【EVA Therapeutics Inc.】Saving Premature Babies with Ig Nobel Prize-Winning "Enteral Ventilation (Enteral Respiration)"! A University-Launched Bio-venture Overcoming the Limits of Neonatal Medicine with a Lung-Independent Respiratory Support

Protecting Babies Whose Lungs Do Not Open. The Dilemma of Existing Ventilators with Side Effects and Limits of Neonatal Medicine

Thank you very much. My name is Hiroshi Ozaki, Representative Director of EVA Therapeutics Inc.

We are a university-launched bio-venture certified by Tokyo Medical and Dental University (now Tokyo Institute of Technology) that is developing the world's first medical device and system called \"Enteral Ventilation (Enteral Respiration)\" to save the lives of newborns (premature babies) whose lungs are not developed. Founded in 2021, the base of this innovation was developed by Professor Takanori Takebe. Last year, he was awarded the Ig Nobel Prize in Physiology for his astonishing invention of administering oxygen-carrying liquid through the anus to let animals breathe (oxygen intake and carbon dioxide discharge) through the intestines.

Currently in Japan, approximately 15,000 newborns annually—about 1% of babies born—face respiratory failure because their lungs are not fully developed or do not open in an incomplete state. Especially in the case of \"extremely low birth weight infants (extremely premature babies)\" who are born with extremely light weight, approximately 50% die, or even if they survive, severe disabilities like cerebral palsy remain, presenting a serious medical issue (unmet medical needs).

Currently, these babies are treated with ventilators that blow air into their lungs. However, the extremely delicate lungs of newborn babies are easily damaged when exposed to the pressure of ventilators or high-concentration oxygen.

Especially, when the carbon dioxide level in the blood rises, trying to lower it by increasing the ventilator output or oxygen concentration too much caused side effects like \"retinopathy of prematurity (risk of blindness)\" and \"serious damage to the brain,\" presenting a dilemma. There was no means in conventional neonatal medicine to safely deliver oxygen to the whole body while protecting the lungs. Our enteral respiration technology overcomes this limit by using the \"intestine\" instead of the lungs to support respiration.

Storing Liquid Oxygen in the Large Intestine via Anus. Verification of Efficacy in Mammals and Safety in Adult Clinical Trial (Phase 1A)

The \"Enteral Ventilation\" system we are developing reproduces the human respiratory physiological mechanism in the intestine.

We use a liquid called \"perfluorodecalin (PFD),\" which is extremely inert. This PFD has a physical property of being able to dissolve an extremely large amount of oxygen. It was originally developed in the United States about 30 years ago as a base for artificial blood, and is a substance whose high safety to the human body has been evaluated.

We bubble this PFD for 5 to 10 minutes using our device introduced in hospitals to saturate it with oxygen. Then, it is injected into the rectum and large intestine of the baby via the anus using a catheter and stored for a certain period.

The mucosa of the rectum is very rich in blood vessels (rectal veins). From the oxygen-rich PFD kept in the intestine, oxygen naturally transfers into the blood through the rectal veins, and at the same time, unnecessary carbon dioxide in the blood is discharged into the PFD. The amount injected is only about 10 cc per kg of body weight, which is about 30 cc for a 3 kg baby. Simply by replacing this once every 4 to 6 hours, we can continue oxygen support for the whole body without damaging the lungs at all.

We have already verified the scientific evidence that administration of this oxygen-containing PFD significantly increases blood oxygen concentration and dramatically reduces carbon dioxide to improve respiration status in small animal experiments (mice/rats) and large animal experiments using pigs with induced respiratory failure. The effect of \"increasing oxygen partial pressure by 5 to 10 mmHg and reducing carbon dioxide partial pressure by several mmHg\" confirmed in pig experiments has sufficient medical effect (clinical significance) to maintain life and avoid side effects for newborns who do not move much and have low oxygen consumption.

Most importantly, this PFD liquid itself is not absorbed by the body at all and is safely discharged from the large intestine as it was put in, showing no transfer into the body. Last year, we completed a safety trial in healthy adult men (Phase 1A clinical trial) and completely proved in human clinical trials that it is extremely safe and does not transfer PFD into the blood at all even when injected from 25 cc up to 1,500 cc into the large intestine.

Value of 1 Million Yen per Course. Global Expansion Roadmap from 100,000 Patient Market in Japan, US, and Europe to ECMO Alternative and Emergency Rescue

Our business model is to package PFD as a medical device as an oxygen carrier, and oxygen-containing formulations as pharmaceuticals, and provide them to medical sites.

The number of newborn respiratory failure patients in major countries in Japan, Europe, and the United States is estimated to be about 100,000 annually. We assume the price per treatment course (1 course) to be around 1 million yen. Considering the value of saving premature babies' lives and preventing severe disabilities like blindness and brain damage, we believe it is an appropriate price setting that is fully worth it medically and economically, including insurance reimbursement. Through this, we target an initial market of about 100 billion yen globally.

Currently, having confirmed the safety in adults, we are actively preparing a pilot study (physician-led clinical study) targeting newborns with Nagoya University Hospital. In parallel, we also plan safety trials of oxygen-containing PFD, and are developing a 250 million yen funding round as Series A to advance these clinical developments.

As a future roadmap, after establishing clinical data for newborns in Japan and the US, we will apply it to temporary respiratory support during adult emergency rescue (999). For example, administering oxygen from the intestine for 1 hour in an ambulance to prevent brain death for patients who cannot breathe due to lung collapse in accidents or disasters.

Furthermore, leveraging the characteristic of delivering oxygen directly to the local area of the intestine, we also eye pipeline development as a therapeutic agent for inflammatory bowel diseases such as ulcerative colitis. In the future, once the practical application of the \"special device that circulates PFD in the intestine\" currently being developed at the university is completed, we can target a huge medical innovation (upside) as an \"ECMO alternative system\" that can manage adult severe respiratory failure for a long period solely by enteral respiration without using massive and high-risk devices like ECMO.

Please support our innovative therapeutic infrastructure to save the future of babies who could not be saved with existing medical technologies, and to save respiratory failure patients worldwide. Thank you very much.

Q&A and Feedback

Commentator (Mr. Fukuda): Thank you, Mr. Ozaki, for the excellent presentation in a rare and severe neonatal field where major pharmaceutical and medical device manufacturers do not easily enter. I understood that the approach of letting them breathe from the intestine without relying on the lungs makes sense physically and anatomically, beyond the topics of the Ig Nobel Prize.

My question is, in this neonatal respiratory failure disease, once treatment is performed and the lungs grow, does the child suffer from recurrence of the same respiratory disease or face aftereffects as they grow up? Or, if they overcome the initial crisis immediately after birth with this enteral ventilation, can they grow healthily after that?

Mr. Ozaki: Thank you for the question. That is a very important point. To put it simply, if they can safely overcome the \"first period\" when the lungs are most immature and fragile with this enteral ventilation, the baby's lungs will develop autonomously as they grow, and they can grow healthily thereafter just like other healthy children.

Many babies' lungs do not open fully at birth, so they inevitably wear ventilators. However, adjustment is very difficult, and side effects like \"retinopathy of prematurity (blindness risk)\" and brain damage due to raising oxygen too much remained as lifelong aftereffects. By \"supporting respiration from the intestine\" with our system during the most delicate period of several days to several weeks, we can promote natural growth without damaging the lungs at all, enabling them to be discharged healthily without aftereffects. Therefore, once they overcome this initial acute phase, it will not recur.

Mr. Fukuda: I see. It is a system to protect and wait for the growth of the lungs without damaging them during the initial delicate period. If lifelong disabilities can be avoided, the price of 1 million yen per course should be evaluated as fully reasonable.

Another point: you mentioned global expansion, but is there any concern that \"individual differences\" in body size and large intestine size between Japanese and Westerners might affect the dosage of PFD and oxygen absorption efficiency?

Mr. Ozaki: Regarding that point, we believe that individual differences between Westerners and Japanese do not have much effect.

This is because, in our system, what acts as the active ingredient (pharmacological effect) is \"oxygen itself.\" The oxygen absorption process is a simple transfer into the veins, and there are no physiological differences due to individual variation. Furthermore, the carrier PFD itself is not absorbed by the body at all. Since it behaves purely as a carrier that is taken out as it was put in, issues of individual variation like metabolism and allergy due to constitution are unlikely to occur.

Therefore, the data and protocols obtained in Japan can be applied almost as they are to clinical developments in the US and Europe, and we are confident that entry into the global market (100,000 patient scale) can be done extremely smoothly.

Mr. Fukuda: I see. Because the carrier is a physical transfer device that is not absorbed, it is easy to develop the same product globally without being affected by race or individual variation.

You also have visions for emergency rescue, ECMO alternative, and large intestinal inflammation treatment in the future. We look forward to your breaking through the physician-led trial at Nagoya University currently in preparation, and moving toward practical application. Thank you.

Mr. Ozaki: Thank you very much for the encouraging feedback. We will do our best to break through the trial and save as many lives as possible.