8/14/2019 4filed

1/7

IOPtima

11. The Company12. Glaucoma

13. The Technology14. Background - Current Non-Penetrating Filtration Surgery(Trabeculectomy)

15. IOPtimas Approach - CO 2 Laser Filtration Surgery16. Intellectual Property (IP)17. Regulatory Pathway18. The Market19. Business Strategy20. Development Status21. Glaucoma Treatments Comparison22. Team

23. References

The Company

IOPtima Ltd. (IOPtima) focuses on the discovery, development andcommercialization of its innovative and proprietary technologies for the treatment of Glaucoma A common eye disease that might lead to loss of sight. IOPtimas initialfocus is on the treatment of glaucoma. Glaucoma is the second leading cause of visionloss in the world affecting millions. The company has developed an innovative, on

penetrating, easy-to-use system, based on CO 2 laser technology, for the treatment of

glaucoma. IOPtima has completed its pre-clinical trials in animal and cadaver eyes. Thetrials showed great effectiveness and safety. The company successfully performed 23human clinical trials. IOPtima believes that its innovative new system will offer significant advantages over traditional therapies for glaucoma, such as simplicity, higher efficacy, lower side effects, lower risks to the patient, and lower costs.

Glaucoma

Glaucoma is a progressive optic neuropathy (a disease of the optic nerve)characterized by damage to the optic nerve and visual field loss, often leading to

blindness. Glaucoma represents a final common pathway resulting from a number of different conditions that can affect the eye; most of them associated with elevatedintraocular pressure - IOP. It has been shown that the most effective means of preventingglaucomatous damage is to reduce IOP, even in cases of "normal" tension glaucoma.Therefore, the primary goal of the treatment is to reduce the elevated intraocular pressure

by medication, laser therapy, implants, or surgery (Trabeculectomy).Approximately 1%-2% of the worlds population over the age of 40 suffers from

glaucoma. Until now, the common treatment has been medication, yet associated with

8/14/2019 4filed

2/7

many side effects and low compliance.

Surgical intervention, though a good treatment for reducing intraocular pressure,is performed mainly as a last resort, due to the many complications inherent in the

procedure, such as intraocular penetration, hypotony, bleeding, infection, inflammation,

etc. Today, about 500,000 surgical procedures are performed annually in the USA. Withthe introduction of a new and safer surgical technique, that number is expected toincrease.

In recent years, a new and safer surgical procedure the non-penetratingtrabeculectomy (deep sclerectomy) has been developed. In this procedure a thin layer of tissue is left behind. The main advantage of this technique, if properly performed, isthat almost all complications such as those found with the conventional trabeculectomyare avoided. The main drawback, however, is that it demands careful and delicatesurgery, relatively long learning curve, performed only by highly skilled surgeons, this, toavoid penetrating the anterior chamber the most common complication in this type of

surgery. And should this occur, then this non-penetrating procedure, as it were, becomes aconventional penetrating trabeculectomy with all its disadvantages.

IOPtima has developed an innovative approach to the non-penetratingtrabeculectomy CO 2 Laser Non-Penetrating Deep Sclerectomy (LNPDS).

Based on IOPtimas unique CO 2 Laser Filtration System OT133 , the non- penetrating trabeculectomy can be performed easily, safely and successfully by any eyesurgeon.

IOPtima expects that with the introduction of the new OT133 system, the

number of surgical procedures is expected to increase dramatically, since it may be usedto reduce IOP in earlier stages than when the current surgery is performed. It may alsoreplace some of the drug therapies that have negative side effects, including causingdamage to the eye after years of treatment and to become the solution for non-compliant

patients.

This approach can change the way glaucoma is being treated today. It does notrequire re-education of the marketplace, but rather comes as a natural response to a long-standing request found on ophthalmologists wish-lists, and is expected to be readilyembraced by them.

The Technology

Background - Current Non-Penetrating Filtration Surgery (Trabeculectomy)

Trabeculectomy is the standard filtration surgery for glaucoma. In this operation, afiltering system is created by making a hole in the sclera of the eye, which then drains the

8/14/2019 4filed

3/7

intraocular fluid through superficial ocular tissue. Numerous postoperative complicationsmay occur however, so the non-penetrating filtration procedure is therefore gainingwidespread popularity. In this procedure a thin layer of membrane is left behind allowing for the free fluid percolation, or oozing, through this remaining tissue

producing the desired effect. When done properly, by a highly skilled surgeon, the

anterior chamber of the eye is not penetrated, decreasing significantly the incidences of early postoperative complications.

The procedure involves dissecting the scleral tissue to approximately 95% (of itsdepth), leaving a residual intact layer of only several dozen microns . Inadvertent

perforation of the thin trabecular membrane is a frequent complication, occurring in asmany as 30%-50% of the cases at the beginning of the learning curve. If, on the other hand, the tissue is not cut deep enough, filtration may not be effective enough to reduceintraocular pressure to the desired level. This conventional procedure is very demandingand requires great skill and vast experience.

IOPtimas Approach - CO 2 Laser Filtration Surgery

IOPtima has developed a dedicated system, the OT133 comprised of a CO 2laser, scanner and micromanipulator. The system offers the eye surgeon a simple, easy-to-use, safe, automatic and self-controlled way of performing non-penetrating filtrationsurgery.

Applying the CO 2 lasers energy to the dry scleral tissue results in localizedablation of the tissue until a thin wall is achieved, and once enough fluid percolatethrough the thin wall, the CO 2 lasers energy becomes ineffective and will not cause anyfurther tissue ablation (i.e., perforation is avoided). Thus tissue ablation automaticallyceases once the desired physiological result (perculation) is achieved.

Those are the unique qualities of the CO 2 laser, it is very effective in ablating drytissue, but its laser energy is absorbed and dissipated when it comes in contact with water.

The use of a scanning device and micromanipulator further assists the surgeon toaccurately control the shape of the ablation and distribution of energy.

Intellectual Property (IP)

IOPtima has filed for two broad patent applications covering different aspects of the technology and method.

Regulatory Pathway

After the company meeting with the FDA, IOPtima expects a 510(K) regulatory

8/14/2019 4filed

4/7

pathway in the US. As reflected in the summary of the meeting and from the FDAresponse, IOPtima should expect to conduct a relatively small study, which will becompared with historical data and with one-year follow-up.

The Market

It is estimated that nearly 67 million people worldwide suffer from glaucoma 8.Glaucoma is a chronic disease and requires life-long therapy. Medication therapy oftenfails because of low patient compliance. Early surgical intervention is sometimes moreeffective than surgery performed after many years of drug therapy. The availability of asafe surgical procedure is expected to increase the number of surgical interventions.

Untreated, glaucoma is the second leading cause of vision loss in the world 9.Approximately 1%-2% of the population aged 40-50 and 8% over 70 have elevatedintraocular pressure 8. As the worlds population becomes older, the number of Americansaged 65 and older grows by 3.3% annually, while those aged 85 and older grows by 6.5%

annually.Most glaucoma patients suffer from glaucoma in both eyes, so for practical

estimates one should consider the number of eyes to be treated as double those of thenumber of glaucoma patients.

In the United States, glaucoma is the leading cause of blindness 8: 100,000 peopleare totally blind from glaucoma 8, approximately 300,000 people are blind in one eye 8 andabout 2,000,000 more have some degree of visual loss from glaucoma 8. It is estimatedthat up to 3 million Americans, aged 40 and over, have glaucoma 9 and 15 million moreare at risk for vision loss from glaucoma 12. In cases of IOP above 25 mmHg, even withoutany indication of vision damage, most ophthalmologists will recommend startingtreatment to lower IOP. Furthermore, research shows that patients with low-tensionglaucoma, who were treated to lower their IOP by 30%, suffered 4 times less thanuntreated patients from glaucomatous optic disc progression or visual loss 11.

Today, about 500,000 surgical procedures are performed annually in the USAalone: 125,000 trabeculectomies, 250,000-300,000 trabeculoplasties, and 75,000-125,000other surgical procedures, representing a total expenditure of approximately $750million 7. Glaucoma accounts for over 7 million doctor-visits each year 8 in the USA, and$2-3 billion are spent globally each year on glaucoma medication 4.

It is accepted that the rest of the world market is 2-3 times that of the US market 7.

Business Strategy

IOPtimas target markets include hospitals, private ophthalmic surgical centersand outpatient facilities. . The OT133 device is designated to be used in ophthalmicsurgery rooms in both ambulatory centers and hospitals. IOPtima believes that the devicewill be adopted first by glaucoma surgeons. The high rate of success using the device

8/14/2019 4filed

5/7

together with the relatively high reimbursement rates, the short learning curve of the procedure and the safety of the procedure will encourage the ophthalmic community toadopt the OT133 system. IOPtima plans to start marketing in Europe, taking advantageof the willingness to adopt new devices. The company plans to sell systems as capitalequipment. However, IOPtima believes that a fee-per-procedure payment model may

create a very interesting opportunity.

IOPtima will also develop a unique disposable eye protector patch , which will beused during the operation and will be specifically designed for it.

Development Status

Pre-clinical animal trials were successfully performed. Data was recorded as tothe number, frequency, and power of the laser applications, the shape of the scanned area,as well as the distance of the laser probe tip from the tissue.

In order to determine the IOPtima technical parameters, reproducibility and tissueeffects prior to human clinical studies, experiments were conducted on human cadaver eyes at the Center for Research on Ocular Therapeutics and Biodevices, Storm Eye

Institute, Charleston , SC, USA (Director David J. Apple, MD) and Sandhurt Eye Centre ,Johannesburg, South Africa.

IOPtima developed two prototypes, performed 23 human clinical trials andcompleted successfully its first stage of the clinical study. The surgical goal was achievedin all cases - early effective IOP reduction with no laser related complications. Theobjectives of the next stage are to evaluate and to achieve intermediate and long-term

efficiency.

Glaucoma Treatments Comparison

Glaucoma can be treated with medication or other treatments, such as laser or eyesurgery, or a combination of methods.

The following table summarizes the main advantages of the OT133 systemcompared to other known treatments for glaucoma:

AttributesOT133 System

Surgery

Non-PenetratingTrabeculectomy

ConventionalTrabeculectom

y

Argon LaserTrabeculopla

sty(ALT/SLT)

GlaucomaImplants

SuccessMore than 95%

(estimate)

60%-75%, the restbecome

trabeculectomies

70% - 90% forat least one

year

75%temporary

effect NA

8/14/2019 4filed

6/7

Penetration NO Yes/NO (in case of success)

Yes NO Yes

Safety Yes NO(if perforates) NO Yes Yes

Complications NO Yes(if perforates)

Yes NO NO

Simplicity Yes NO NO Yes Yes

Medicationafter surgery

Usually no Usually no Usually no Yes Usually no

Team

Dr. Joshua Degani CEOProfessor Ehud Assia - CSODr. Nir Berzak Project manager Dr. Adi Shargil CTODr. Ami Eyal Medical Director Richard Naimer COO

Dr. Gal Ehrlich IP amd RegulationRonit Gross Strategy and business development

8/14/2019 4filed

7/7

References

24. Benjamin F. Boyd, M.D. The Role of Non-Penetrating Filtering Operations for Open Angle Glaucoma. Highlights of Ophthalmology . Vol 28 N 04, 2000Series; 24-33.

25. Carlos Argento M.D., Ana C. Sanseau M.D., Daniel Badoza M.D., Javier Casiraghi M.D. Deep scleretomy with a collagen implant using the excimer laser. J Cataract Refract Surg . Vol 27, April 2001; 504-506.

26. David A. Therkelsen, William R. Quirk. Riding the Next Wave: 2001Refractive Surgery Update and Outlook. Dain Rauscher Wessels ,Ophthalmology. May 2001.

27. Theodore J. Huber, Anthony Sterling. Medical Devices-Eyecare IndustryOverview, A Renaissance of New Technologies, Equity Research. Bank of

America Securities . November 2000.28. David A. Gruber M.D., Russell W. Johnson, Rosanne F. Ott. Medical

Technology Industry, Ophthalmology In The Millennium, Equity Research.

Usboncorp, Piper Jaffray . April 1999.29. Eve J. Higginbotham M.D., Baltimore M.D. Reaffirming the Role of the Laser In Glaucoma Management. Arch. Ophthalmology . Vol 117, August 1999;1075-1076.

30. http://www.optistock.com/overview.htm31. http://www.glaucoma.com/fs-glaucoma-stats.html .32. http://www.glaucoma.net/gany/faq/patindex.html .33. http://www.revophth.com/2001/november/feature6.htm .34. Collaborative Normal-Tension Glaucoma Study Group. Comparison of

glaucomatous progression between untreated patients with normal-tensionglaucoma and patients with therapeutically reduced intraocular pressures.

American Journal of Ophthalmology . Vol 126, 1998; 487-497.http://www.nei.nih.gov/health/glaucoma/glaucoma_facts.htm.