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ET-traps Limited Novel therapeutics

Key Considerations

ET-traps Limited is a biotechnology company targeting diabetes, as well as other diseases.

This is a platform therapeutic that will be used for the treatment of diabetes. The platform will be adapted to treat other diseases creating multiple distinct income streams.

This is considered by the world leading experts in the field of endothelin-1 as one of the most exciting technologies currently in development and has already won a number of prestigious awards.

This patented technology comes from extensive pre-clinical work conducted by teams at Cambridge University (UK), Oxford and Canada.

The technology was awarded the first prize as the most promising idea for developing a novel therapeutic at the Biotech startup Cambridge, UK. We are the world's first to have created a soluble form of a GPCR in terms of its ligand binding ability (in this case the ligand being endothelin-1). This is successfully recognised as a major breakthrough for medicine as GPCRs are very important drug targets.

ET-traps Limited is aiming to become a potential therapeutic for Diabetes.

The Science

ET- traps are antibody – based fusion proteins, which potently bind and can sequester increased levels of ET-1 that are prevalent in diseases like diabetes.

ET-traps merely sequester pathologically elevated endothelin-1 back to (or as close to) physiological levels – no associated side-effects / toxicology

ET-traps is an Fc-fusion protein (FFP) and so has a longer serum half life. Furthermore, ET-traps have a very high binding affinity to endothelin-1 (almost 1000 fold higher than currently used ERAs). This leads to improved patient dosing (less medicine producing efficacious, therapeutic effect)

FFPs can be modulated more easily so that the therapy doesn’t elicit any negative immune reaction

Other therapies in development are mainly antagonists that COMPLETELY block/ inhibit actions of endothelin-1, which are critical for normal, physiological functions

Other therapies have a lower binding affinity leading to higher patient dosing

ET antagonists are associated with side effects. On the other hand, our ET-traps require a smaller dosage (both the amount and frequency is less); they have a much higher binding affinity and are not at all toxic for use. As mentioned before, with our technology of ET-traps, we are not completely blocking the function/activity of endothelin-1 and so, our technology is not associated with any side effects/ toxicity.

ET-traps Limited Intellectual Property portfolio comprises of patent covering formulation of ET-traps. The Company's filing strategy has preserved substantial scope for further broadening of method claims to encompass other therapeutic uses and extend patent life.

ET-traps is a potential therapeutic tool in treating diabetes that ameliorates pathological markers to the normal levels.

Investment Highlights

• The first ET-traps Limited product developed for diabetes (ET-traps) is proven in animals and would be progressing to human trials.

• Excellent portfolio patent protection.

• Significant growth opportunities in global markets.

• Multiple income streams by adapting the platform technology to treat other diseases, including cardiovascular diseases and neurodegenerative disorders.

• The science being used is proven; thereby de-risked and adapted from existing technology with independent confirmation completed.

• Already received academic and industrial awards including winner of the Biotech startup award at the Judge Business School of the University of Cambridge, in association with Astra Zeneca.

• Base case: Targeting enterprise value by year 7 of $7.2bn.

Proprietary technology with unique curative potential.

The market size, in 2019, for the global diabetes drugs market was registered to be USD 76.5 billion, and the market is expected to record a CAGR of 5.65% during the forecast period, 2019-2024.

• As per a WHO report, the global prevalence of diabetes among adults of over 18 years had accelerated from about 4.7%, in 1980, to over 8.5%, in 2014.

• Diabetes prevalence has been rising rapidly in the middle- and low-income countries. In 2015, about 1.6 million deaths were directly associated with diabetes, which was around 2.2 million in 2012.

• Almost half of all deaths attributable to high blood glucose occur before the age of 70 years. WHO projects that diabetes is likely to be the seventh leading cause of death by 2030.

• Statistics prove that one in ten individuals in the world has diabetes and a rise in this trend is expected to take the situation to one in three by 2050 (according to the Center for Disease Control and Prevention).

• The growing prevalence of diabetes is the major driver for the global diabetes care drugs market. Additionally, rising awareness regarding diabetes care, growing prevalence of obesity, and technological advancements are further driving the market.

The market size, in 2019, for the global diabetes drugs market was registered to be USD 76.5 billion, and the market is expected to record a CAGR of 5.65% during the forecast period, 2019-2024.

The Competitive Advantages

• The advantage of ET-traps over ET antagonists is that we are not completely blocking the actions of ET-1, which of course are essential to normal physiology. With the ET-traps, we are merely (potently) binding and sequestering pathologically elevated levels of ET-1, without completely blocking ET-1 function.

The binding affinity of our ET-traps is in the pico molar range, which is nearly 1000-fold higher than ERAs (that are currently in clinical use). Furthermore, the dissociation of our ET-traps once bound to ET-1 is very slow. This would aid the agenda of binding (excess) ET-1 and excreting it out of the body.

We did not detect any toxicology with the ET-traps in our in vitro and in vivo work done in the diabetes disease space. Please note, lowering the dosage of the antagonist (inhibitor drug) or the number of days administered per week, might help mitigate the side effects but a lower dose of the inhibitor drug may mean lower efficacy and therefore less symptom relief.

• Fc-fusion proteins (FFPs), which are our ET-traps, are also beneficial over the more common 'therapeutic antibodies' for different reasons. FFPs have a longer serum half-life. Therefore, FFPs persist longer to bind their targets and have their therapeutic effects. This means (and importantly so) that patient dosing is reduced and patients need to take the therapy less often. Furthermore, FFPs can be modulated more easily so that the therapy does not elicit any negative immune reaction. In fact, the study by Ying et al. (2012) describes how a Fc-fusion (as are the ET-traps) is not immunogenic. This is again very important when developing a therapeutic. The study by Chames et al. (2009) discusses further the limitations of therapeutic antibodies.

Finally, a simple economic/financial comparison states how the TNF -alpha FFP has roughly 7.6 billion dollars per year sales - close to a billion higher than the most successful therapeutic antibodies. These figures truly give the value of Fc-based therapeutics.

The ET-traps of course are FFPs and given the positive in vitro and in vivo studies, may provide a successful alternative to antibodies and a potential therapy for diabetes (and possibly beyond).

• A treatment that is scalable to meet the global market demand. Off-the-shelf, bulk production suitable for storage and for global distribution.

• The proven technology should enable accelerated approval of other disease treatments, such as cardiovascular and neurodegenerative diseases.

A uniquely qualified organisation with an experienced management team.

The Team

Dr Arjun Jain is the Managing Director and Chief Scientific Officer, ET-traps Limited, UK. He has a PhD in Reproductive Biochemistry from the University of Cambridge and has completed a Marie Curie Postdoctoral Research Fellowship at the TransCure research Institute in Bern, Switzerland. Based on his research, he has designed the therapeutic tool that this project is based on. He has done some ground breaking research in the field of endothelin-1 and is the first in the world to have created a soluble form of a G-protein coupled receptor (GPCR) in terms of its ligand binding ability. In this case, for endothelin-1, which has been termed ET-traps. For this, a patent has been filed.

Ira Jansen

Ashok Jain

Vidhi Mehrotra

Nicole Johnson

Daniel Schneider

Use and application of funding

The company is looking for investment for £7.5m to complete advanced pre-clinicals, regulatory and Phase I clinical trials.

The use and application of funds are as follows:-

• Pre-clinical and Phase I clinical testing - £4.5m

• Patent related expenses - £0.5m

• Contingency (incl. regulatory, general & administration) - £2.5m

We welcome interest from potential investors. Please contact us by email in the first instance.

A novel treatment for Diabetes with platform expansion opportunities.

Legal disclaimer: The ET-traps technology and the drugs that may be derived from it have not received any approval as yet by regulatory authorities.

©2019 ET-traps Limited All rights reserved.

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