Keratoconjunctivitis

On October 15, 2024, TRIANA Biomedicines announced a major announcement that it has entered into a strategic collaboration and licensing agreement with world-renowned pharmaceutical giant Pfizer. At the heart of this agreement is a joint effort to develop a series of novel molecular gel degraders that will target multiple key targets in multiple disease areas, including but not limited to oncology. Under the terms of the agreement, TRIANA Biomedicines will receive an upfront payment of $49 million from Pfizer. In addition, TRIANA is eligible to receive more than $1.5 billion in potential milestone payments in the future, as well as tiered royalties based on product sales. TRIANA will be responsible for discovering and identifying potential drug molecules in the early stages of drug development, while Pfizer has exclusive options on these drug candidates and will be responsible for the preclinical and clinical development of these drug candidates. TRIANA Biomedicines is a leading company in the field of biotechnology focused on building a leading molecular gel discovery platform. The platform is built with an advanced AI algorithm that identifies protein surface features that may interact with proteins, and validates and tests them on existing protein-action networks. With this algorithm, TRIANA is able to predict which target proteins have greater affinity and sequence the E3 ligases that are most likely to form complexes with the target proteins. In addition, TRIANA introduced the Five Rules of Drug screening in the selection of molecular gel, which is a method of screening for the chemical properties of oral pharmaceutical small molecule compounds. These rules include no more than five hydrogen bonds and a molecular weight of less than 500, which help improve the absorption rate of the drug in the body. Molecular gel deactivator is a small molecule that can induce the interaction between the E3 ubiquitin ligase substrate receptor and the target protein, and is degraded by the proteasome through the ubiquitination process. Different from PROTAC technology, molecular glue degraders have dual ligand structure characteristics for E3 ubiquitin ligase and target protein, and can bind to both proteins at the same time to promote their ubiquitination, so as to achieve the degradation of non-drug-resistant targets and protein-protein interactions. Molecular rubber degraders have the characteristics of smaller molecular weight, simpler chemical structure, less space interference and better druggability, but it is relatively difficult to design. The identification of molecular gel compounds requires a wide range of rational studies, including structural biology, biochemistry, biophysics, spectroscopy, and gene mutomics. Molecular gel degraders have shown the ability to target unproducible proteins (such as transcription factors and splicing factors), and their classification mainly includes: (1) molecular gel degraders targeting CRLs ligase; (2) Molecular gel inhibitors targeting cyclin-dependent kinases; (3) Molecular gum degraders targeting cytochrome P450 1B1; (4) Molecular gel degraders targeting transcription suppressor BCL6; (5) Molecular gel deactivators targeting epidermal growth factor receptors. According to incomplete statistics, there are more than 240 kinds of molecular glue reducers currently in research, and most of them are concentrated in the fields of cancer, cardiovascular diseases, autoimmune diseases, kerato-conjunctivitis, organ transplantation, anemia and other diseases. These research and development efforts are expected to offer new possibilities and hope for the future treatment of these diseases.

Heidelberg, Germany, Cambridge, MA, USA, and CLERMONT-FERRAND, France, October 2, 2024 – Novaliq, a biopharmaceutical company focusing on first- and best-in-class ocular therapeutics based on the unique EyeSol® water-free technology, and Laboratoires Théa (Théa), the leading independent eye care group in Europe, announce European Commission approval of Vevizye® (ciclosporin 0.1% eye drops solution) in Europe and the closing of a partnership under which Théa has acquired the rights to commercialise the product in Europe and selected countries in the Middle East and North Africa (MENA). Vevizye® is based on Novaliq’s proprietary EyeSol® technology and the only water-free ciclosporin 0.1% eye drops solution approved in the European Union for the treatment of moderate to severe dry eye disease (keratoconjunctivitis sicca) in adult patients which has not improved despite treatment with tear substitutes. “Our partnership with Novaliq highlights our dedication to delivering innovative treatments to all patients.”, stated Jean-Frédéric Chibret, President of the Théa Group. “We are looking forward to launching Vevizye® to complement our range of non-preserved treatments for dry eye, a disease that has substantial impacts on the quality of life of many patients.” Dry eye disease (DED) is one of the most common ocular surface disorders, affecting approximately 15 million diagnosed patients in the five largest European countries(1) and is difficult to treat(2). In Europe, there is a need for additional prescription treatments intended for adults suffering from moderate to severe dry eye disease. “We are thrilled to partner with Théa, the leading ophthalmic pharmaceutical company in Europe, to bring Vevizye® to patients. Théa’s focus on innovation, its leading commercial capabilities and the strong track record in Europe makes them the perfect partner for Novaliq” said Christian Roesky, Ph.D., Chief Executive Officer Novaliq. About ESSENCE 1(3) & ESSENCE 2(4) clinical studies The efficacy of Vevizye® for the treatment of dry eye disease was demonstrated by two randomised, multicentre, double-masked, vehicle-controlled studies (ESSENCE-1(3) and ESSENCE-2(4)). The change from baseline in total corneal fluorescein staining (tCFS) score at Day 29 was the primary endpoint in both trials. At Day 29, a statistically significant reduction in tCFS favouring Vevizye® was observed in both studies. Up to 71.6% of patients responded within four weeks with a clinically improvement in total corneal fluorescein staining. All other key secondary ocular surface sign endpoints (tCFS at Day 15, conjunctival staining at Day 29 and central corneal staining at Day 29) showed statistically significant effects favouring Vevizye® in both studies. Continued improvement under therapy in both signs and symptoms of DED were demonstrated over a period of up to 56 weeks.(5) About VEVIZYE® The product was approved by the US Food and Drug Administration (FDA) in May 2023 as VEVYE®. In the European Union (EU) the eligibility to the centralised procedure under Article 3(2)(b) of Regulation (EC) No 726/2004 was based on the “interest of patients”. Vevizye® is indicated for the treatment of moderate to severe dry eye disease (keratoconjunctivitis sicca) in adult patients, which has not improved despite treatment with tear substitutes. Vevizye® is approved in all 27 EU member states. Full European Summary of Product Characteristics for Vevizye® is available from the EMA website at www.ema.europa.eu . At time of publication of this press release, the full SPCs have not been yet published online. Additional regulatory applications are under review in several countries, including China, Australia, and New Zealand. About Novaliq Novaliq is a private biopharmaceutical company focusing on the development of first- and best-in-class ocular therapeutics. Novaliq developed EyeSol®, a novel drug category of water-free topical eye medicines. Two FDA-approved EyeSol® medicinal products for dry eye disease – Miebo® and Vevye® – are on the market in the US and are beginning to revolutionize patient care. The Novaliq R&D pipeline provides multiple development opportunities in ophthalmology and retina therapies. Novaliq is headquartered in Heidelberg, Germany and has an office in Cambridge, MA, USA. The long-term single shareholder is dievini Hopp BioTech holding GmbH & Co. KG, an active investor in Life and Health Sciences companies. More on www.novaliq.com. About Laboratoires Théa Théa is the leading independent European pharmaceutical company specialized in the research, development, and commercialization of eye care products. Based in Clermont-Ferrand, France, this family-owned and run company comprises more than 2,000 collaborators and has expanded by opening more than 35 affiliates and offices in Europe, North Africa, North and South America, and the Middle East. Its products are available in 75 countries. In 2023, Théa’s turnover reached €923 million. More on www.laboratoires-thea.com. Recommended Readings Global Data. Dry Eye Syndrome: Seven-Market Drug Forecast and Market Analysis Update | December 2022 Jones et al. TFOS DEWSII Management and Therapy Report. The Ocular Surface. 2017; 15 (3): 575-628 Sheppard et al. A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study. Cornea. 2021 Oct 1;40(10):1290-1297 Akpek et al. Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease The ESSENCE-2 Randomized Clinical Trial. JAMA Ophthalmology. 2023; 141(5):459-466 Wirta et. al. Long-Term Safety and Efficacy of a Water-Free Cyclosporine 0.1% Ophthalmic Solution for Treatment of Dry Eye Disease: ESSENCE-2 OLE. Cornea. 2024 May 21.

Presentation at the American Academy of Optometry (AAOPT) 2023 showed significant improvements with CEQUA® for topical ophthalmic use in both corneal fluorescein staining (CFS) and symptom questionnaire scores starting at 4 weeks and continuing to 12 weeks Study design mirrors real-world experience with dry eye disease, including allowing use of artificial tears and measurement of CFS in all five corneal zones MUMBAI, India and PRINCETON, N.J., Oct. 12, 2023 /PRNewswire/ -- Sun Pharmaceutical Industries Limited (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715, "Sun Pharma" and includes its subsidiaries and/or associate companies) today announced the presentation of Phase 4 data showing that CEQUA® (cyclosporine ophthalmic solution) 0.09% induces sustained improvement in the signs and symptoms of dry eye disease (DED). CEQUA ophthalmic solution is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye). In a presentation at the American Academy of Optometry (AAOPT) 2023 annual meeting in New Orleans, La., researchers reported that CEQUA elicited significant improvement in corneal fluorescein staining (CFS, a test used to detect damage to the cornea) and in modified Symptom Assessment in Dry Eye (mSANDE) scores in patients with DED whose disease was uncontrolled on Restasis® (cyclosporine ophthalmic emulsion) 0.05% therapy.1 In the 12-week Phase 4 multicenter study, twice-daily administration of CEQUA improved CFS and mSANDE scores starting at Week 4 of treatment and maintained these improvements through Week 12. CEQUA offers a high concentration of cyclosporine for ophthalmic use and is the first and only U.S. Food and Drug Administration (FDA)-approved cyclosporine treatment delivered with nanomicellar NCELL® technology, which helps to improve the bioavailability of cyclosporine, resulting in improved ocular tissue penetration. "We were greatly encouraged to observe significant improvements in dry eye signs and symptoms as early as four weeks into treatment with CEQUA, and to see even greater improvements at eight weeks and again at 12 weeks," said lead investigator Josh Johnston, OD, FAAO, of Georgia Eye Partners in Atlanta, Ga. "Moreover, by assessing corneal fluorescein staining in all five zones of the cornea, we were able to attain a more complete characterization of corneal health than in many dry eye disease trials, which typically assess only a few corneal areas." The study enrolled adults with DED inadequately controlled (i.e., still symptomatic and/or exhibiting disease signs) on current Restasis® therapy for at least three months, and who had a history and clinical diagnosis of DED for at least three months before screening/baseline. Patients received one drop of CEQUA in each eye twice daily for 12 weeks. Investigators assessed CFS and mSANDE scores at baseline and at Weeks 4, 8, and 12, and/or upon early discontinuation from the study. CFS was scored on a 0-4 grading scale in 0.5-point increments, with a score of 0 indicating no stain (i.e., healthy cornea) and a score of 4 reflecting a severe stain; investigators calculated a total CFS score by summing all five corneal area scores. The mSANDE questionnaire assessed frequency and severity of DED symptoms of dryness and irritation on a 0-100 scale, with 0 representing very low frequency/severity and 100 indicating very high frequency/severity. Dr. Johnston and colleagues presented results from 124 patients in the modified intent-to-treat (mITT) population. The mean (standard deviation [SD]) age of the patients was 65.5 (11.6) years; 110 of the patients (88%) were female. The mean (SD) total CFS score was 5.7 (3.37) at baseline, and improved significantly (P <0.0001) to 4.0 (3.12) at Week 4, 2.9 (2.54) at Week 8, and 2.7 (2.36) at Week 12. Similarly, the mean (SD) mSANDE score was 67.1 (21.05) at baseline and improved significantly (P <0.0001) to 48.4 (23.31) at Week 4, 44.2 (24.28) at Week 8, and 38.3 (25.99) at Week 12. CEQUA was generally well tolerated in the study, consistent with its established safety profile, and there were no new safety signals in the trial. Overall, 58 patients (43.3%) reported at least one treatment-emergent adverse event (AE); most AEs were mild in severity (73.8%). The most common treatment-related AEs were instillation site irritation and instillation site pain; all other treatment-related AEs occurred in fewer than 2% of patients. "In addition to the rapid and sustained symptomatic improvement in patients with dry eye disease treated with CEQUA, this study is notable for its design, which allows for use of artificial tears, thus replicating real-world conditions as closely as possible for a controlled clinical trial," noted Brittany Mitchell, OD, Head of Medical Affairs, Ophthalmics, at Sun Pharma. "The data presented at the American Academy of Optometry meeting represent the first of a series of assessments from this trial, with results thus far consistent with the efficacy, safety, and convenient dosing of CEQUA. We look forward to sharing additional information as we continue to analyze the data from this trial." About CEQUA® CEQUA® (cyclosporine ophthalmic solution) 0.09% is a patented, novel, proprietary nanomicellar NCELL formulation of cyclosporine in a clear, preservative-free, aqueous solution. It is indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye), an inflammatory disease that afflicts more than 16 million people in the U.S.2 CEQUA is the first and only U.S. Food and Drug Administration (FDA)-approved cyclosporine treatment delivered with nanomicellar NCELL technology, which helps to improve the bioavailability and physicochemical stability of cyclosporine, resulting in improved ocular tissue penetration. CEQUA is dosed twice daily and is available as a single-use vial. In a multicentered, randomized, double-masked, vehicle-controlled Phase 3 confirmatory study involving 744 patients with dry eye, investigators observed clinically and statistically significant improvements in tear production and ocular surface integrity in patients treated with CEQUA, compared to vehicle. CEQUA treatment was well tolerated in the Phase 3 trial; treatment-emergent adverse events were primarily mild in intensity. In a prior Phase 2b/3 clinical trial with 455 patients, CEQUA demonstrated clinically and statistically significant increases in tear production (16.8% of patients with an increase of ≥10 mm in Schirmer's score from baseline after 84 days of treatment, versus 8.6% for vehicle; p<0.01) and was well tolerated by the study population. Additionally, several key secondary endpoints showed statistically significant improvements compared to vehicle. From both clinical trials, the most common adverse reaction following the use of cyclosporine ophthalmic solution 0.09% was instillation site pain (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of the patients were eye irritation, blepharitis, urinary tract infection, headache, and bronchitis. INDICATIONS AND USAGE CEQUA® (cyclosporine ophthalmic solution) 0.09% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination: To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip to the eye or other surfaces. Use with Contact Lenses: CEQUA should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of CEQUA ophthalmic solution. ADVERSE REACTIONS The most common adverse reactions reported in greater than 5% of patients were pain on instillation of drops (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of patients were blepharitis, eye irritation, headache, and urinary tract infection. Please click for Full Prescribing Information & for more information visit CEQUAPRO.com About Dry Eye Disease Dry eye is a burdensome, chronic disease affecting millions of patients around the world, with a significant population, greater than 16 million patients, present in the United States.2 Dry eye disease, as defined by the National Eye Institute (NEI, a division of the U.S. National Institutes of Health), occurs when the quantity and/or quality of tears fails to keep the surface of the eye properly lubricated. The disease causes a scratchy sensation or a feeling that something is in the eye. Other symptoms include stinging or burning, episodes of excess tearing following periods of stress, discharge, pain, and redness in the eye. The risk of developing dry eye increases with advancing age and is more common in women than in men. Disclaimer: Statements in this "Document" describing the Company's objectives, projections, estimates, expectations, plans or predictions or industry conditions or events may be "forward looking statements" within the meaning of applicable securities laws and regulations. Actual results, performance or achievements could differ materially from those expressed or implied. About Sun Ophthalmics Backed by Sun Pharma's global expertise in R&D, Sun Ophthalmics (the branded ophthalmic division of Sun Pharma's wholly owned subsidiary) is leading the way through the development of innovative products and in partnership with eye care professionals. In addition to CEQUA® (cyclosporine ophthalmic solution) 0.09%, Sun Ophthalmics markets BromSite® (bromfenac ophthalmic solution) 0.075% and XELPROS® (latanoprost ophthalmic solution) 0.005% in the U.S. Sun Ophthalmics' dedicated team is focused solely on the needs of eye care professionals, offering timely, knowledgeable support at every turn. The company strives to deliver products built on unique platforms that integrate seamlessly into the eye care practice, helping eye care professionals to continue providing quality medicine. Discover a brighter future in eye care at . About Sun Pharmaceutical Industries Limited (CIN - L24230GJ1993PLC019050) Sun Pharma is the world's fourth largest specialty generics company with presence in Specialty, Generics and Consumer Healthcare products. It is the largest pharmaceutical company in India, and is a leading generic company in the US as well as Global Emerging Markets. Sun's high growth Global Specialty portfolio spans innovative products in dermatology, ophthalmology, and onco-dermatology and accounts for over 16% of company sales. The company's vertically integrated operations deliver high-quality medicines, trusted by physicians and consumers in over 100 countries. Its manufacturing facilities are spread across six continents. Sun Pharma is proud of its multi-cultural workforce drawn from over 50 nations. For further information, please visit and follow us on Twitter @SunPharma_Live References: Johnston, J. Effect of OTX-101 0.09% on corneal staining and SANDE scores in patients with dry eye disease uncontrolled on cyclosporine ophthalmic emulsion 0.05%. Abstract presented at American Academy of Optometry 2023; October 12, 2023; New Orleans, LA. New study focuses on scope of dry eye disease in the U.S. American Optometric Association; 2017. Available at: . Accessed September 10, 2019 © 2023 Sun Pharmaceutical Industries, Inc. All trademarks are the property of their respective owners. Company Codes: Bombay:524715, India:EQSUNPHARMA