Contents

I. Alcon Background

II. Dry Eye Disease

III. AR-15512

IV. Vyluma Background

VI. Pediatric Myopia

VII. NVK002

VIII. My Thoughts: Will Alcon acquire Vyluma

1
Alcon Background
Alcon is the world’s largest eye care device company that began with humble beginnings,
but has since innovated both surgical and vision care products to improve the lives of over
260 million people.
Today, Alcon is the largest eye care device company in the world.1 But its origins began in Fort
Worth, Texas in 1945 when two pharmacists, Robert Alexander and William Conner, opened a
small pharmacy, combining the first syllables of their last names to call it Alcon. 2 Two years
later, Alcon Laboratories, Inc. became incorporated and the company started manufacturing
specialty pharmaceutical products.2 In 1971, Alcon went public with a listing on the New York
Stock Exchange.2

Over the years, Alcon has innovated through both its businesses: surgical and vision care.3 Their
products touch the lives of more than 260 million people in over 140 countries each year living
with conditions like cataracts, glaucoma, retinal diseases and refractive errors. 4

Dry Eye Disease

Dry eye disease affects more than 16.7 million Americans, yet there is no current treatment
option that efficiently keeps the disease under control.
Dry eye disease (DED) is one of the most common ocular surface disorders.4 Dry eye happens
when your eyes don’t make enough tears to stay wet or when your tears don’t work correctly.5
This can make your eyes feel uncomfortable, and in some cases it can also cause vision
problems.5 Dry eyes are caused by a variety of reasons that disrupt the healthy tear film that
keeps the surface of your eyes lubricated, smooth, and clear.6 Your tear film has three layers:
fatty oils, aqueous fluid and mucus and problems with any of these layers can cause dry eyes.6
Reasons for tear film dysfunction are many, including hormone changes, autoimmune disease,
inflamed eyelid glands or allergic eye disease.6 For some people, the cause of dry eyes is
decreased tear production or increased tear evaporation, which can be caused by certain
medicines, medical conditions, aging, and corneal nerve desensitivity.6 More than 16.7 million
Americans are affected by this disease and studies show that this portion of the population will
continue to grow.7

1
https://investor.alcon.com/home/default.aspx
2
https://www.alcon.com/about-us#history
3
https://www.alcon.com/about-us#business-focus
4
https://www.alcon.com/media-release/alcon-announces-positive-topline-results-phase-3-comet-trials-ar-15512-
novel-topical
5
https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye
6
https://www.mayoclinic.org/diseases-conditions/dry-eyes/symptoms-causes/syc-20371863
7
https://dryeyedirectory.com/dry-eye-statistics/

2
Link: https://www.carolinaeye.com/dry-eye-southern-pines/

Treatment for dry eye varies from something simple like lifestyle changes to something more
serious like surgery.5 Artificial tears, which are an over-the-counter treatment, are the most
common initial treatment to alleviate DED symptoms.8 For those with more serious DED,
doctors may prescribe pharmacologic topical therapies, like cyclosporine and lifitegrast, which
target inflammation.7

More recently, increased attention has been placed on the neuronal regulation of tear production. 7
The trigeminal nerve provides the pathway for parasympathetic stimulation of the lacrimal
functional unit, where sensory stimulation of the cornea and conjunctiva occurs, which is
essential for initiating basal tear production.7 Therefore, reduced or dysfunction of the corneal
sensory nerves has been hypothesized to contribute to the development of DED.7 The potential of
targeting neuronal pathways as a DED treatment option was demonstrated by the approval of
varenicline, an intranasal nicotinic acetylcholine receptor agonist believed to stimulate the
lacrimal functional unit via receptors located on the trigeminal nerve. 7

8
https://www.sciencedirect.com/science/article/pii/S1542012422000751?via%3Dihub#bib6

3
Link: https://neupsykey.com/neuromodulation-for-treatment-of-dry-eye/

Although varenicline does relieve the discomfort of DED, many users have noted side effects,
like coughing, throat irritation, and sneezing.9 Also, the price of varenicline tends to be at least
$100 for a 30-day supply.8

Another recently developed DED treatment option is perfluorohexyloctane ophthalmic solution

(Miebo), which was approved by the FDA in May 2023.10 Miebo is the first & only Rx eye drop
that directly targets tear evaporation.11 It is made from only one ingredient and it’s both
preservative and steroid-free.11 Although excessive tear evaporation is a leading cause of DED, it
is just one cause and not representative of all DED patients.12 Additionally, a common side ffect
of Miebo is blurred vision.13

9
https://www.drugs.com/comments/varenicline/tyrvaya.html
10
https://www.medicalnewstoday.com/articles/latest-treatment-for-dry-eye-syndrome#first-line
11
https://www.miebo.com/
12
https://www.fiercepharma.com/pharma/no-tears-here-bausch-lomb-bags-fda-approval-dry-eye-disease-drop-
targeting-tear-evaporation
13
https://www.everydayhealth.com/drugs/miebo#:~:text=What%20are%20the%20side%20effects,blurred
%20vision.

4
The most established and popularly used drug to treat DED is Restasis.14 The active ingredient in
Restasis, cyclosporine, is an immune-suppressing drug (immunosuppressant) and it limits your
immune system’s ability to produce certain enzymes, proteins that make it easier for certain
chemical reactions to happen in your body.15 In this case, the enzymes are the type that cause
inflammation.15 For most people, inflammation is a helpful process as it signals your immune
system to send specialized cells to a specific area to stop disease progress and repair damage. 15
But if you have excessive inflammation, it can do more harm than good.15 In your eyes,
inflammation can make it harder for your body to produce tear fluid.15 Limiting eye
inflammation means you have more available tear fluid, which treats dry eye.15

However, with Restasis burning in the eye is a common side effect.16 Also, patients with severe
DED frequently have a poor response to normal twice per day application of Restasis, even after
several months of treatment, and often benefit from an increased dosing application of three or
four times per day, which is difficult to adhere to and takes much more time out of a patient’s
daily life.14

Most prescription treatments for DED address signs and symptoms by targeting tear production
or inflammation.17 Additionally, many existing prescription options for dry eye disease are
generally regarded by many eye care professionals and patients as inadequate due to low
treatment efficacy, slow onset of action, and poor tolerability.4

AR-15512
AR-15512 is a novel product candidate to treat DED that targets TRPM8 and is currently
in the process of filing an NDA for FDA approval.
On August 22, 2022, it was announced that Alcon would acquire Aerie Pharmaceuticals, Inc for
about $770 million.18 Commercial products, Rocklatan and Rhopressa, were added to Alcon’s
ophthalmic pharmaceutical portfolio, as well as AR-15512, a Phase 3 product candidate for
DED.5 AR-15512 is a topical transient receptor potential melastatin 8 (TRPM8) agonist. 4
TRPM8 receptors are cold-sensitive thermoreceptors that are selectively expressed by branches
of the trigeminal nerve located in the cornea and eyelid.7 These receptors are associated with the
detection of ocular surface dryness and are activated by evaporative cooling and
hyperosmolarity, leading to stimulation of tear production.7 In addition, agonists of TRPM8
promote a cooling sensation that may be beneficial for reducing ocular discomfort and pain. 7

14
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181191/#:~:text=There%20are%20currently%20only
%20two,Allergan%2C%20Irvine%2C%20CA).
15
https://my.clevelandclinic.org/health/drugs/19190-cyclosporine-ophthalmic-emulsion
16
https://www.goodrx.com/restasis/restasis-side-effects
17
https://pubmed.ncbi.nlm.nih.gov/37930231/#:~:text=Perfluorohexyloctane%20(PFHO)%20ophthalmic
%20solution%20(,signs%20and%20symptoms%20of%20DED.
18
https://www.alcon.com/media-release/alcon-acquire-aerie-pharmaceuticals-inc-enhancing-its-ophthalmic-
pharmaceutical

5
Thus, TRMP8 agonists, such as AR-15512, may have a dual role in the potential treatment of
DED by both stimulating tear production and reducing ocular discomfort.7

Link: https://s1.q4cdn.com/963204942/files/doc_presentations/2024/Jan/10/alcon-2024-jp-morgan-healthcare-
conference-presentation.pdf

On January 9, 2024, Alcon announced positive topline results from the two pivotal Phase 3
clinical trials (COMET-2 and COMET-3) evaluating the efficacy and safety of AR-15512. The
primary endpoint of the proportion of subjects with at least a 10-mm increase in unanesthetized
Schirmer’s score (a measure of tear production) achieved statistical significance at Day 14
[p<0.0001], which is consistent with the proposed mechanism of action of AR-15512.4

6
Link: https://s1.q4cdn.com/963204942/files/doc_presentations/2024/Jan/10/alcon-2024-jp-morgan-healthcare-
conference-presentation.pdf

In these studies, additional data derived from secondary endpoints demonstrated the rapid onset
and sustained tear production associated with AR-15512, as early as Day 1 and as persistent to
Day 90. Overall, AR-15512 was well tolerated and no serious ocular adverse events were
reported. Alcon anticipates filing the NDA for AR-15512 with the FDA in mid-2024.4

Vyluma Background
Vyluma is a biopharmaceutical company that focuses on developing treatments for
pediatric myopia in order to prevent even more detrimental eye diseases later on in life.
The word “Vyluma” originates from different languages across the globe and carries the
meaning to expand and open to light, which reflects the company’s goal to serve a global
population by providing meaningful and effective pharmaceutical ophthalmic solutions. 19 Today,
nearly 4 billion people live with a disorder that prevents the eye from properly processing light
the way a normal, healthy eye would.11 Without improving the quality of treatments available to
prevent vision loss and deterioration, projections expect more than 5 billion people could
experience some form of vision loss by 2050.11 Vyluma’s leading pipeline program, NVK002,
addresses the great unmet need to slow down the progression of myopia, also known as
nearsightedness, in children so they are not at risk for blinding diseases in the future.11

Link: https://vyluma.com/pipeline/

Pediatric Myopia
The number of children that suffer from myopia is on the rise both in the US and globally
and it can lead to even more dangerous eye diseases.

19
https://vyluma.com/our-story/

7
Myopia or nearsightedness is a condition where things that are far are harder to see.20 Myopia
results from either an abnormal elongation of the eyeball or an abnormal curvature of the cornea,
blurring objects viewed at a distance.12

Link: https://www.childrenshospital.org/conditions/myopia

A child’s eyes grow the fastest when they are between the ages of 6-18 years old and if their eye
grows irregularly, it can lead to vision problems like myopia.12 Today in the U.S., about 40% of
kids have myopia, compared to just 20% three decades ago, but this is not only a US problem,
because by the year 2050, myopia is expected to affect half the world’s population.12 The steady
progression of myopia over time can result in high myopia and significantly increases one’s risk
of retinal detachment, myopic macular degeneration, glaucoma, cataracts, and ultimately
blindness.12

The first line treatment for myopia is glasses, which do correct vision but do not treat the
underlying disease or help to slow myopia progression.12 There are currently no approved
pharmaceutical treatments to slow the progression of myopia in both the US and Europe.12
Contact lenses such as orthokeratology (hard contacts which reshape the cornea) as well as soft
multifocal contact lenses are available, but these specialty contacts can be expensive. 12

NVK002

20
https://vyluma.com/pediatric-myopia/

8
NVK002, a novel drug to treat pediatric myopia, is Vyluma’s leading pipeline program that
is currently under review by the FDA with an update expected in January 2024.
NVK002 is a novel, investigational, preservative-free low-dose atropine eye drop which is
administered nightly, as a single drop to both eyes.12 NVK002 uses Vyluma’s proprietary
technology, to address stability, tolerability, and safety.12 Atropine for myopia addresses the
anatomic changes (i.e., longer ocular axial length) associated with myopia progression, which
cannot be easily achieved with spectacles or contact lenses.21

Atropine is a natural alkaloid occurring in plants of the Solanaceae family and is mostly
extracted from Atropa belladonna.22 In the eye, atropine is used for cycloplegia and mydriasis.13
In the eye, atropine induces mydriasis by blocking contraction of the circular pupillary sphincter
muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial iris
dilator muscle to contract and dilate the pupil.13 Atropine induces cycloplegia by paralyzing the
ciliary muscles, whose action inhibits accommodation to allow accurate refraction in children,
helps to relieve pain associated with iridocyclitis, and treats ciliary block (malignant)
glaucoma.13 However, both pupil dilation and cycloplegia represent problematic side effects
without therapeutic benefit for myopia control.13 Furthermore, the first studies using atropine eye
drops to slow myopia progression in children used 1% atropine, but these had significant side
effects – enlarged pupils made a child sensitive to light, and blurred their close-up vision. 23
Newer studies have investigated lower concentrations of 0.01% up to 0.05%, which have
minimal side effects.24

On June 6, 2023, Vyluma announced that the FDA has accepted the NDA for NVK002 for
review.25 A Prescription Drug User Fee Act (PDUFA) goal date of January 31, 2024, has been
assigned by FDA.13 Vyluma’s NDA is supported by positive results from its landmark, three-
year, placebo-controlled international Phase III CHAMP (Childhood Atropine for Myopia
Progression) clinical study, evaluating the safety and efficacy of NVK002 in nearly 600
children.13 NVK002 at a dose of 0.01% achieved statistically significant and clinically
meaningful differences from placebo at month 36 in the key outcome measures of responder
analysis, mean change from baseline in Spherical Equivalent Refraction (SER), and mean change
from baseline in axial length.13 NVK002 demonstrated strong safety and tolerability when
compared to placebo with no serious ocular adverse events reported.13

My Thoughts: Will Alcon acquire Vyluma

21
https://vyluma.com/areas_of_focus/pediatric-myopia/
22
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522992/
23
https://www.sciencedirect.com/science/article/abs/pii/S0161642006007597
24
https://pubmed.ncbi.nlm.nih.gov/34627809/
25
https://vyluma.com/press_release/vyluma-announces-fda-acceptance-of-new-drug-application-for-nvk002-its-
novel-investigational-treatment-for-pediatric-myopia/

9
I don’t believe Alcon will acquire Vyluma, at least in the near future, because of the lack of
substantial market value in pediatric myopia and lack of extensive data regarding atropine
drops to treat myopia.
When I initially completed my research, I couldn’t help but compare Aerie Pharmaceuticals to
Vyluma and ask myself why did Alcon acquire Aerie and not Vyluma. The majority of Vyluma’s
pipeline is dedicated to addressing pediatric myopia. Although there is a market for this and it
can be a detrimental issue, I, along with the majority of people, believe it’s an inevitable that
must be adapted to or treated later on in life when a disease or more serious condition arises as a
result. I admire Vyluma’s mission and value of prevention, but I don’t think this matches well to
Alcon, who is dedicated to innovating new products for those living with cataracts, glaucoma, or
retinal diseases.

Also on Vyluma’s pipeline, NVK002 is a late stage product candidate and in the US NVK002 is
currently pending FDA approval. My sense of acquisitions in the biopharma space is that
companies looking to acquire another company are more focused on early or middle stage
product candidates rather than already approved products. In my mind this is because those
candidates have more potential to be revolutionary in whatever area they were discovered for,
which means that companies can potentially make even more money of it.

As I learned more about atropine eyedrops, doubts also arose. According to an article published
in July 2023, a randomized controlled trial conducted by the Pediatric Eye Disease Investigator
Group and funded by the National Eye Institute (NEI) found that use of low-dose atropine
eyedrops (concentration 0.01%) was no better than placebo at slowing myopia progression and
elongation of the eye among children treated for two years.26 These findings contradicted with
earlier trials, mostly in East Asia, which showed a benefit from 0.01% atropine in slowing
myopia.17 These mixed results show that more research is needed in this area. Director of the
NEI, Michael Chiang, posed some important questions, “Would a different dose be more
effective in a US population? Would combining atropine with other strategies have a synergistic
effect? Could we develop other approaches to treatment or prevention based on a better
understanding of what causes myopia progression?”. Until we can answer questions like this and
more, I don’t believe Alcon will take the leap and acquire Vyluma.

26
https://www.nih.gov/news-events/news-releases/low-dose-atropine-eyedrops-no-better-placebo-slowing-myopia-
progression

10