I am Dr Norman Godin, gastoenterologist and endoscopist in Geneva, Switzerland, who over several years have invented and developed new patented medical devices for endoscopic treatment of heartburn (GERD/GORD) and obesity. I am focusing on Patients who have chronic heartburn, take constant medication (PPIs such as Nexium omeprazole, pantoprazole, etc...,.and consider surgery (Nissen or Toupet operations). But a recent Scandinanvian paper pubished online on September 8th 2023 in Gastroenterology showed that surgery (Nissen) does NOT prorect better from developing a precancerous condition called Barrett's esophagus over time that can lead to the development of adenocarcinoma of the esophagus, the most frequent deadly cancer of the esophagus in the Western World Today. Our new devices (the GARDTM for Gastroesophageal Anti-Reflux Devices) to treat this condition affecting 20-30 million people in the West and the new patented technologies to keep the devices in position in the esophagus. see: www.zinormedical.com. An investment of USD 1 million would help achieve all the necesssary Regulatory Requirements to the First-in-Humans study in the World. The origin of the investments might well determine in what country or continent this study will be carried out.
Executive Summary, BARRETT’S ESOPHAGUS
October 2023
1. Introduction to Biomedix SA
Biomedix SA, Geneva, Switzerland is a medical device company, focusing on developing break-through ideas for the gastroenterology device market. Founded and led by an experienced and respected gastroenterologist, Biomedix SA focuses on envisioning and providing proof- of-concept for new devices, related to the diagnosis, management and treatment of gastro-(o)esophageal reflux (GERD/GORD in British spelling) and particularly Barrett’s esophagitis (metaplasia), Refractory GERD, a frequent condition for which there is presently no good medical (pharmaceuticals) nor surgery as Refractory GERD is defined as a reflux like disease not responding to Proton Pump Inhibitors and many other GERD subgroups.
A. Gastroesophageal Reflux Disease is defined as chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomach and is associated with a hiatus hernia and/or a weak lower esophageal sphincter.
Reflux esophagitis results from strong hydrochloric acid (HCl) secreted by the stomach coming back up into the esophagus. The lining of the stomach is better protected from the HCL it produces than the lining of the esophagus. When acid is in recurrent contact with the lining of the esophagus, particularly when the patient is recumbent (sleeping at night), the esophagus will develop inflammation and ulcers, which are painful and at times can cause narrowing of the esophagus (stenosis that are rare today with the diagnostic and therapy means we have). Often, as we see in daily gastroscopies, there is bile in the stomach that refluxes from the duodenum backwards through the pylorus into the stomach and mixes with gastric HCL and refluxes again in the esophagus. At least in animals and I believe also in humans, reflux of HCL and bile is a risk factor for precancerous lesions (Barrett’s esophagus)
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and adenocarcinoma of the esophagus. So blocking reflux of HCl only or HCl and bile could very well block or at least delay any progress of the first stage of Barrett’s (metaplasia or non-dysplastic) that we want to deal with before the development of low-grade dypsplasia, high-grade dysplasia, non-invasive than invasive cancer of the esophagus.
According to El Serag et al who reviewed 13 epidemiological studies, 18% to 27% of the USA adult population is affected by GERD, implying that the total number of sufferers affected at least 50 million people in the USA alone.1 Prevalence rates found in Western Europe are between 9% and 25%, meaning an additional 30 to 75 miillon people are affected, some as a benign condition but many as a moderate and severe disease.
In addition, most patients seen by the gastroenterologists have already been treated with medication by their general practitioners, in particular with Proton Pump Inhibitors (PPIs). The general information you will find online from MedlinePlus from the US National Library of Medicine is the following: Here is a copy of this information:
Proton pump inhibitors
Proton pump inhibitors (PPIs) are medicines that work by reducing the amount of stomach acid made by glands in the lining of your stomach.
How PPIs Help you
Proton pump inhibitors are used to:
• Relieve symptoms of acid reflux, or gastroesophageal
reflux disease (GERD). This is a condition in which food 3
or liquid moves up from the stomach to the esophagus
(the tube from the mouth to the stomach).
- Treat a duodenal or stomach (gastric) ulcer.
- Treat damage to the lower esophagus caused by acid
- reflux.
- Types of PPIs
- There are many names and brands of PPIs. Most work equally as well. Side effects may vary from drug to drug.
- Dexlansoprazole (Dexilant), Esomeprazole (Nexium), also available over-the-counter (without a prescription) . Lansoprazole (Prevacid), also available over-the-counter (without a prescription)
- Omeprazole (Prilosec), also available over-the-counter (without a prescription)
- Pantoprazole (Protonix)
- Rabeprazole (AcipHex)
- Zegerid (omeprazole with sodium bicarbonate), also
- available over-the-counter (without a prescription)
- Taking Your PPIs
- PPIs are taken by mouth. They are available as tablets or capsules. Commonly, these medicines are taken 30 minutes before the first meal of the day.You can buy some brands of PPIs without a prescription. Talk to your health care provider if you find you have to take these medicines on most days. Some people who have acid reflux may need to take PPIs every day. Others may control symptoms with a PPI every other day.If you have a peptic ulcer, your doctor may prescribe PPIs along with 2 or 3 other medicines for up to 2 weeks. Or your provider may ask you to take these drugs for 8 weeks.
- If your provider prescribes these medicines for you:
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- Take all of your medicines as you are told.
- Try to take them at the same time each day.
- Do not stop taking your medicines without talking with your provider first. Follow up with your provider regularly.
- Plan ahead so that you do not run out of medicine. Make sure you have enough with you when you travel.
- Side Effects
- Side effects from PPIs are rare. You may have a headache, diarrhea, constipation, nausea, or itching. Ask your provider about possible concerns with long-term use, such as infections and bone fractures.
- If you are breastfeeding or pregnant, talk to your provider before taking these medicines.
- Tell your provider if you are also taking other medicines. PPIs may change the way certain medicines work, including some anti-seizure medicines and blood thinners such as warfarin or clopidogrel (Plavix).
- When to Call the Doctor
- Call your provider if:
- You are having side effects from these medicines
- You are having other unusual symptoms
- Your symptoms are not improving
Alternative Names
PPIs
World market of PPIs on Google:
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The global proton pump
inhibitors market is expected to grow from
$3.15 billion in 2022
to $3.30 billion in 2023 at a compound annual growth rate (CAGR) of 4.5%.
The annual market for surgery (Nissen, complete fundoplication
and Toupet, partial fundoplication for GERD are harder to
assess) maybe up to a $ 1 billion a year worlwide.
A.
Long-term treatment of GERD/prevention of Barrett’s
esophagus.
A recent article in Gastroenterology determined that
surgery in the long-term (Nissen anti-reflux
fundoplication) does NOT protect better from the risk of
developing adenocarcinoma of the esophagus than
long-term medication, which one the main purposes for
the Nissen fundoplication. Also, we know from
experience, that even after Nissen fundoplication, a lot
of patients start taking PPIs again. The consequences of
this article is to open up the market to other solutions
for example the GARDTM for GERD Method developed
by Biomedix SA, Geneva/Zinormedical as many patients
do not want to take medications daily for decades and
anti-reflux usually laparoscopic surgery does not
protect better from having some degree of reflux despite
surgery or developing adenocarcinoma of the
esophagus than long term medication. So what
alternative is left? See this landmark publication.
Antireflux surgery versus antireflux medication and risk of esophageal adenocarcinoma in patients with Barrett's esophagus.
Johan Hardvik Åkerström 1 et al. Gastroenterology, September 8th, 2023. So,the Conclution of the paper and
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I quote is: “Conclusion: Patients with Barrett's esophagus who undergo antireflux surgery do not seem to have a lower risk of esophageal adenocarcinoma than those using antireflux medication. So is there an alternative for decades long treatment with PPIs and we are not even addressing the controversial issue of the long-term risk of using PPIs for the patients.
That does the tubular GARDTM do? The tubular GARD TM is a simple silicone (or other plastics) tube, that left food pass from the mouth into the stomach but stops reflux or regurgitation (including vomiting
It is possible that the Tubular GARD that prevents reflux of ACID AND BILE could achieve what anti-reflux surgery does not do as it will block reflux of all gastric content, not only hydrochloric acid content that is blocked or I should the reflux content is much less acid, but bile contents can be blocked by sucralfate but it works much less well than PPIs do for acid. It has been hypothesized that some bile acids at a certain pH with time are carcinogenic, that may very be why Barrett’s esophagus gets worse very slowly or adenocarcinoma of the esophagus Is often discovered at the first EGD (Esogastro-duodenoscopy) In addition to relieving patients from their reflux symptoms, help them lose weight by eating more slowly if the tubes are longer and forcing them to eat more slowly (part of the obesity method called “restriction” and “malabsorption” can occur with longer tuber into the stomach, mimicking a “sleeve gastrectomy” but without cutting. The only issue is the risk or possibility of blocking vomiting or that vomiting is so powerful that the devices might move (and probably fall in the stomach). So if a adult patient is known to vomit occasionally, either the GARD
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should not be placed or a lamellar GARD model can be used that will allow vomiting and might also be sufficient is Hydrochloric acid reflux is not severe at esophageal pH measurement (For example, values of pH reflux between 4% a 9.9% of the time at a pH of less than pH 4 (normal value: less than 4% of the time at pH less than 4.
See a model of pH metric reading.
We decided to focus on chronic reflux and decrease the risk of cancer of the esophagus in reflux as mentioned before and blocking, acid reflux, bile reflux and any stomach mixture with food/drinks that might increase symptoms like coffee among others and maybe increase the risk of precancerous lesions with Barrett’s esophagus with its 3 stages before cancer is developed. As out patients, more than 95% of Barrett’s esophagitis are patients with metaplasia which is the first grade of Barrett’s, before low grade dysplasia and high grade dysplasia that comes right before local development of esophageal adenocarcinoma.In summary, The etiology of esphageal carcinoma
includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. However, for the market, there are many other indications for the GARDTM Refractory GERD (GERD/GORD that does not respond or respond well to PPIs), chronic cough not caused by a pulmonary or a cardiac problem, voice changes or voice loss.
Another very important advantage of the tubular GARD is that it is easy to place a longer tube into the stomach and treat at the same time reflux AND excess weight.
Also the technology that Biomedix SA/zinormedical is developing can be placed for a number of years (starting probably for up to 3 years than longer) and CAN TREAT GERD AND
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OBESITY THAT ARE OFTHEN LINKED.
B.Biomedix SA Focus Areas: Refractory GERD,. Refractory GERD/GORD.
GERD Reflux esophagitis results from strong hydrochloric acid (HCl) secreted by the stomach coming back up into the esophagus. The lining of the stomach is better protected from the HCL it produces than the lining of the esophagus. When acid is in recurrent contact with the lining of the esophagus, particularly when the patient is recumbent (sleeping at night), the esophagus will develop inflammation and ulcers, which are painful and at times can cause narrowing of the esophagus (stenosis).
In adults, heartburn is the major symptom of acid in the esophagus, characterized by a burning discomfort behind the breastbone (sternum). The esophagus is also at risk of developing cancer in a Barrett’s esophagus which is a pre- cancerous condition characterized by a change in the lining (mucosa) of the esophagus (metaplasia, dysplasia) as mentioned before.
Another indication (and there are several) is to treat Refractory GERD with the GARDTM Method.
According to El Serag et al who reviewed 13 epidemiological studies, 18% to 27% of the USA adult population is affected
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by GERD, implying that the total number of sufferers affected at least 50 million people in the USA alone.2 Prevalence rates found in Western Europe are between 9% and 25%, meaning an additional 30 to 75 miillon people are affected, some as a benign condition but many as a moderate and severe disease.
In addition, most patients seen by the gastroenterologists have already been treated with medication by their general practitioners, in particular with Proton Pump Inhibitors (PPIs). They have either not or have only been partially relieved by medication and then we enter in the category called “refractory GERD/GORD) which clearly seen by gastroenterologists/endoscopists in referral centers as classical GERD that has responded to diet and PPIs have been taken care of. Some of the patients have symptoms that recurr after stopping medication or they have atypical symptoms such as chronic cough, chronic sore throat, voice changes, etc...(known as LPR or laryngo-pharyngeal reflux) as well as non-cardiac chest pain are the more common conditions.2
Some of these patients have either no hiatus hernias at endoscopy and no signs of esophagitis demonstrating reflux and additional tests are usually done in specialized centers such as measuring acid reflux in the esophagus (pH metric studies) for 24 to 48 hours or impedance pH metric tests are sometimes performed that can demonstrate the presence of reflux. These tests are not widely available and results are sometimes difficult to read, particularly the impedance tests. It is estimated that up to 30% of patients have atypical symptoms and it is not clear if these patients have reflux or not and if their symptoms are caused by reflux, corresponding up to 10 to 15 million people in the US alone.
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Patients who have typical symptoms and do not respond to medical therapy are considered to have “refractory GERD”. These patients are further divided into those who have abnormal esophageal pH tests and those who do not.
Those refractory patients who have abnormal esophageal pH tests but do not respond to current therapy are a particular problem for gastroenterologists because we do not know what to offer them. Should we recommend surgery? This is a difficult decision to make and most gastroenterologists fear that the patients will be worse off after surgery so they do not know what to offer them as drugs do not work and surgery is usually not recommended for fear of making symptoms worse.
This is the main indication for the DM-GARDTM and Therapeutic GARDTM
In fact, there are essentially 3 stages for implantation.
- Is work up that has to rule out Barrett’s esophagus (a precancerous lesion) or reflux esophagitis among other less common disease.
- The specialized work-up described above: esophageal pH metric studies, etc..
- The placement of a temporary device (the DM- GARDTM) to mitigate the risk of using the Therapeutic device the Th-GARDTM) allowing GI endoscopists to do a trial period (a little bit as if a surgeon could test an operation on a patient before really operating on the patient) which we can achieve with this method and to my knowledge is a first in all the different stenting
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technologies, not only in gastroenterology but also in vascular, coronary, urology and neurology, taking advantage of the accessibility of the esophagus to endoscopy compared to all these other medical specialties.
4. Newer technique among which techniques derived from Apollo’s endosurgery technique but also patented techniques that can be used as well that have nothing to do with Apollo’s endosurgery techniques per se even if the ultimate goal to keep a medical device in a normal esophagus (without stenosis) is said to be non-feasible in humans by combining as mentioned previously different medical devices with new methods, new delivery systems, new fixation systems and the use of some patented classical medications with new methods recently approved by the US patent office (USPTO)
C.Obesity with or without GERD
Bigger (longer Stent for OB) longer tubes.
At present time, the devices are tested in animals in Europe and Biomedix SA, Geneva (and Dr Norman Godin, the founder and CEO of the company) is interested in finding a US partner to progress in Europe and the US pretty much with parallel work.
MARKET: As far as the potential market of the GARDTM for refractory GERD, I will let you figure it out for yourself.
If there are potentially at least 10 million patients in the US with refractory GERD that can be treated with this technique. You can easily figure out the potential market if Biomedix
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SA’s technology is used with let’s say a slightly modified version of the Overstitch sx Endoscopy Suturing System adapted to the Therapeutic GARDTM
A Discount Cash Flow is available.
D. INVESTORS.
BIOMEDIX SA Geneva/Zinormedical is offering a first round 200 shares at CHF 5000- a share for a total of CHF 1 million. This will allow Biomedix to complete in 2024 all the pre- clinical work (toxicology tests, more animal tests, upscale manufacturing of the devices and
do all the Regulatory work to start cliical trials in 2025.
A second round of 200 shares for this time CHF 10’000 each share will be sold to investors for CHF 2 million.
Biomedix will first work on the CE mark and contact US gastroenterology/endoscopy specialist in the US to start larger clinical trials in the US in order to get FDA approval with the US branch
of Biomedix, namely Zinormedical USA.
Contact Details:
Dr. Norman Godin
14, Quai du Seujet 1201,
email:
[email protected] Tel: +41 22 738 1646
Fax: +41 22 738-2071
For your information Norman Godin is a Former Fellow in Gastroenterology at the Mount Sinai Hospital in New York
City, trained at the time by Jerry Waye that most gastroenterologist/endoscopists trained and practicing since the XXth century have heard about or have personally known as he was one of the pioneers of GI endoscopy in New York, the US and the World.
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References
1. El-Serag HB1, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review.
Gut. 2014 Jun;63(6):871-80. doi: 10.1136/gutjnl-2012-304269. Epub 2013 Jul 13.
2. Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors.
Gut. 2012 Sep;61(9):1340-54. doi: 10.1136/gutjnl-2011-301897. Epub 2012 Jun 8. Review
- This section draws from http://en.wikipedia.org/wiki/Obesity
- Kleinman L. et al. Willingness to pay for Complete Symptom Relief of Gastroesophageal Reflux Disease. Arch. Intern. Med. 2002; 162: 1361- 1366
- Proton Pump Inhibitors Accelerate Endothelial Senescence. Circ Res. 2016 Jun 10;118(12):e36-42. doi:
- 10.1161/CIRCRESAHA.116.308807. Epub 2016 May 10.
Yepuri G1, Sukhovershin R1, Nazari-Shafti TZ1, Petrascheck M1, Ghebre YT1, Cooke JP2.
- Patents:
- Patent PCT/EP2012/069487 filed October 2012 entering National phases in Europe: European patent application EP 12766697.2 and USA (Helical spring) patent application: Application No.: 20140249464 (FIND ON GOOGLE PATENT)
- - Patent 6,764,518, Jul 20, 2004 (first ring patent)
- - Patent 5,861,036, Jan 19, 1999 (tubular valve)
- SEE THE NATIONAL LIBRARY OF MEDICINE AT: www.pubmed.gov Where there are about 30’000 references for GERD.