THE PROBLEM YOUR PROJECT SOLVES

COVID-19 is the worst pandemic of our era. Up to 10% of the affected die. The human and economic consequences are devastating, and it is only the beginning.

The World Health Organization declared the coronavirus COVID-19 disease as a pandemic on March 11, 2020. Since then, this number has been increasing worldwide, putting people's lives and the global production system in danger. The contagion capacity of COVID-19 is at least double that of seasonal influenza, allowing it to spread to 185 countries and infect 2.7 million people. Almost 200.000 people died in just a few weeks, although there are health institutions that indicate that the numbers are probably worse because the official computations do not record all the cases.

This has forced most countries to take drastic measures, quickly confining the population and restricting individual liberties. These measures have generated an unprecedented economic impact that some institutions, such as the IMF, have indicated to be only comparable to the Great Depression of 1929. The loss of gross domestic product jobs is devastating, only in the western world and in just a few weeks. Many experts warn that COVID-19 and the following mutations of it will be with us for decades.

Globally, up to 20% of affected people develop serious complications that require hospitalization, and up to 10% die from the disease. The main problem that health systems are facing is that 20% of affected people require hospitalization and a large number of these cases need ventilators in an intensive care unit due to pulmonary complications due to this infection. A large number of patients who require this type of care can overwhelm the healthcare systems.

Unfortunately, current treatments in development are either not effective, toxic, or require a long process of approval and production. They would not even be effective against subsequent mutations.

1) VACCINES. Such as the CureVac vaccine, a German COVID-19 vaccine, which has recently boosted the German company into the limelight. Also, the governments of China and the US are developing their vaccines. The time required for their development and validation is extensive, so if they are effective, they won’t be available for a long time. Vaccines are only effective on non-infected people and, as previously mentioned, with the current version of COVID but not with successive modified (mutated) versions. The cost of production of the vaccines is extremely high, the processes to apply them to all the world population are arduous, and of course, both are time-consuming.

2) CELL ROUTE BLOCKERS. Such as the PharmaMar treatment, a Spanish company that has reported positive results in the preclinical phase when using its compound Plitidepsin (Aplidine) and Chloroquine. These treatments use very common routes to all the cells of the body, so its possible toxic effects used in critically ill patients are yet to be verified. The regulatory path of approval will be presumably long, and may also only be effective for COVID-19, which is allegedly sensitive to this pathway and there is no clinical evidence of efficacy.

3) ANTIRETROVIRALS. There are previous treatments like HIV/AIDS antiretrovirals, that are under investigation with clinical trials in several countries. Another antiretroviral treatment is Remdesivir, but it has reportedly failed in its first randomized clinical trial. The results are still not clear and have a high toxicity profile, a reduced safety profile, a high production complexity which can be a limiting factor of accessibility and, usually, a high economic cost that can jeopardize the sustainability of the Health systems.

THE SOLUTION YOU BRING TO THE TABLE

COVID does not provoke death by itself but its inflammatory effects, especially damaging the lungs. We have found an effective treatment to avoid this lung damage without side effects and with quick wide-scale availability, which is the only solution to save millions of lives and billions of euros worldwide.

The NeuroKinin 1 receptor, or NK1R, is a factor shared by all cells in the body and is especially involved in inflammatory cells. Its activation mechanism normally works in healthy cells, so the receptor is only activated if necessary to repair bodily damage, such as wounds, or in the natural growth process of humans from children to adults. Unfortunately, this natural process does not work well in inflammatory processes like the one induced by COVID. Blocking the receptor prevents the damaging inflammatory process caused by COVID and restores cells to their normal balance.

We have found that this catastrophic process could be interrupted by directly blocking the receptors (NK1R) with an antagonist. This stops the development of the inflammation process and more specifically the inflammatory "storm" induced by the COVID virus, restoring cells and organs to their normal balance (homeostasis). The good news is that this mechanism only affects inflamed cells, not healthy ones.

The canonical clinical development of a drug can take 5 years. In our case, thanks to the fact that it is an already approved drug that we repositioned for this indication, the exceptional situation due to the COVID alert and thanks to having solid proof of concept, we can follow an accelerated approval procedure that allows us to reduce it to 4 months.

We have developed a product called PVT-COVID for COVID patients. PVT-COVID is based on an existing drug, Aprepitant, an NK1R antagonist. It has proven effective in several papers and in our recent investigations with in-vivo models in preventing severe damage after lung injury. This damage is produced by COVID-19 and any virus of the COVID family. So, PVT-COVID could potentially prevent the deaths caused by lung injury due to COVID.

THE BENEFITS OF OUR PROPOSAL ARE:

1. PVT-COVID prevents severe lung and other vital organ damage, such as the one caused by COVID in almost 20% of the infected population. That is the main cause of these patients requiring hospital care including assistance in intensive care units with assisted ventilation. If severe lung damage can be avoided, the illness presents mild symptoms that do not threaten the patient's life, allowing them to fully return to their productive lives.

2. PVT-COVID is not specifically and exclusively useful in the prevention of severe lung damage caused by COVID-19 in its current version, but rather, its mechanism of action is nonspecific, avoiding this potential damage caused by any virus of the COVID family, both in its current version and in successive versions. In other words, even though one of the lines of action that is being developed is the manufacturing of a vaccine against COVID-19, they will be of little use given that the development deadlines of this vaccine will come when most of the world population will have already been infected. Furthermore, these vaccines will not be effective against future new versions of COVID, while PVT-COVID will be effective and useful for this and for subsequent versions of COVID.

3. The PVT-COVID drug already exists, which saves time in its development, it is easy and cheap to produce, it is safe since it is already known and has been used in clinics for years. For this reason we can have the necessary amount of the drug to potentially treat millions of people around the world and eventually save thousands of lives while saving millions of productive hours in a short time and at a sustainable cost to health systems. Treatment with AntiNK1R protects the vital organs, such as the lungs, against injury by reducing the inflammatory storm provoked in diseases, as produced by COVID-19. PlusVitech has evidence of the lung injury effects at the macroscopic, microscopic, and biochemical levels that can be avoided by AntiNK1R.

Moreover, Vanda Pharmaceuticals is running a Phase 3 clinical trial in collaboration with Northwell Health to use NK1 receptor antagonists, given their proven anti-inflammatory effects to treat lung disease responsible for deaths caused by COVID-19. The double-blind trial has been directly approved in phase 3 by the FDA in 300 patients with pneumonia caused by COVID-19 and a time horizon of only 14 days to verify its effectiveness (https://www.bioworld.com/articles/434461-vanda-kicks-off-phase-iii-trial-of-tradipitant-in-covid-19). Vanda Pharmaceuticals Inc. is a Washington-based pharmaceutical company listed on NASDAQ (VNDA) which has achieved a growth of + 53.60% in its price, increasing its capitalization by more than 331 million dollars, thanks to this research in the last month. Northwell Health is the largest healthcare company in New York State, the current epicenter of the worldwide pandemic. The trial hospital is the prestigious Lenox Hill Hospital in New York City. The drug used in the study is an NK1 receptor antagonist called Tradipitant. Tradipitant is a neurokinin-1 receptor antagonist licensed by Eli and Lilly Company to Vanda. It is currently under clinical development for gastroparesis, motion sickness, and atopic dermatitis. The clinical trial started on April 13, 2020, and is described in the following link: https://clinicaltrials.gov/ct2/show/NCT04326426. With expected results on August 1, 2020. This drug is still in the development phase and has not been approved for use in humans and, therefore, its availability is very limited. Also, in the event of approval, its production and distribution on a large scale would require several months, which has been recognized by the CEO of Vanda recently in a video interview for Yahoo Finance (https://finance.yahoo.com/video/vanda-pharmaceuticals-ceo-reacts-fda-211405570.html). Therefore, PVT-COVID is superior due to its higher safety profile and its current approval for humans. Also, it could be immediately accessible since it is available in a hospital pharmacy.

WHAT YOU HAVE DONE DURING THE WEEKEND

• Developed the business model and a complementary business model.
• Calculated the economic forecast.
• Improved the roadmap, especially clinical trial.
• Scanned and proposed some hospitals as candidates for conducting the phase II clinical trial in Spain, Italy, and the UK.
• Contacted with some national and regional authorities and international investors.
• Improved the pitch deck.
• Pivoted several times the business model.
• Make the presentation and the video pitch.
• Sent suggestions to the CRO about the draft clinical trial protocol.

THE SOLUTION'S IMPACT ON THE CRISIS

The COVID pandemic is having catastrophic consequences in Europe and other territories with a high cost in human lives, for health systems, and for the welfare system. Our plan includes the following actions:

1 APPROVAL OF USE FOR OUR DRUG IN EUROPE: Obtain the approval for COVID indication from the European Medicines Agency (EMA) developing a clinical trial conducted by PlusVitech.

2 LICENSING TO PHARMAs FOR QUICK DISTRIBUTION IN THE WORLD: Licensing to pharma companies that already manufacture Aprepitant or other drugs in order to accelerate the global distribution to hospitals. We will offer a license (without exclusivity) to all these pharmas to maximize the number of doses immediately available at the best price. We will also authorize these companies to perform clinical trials or direct approvals based on ours in the rest of the countries with an obligation to share the results of the tests to make the information available to everyone. We have the support of the law firm JA Kemp to help us in the process of licensing. Moreover, our in-house pharma advisor and JA Kemp (London) have a large experience in both in-licensing and out-licensing processes.

3 DIVULGATION: Communicating the clinical trial results and clinical practice protocols with the authorized drug providers (past step) to the international press, high impact journals, and national health authorities worldwide (or regional authorities if the powers are delegated).

OUR OBJECTIVES ARE:

1. Equity: Providing an effective treatment that prevents the lethal effects of COVID resulting in hospital admissions and deaths. It is also a safe drug, with a sustainable cost and immediately available to all people.

2. Accessibility: Creating a network of synergies and enhancing effect with and among pharmaceutical companies to guarantee rapid access of our drug to all countries, so that a balanced economic return is guaranteed for participating companies and that the drug be accessible to all patients worldwide, in any context of financial resources.

3. Universalization of knowledge: Creating a tool that allows the entire medical community in the world to evaluate the information generated in clinical studies that are carried out with our drug as an easy and useful tool in decision-making in the care of patients with COVID.

We are preparing open-labeled randomized controlled pragmatic clinical trials to evaluate the effectiveness of PVT-COVID in adult patients with SARS-CoV-2 (COVID-19) infection. We will conduct a clinical trial Phase II-III called “I WILL RESIST” with the MSD's original Aprepitant Emend drug, available worldwide. Alternative sites for a clinical trial: A) Spain: Hospital Virgen del Rocio (Sevilla), Hospital de la Princesa, Hospital Clínico San Carlos y Hospital La Paz (Madrid); B) United Kingdom: Nightingale Hospital London, Nightingale Hospital Birmingham and C) Italy: OGR Hospital Torino and Policlinico of Milan.

The normal process of a regulatory process is up to 10 years. In the case of repositioned drugs, it can be reduced to 1 year. In the exceptional circumstances of alert-COVID, we can reduce this period to a few months. Our business model is based on the licensing strategy for big pharmaceutical companies in exchange for a percentage of sales. In this way, we ensure instantaneous mass production and global distribution capacity, since they are companies that have great capacity and distribution channels in all countries of the world. We understand that this strategy is the best possible one given the global emergency situation due to the COVID pandemic, which we have never experienced before. So, we will offer the use license for COVID to pharma companies who currently produce and sell:

• Aprepitant based drugs: MSD, Glenmark pharmaceuticals, Sandoz.
• Other NK1R blocking based drugs: Maropitant -Pfizer-, Casopitant -GlaxoSmithKline-, Vestipitant -GlaxoSmithKline-, Netupitant -Roche / Helsinn, Lanepitant -Lilly-, Rolapitant -ScheringPlough-.

Licensing is an official permission or permits to do, use, or own something. A licensor may grant a license under intellectual property laws to authorize a use (such as a patented invention) to a licensee, sparing the licensee from a claim of infringement brought by the licensor. Intellectual property licensing plays a major role in business. Business practices such as franchising, technology transfer, publication, and character merchandising entirely depend on the licensing of intellectual property. The advantage of licensing is that the firm does not have to bear the development and risks associated with opening a foreign market. The payment method for licensing is usually agreed by an upfront payment, followed by payment for agreed milestones and payment of royalties on benefits. The global prescription drug market is growing at 6.5 percent annually and is expected to reach $ 1.06 billion by 2022. To take advantage of this market opportunity, major biopharmaceutical companies are creating their own venture capital funds and partnering with new companies or technology licenses to feed their own medicine pipelines. For instance, Takeda Pharmaceutical Company Limited was purchased by Spanish-born company TiGenix (2018) – € 0.52 billion.

Ir order to guarantee compliance with the objectives set out above, PlusVitech will establish the following licensing terms:

• Non-exclusivity (open to all pharmas that can manufacture our drug).
• Obligation of approval in the licensed territories.
• Limitation on sale price.
• Accessibility to all people in any economic resource setting.
• Allowal of a fair profit margin for licensed pharmaceutical companies without passing the cost to the patients.
• The right to access the clinical data they generate related to the studies they perform on COVID patients.
• The right to feed this data into our COVID patient care support tool that will be available to all physicians worldwide.

The team and advisors include:

• Management team with experience in international projects.
• Scientific and medical team with experience in hospital clinical assistance and participation in Clinical Trials.
• Team with extensive experience in international logistics.
• Advisory board with senior experts.

This project is protected by industrial property rights by means of a worldwide patent application that protects the use of any NK1 receptor blocker for COVID.

• Application number: EP20382221.8.
• Priority Date: 23 March 2020.
• Patent Attorney: J A Kemp (London).

As support for the realization of the project we have our partners:

• J A Kemp (London), one of the leading patent attorneys offices in the biotechnology sector, which manages the patent portfolio.
• Andalusian Public Health System to carry out the necessary clinical trials.
• Andalusian Network of Biobanks to obtain the samples.
• Andalusian Health Foundation for support in the management of necessary procedures for clinical trials.
• Trusted manufacturer with the capacity to manufacture the necessary quantities of the drug with quality assurance according to the EU GMP standards.
• CROs: Premier Research (Worldwide), Delos Clinical (Spain), Econix (Turkey), Cliantha Research Limited (CRO- India), CNS Clinical Network Services Pty Ltd (CRO- Australia) for the monitoring of clinical trials.
• Asphalion, consultant for the monitoring of regulatory RoadMap and advice on procedures for approval in EMEA. IMIM, Hospital del Mar Institute for Medical Research.
• University of Salamanca, Institute of Biomedical Research of Salamanca, access to laboratories, and qualified personnel for trials.

THE NECESSITIES IN ORDER TO CONTINUE THE PROJECT

We are starting a clinical trial as soon as possible whenever we get the required funding. For this, we would like to have contacts with hospitals and also funding for the clinical trial. The cheapest version of the clinical trial (Phase II) is €555K in one hospital in one country (Spain) with 100 COVID patients. We have already sent the draft protocol to the Spanish Agency of Medicines and Medical Products.

We have opened an investment round to fund the clinical trial. We have already raised €200K in this recently opened investment round, and totally €1,4M since the creation of the company.

We offer our investors a clear exit strategy (buyback by founders or selling the company). We estimate an investment ROI for investors of more than 10x in 3 years, and more than 30x in 4 years, based on 2x net profit estimation and average deals pharma/biomed/biotech industry according to McKinsey (over 300M€).

THE VALUE OF OUR SOLUTION(S) AFTER THE CRISIS

COVID-19 is the worst pandemic of our era. Up to 10% of the affected die. The human and economic consequences are devastating, the number of people infected has been increasing worldwide, and there is an alert of new successive waves of the virus putting people's lives and the global production system in danger. The biotechnological solutions that are being proposed are toxic, expensive, potentially ineffective, and/or scarcely scalable and applicable to the world population.

We propose an effective, economically sustainable, easily scalable, and universally applicable solution that takes advantage of a drug that already exists with proven efficacy in the treatment and prevention of damage caused by COVID. Our solution creates an ecosystem through balanced licenses to large pharms with massive production and worldwide distribution capacities to reach the entire global population as soon as possible.

Our solution represents a global solution to the COVID pandemic and scrupulously respects the principles of equity, universality, and quality by creating a network for the global use of individual experiences and information in a sustainable model over time.

• Pitch deck/Elevator pitch: Attached to this DevPost project (we have already sent to international investors)
• Website of the project: https://www.plusvitech.com/covid-19?lang=en
• Reviewed clinical trial protocol: Confidential (but it exists)