Full Press Release Details
audited results for the year ended 31 March 2022
and NEW YORK, August 16, 2022. OKYO Pharma Limited (NASDAQ: OKYO; LSE: OKYO) (the "Company")
is pleased to announce its final audited results for the year ended 31 March 2022.
of OKYO-101 studies during the last year
| OK-101 is designed to target a chemokine-like receptor 1, or CMKLR1, which is a G protein-coupled receptor, or GPCR, expressed on macrophages, monocytes, plasmacytoid/myeloid dendritic cells, natural killer cells and nonhemopoietic cell types, such as endothelial and epithelial cells. Activation of CMKLR1 by its endogenous peptide ligand chemerin is known to modulate inflammation, but natural ligands for CMKLR1 have short half-lives due to rapid inactivation. | ||
| A major issue with topical administration of any drug designed for treating DED is the requirement that the drug have adequate drug residence' time at the ocular site. The drug candidates we have developed are designed to combat washout by including a lipid anchor' within the candidate drug molecule to enhance the residence time of the drug in the eye. We refer to our candidates for DED as "lipidated-chemerin" analogues to highlight this pharmacologic characteristic. | ||
| Animals induced with scopolamine to generate acute DED showed a statistically significant increase in corneal permeability relative to na ve non-stressed animals. The addition of cyclosporine to scopolamine-induced DED animals showed a statistically significant reduction of permeability (p 0.001). Notably, OK-101 demonstrated a dramatic reduction of DED-induced corneal permeability as well (p 0.001). | ||
| OK-101 was topically administered to mice in comparison to the positive control gabapentin which was administered via intraperitoneal injection. Pain relief was evaluated by an eye-wipe count, and OK-101 was shown to reduce corneal pain similar to that of gabapentin, a commonly used oral drug for neuropathic pain. Notably, the drug concentration of OK-101 used in this study was identical to that used in mouse models of DED that demonstrated ocular anti-inflammatory activity. OK-101 had no effect on corneal epithelial integrity compared to gabapentin or balanced salt solution. | ||
| A separate series of experiments was also performed to evaluate ocular tolerance of OK-101 in rabbits via repeated ocular instillation followed by clinical ophthalmic observations. Rabbit ocular tolerance tests on OK-101 showed no adverse signs such as inflammation, chemosis or hyperemia and no signs of local irritation. | ||
| During the fourth quarter of 2021 we successfully manufactured a 200-gram batch of OK-101 drug substance needed for the IND-enabling studies. | ||
| On February 15, 2022, we announced the successful completion of the pre-IND meeting facilitated by Ora with the FDA regarding development plans for OK-101 to treat DED. Both nonclinical and clinical development milestones were covered in the pre-IND meeting, with the FDA agreeing that our first human trial would be a Phase 2 safety and efficacy trial in DED patients. |
of OKYO-201 studies during the last year
| OK-201 is designed to activate a human MAS-Related G Protein-coupled Receptor (MRGPR), which is a promising analgesic target. This receptor is expressed mainly in sensory neurons and is involved in the perception of pain. Activation of MRGPR by BAM peptide inhibits pain by modulating Ca2+ influx. | ||
| On April 28, 2021, we announced positive results of OK-201, a non-opioid analgesic drug candidate delivered topically, as a potential drug to treat acute and chronic ocular pain. Importantly, OK-201 demonstrated a reduced corneal pain response equivalent to that of gabapentin, a commonly used oral drug for neuropathic pain. These observations demonstrated preclinical proof-of-concept' for the topical administration of OK-201 as a potential non-opioid analgesic for ocular pain. |
strategy of OKYO-101
| To support our work, we signed an agreement on April 13, 2021 with Ora, Inc., or Ora, a major clinical research organization ("CRO"), specializing in ophthalmic drug development. | ||
| Based on the results from earlier DED animal model studies that have been performed with OK-101 as well as the additional animal study showing the potential of OK-101 to reduce corneal neuropathic pain, we are moving forward with plans to file an IND to treat DED in the fourth quarter of 2022. | ||
| Followed by the subsequent initiation of a Phase 2 trial of OK-101 to treat DED patients in the first quarter of 2023. | ||
| Once we are clinically evaluating OK-101 to treat dry eye, we will also undertake the plan to explore the drug candidate's potential to suppress the inflammation associated with uveitis and allergic conjunctivitis. In support of this plan, we will be exploring preclinical development of OK-101 for the uveitis indication by first establishing proof-of-concept' for this indication utilizing animal model studies of anterior uveitis to evaluate the potential of OK-101 to suppress the inflammation associated with uveitis. | ||
| We also plan on conducting proof-of-concept' studies using OK-101 for the treatment of chronic and seasonal allergic conjunctivitis using a conjunctival allergen challenge animal model to investigate the potential of OK-101 to suppress the inflammation associated with allergic conjunctivitis. |
strategy of OKYO-201
the next year, we have decided to maintain this drug candidate at the exploratory level.
| Total comprehensive loss of 3,976k (2021: 2,994k) | ||
| Cash balance at 31 March 2022 2,056k (31 March 2021: 4,992k) |
| OKYO Pharma Limited | Gary S. Jacob, Chief Executive Officer | +44 (0)20 7495 2379 | ||
| Gabriele Cerrone, Non-Executive Chairman | ||||
| Optiva Securities Limited | Robert Emmet | +44 (0)20 3981 4173 | ||
| (Broker) |
further information, please visit the Company's website at http://okyopharma.com/.
from the annual accounts for the year ended 31 March 2022 are set out below
Directors present their strategic report for the Company, OKYO Pharma Limited ("OKYO" or the "Company") and its
subsidiary, (together the "Group") for the year ended 31 March 2022.
Pharma Limited (LSE: OKYO, NASDAQ: OKYO) is a preclinical biopharmaceutical company developing next-generation therapeutics to improve
the lives of patients suffering from inflammatory eye diseases and ocular pain. Our research program is focused on a novel G protein
coupled receptor (GPCR) which we believe plays a key role in the pathology of the inflammatory eye diseases that are the target of this
technology. Our therapeutic approach is focused on targeting inflammatory and pain modulation pathways that drive these conditions. We
are presently developing OK-101, our lead preclinical product candidate, for the treatment of dry-eye disease. We also plan to evaluate
its potential in benefiting patients with ocular neuropathic pain, uveitis and allergic conjunctivitis. We have also been evaluating
OK-201, a bovine adrenal medulla, or BAM, lipidated-peptide preclinical analogue candidate for ocular neuropathic pain that is currently
in an exploratory preclinical stage.
have not yet submitted an application to the Food and Drug Administration ("FDA") for any of our product candidates. We have
however significantly advanced our ongoing Investigational New Drug ("IND) enabling work on our lead candidate OK-101 during this
past year for an IND submission for OK-101 to treat dry eye and are presently on schedule to file an IND on OK-101 to treat dry eye disease
in the fourth quarter of 2022.
our lead preclinical product candidate, is focused on keratoconjunctivitis sicca, commonly referred to as DED, which is a multifactorial
disease caused by an underlying inflammation resulting in the lack of lubrication and moisture in the surface of the eye. DED is one
of the most common ophthalmic conditions encountered in clinical practice. Symptoms of DED include constant discomfort and irritation
accompanied by inflammation of the ocular surface, visual impairment and potential damage to the ocular surface. There are presently
approximately 20 million people suffering from DED in the U.S. alone (Farrand et al. AJO 2017; 182:90), with the disease affecting approximately
up to 34% of the population aged 50+ (Dana et al. AJO 2019; 202:47), and with women representing approximately two-thirds of those affected
(Matossian et al. J Womens Health (Larchmt) 2019; 28:502-514). Prevalence of DED is anticipated to increase substantially in the
next 10-20 years due to aging populations in the U.S., Europe, Japan and China and use of contact lenses in the younger population. We
believe this increase in prevalence of dry eye syndrome represents a major expanding economic burden to public healthcare. According
to Market Research Report, Dry Eye Syndrome, December 2020, the global DED market in 2019 was approximately $5.22 billion, with the market
size expected to reach $6.54 billion by 2027. In addition, DED causes approximately $3.8 billion annually in healthcare costs and represents
a major economic burden to public healthcare, accounting for more than $50 billion to the U.S. economy annually.
present, there are three major prescription drugs used to treat DED: 1) Restasis (cyclosporin), 2) Xiidra (lifitigrast) and 3) Tyrva
(varenicline). However, DED continues to be a major unmet medical need due to the large number of patients not well served by present-day
treatments due to their lack of adequate efficacy, slow onset of action and poor side effect profile. The development of new drugs to
treat DED has been particularly challenging due to the heterogeneous nature of the patient population suffering from DED, and due to
the difficulties in demonstrating an improvement in both signs and symptoms of the disease in well-controlled clinical trials. The evidence
from over 40 years of scientific literature, however, suggests inflammation as the most common underlying cause of DED. Consequently,
development of new therapeutic agents that target inflammatory pathways is crucial in improving symptoms in DED patients. OK-101 is focused
on an anti-inflammatory pathway for treating dry eye.
is designed to target a chemokine-like receptor 1, or CMKLR1, which is a G protein-coupled receptor, or GPCR, expressed on macrophages,
monocytes, plasmacytoid/myeloid dendritic cells, natural killer cells and nonhemopoietic cell types, such as endothelial and epithelial
cells. Activation of CMKLR1 by its endogenous peptide ligand chemerin is known to modulate inflammation, but natural ligands for CMKLR1
have short half-lives due to rapid inactivation. Discovery of OK-101, a stable, high potency CMKLR1 agonist by On Target Therapeutics
(technology licensed to OKYO Pharma Limited) provided an important step toward the development of a new class of anti-inflammatory therapeutics
that can be applied to the treatment of ophthalmic diseases including DED, uveitis and ocular pain.
key driver in the development of OK-101 to treat DED, uveitis and other ocular conditions was an analysis of the inherent advantages
and difficulties associated with the treatment of ocular conditions. One of the major issues with topical administration of any drug
designed for treating DED is the requirement that the drug have adequate drug residence' time at the ocular site to afford
a pharmacologic benefit before being washed out through natural processes of tear enhancement and lacrimal tear drainage. The drug candidates
we have developed are designed to combat washout by including a lipid anchor' within the candidate drug molecule to enhance
the residence time of the drug in the eye. We refer to our candidates for DED as "lipidated-chemerin" analogues to highlight
this pharmacologic characteristic.
potential efficacy of OK-101 to treat DED has previously been tested in mouse models of acute dry eye disease using the measure of corneal
permeability of scopolamine-treated animals to evaluate effectiveness of drug candidates to treat dry eye disease. OK-101 demonstrated
a clear reduction of DED-induced corneal permeability (p 0.001) in scopolamine-treated animals. OK-101's effect in reducing
DED-induced corneal permeability was virtually identical to that of the cyclosporine positive control animals included in the study and
close to the baseline corneal permeability observed in control animals.
potency of OK-101 was first determined in a cell-based PathHunter -Arrestin assay. This assay monitors the activation of a
GPCR in a homogenous, non-imaging assay format using a technology developed by DiscoverX called Enzyme Fragment Complementation (EFC)
with -galactosidase ( -Gal) as the functional reporter. The enzyme is split into two inactive complementary portions (EA for
Enzyme Acceptor and PK for ProLink) expressed as fusion proteins in the cells. EA is fused to -Arrestin and PK is fused to human
Chemokine-like receptor 1, CMKLR1. Activation of CMKLR1-PK induces -Arrestin-EA recruitment, forcing complementation of the two
-galactosidase enzyme fragments (EA and PK). The resulting functional enzyme hydrolyzes substrate to generate a chemiluminescent
signal, which is measured using chemiluminescent PathHunter Detection Reagents.
Design: PathHunter cell lines co-expressing the ProLink (PK) tagged GPCR (human Chemokine-like receptor 1, CMKLR1) and the Enzyme
Acceptor (EA) tagged -Arrestin were expanded from freezer stocks according to standard procedures. Cells were seeded in a total
volume of 20 L into white walled, 384-well microplates and incubated at 37 C for the appropriate time prior to testing. For agonist
potency determination, cells were treated with various concentrations of peptide to induce response and incubated at 37 C for 90
minutes. Assay signal was generated through a single addition of 12.5 or 15 L (50% v/v) of PathHunter Detection reagent cocktail,
followed by a one-hour incubation at room temperature. Microplates were read following signal generation with a PerkinElmer EnvisionTM
instrument for chemiluminescent signal detection. Compound activity was analyzed using CBIS data analysis suite (ChemInnovation, CA).
further characterize the potential efficacy of OK-101 to treat DED, OK-101 was tested in a mouse model of acute DED. Animals were divided
into five separate cohorts that included: 1) non-stressed control animals untreated throughout the study, 2) animals treated with scopolamine
to induce acute DED, 3) animals treated with scopolamine to induce acute DED and treated with 0.1% cyclosporine as a positive control,
4) animals treated with scopolamine to induce acute DED and treated with phosphate buffer solution (the vehicle used for OK-101 delivery),
and 5) animals treated with scopolamine to induce acute DED and treated with OK-101 in phosphate buffered solution.
in cohorts 1) and 2) were left untreated with test agents throughout the 5-day period, whereas animals in cohorts 3), 4) and 5) were
treated with either cyclosporine, or CS, vehicle or OK-101, respectively, twice a day during the 5-day period via bilateral topical administration
of the respective agents. On the fifth day, all of the animals were assessed for efficacy by evaluating corneal permeability, a measure
of dry-eye effectiveness, in live animals, as well as by exploring the impact of respective treatments on immune response.
induced with scopolamine to generate acute DED showed a dramatic, statistically significant increase in corneal permeability relative
to na ve non-stressed animals. The addition of cyclosporine to scopolamine-induced DED animals showed a statistically significant
reduction of permeability (p 0.001). Notably, OK-101 demonstrated a dramatic reduction of DED-induced corneal permeability as well
(p 0.001). OK-101's effect in reducing DED-induced corneal permeability was virtually identical to that of the cyclosporine
positive control and close to the baseline corneal permeability observed in non-stressed control animals.
the in-life portion of the study, immunohistochemistry was performed on frozen sections of enucleated mouse eyes to measure CD4+ T-cell
infiltration into the conjunctival epithelium of the eye. Animals induced to develop acute DED and not treated with drug (Vehicle animals)
showed significant infiltration of CD4+ T cells within the conjunctival epithelium, whereas OK-101 demonstrated a statistically significant
(p 0.01) reduction in dry-eye-induced enhancement of CD4+ T-cells. In fact, the level of CD4+ T cells observed in OK-101 treated
animals was equivalent to the CD4+ T cell level observed in na ve untreated animals.