Cyclosporine (Huons)

BEDFORD, Mass., Oct. 03, 2023 (GLOBE NEWSWIRE) -- Ocular Therapeutix Inc. (NASDAQ: OCUL), a biopharmaceutical company focused on the formulation, development and commercialization of innovative therapies for diseases and conditions of the eye, today announced the initiation of its first pivotal clinical trial to evaluate OTX-TKI, the Company’s axitinib intravitreal implant, for the treatment of wet age-related macular degeneration (wet AMD). OTX-TKI is also being developed for the treatment of diabetic retinopathy and other retinal diseases. "We are thrilled to announce the initiation of our pivotal trial evaluating OTX-TKI for the treatment of wet AMD and look forward to working with clinical sites across the US," said Antony Mattessich, CEO of Ocular Therapeutix. “With the activation of our first clinical site in the US, we believe we are on target to enroll our first subject before year end. The trial is a crucial step forward for our clinical program as we make progress toward our goal of bringing a transformative new treatment that can truly make a difference for wet AMD to patients coping with vision loss." Ocular Therapeutix has requested a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration (FDA) regarding the design of the trial, which is designed as a superiority trial that will enroll approximately 300 evaluable wet AMD subjects who are treatment naïve in the study eye. The trial is designed to be a multi-center, parallel-group trial that will be run primarily at U.S. sites with subjects randomized to one injection of aflibercept or one implant of OTX-TKI followed by as needed supplemental anti-VEGF treatment based on pre-specified criteria. The safety and efficacy of OTX-TKI will be assessed by measuring best corrected visual acuity (BCVA) and central subfield thickness (CSFT) at 36 weeks. While this institutional review board (IRB) approval has been received, the Company does not intend to enroll a subject before the SPA feedback is received from the FDA. Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada, has agreed to be the principal investigator for the OTX-TKI pivotal Phase 3 trial. Dr. Khanani is an internationally renowned retina specialist with extensive experience in clinical trial design for the treatment of age-related macular degeneration. He has served as a principal investigator for numerous clinical trials evaluating novel treatments for wet AMD and other retinal diseases. “Anti-VEGF agents have revolutionized the treatment of wet AMD, but numerous real-world patients experience vision loss due to their inability to adhere to the demanding treatment regimen involving frequent injections,” said Dr. Khanani. “OTX-TKI has shown the potential to reduce treatment burden while maintaining vision and anatomy for patients with wet AMD. The OTX-TKI pivotal trial design is unique as it is based on the latest FDA guidance for wet AMD. As a field, we must continue to push for the approval of new therapies while making sure we appropriately manage our patients who participate in these clinical trials. I look forward to working with Ocular Therapeutix, the regulatory agency and the retina community to harmonize regulatory endpoints with clinical practice.” David Brown, MD, FACS, a renowned leader in the retina community, is the co-chairman of the medical leadership board at Retina Consultants of America (RCA) which has agreed to participate in the trial. Dr. Brown has pioneered research and treatment in retina, publishing more than 300 national meeting presentations, abstracts and scientific papers, including many of the primary papers that established the use of anti-VEGF agents for AMD, diabetic retinopathy and retinal vein occlusion. “This pivotal trial is thoughtfully designed to satisfy the FDA’s latest guidance in wet AMD, while also balancing the needs of subjects who enter it,” said Dr. Brown. “The sites at RCA are excited to be a part of the OTX-TKI program as we continue our mission to develop better treatments for patients in the fight against retinal blindness.” The pivotal trial was initiated based on the previously announced positive 12-month top-line data from the Company’s 21-subject U.S.-based Phase 1 trial of OTX-TKI for the treatment of wet AMD. Data from this trial were presented at the Clinical Trials at the Summit 2023 Meeting held in Park City, Utah in June 2023. In that trial, subjects treated with a single implant of OTX-TKI were observed to have an 89% reduction in treatment burden compared to subjects treated with aflibercept while maintaining visual acuity and retinal thickness through 12 months. Subjects in the OTX-TKI arm had mean changes from baseline of -1.0 letters in BCVA and +20.2 μm in CSFT at 12 months, comparable to mean changes from baseline for subjects in the aflibercept arm of +2.0 letters and -2.2 μm. 60% of OTX-TKI subjects remained rescue-free up to 12 months. As of the April 14, 2023 data cut-off date, no drug-related ocular or systemic serious adverse events through 12 months were observed in the OTX-TKI arm. About OTX-TKI OTX-TKI is an investigational bioresorbable, hydrogel implant incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties, being evaluated for the treatment of wet age-related macular degeneration (wet AMD) and other retinal diseases. About Ocular Therapeutix, Inc. Ocular Therapeutix, Inc. is a biopharmaceutical company focused on the formulation, development and commercialization of innovative therapies for diseases and conditions of the eye using its proprietary bioresorbable hydrogel-based formulation technology. Ocular Therapeutix’s first commercial drug product, DEXTENZA®, is an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery and ocular itching associated with allergic conjunctivitis. Ocular Therapeutix’s earlier stage development assets include: OTX-TKI (axitinib intravitreal implant), currently in a Phase 1 clinical trial for the treatment of diabetic retinopathy and a pivotal Phase 3 trial for wet AMD; OTX-TIC (travoprost intracameral implant), currently in a Phase 2 clinical trial for the treatment of primary open-angle glaucoma or ocular hypertension; and OTX-CSI (cyclosporine intracanalicular insert) for the chronic treatment of dry eye disease and OTX-DED (dexamethasone intracanalicular insert) for the short-term treatment of the signs and symptoms of dry eye disease, both of which have completed Phase 2 clinical trials. Forward Looking Statements Any statements in this press release about future expectations, plans, and prospects for the Company, including the development and regulatory status of the Company’s product candidates, including the timing and design of the Company’s pivotal trials of OTX-TKI for the treatment of wet AMD; the Company’s plans to advance the development of OTX-TKI; the Company’s cash runway and sufficiency of the Company’s cash resources; and other statements containing the words "anticipate," "believe," "estimate," "expect," "intend", "goal," "may", "might," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the timing and costs involved in commercializing DEXTENZA or any product or product candidate that receives regulatory approval, including the conduct of post-approval studies; the ability to retain regulatory approval of DEXTENZA or any product or product candidate that receives regulatory approval; the ability to maintain and the sufficiency of product, procedure and any other reimbursement codes for DEXTENZA; the initiation, design, timing, conduct and outcomes of clinical trials, including the first pivotal trial of OTX-TKI for the treatment of wet AMD; uncertainties as to the response from the FDA regarding the SPA submission for OTX-TKI, including the risk that the FDA will not agree with the design of the first pivotal trial under the SPA; the risk that even if the FDA agrees with the design of the first pivotal trial under the SPA, the FDA will not agree that the data generated by the trial could support marketing approval; uncertainty as to whether the data from earlier clinical trials will be predictive of the data of later clinical trials, particularly later clinical trials that have a different design than the earlier trials; availability of data from clinical trials and expectations for regulatory submissions and approvals; the Company’s scientific approach and general development progress; uncertainties inherent in estimating the Company’s cash runway, future expenses and other financial results, including its ability to fund future operations, including clinical trials; Company’s existing indebtedness and the ability of the Company’s creditors to accelerate the maturity of such indebtedness upon the occurrence of certain events of default; the Company’s ability to enter into strategic alliances or generate additional funding on a timely basis, on favorable terms, or at all; and other factors discussed in the “Risk Factors” section contained in the Company’s quarterly and annual reports on the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Investors Ocular Therapeutix Donald Notman Chief Financial Officer dnotman@ocutx.com or ICR Westwicke Chris Brinzey, 339-970-2843 Managing Director chris.brinzey@westwicke.com Media ICR Westwicke Ben Shannon, 443-213-0495 ben.shannon@westwicke.com

STOCKHOLM, Sept. 29, 2023 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (NASDAQ Stockholm: CALTX) ("Calliditas"), today announced the presentations of new biomarker and subgroup analyses from the Phase 3 NefIgArd study with Nefecon (TARPEYO® (budesonide) delayed release capsules/Kinpeygo®) in adults with Primary IgA nephropathy (IgAN). The data was presented in both posters and oral presentations at the 17th International Symposium on IgA Nephropathy (IIGaNN), held in Tokyo, Japan, on September 25-27, 2023. "We are proud to have showcased new data at this year's International Symposium on IgAN in Tokyo," said Richard Phillipson, Chief Medical Officer at Calliditas. "Taken together, the positive findings from our biomarker and patient subgroup analyses from our Phase 3 NefIgArd study indicate that Nefecon treatment results in a coordinated immunological response with the potential to modulate the intestinal immune network responsible for IgA production. These additional findings further reinforce the potential of TARPEYO in enabling physicians to proactively manage and potentially mitigate the impact of the disease by targeting the source and slowing kidney function decline." Biomarker Analyses IgA-containing immune complexes (IgA-IC) have previously been shown to accumulate in renal tissue, where they trigger inflammation and scarring in the glomeruli. Investigation of the effect of Nefecon on circulating levels of IgA-IC in the Part A population of the NefIgArd clinical trial (n=160) revealed that patients treated with Nefecon 16mg/day exhibited a statistically significant decrease in IgA-IC levels compared to patients who received placebo when evaluated at the 3-, 6- and 9-months post randomization. Suppression by treatment with Nefecon of both IgA-IC formation and galactose-deficient IgA1 as previously reported offers an unprecedented opportunity to target the fundamental immune abnormalities that drive IgA deposition in the kidney and development of IgAN. An additional analysis of the 160 patients enrolled in Part A of the Phase 3 NefIgArd clinical study was conducted to assess the levels of three soluble factors known for modulating B cell maturation in gut-associated lymphoid tissue (GALT) BAFF, APRIL and sBCMA. Levels of BAFF were decreased at the 3-, 6-, and 9-months post treatment mark compared to placebo. Levels of APRIL were significantly reduced at the 3- and 6-months timepoints and levels of sBCMA were decreased at the 6-months timepoint. These data further support the potential disease-modifying effect of Nefecon in IgAN and reinforce the central role of the gut-kidney axis in the pathogenesis of IgAN. To further understand the impact of Nefecon on chemokine signaling in IgAN patients, the levels of three circulating chemokines known to be present in the intestinal tract at the site of IgA production, CXCL5, CCL13 and CCL11, were assessed in the Part A patient population portion of the NefIGArd trial (n=160). Dr. Barratt and colleagues reported that treatment with Nefecon 16 mg/day resulted in a statistically significant decrease in the levels of CXCL5 and CCL13 and an increase in levels of CCL11 at 3-, 6- and 9-months post-treatment when compared to placebo. These biomarker data provide additional evidence for a mucosal mechanism of action of Nefecon in IgAN and support previous observations that disordered lymphocyte trafficking and mucosal dysregulation likely contribute to the pathogenesis of IgAN. Patient Subgroup Analyses The full two-year results of the Phase 3 NefIgArd trial (n=364 patients) were further analyzed to assess potential differences in response to Nefecon treatment based on self-reported Asian (n=83) or White (n=275) ancestry in patients with IgAN. Treatment with Nefecon 16 mg/day over a 9-month period resulted in clinically meaningful preservation of kidney function in both subgroups, as evidenced by ameliorated eGFR and proteinuria in these two subgroups when compared to placebo subgroups. NefIgArd Sub-Analyses Full analysis of the Phase 3 NefIgArd study over the entire 2-year study period of the 364 patients (1:1 patient randomization to Nefecon 16 mg/day or placebo) enrolled in the study revealed clinically meaningful impact on three key markers of IgAN disease progression as evidenced by: A statistically significant benefit of Nefecon over placebo in estimated glomerular filtration rate (eGFR) over the two-year study period, which consisted of nine months of treatment with Nefecon or placebo, followed by a 15-month follow-up period off the study drug. A clinically significant reduction in proteinuria was found to be durable for the entire 15-month follow-up period off the study drug. Relevant decrease in microhematuria was also observed during Part B of the study, with fewer patients in the Nefecon treatment group exhibiting microhematuria at follow up visits compared to the placebo group. Indication TARPEYO® (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory clinical trial. Important Safety Information Contraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations. Warnings and Precautions Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression. Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B). Risks of immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg., chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines. Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects. Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO patients and ≥2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weight increase (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%). Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide. Use in specific populations Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism. Please see Full Prescribing Information. About TARPEYO Calliditas has introduced TARPEYO, the first FDA-approved therapy for the treatment of the autoimmune renal disease primary IgA Nephropathy, or IgAN, to reduce proteinuria in adults with primary IgAN who are at risk of rapid disease progression, generally a UPCR≥1.5g/g. This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. TARPEYO is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. TARPEYO is as a 4 mg delayed release capsule and is enteric coated and designed to remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. It is unclear to what extent TARPEYO's efficacy is mediated via local effects in the ileum vs systemic effects. About the NeflgArd Study The global clinical trial NefIgArd is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN (N=364), as an addition to optimized RAS inhibitor therapy. Part A of the study included a 9-month blinded treatment period and a 3-month follow-up period. The primary endpoint was UPCR, and eGFR was a secondary endpoint. Part B included a 12-month observational period off drug and assessed eGFR over the entire 2-year period for patients who were treated with the TARPEYO or placebo regimen in Part A. The full NefIgArd trial met its primary endpoint. Topline data from the full NefIgArd study were reported on March 12, 20 About Primary Immunoglobulin A Nephropathy Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger's Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 is recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease. IgAN most often develops between late teens and late 30s. For further information, please contact: Åsa Hillsten, Head of Investor Relations, Calliditas Tel.: +46 76 403 35 43, email: [email protected] The information was sent for publication, through the agency of the contact person set out above, on September 29, 2023, at 14.00 p.m. CET. The following files are available for download: SOURCE Calliditas Therapeutics