Implantica’s Solution to Acid Reflux, RefluxStop^®

RefluxStop^® treats acid reflux without affecting the food passageway, an innovative method that will possibly create a paradigm shift in acid reflux treatment. This ingenious device is a non-active implant and is placed on the upper part of the stomach through laparoscopic (key hole) surgery. CE mark approval was granted August 8, 2018, on the strength of a multi-center clinical investigation in which the safety, effectiveness, and performance of the device in patients was demonstrated.

RefluxStop^® restores the body’s natural anatomy and physiology, treating acid reflux without encircling the food passageway.

Acid reflux is the second largest treatment field in the world, with over 1 billion sufferers globally¹. RefluxStop^® treats the symptoms of acid reflux by eliminating the regurgitation of stomach fluid.

1. 1. Nirwan, J.S., Hasan, S.S., Babar, ZUD. et al. Global Prevalence and Risk Factors of Gastro-oesophageal Reflux Disease (GORD): Systematic Review with Meta-analysis. Sci Rep 10, 5814 (2020). https://doi.org/10.1038/s41598-020-62795-1

Acid reflux sufferers consumed drugs for USD 24 billion in 2010². We expect that the surgical treatment addressable market to grow substantially to reach a couple of million operations yearly³, and the clinical trial results support that RefluxStop^® has the potential to completely change the treatment of acid reflux.

We expect the addressable market to reach 2.4 million operations yearly³.

1. 1. Stuart 2005
2. 2. AstraZeneca 2010
3. 3. The Karolinska Institute Review Article, not yet published

RefluxStop^® Design Thesis

• RefluxStop^® device hinders the reflux process – which occurs due to anatomical misalignment associated with suboptimal belch-like fundus contractions also including fluid, in combination with relaxation of the sphincter.
• RefluxStop^® device also acts as a mechanical stop, preventing the LES from moving into the thorax. Due to the pressure in the abdomen, the lower esophageal sphincter (LES) thereby can function normally.

The device works with a proven concept to prevent the closing sphincter from gliding up into the thorax through the opening in the diaphragm breathing muscle. When this happens, the sphincter muscle enters the chest, and while breathing, it does not have enough power to close.

As per the design thesis’ double mechanism, RefluxStop^® device is intended to treat acid reflux without affecting the food passageway, including hindering the LES from entering the thorax.

RefluxStop^® surgical procedure named the Forsell procedure after the inventor involves a reconstruction of the angle of His, a small left side adherence of the stomach to the esophagus, in broader terms also a fundoplication. RefluxStop^® device is invaginated in the fundus wall and thus reinforces the created cuff.

RefluxStop^® Operating Technique

Sutures

With RefluxStop^® device enclosed in the fundoplication cuff it becomes thicker/deeper, allowing the cuff to be created with less circumferential distribution, thereby reducing side effects related to the food passageway and at the same time treating GERD more efficiently.

Placing RefluxStop^® at fundus

Removal of tool

Finalized procedure

RefluxStop^® Clinical Investigation

RefluxStop^® obtained CE mark certification on August 8, 2018. The approval enables Implantica to market and sell RefluxStop^® in member countries of the European Economic Area and Switzerland. Implantica, under confidentiality, informs about the clinical investigation month 6 results and the intended use of RefluxStop^®.

24-hour pH monitoring showed a 95% improvement after RefluxStop^® surgery, with the percentage of overall time with pH less than 4 substantially reduced to 0.8% at month 6, an excellent result. As soon as the results are published, they will be disclosed in more detail.

Using a validated questionnaire, GERD symptoms in total GERD-HRQL score were assessed before and 6 months after RefluxStop^® surgery.

Results at month 6-8 showed an average improvement of 91% in the total GERD-HRQL score with 97.9% having > 50% improvement (p-value<0.001). The total score dropped to 2.6 at month 6-8. One patient experienced less improvement because the device was placed too low at surgery.

No safety concerns were associated with the RefluxStop^® device at month 6. There were no deaths, no device deficiencies, device related complications (no ADEs, no SADEs), no device explantations and no complications (AEs) leading to withdrawal.

In comparison to a literature review and meta-analysis on Nissen fundoplication performed by the Karolinska Institute (978 articles reviewed – 50 randomised articles selected), the results of the RefluxStop^® clinical investigation show (95% confidence intervals):

• Heartburn: 60% symptom reduction
• Dysphagia: 70% symptom reduction
• Odynophagia: 100% symptom reduction

At month 6 after surgery all patients with evaluable data stopped taking PPIs.⁴ As soon as the results are published, they will be disclosed in more detail.

1. 4. 1 patient was abroad at the 6 months data collection – presenting successful 1 year results
   1 patient is no longer contactable – presented successful 3 months results
   1 patient did not undergo the planned examinations and additional esophageal manometry showed motility disorder (EMD)

Acid reflux complications, progression, and cancer risk

Acid reflux creates precancerous changes in the lower esophagus, called Barrett’s esophagus, by iterative damage caused by stomach fluid found in 10-15% of acid reflux patients⁴. For daily sufferers the incidence is even higher probably at 20%⁵. The most common treatment method, drug therapy, does not prevent acid reflux but only reduces the acidity in the regurgitating stomach fluid, and the majority of patients continue to experience heartburn now and then. 59% of drug users continue to intermittently have acid reflux⁶ and only 1 out of 9 become completely symptom free.⁶

The current standard of care surgical treatments of acid reflux often lead to complications, such as swallowing problems, because they encircle the food passageway. RefluxStop^® has a unique mechanism of action and does not encircle the food passageway thereby reducing complications, as supported by the clinical investigation.

Acid Reflux is a progressive disease and if left untreated, can lead to serious health consequences, including for some, esophageal cancer.

The stages of progression of untreated GERD:

Disclaimer: There is no clinical data showing that RefluxStop^® can lower a patient’s risk of developing cancer.

1. 5. Semin Gastrointest Dis. 2003 Jul;14(3):128-35, Barrett’s esophagus and risk of esophageal adenocarcinoma, Cossentino MJ1, Wong RK
2. 6. Moreira Faulhaber & Weber Furlanetto, Arch Intern Med. 2010
3. 7. Raghunath AS, Hungin AP, Mason J, Jackson W 2009
4. 8. Hvid-Jensen F, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. New England Journal of Medicine. 2011;365(15):1375–1383. [PubMed

Benefits of RefluxStop^®

Treats GERD without encircling food passageway

RefluxStop^® successfully treats acid reflux by restoring and maintaining the body’s natural anatomy without encircling the food passageway, thereby minimizing common side effects commonly associated with standard of care acid reflux surgical procedures.

Successful 4-year clinical trial results:

• 95% of patients did not need to take daily PPI medication

• 95.5% (42/44) of subjects had no or minimal/occasional episodes of regurgitation, and all (100%) subjects experienced improvement in regurgitation compared to baseline

• GERD-HRQL score decreased by 90% from a baseline of 29.5 (24–33) to 3.0 (0–9.2) at 4-year follow-up

• 95.5% (42/44) of patients were satisfied at 4 years

• 93% of patients had resolution or improvement in gas-bloating

Safety issues during the clinical trial

• No complications related to the RefluxStop^® device during the entire study period
• No device deficiencies
• No deaths related to RefluxStop^® and its procedure
• No device explantations
• No migration/erosion
• No esophageal dilatation required

Field Description

Acid reflux or gastroesophageal reflux disease (GERD) is the term describing a condition in which liquid, acid content of the stomach, regurgitates (or refluxes) up to the esophagus, the tube connecting the stomach with the throat. The condition is common and almost everyone experiences this from time to time. Acid reflux affects people of all ages and backgrounds. The condition turns into the chronic disease gastroesophageal reflux disease, commonly referred to as GERD, when the frequency of acid reflux is abnormal.

GERD is one of the most highly prevalent diseases in the world with 31% of people suffering on a weekly basis⁹ and around 400 million with daily problems¹⁰. GERD has a considerable financial impact on society¹¹.

The most common symptom of GERD is heartburn, a burning pain from behind the sternum, the breastbone. Other symptoms in more advanced cases are chest pain, difficulty swallowing, pain when swallowing, coughing, wheezing and/or vomiting. Sleeping disorder often becomes part of these patients’ everyday life as lying down increases the risk of acids entering the esophagus. For all GERD patients, their quality of life is severely affected.

1. 9. Zebrowski & fox-tucker, 2006
2. 10. Stuart 2005
3. 11. Brook et al., 2007; El-Serag, 2007