhance distribution, to expand geographically, to develop a new product, to finance an acquisition, or anything else.
Growth equity firms differ from VC firms because they target more mature companies. Many, if not most, companies here already generate revenue and are cash flow-positive – but they need additional funding to expand and hire more people.
Growth capital firms differ from buyout firms because they generate their returns by improving and growing businesses, while, as we’ll see very soon, buyout firms emphasize value creation through financial engineering and cost cutting.
Example: A growth equity firm might invest in a $30 million revenue company with $5 million in EBITDA because they see an opportunity to grow it to $60 million in revenue with $15 – $20 million in EBITDA in 3-5 years.
That company would be “too small” for most buyout firms – but “too big” or “too slow-growing” for most VC firms.
Growth equity is a very popular strategy in emerging markets since local businesses don’t always have access to capital from the domestic banking system or capital markets. In addition, the intellectual capital provided by the PE firm is often sought after because it can help companies expand globally and achieve a world-class status.
Growth PE firms
Mother in UK lost three of her limbs
Mother lost three of her limbs after hospital failed to spot she was suffering from sepsis:
https://www.telegraph.co.uk/news/2018/03/11/mother-lost-almost-limbs-hospital-failed-spot-suffering-sepsis/
This is another sad instance of someone whose limbs could have been saved through use of the filter. It appears that it was primarily the hospital's staff's failure to follow protocol. It is also an indication of a lack of awareness of the device - which had a MedTech Innovation Briefing (MIB) published for the treatment of sepsis in 2016, by the National Institute for Health and Care Excellence (NICE) in the United Kingdom (U.K.).
Renewed interest in whole blood transfusions
Interesting that Hemodefend, which had disappeared into the background the last couple of years, has quietly been moving forward and appears as a focal point again for the company in terms of their trial strategy here in the U.S. From what I remember back in 2015 the ABLE trial that was conducted in Canada and Europe did not demonstrate the negative impact on 90-day mortality from aged blood transfusions that they were expecting. However the company continued to build out the prototype for their inline filter for the bag and kept moving this product forward through the R&D cycle and working with the NIH on the SBIR contract behind the scenes.
Saw this blog article the other day which was about the renewed interest in blood centers for 'whole blood transfusions': "Blood centers across the country are seeing a renewed interest in whole blood transfusions. The main fuel to this fire appears to be the recent change from AABB and the forthcoming 31st edition of Standards for Blood Banks and Transfusion Services which allows for the use of low titer group O whole blood in emergent situations for recipients of unknown blood type (AABB News, 2017)."
https://www.bloodbuy.com/blog/2018/2/28/whole-blood-industry-replicated-but-not-duplicated
Back in 2015 when the NIH awarded the company the $1.5M Phase 2 SBIR contract and this was mentioned in the press release and the fact they are fine tuning the beads for various blood transfusion scenarios (emphasis mine):
"This contract follows the successful completion of a $203K Phase I SBIR contract for HemoDefend™ awarded in September 2013, and is designed to bring the HemoDefend™ in-line blood filter to human testing, a required major step towards commercialization. In addition, the contract will also fund development of new polymers that could enable safer whole blood transfusions, a potentially life-saving advance in the treatment of trauma and military combat casualty victims. CytoSorbents will again collaborate with Dr. Larry J. Dumont, MBA, PhD, Director of the Center for Transfusion Medicine Research and Associate Professor of Pathology at the Geisel School of Medicine at Dartmouth.Dr. Dumont stated, “The HemoDefend technology was easy to use and performed well in the Phase I SBIR program, removing a wide range of contaminants from packed red blood cells that are implicated in transfusion reactions and adverse clinical events. We plan to work with CytoSorbents in this Phase II SBIR to further optimize the technology and advance it to the next phases of human testing and potential commercialization.”
Hemodefend, IMO could be the sleeper product and it has a significant revenue potential for the company should they choose to develop it or in most likely out-license it to a prospective partner.
From Zack's report: "According to the World Health Organization (WHO), there are more than 80 million blood donations each year worldwide with each donation generating multiple blood transfusion products such as packed red blood cells (pRBCs), platelets, fresh frozen plasma, and cryoprecipitate. Every year there is an estimated 150 - 200 million transfusions administered worldwide with, according to the American Red Cross, more than 30 million in the U.S. alone. CytoSorbents target market for the technology are pRBCs, platelets, and whole blood, which represent more than half of all blood transfusions annually. HemoDefend can be configured either as an in-line filter design or what the company has termed "Beads in a Bag". About one-half of all transfusions use "packed red blood cells" (pRBC)"
Russian tender was for NMITS
the "National Medical Research Center of Children Health" Russian Federation Ministry of Health located in Moscow (119991, GSP-1, Moscow Lomonosov Prospect). Use: "supply single-use systems CytoSorb for the needs of intensive care unit in accordance with Annex ? 1 "TOR"." Manufacturer origin lists Cytosorbents United States, Italy.
Tender order from Russia
This is the first activity I have seen direct evidence of coming out of Russia - Moscow (1 100 000 rubles - approx $19k). I did not sign up to download the details but to view the page you will need to translate it. It was dated today.
http://rostender.info/region/moskva-gorod/32354927-tender-postavka-sistem-odnokratnogo-primeneniya-cytosorb-dlya-nujd-otdeleniya-reanimacii-i-intensivnoj-terapii
Biocon case report - Viper snake bite
Interesting report on what appears the first case of Cytosorb used for a snake bite resulting in sepsis and multiple organ failure.
A CASE OF VIPER SNAKE BITE PRESENTING WITH GANGRENE AND SEPSIS ASSOCIATED
MULTIORGAN FAILURE, SUCCESSFULLY TREATED WITH CYTOSORB® AS AN ADJUNCT
THERAPY- A CLINICAL EXPERIENCE
February 5, 2018
Viper snake bites are known to cause local complications
like necrosis and cellulitis and systemic complications such
as coagulopathy, acute renal failure (ARF), and haemolysis.
We report a case of 32-year young male patient who was
bitten by a viper. He developed cellulitis, sepsis, acute
renal failure, and disseminated intravascular coagulation
(DIC). Patient also developed acute respiratory distress
syndrome (ARDS) probably due to the direct toxic effect of
venom on pulmonary vascular endothelium. He was treated
with standard care of treatment along with a novel
extracorporeal cytokine adsorption device Cytosorb® as an
adjunct therapy. After Cytosorb® treatment, all his renal,
haematological and respiratory parameters returned to
normal. The post-Cytosorb® APACHE II and SOFA score
was reduced to 11 and 8 from a baseline value of 29 and
15 respectively.
https://jebmh.com/assets/data_pdf/Rajib_Paul_-_FINAL.pdf
"CTSO is in the early innings of a palatable growth story"
Andrew D’silva must have liked what he heard on the Q3 call in November and the follow-up Q4 pre-announcement.
"We feel comfortable with our estimates at this time, as the sequential top line increase we are modeling is relatively modest and is below historical growth trends, despite the fact CTSO recently obtained a dedicated reimbursement code in its largest market of Germany. As such, we believe the Street’s estimates, which are mixed but relatively close to ours, are reasonable as well. We continue to believe CTSO is in the early innings of a palatable growth story and will continue to benefit from: its 15 at the start of ’16); notable strategic partnerships; a dedicated reimbursement procedure code established in Germany; increased interest in new indications such as CAR-T therapy; expanding CytoSorb (CS) distribution footprint." Their last price target I saw was a conservative $11.25.
Fort Worth father now an amputee after flu complications
http://www.wfaa.com/news/local/fort-worth-father-now-an-amputee-after-flu-complications/514719012
The husband and father of two was airlifted to Baylor Hospital in Dallas on January 6 where he has been for the past four weeks, most of that time intubated and in and out of consciousness.
He spoke with WFAA via Skype from his hospital room Sunday and in a voice just above a whisper shared what the last month has been like
"One minute you’ve got the flu and the next minute you’re septic," Herndon said.
Jaye Herndon says her husband had no underlying medical conditions that would make him more susceptible to more than just typical flu symptoms, like high fever and aches.
"He had a 104.7 temperature right away," Herndon said. "And then he had trouble breathing. We didn't wait, we went to the ER. It was that quick."
Effects of the septic shock led to blood clots in his extremities. Earlier this month both of his feet and lower legs were amputated right above the ankle.
His wife, a nurse by profession, says he will likely lose most of his fingers as well.
New on Pubmed: Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins
Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads.
Gruda MC1, Ruggeberg KG1, O'Sullivan P1, Guliashvili T1, Scheirer AR1, Golobish TD1, Capponi VJ1, Chan PP1.
Author information
Abstract
OBJECTIVE:
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.
MEASUREMENTS AND MAIN RESULTS:
Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-a trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent.
CONCLUSIONS:
This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.
Flu epidemic spreading across US
According to the CDC, this is the worst outbreak in their 13 years of tracking influenza. State of Alabama has declared state of emergency this week. In total, the flu has killed 85 adults and 20 children in the United States and last week, the CDC reported that the hospitalization rate for people with the flu DOUBLED. The doctors are running out of medication, ambulance services are strained and even IV bags are in short supply. Influenza is impacting 46 states. 80% of the cases in the US are the deadly H3N2 and as usual this year’s flu vaccination does NOT protect against the H3N2 strain. If this outbreak continues to worsen it would be something to see an emergency use authorization for the device from HHS.
An Effective Treatment Strategy for Cytokine Storm in Severe Influenza
Posted: July 25, 2017
Despite the use of vaccines and antiviral therapies such as oseltamivir, severe influenza kills thousands to tens of thousands of Americans each year. Flu infection often leads to a vigorous immune response and body-wide inflammation, leading to the hallmark symptoms of high fever, cough, headache, muscle and joint pain, and severe fatigue. However, when the inflammation becomes excessive, driven by the overproduction of inflammatory mediators called cytokines, this “cytokine storm” can rapidly kill cells, causing severe tissue damage while precipitating organ dysfunction and failure, particularly of the lungs, kidneys, and circulatory system. It is life-threatening, even for already hospitalized patients. Immunomodulatory therapy has been proposed as a possible way to improve the outcome, with or without antiviral agents.
Anti-inflammatory and immunosuppressive drugs have not been successful in treating cytokine storm and improving survival. Nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, are used commonly to treat mild to moderate inflammation, but have not demonstrated the ability to control cytokine storm. Similarly, corticosteroids have also had mixed results, and their use for treating severe influenza is not recommended due to an increased risk of hospital-acquired infections and death.1-5 Other experimental approaches, such as the use of statins, have shown some success when used with other agents to alter the body’s immune response.1,2
Antioxidants such as N-acetylcysteine can inhibit viral replication, which in turn reduces production of inflammatory mediators.1 Peroxisome proliferator-activated receptors help regulate inflammation, and their agonist agents have been used to combat the inflammatory response.1 There has been evidence that sphingosine-1-phosphate receptor 1 ligands can suppress inflammation resulting from influenza infection.3 However, these treatments remain experimental, and more effective strategies are needed.
A nonpharmacologic treatment for cytokine storm currently used in Europe is based on a novel blood purification technology. CytoSorb therapy from CytoSorbents Corp. (Monmouth Junction, NJ) uses biocompatible, porous polymer beads in a hemoperfusion cartridge to adsorb mid-sized inflammatory mediators such as cytokines and toxins from the blood. Whole blood is repeatedly pumped out of the body and through the sorbent cartridge using standard dialysis machines, with purified blood recirculated back to the patient.
Case study
A 56-year-old man had severe H1N1 influenza and was receiving the antiviral drug oseltamivir. He developed multiple organ failure and septic shock and was treated with vasopressors. The patient had acute respiratory distress syndrome and was on mechanical ventilation. He also developed acute renal failure requiring hemodialysis. The classic antiviral cytokine IFN-? was undetectable, but the patient had true cytokine storm with interleukin-6 levels greater than 8000 pg/mL. Because IFN-? peaks relatively quickly in influenza infection, the patient may have been at the end of active viral infection but suffered from the consequences of cytokine storm.
Despite continued treatment with oseltamivir, vasopressors, and broad-spectrum antibiotics, including piperacillin/tazobactam and erythromycin, the patient did not improve. CytoSorb blood purification was started at 250 mL/min for six hours per day, for a total of seven days. Kidney function improved and dialysis was discontinued one day after CytoSorb treatment. Rapid improvements in hemodynamic stability were also observed, and the patient was weaned off all vasopressors within three days of treatment. The patient’s IL-6 levels were reduced from 8076 pg/mL before treatment to 94 pg/mL after treatment. The patient went on to fully recover.
Conclusion
CytoSorb blood purification technology has been used successfully in a number of conditions in which deadly inflammation can lead to organ injury and failure, and is a promising therapeutic approach to treating critically ill patients. For more information, visit http://cytosorbents.com/products/cyto-sorb/.
Could be the reason for the uptick in volume and price appreciation today.
"CTSO preannounced expected Q4 revenue of ~$4.6M including
product sales of ~$4.2M, implying new records for both. This also
implies product sales growth of 58% on a yoy basis and about 20%
compared to the $3.5M posted in Q3 the previous record high. We
have since made upward adjustments to our Q4 numbers, as well as
to our forecasted product sales in the out-years in our model.
IDE for REFRESH II was approved by FDA in December. The multicenter,
randomized, controlled U.S. study is expected to enroll up to
400 patients which are undergoing elective open heart surgery for
valve replacement or aortic reconstruction with hypothermic cardiac
arrest. As we had hoped, the primary endpoint, reduction of acute
kidney injury (AKI) as measured by KDIGO, is outcomes-based. We
had a chance to sit down with Dr. Chan earlier this week in San
Francisco shortly following his presentation at the Biotech
Showcase. Most of our questions revolved around REFRESH II
given that it currently represents the potential gateway for CytoSorb
to enter the U.S. market. We came away feeling confident in the
robustness of the trial design and, by extension, the potential
commercial appeal of CytoSorb if the trial is successful."
Biocon reorganized CytoSorb into a separate division I believe towards the end of 2016/start of 2017. They are always listed as one of the company's top key partners so hopefully that restructuring is an indication they are putting even more resources behind CytoSorb and they will be seeing the results of that. It seems this may be the case as your contacts are indicating. Thanks for confirming this Psuforlife.
SWACELSO Scientific Forums Jan 2018
There hasn't been a lot of updates on Biocon's progress or other news coming out of India but there is still activity going on.
https://www.swacelso-2018.com/
Workshop on various Extracorporeal therapies & ECMO (which includes CRRT, Cytosorb therapy, Plasmapheresis) – 19 January 2018, From 10 am to 6 pm
Cytosorb for removing critical accumulation of Rivaroxaban
The article below was just posted in this month's Blood Purification Journal. Rivaroxaban, sold under the brand name Xarelto, among others, is an anticoagulant medication (blood thinner), which is taken by mouth. It is commonly used to prevent blood clots. It was initially developed by Bayer. The most serious adverse effect is bleeding, including severe internal bleeding especially in the gastrointestinal tract.There is currently no antidote for rivaroxaban (unlike warfarin, the action of which can be reversed with vitamin K or prothrombin complex concentrate), meaning that serious bleeding may be difficult to manage.
https://www.karger.com/Article/FullText/484923
Extracorporeal Hemoperfusion as a Potential Therapeutic Option for Critical Accumulation of Rivaroxaban
Koertge A.a · Wasserkort R.a · Wild T.a · Mitzner S.a,b
Because of its efficacy, ease of dosing, and safety, the direct oral anticoagulant rivaroxaban is increasingly applied in a number of indications, for example, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation [1] and treatment of deep vein thrombosis and pulmonary embolism [2]. Median therapeutic peak plasma concentrations range from 46 to 270 µg/L, depending on the respective indication [3]. However, there are concerns regarding the accumulation of the drug in patients with impaired renal clearance or in case of overdosing, potentially leading to an increased risk of bleeding [4]. With its high degree of protein binding of 92–95% [3], rivaroxaban is regarded as non-dialyzable, as also suggested by results from a clinical study conducted by Dias et al. [5]. Since protein binding is regarded as not a limiting factor in hemoperfusion [6], the removal of rivaroxaban, as for example by commonly available coated charcoal cartridges, has been deemed possible, but experimental evidence is still lacking [7]. While Andexanet alfa may offer a promising approach to reverse the FXa inhibitor-mediated anticoagulation of rivaroxaban, it has not yet been approved [8]. In case of rivaroxaban-related major bleeding events or emergency interventions with a high bleeding risk, therefore, a fast and effective countermeasure is urgently needed.
Here, we present experimental work to remove rivaroxaban from the blood by means of hemoperfusion using an approved adsorption device (CytoSorb®; CytoSorbents Europe, Germany). Currently, CytoSorb is used mainly in patients with severe infections and sepsis (cytokine storm). We applied a model device containing 60 mL of the adsorbent polyvinylpyrrolidone-coated polystyrene-divinylbenzene copolymer in an in vitro recirculation system to remove high plasma concentrations of rivaroxaban (571 ± 20 µg/L) from citrate-anticoagulated human whole blood (1,000 mL, flow rate 40 mL/min) during 120 min of hemoperfusion (Fig. 1a). Molecules are captured on the internal pore surface of polystyrene-divinylbenzene by nonspecific hydrophobic interactions, whereby solutes with molecular weights equal to and larger than that of albumin, particularly clotting factors, are excluded from adsorption by adjustment of the pore size distribution [9].
Blood pH was monitored during the experiments using an ABL90 FLEX blood gas analyzer (Radiometer, Denmark) and adjusted to a range from 7.35 to 7.45 by administration of Tris buffer. Warming of the blood to 37°C was conducted with an infrared blood warmer (Fluido; The Surgical Company, Germany). Rivaroxaban concentrations were determined photometrically using a chromogenic anti-factor Xa activity assay (BIOPHEN Heparin LRT; HYPHEN BioMed, France) and calibrators with rivaroxaban concentrations of 0, 276, and 497 ng/mL. Analyses were performed by the central laboratory of the University Medicine Rostock.
Within 1 hour of recirculation, 91.6% of the rivaroxaban was removed from the blood, resulting in a plasma concentration of 47.6 µg/L (Fig. 1b). The same recirculation system without a CytoSorb column showed only minor depletion and loss over a test period of 5 h. The final value is above the threshold of 30 µg/L for which direct oral anticoagulant antidote administration in patients requiring emergency interventions is recommended [8]. After 120 min of hemoperfusion, the CytoSorb was saturated as indicated by only minor changes in outlet concentration and the decreased plasma clearance and extraction ratio (Fig. 1c).
Therefore, the application of a second CytoSorb after 60 min could be beneficial for a faster removal of such high accumulated plasma concentrations as applied in the present study. For normal therapeutic concentrations below 300 µg/L, however, we expect the rivaroxaban plasma concentration to be reduced below the critical threshold with a single adsorber in 30–60 min.
Considering the low volume of distribution of the drug and the terminal half-life of 0.62 L/kg and 5–13 h [3], respectively, the present results suggest that CytoSorb hemadsorption columns may offer a suitable means to rapidly reverse the anticoagulant effect of rivaroxaban in vivo. Additional testing is required to verify these findings in in vivo studies.
If they have filed and there were revisions requested (hence the delay), I am wondering if some of the upcoming FDA proposals would have influenced them, if at all. You can't say Scott Gottlieb isn't trying to bring some change to that organization. He had the articles below posted on his blog a week or so ago regarding two upcoming guidance documents coming out early 2018 related to FDA’s medical device review program, which impacts both 501k and PMA pathways.
https://blogs.fda.gov/fdavoice/index.php/2017/12/advancing-policies-to-promote-safe-effective-medtech-innovation/
And this from a few days ago
https://blogs.fda.gov/fdavoice/index.php/2017/12/new-steps-to-facilitate-beneficial-medical-device-innovation/
"We will be updating FDA’s requirements for accepting foreign clinical data used to bring new medical devices to market. While helping to ensure the quality and integrity of clinical trial data and the protection of study participants, this rule should also reduce the burden on industry because it will harmonize with the standards currently used in drug regulation."
Agree, the hiring of Dr. Mortensen and his coming in to replace Dr. Bartlett definitely impacted the company's timeline for the trial design and submission. On the positive side he has some blue chip credentials (global development at Pfizer, Glasko and Merck) and has extensive experience dealing with the FDA on regulatory approvals. So I am glad that he is leading this effort.
I have not been expecting much of a impact in the stock price whenever the news is announced. However, due to how long it has taken and based on the number of questions from analysts over the course of the last couple of quarters concerning REFRESH II, there is a lot of uncertainty around it. It wouldn't surprise me to see some bump in stock price once the news hits and the specifics are then known.
Ping, there is a third possibility.... which is that they just filed it later than you projected. Your premise from a previous post:
"My guess is that their meeting with the FDA and subsequent IDE application filing was sometime between Oct 18 to Nov 8."
But as of the last earnings call on November 9th, they has only met with the FDA and were still in discussions:
"As an update to REFRESH 2, we met with the FDA and are in collaborative discussions with them, designed to drive final IDE application approval. The current trial remains focused on high risk valve replacement patients. And once we finalize our discussions with the FDA, we plan to have an update on the final design in the near future. And pending those FDA discussions, we anticipate the start of REFRESH 2 this quarter."
So it could be a reasonable explanation that these discussions took them deeper into November than you had originally thought, which would mean we would be right around now at the end of the 30-day window.
From reading the last transcript, the analysts peppered Dr. Chan with lots of questions about REFRESH II and the from his comments, it appears the company's challenge with the IDE is designing a trial with a primary endpoint they think will drive adoption in sales and reimbursement while demonstrating clear clinical benefit of the device and the causative effect of the organ dysfunction during or as a result of the surgery.
I guess the positive aspect of the trial design is that they are leveraging the clinical centers and ethics committees from REFRESH I and that they are similar protocols.
Interested to know your thoughts on this and whether you think this could be a possible scenario. Your second scenario (declined submission) I don't see happening but that is just my opinion.
I posted some additional details concerning this back in November. "“FDA has been working closely with DOD to bring freeze-dried plasma to our troops and anticipates that these products will be fully approved for safe and effective use for our armed forces as early as 2018,” an agency official told Politico this week."
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=136059477