VDP-91: TelomEYE

[Rhys]

One-liner: TelomEYE is an early-stage pre-clinical startup developing an eye drop formulation to maintain/lengthen telomeres with a view to delaying presbyopia, dry eye syndrome and other age related conditions of the eye.

Longevity Dealflow WG team

Shepherd: Rhys Anderson

Other squad members: Paolo Binetti

Simple Summary

TelomEYE have developed an eye-drop formulation to extend the length of telomeres with a view to targeting several age-related ophthalmic conditions. Pre-clinical studies in rabbits showed the formulation was capable of delaying telomere attrition and maintaining corneal endothelial cell number over a 6 month period. TelomEYE have raised 800k USD, filed several patents and are now ready to take this formulation to Phase I and II human clinical trials for presbyopia and dry eyes syndrome. Concomitantly, they will be performing preclinical studies to test their formulation on cataracts and macular degeneration with a view to taking these to clinical trials in the near future.

Problem

Human eyes succumb to numerous age-associated conditions which severely impact our vision. One such condition is presbyopia, whereby a gradual decline in refractive function prevents us from focusing light correctly resulting in an ability to focus on nearby objects. This begins to affect everyone from around 40 years of age onwards and currently affects 2 billion people. Dry eye syndrome also presents with age and currently market size 5.4 billion USD. Other age-related conditions include cataracts with 354M patients and macular degeneration 195M patients.

Telomeres, the protective caps at the end of chromosomes, undergo age-related attrition, and once a threshold of critically short telomeres is reached, cells can undergo apoptosis or senescence. With age, human corneal endothelial cell number declines, leading to a reduction in endothelial cell density (ECD), resulting in a thinner cornea which is associated with a decline in eyesight. Patients with dysfunctional telomeres, such as dyskeratosis congenita, have poor eyesight, thus adding mechanistic target validation.

Opportunity

TelomEYE have developed a daily use eye-drop formulation aiming to prevent the cellular aging of eye tissues and delay the onset of presbyopia and dry eyes syndrome by preventing age-related telomere attrition. The lead compound is an off-patent telomerase activator that is currently used in supplements.

A 6 month pre-clinical study testing the eye-drop formulation on 40 mid-aged New Zealand rabbits showed it could reduce telomere attrition and prevent corneal endothelial cell loss in rabbit eyes.

TelomEYE are now looking to take this formulation to Phase I and II human safety and efficacy studies, with Phase II studies to be performed for 12-18 months on individuals between 45-65 years old, who will use the eye drop during this period twice daily. Near vision as well as the number of corneal cells will be measured to give certain insight if they can prevent and/or cure presbyopia and dry eyes. Telomeres will be measured (cells will be collected via a special ocular strip from the cornea). So we will have solid numeric data about the efficiency of our eye drop. If successful, the plan is to negotiate with international pharma companies actively investing in ophthalmology for acquisition and exit.

In addition to the human clinical trials, TelomEYE will also perform further preclinical studies in rabbits to test if the eye-drop is effective in treating cataract and macular degeneration (intravitreal injection). If promising, the team will look to raise further money to run additional clinical trials for these indications.

Experimental plan

Link to TelomEYE pipeline

• In vitro tests (3 months)
• Animal models (6 months - running more detailed tests than previously performed)
• Phase I human safety test (3 months)
• Phase II human efficacy test (12-18 months)
• Additional genetic tests and reports (6 months)

IP Roadmap

Patent Application for the Treatment Idea in Turkey: Granted in Turkey without investigation in 2020. Applied for the examination and still under process.

Patent Application for The Formulation in Turkey: Under examination.

Patent Application for the Formulation in the USA: Awaiting to hear from US patent office for examination.

Patent Application for the Formulation in Canada: applied for examination

Trademark Application of TelomEYE: Granted for USA, Canada, Japan, Turkey and EU zone (approx 40 countries) by WIPO.

Team

CEO - Kubi Turkmen (Businessman & Entrepreneur)

Experience in pharmaceutical and anti-aging businesses since 1995. Runs companies operating in Turkey and Canada. Running the business development part of the TelomEye project. Invested and supported early steps of the project.

CMO - Iskender Alkin Solmaz MD (ophthalmologist & Oculoplastic Surgeon)

Graduated from Medical School in 2003 and ophthalmology in 2009. Currently working as an oculoplastic surgeon in Istanbul. Inventor of the TelomEye technology and treatment approach for this unique formulation. Designed and conducted the studies to prove the treatment concept.

CSO - Isilay Kavadarli MD (Ophthalmologist, Cataract and Refractive Surgeon)

Graduated from Medical School in 2005 and ophthalmology in 2011. Currently working as an anterior segment surgeon in Istanbul. Responsible for scientific research in TelomEye Project. Designed and ran the preclinical and clinical studies.

Canan Sevimli Gur, Assc. Prof (Biotechnologist-Biochemical Engineer)

More than 20 years experience in Biomedical Technologies. Head of Izmir Katip Celebi University, Pharmaceutical Basic Science Department. Optimized the drug formulation and run the safety-efficacy dose determination.

Budget and VitaDAO Funding Terms

$100k via a Sponsored Development Agreement in exchange for 1% of the Net Company Receipts (valued at $10M USD based on a previous $800k equity raise), encompassing all indications listed in the pipeline, however, further fundraises will be required to run clinical trials for AMD and cataracts (if preclinical studies are promising).

Clinical studies will be performed in Turkey as the scientific team is based there and running clinical tests according to international pharmaceutical standards is cheaper than in the USA and Canada.

• Eye drop clinical studies : 675.500 USD
• Patents: 80.000 USD
• Company Expenses: 180.000 USD
• Spare budget: 64.500 USD

## VitaDAO’s available funds

For context, (as of Feb 1st, 2023) VitaDAO funded 15+ projects with $3.5m+, and has ~$4.3m in liquid funds remaining (before further fundraising), which will be used for:

1. Funding new projects

2. Operations, including sourcing, incubation, evaluation, & community growth

3. Follow-on funding, including for projects VitaDAO will spin out

Strengths

• Their in-vivo results are a proof of concept of telomere lengthening
• The active compound has been granted a GRAS (Generally Recognized As Safe) status as medical food
• No such eye drop to prevent / delay and treat presbyopia and other conditions of eye.
• Affordable price in any country.
• The company has identified multiple clinical opportunities, including AMD, which is an unmet need
• A company developing a similar products, Encore Vision, was acquired for $465m in 2016

Risks

• Telomere shortening is recognized to be a cancer-protecting mechanism, and telomerase overexpression is a cancer hallmark, therefore long-term safety is unknown.
• The company does not have a functional proof-of-concept for presbyopia as there is no widely accepted animal model for in-vivo derisking
• Presbyopia is not an unmet need: the proposed solution should be significantly better than the current standard of care, namely eyeglasses.
• The lead compound is off-patent, so IP protection is likely to be weak

• Agree
• Revisions Requested (Detail in Comments)
• Disagree

[bowtiedshrike]

Weaknesses that I see in the presented data: telomere length only increase 10% units. Not clear to me that will be physiologically relevant, especially given the lack of stats and n. The cell number study has larger differences in starting counts than it does in ending counts-- the variability in the starting cell counts is too much to conclude anything. Also no error bars, stats, or # of rabbits used. In addition to positive/negative control, what about the other eye? Treat one eye and leave the other untreated would help control for inter-animal differences.

If there’s no good animal model for presbyopia, why pursue that indication first, instead of something with a model?

If patents were only filed in the US, Canada and Turkey (ie not Europe), that means the US market is key to developing this. How well do international clinical trials persuade the FDA to approve a new treatment?

[EliMo]

The tech vs impact just doesn’t do it for me.

[Rhys]

Thanks for this, here are answers from the TelomEYE team:

Weaknesses that I see in the presented data: telomere length only increase 10% units. Not clear to me that will be physiologically relevant, especially given the lack of stats and n.

The aim of the study was to prevent the aging of ocular tissues. To objectively measure the aging parameters, we counted the endothelial cells, which were the easiest and most convenient parameter in animal models. These cells cannot replicate, and their number is fixed since the beginning, but their number declines after the age of 40, which leads to vision problems.

Our main goal in applying eye drops was not to increase the number of telomeres (although it is very beneficial for cellular health) but to maintain the number of cells. In this experiment, we maintained the number of corneal endothelial cells by activating telomerase (these cells are telomerase deficient). Therefore, a 10% increase in telomere length is indeed relative but it is a very good thing for cells.

As we stated in the study protocol, the decrease in cell number with aging is mainly caused by senescent cells due to telomere erosion, as many clinical studies indicate.

The cell number study has larger differences in starting counts than it does in ending counts-- the variability in the starting cell counts is too much to conclude anything.

The number of corneal endothelial cells decreases with aging. Because these cells do not divide and renew, when some cells die, the remaining cells enlarge and cover the space. This is a very characteristic feature of these special cell lines. This is why we have chosen these special cell lines for our experiment. Normally, corneal endothelial cells have nothing to do with presbyopia, cataract, or macular degeneration.

We chose this cell line because with aging, they start to decrease in number as a result of programmed cell death, and we know that protecting telomeres (not increasing their length) can stop or slow down programmed cell death. We had the chance to calculate the almost exact number of these cell lines from birth.

If we were able to stop the aging of the corneal endothelial cells, we hypothesized that we could do the same in the cornea and retina to prevent presbyopia, cataract, glaucoma, and macular degeneration.

Also no error bars, stats, or # of rabbits used. In addition to positive/negative control, what about the other eye? Treat one eye and leave the other untreated would help control for inter-animal differences.

Stats and bars we can send them, 40 eyes of 20 new zealand rabbits is used. We used one eye for treatment and the other as control

If there’s no good animal model for presbyopia, why pursue that indication first, instead of something with a model?

Our animal model gives us clue regarding the aging of eye tissues. We tested the model on animals succesfully and next step is to check presbyopia on human model. Presbyopia and dry eyes happens almost all human after age of 40’s and easy to follow. Therefore our main goal is to observe presbyopia but this will provide more data about the other diseases of aging eye tissues.

Would like to clarify a few points.

1- The reason we designed the animal experiments on corneal endothelial cells is that those cell lines don’t have the ability to divide and renew. At birth, we all have a certain number of endothelial cells that are very important for maintaining clear corneal tissue. With aging, the number of those cells decreases and the remaining ones cover the spaces. We can count and calculate the number of those cells per mm2 for humans and animals with a specular microscope easily. And we know that at a certain age, those cell lines start to decrease in number. Our purpose was to use our unique formulation to protect the telomeres of these cells and to slow down or even stop the effects of aging. The corneal endothelial cells were perfect candidates for seeing the effects of our eye drop because we could count them. During animal experiments, we found that the eyes we used for treatment were stable in the number of cells while the control groups’ cell count declined as in the normal aging process. That meant if we can protect the endothelial cells, then we can protect the ciliary muscle cells (which will stop presbyopia), lens cells (protect cataract formation), and photoreceptors (protect macular degeneration).

2- The reason we planned the human trials basically for presbyopia is that presbyopia is one of the most common ophthalmological problems that doesn’t have a treatment option other than near glasses. Our experiment on rabbits with solid quantitative data of the corneal endothelial cells showed us that we will have the chance to affect the mechanism of presbyopia formation and we would have a chance to stop it if we use it as an eyedrop form. For humans, it is possible to go on with experiments targeting near vision tasks, unlike animals.

3- The logic behind the treatment protocol is to use topical treatment modalities for eyes. That means drops, ointments, sprays, slow-release forms, intravitreal injections. With topical administration, the formula only affects that certain part of the eyes treated. Anatomically, eyes can be divided into anterior and posterior chambers. When you apply a drop and see the effects on corneal endothelial cells, that means you are in the anterior chamber, and the treatment will affect other anterior chamber structures related to presbyopia and cataract formation as long as it is at the site.

4- For macular degeneration, the formula should affect the posterior chamber, so intravitreal injection is the method of choice to deliver the treatment for that part of the eyes in modern medicine. Oral tablet or intravenous delivery methods unfortunately can’t reach those structures because of the retina blood barrier.

If patents were only filed in the US, Canada and Turkey (ie not Europe), that means the US market is key to developing this. How well do international clinical trials persuade the FDA to approve a new treatment?"

As you may know, filing a patent worldwide costs a fortune (roughly >200,000 USD, plus maintenance fees, etc.). Due to a lack of funding, we wanted to focus on strategic countries first and invest our funds in clinical trials.

On the other hand, the potential buyers of this eye drop are in the USA. Therefore, we prioritized the USA patents. We are not willing to apply for FDA registration. This must be solved with the pharmaceutical company that will acquire this formulation. They already have an expert team for patent filings, and their registration team works with the FDA.

[bowtiedshrike]

The data show telomeres in units, but nothing about cell #s. Given the statements about cells decreasing with age, does that mean rabbits of different ages were used for the in vivo testing between the control and eye drops? Since there’s 2900 cells at start in the control vs 2500 cells at start in the treatment. If the other eye was used for the controls, how are there different cell numbers between the eyes?

And protecting muscle cells is a different ballgame than protecting endothelial cells.

The lack of pursuing FDA registration implies to me that the company is looking for a quick flip. In the best case scenario for the results, who would buy this company? If the IP protection is weak because the lead compound is off-patent, there’s no protection for Europe, and the clinical trials were all done in Turkey, what would the valuation of the company (or the tech) be?

[consigli3re]

Any updates @Rhys before I archive this proposal?