Cyclosporine

STOCKHOLM, April 18, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ("Calliditas"), today announced additional data analyses from the 2-year Phase 3 NeflgArd trial evaluating Nefecon (TARPEYO® (budesonide) delayed-release capsules/Kinpeygo®) in patients with IgA nephropathy (IgAN), were presented at the ISN World Congress of Nephrology in Buenos Aires, Argentina on April 13-16, 2024. "We were pleased to share additional analyses from the 2-year Phase 3 NeflgArd trial of Nefecon in IgAN at this year's World Congress of Nephrology," said Richard Philipson, Chief Medical Officer of Calliditas. "These additional data further reinforce the impact of Nefecon across the entire study population, irrespective of baseline UPCR levels or patient's racial and ethnic backgrounds." Poster presentation details are below and will be available on the Presentations and Publications page on the Calliditas' corporate website following the meeting. Poster Presentation Analyses: Poster Title: "Nefecon treatment provides kidney benefits for patients with IgAN that extend to those with low levels of UPCR: A sub-analysis of the phase III NefIgArd trial" An extended analysis of patients with baseline UPCR levels above and below 0.8 g/g was performed to further explore the potential benefits of Nefecon. In the full analysis involving 364 patients regardless of baseline UPCR, Nefecon treatment consistently improved the estimated glomerular filtrate rate (eGFR) over the 2-year study period compared to placebo. 72 patients with a baseline UPCR <0.8 g/g experienced sustained eGFR improvement (p=0.0026), which persisted for up to 18 months after treatment initiation, even after the treatment cessation at month 9. Those patients also achieved an eGFR slope of -0.25 mL/min/1.73 m2 per year, indicating that Nefecon treatment may support them in reaching the RaDaR treatment target of an eGFR decline of <1 mL/min/1.73 m2 per year. This objective is pivotal in mitigating the risk of kidney failure in their lifetime. Poster Title: "eGFR decline in patients with IgAN treated with Nefecon or placebo: Results from the 2-year NefIgArd Phase 3 trial" During the 9-month treatment period, Nefecon showed a 30% reduction in UPCR compared to the placebo, sustained for 2 years. The percentage of patients with a confirmed 30% reduction in eGFR or kidney failure was lower in the Nefecon arm compared to placebo, and the time to such events was significantly delayed with Nefecon (hazard ratio [HR] 0.45; 95% confidence interval 0.26, 0.75]; p=0.0014 [1-sided]). Supplementary analysis with rescue medication yielded similar results, irrespective of the handling of rescue medication: Rescue medication counted as an event: HR 0.51 (95% CI 0.33, 0.79), Regardless of rescue medication: HR 0.44 (95% CI 0.27, 0.71). The treatment effect of Nefecon on the risk of kidney function decline was consistent regardless of baseline UPCR. These findings strongly suggest preserved kidney function and provide support for Nefecon as a disease-modifying therapy in patients with IgAN. Poster Title: Nefecon effect on quality of life in patients with IgAN: SF-36 results from the Phase 3 NefIgArd trial" The 2-year results of quality of life (QoL) analyses based on 36-Item Short Form Survey (SF-36) assessments at 9 and 24 months revealed no meaningful differences in any QoL domain between Nefecon and placebo groups after 9 months of treatment. These SF-36 scores remained consistent after 15 months of off-drug observational follow-up further supporting the benefit/risk profile of Nefecon. Poster Title: "Nefecon treatment response in Asian and White patient populations with immunoglobulin A nephropathy: A 2-year analysis of the Phase 3 NefIgArd trial" The responses to Nefecon treatment from the full 2-year NefIgArd trial were assessed in patients identifying as Asian (n=83) or White (n=275). Regardless of race and ethnicity, Nefecon showed a favorable change in eGFR compared to placebo of 5.5 mL/min/1.73 m2 in Asian patients and 4.8 mL/min/1.73 m2 in White patients. Nefecon also demonstrated greater reductions in UPCR at 9 and 24 months with notable delays in kidney function decline events. These effects were consistent across races and ethnicities. Additionally, Nefecon significantly reduced the rate of microhematuria in both Asian and White patients. Overall, these findings highlight Nefecon's efficacy and tolerability across different racial and ethnic groups. Indication TARPEYO is indicated to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. 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 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. Chickenpox 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 (e.g., 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 or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where corticosteroids may have unwanted effects. Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients, and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increased (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increased (6%). 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 TARPEYO is an oral 4mg delayed release formulation of budesonide, 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. About the NeflgArd Study NefIgArd was a global, 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 RASi therapy. Patients were randomized 1:1 to receive 16 mg/day oral capsules of TARPEYO or matching placebo for 9 months, followed by a 15-month observational follow-up period without the study drug. The primary efficacy endpoint was time-weighted average of eGFR over 2 years. The time-weighted average of eGFR over 2 years showed a statistically significant treatment benefit with TARPEYO versus placebo (difference 5•05 mL/min per 1•73 m² [95% CI 3•24 to 7•38], p<0•0001). The favorable effect of TARPEYO on eGFR was seen by Month 3 (the earliest assessment) and did not appear to increase in magnitude over two years. At the end of Year 2, there was a 5.9 mL/min/1.73 m2 difference in the mean change from baseline in eGFR between TARPEYO and placebo (95% CI: 3.3 to 8.5 mL/min/1.73 m2; p<0.0001). The effect on kidney function seen during the 9-month treatment period persisted following completion of treatment through the end of the study but the overall effect on the long-term rate of decline has not been established. The most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO treated patients and ≥2% higher than placebo) were peripheral edema (17%), hypertension (12%), muscle spasms (12%), acne (11%), headache (10%), upper respiratory tract infection (8%), face edema (8%), weight increase (7%), dyspepsia (7%), dermatitis (6%), arthralgia (6%), and white blood cell count increase (6%). 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 IR & Sustainability, Calliditas Tel : +46 76 403 35 43, Email : [email protected] The information was sent for publication, through the agency of the contact persons set out above, on April 18, 2023, at 13.00 p.m. CET. This information was brought to you by Cision The following files are available for download:

46.2% of patients demonstrated a 1- or 2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) at 40 weeks in the AXPAXLI arm, compared to 0% in the control arm No patients in the AXPAXLI group experienced worsening in DRSS compared to 12.5% in the control arm at 40 weeks AXPAXLI was generally well tolerated with no inflammation observed Ocular intends to present the Phase 1 HELIOS study at an upcoming meeting BEDFORD, Mass., April 18, 2024 (GLOBE NEWSWIRE) --Ocular Therapeutix, Inc. (NASDAQ:OCUL) (“Ocular”), a biopharmaceutical company committed to enhancing people’s vision and quality of life through the development and commercialization of innovative therapies for wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), and other diseases and conditions of the eye, today announced positive topline results from the Phase 1 HELIOS study evaluating AXPAXLI versus a sham control in patients with moderately severe to severe non-proliferative diabetic retinopathy (‘NPDR’, NCT05695417) without diabetic macular edema (DME). Ocular plans to present the study results at an upcoming meeting. Summary of Topline Phase 1 HELIOS Results: Safety: AXPAXLI was generally well tolerated with no inflammation observed including no incidence of iritis, vitritis or vasculitis Efficacy Results: 6 of 13 (46.2%) patients in the AXPAXLI group experienced a 1 or 2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) at 40 weeks, with 2 of the 6 having a 2-step improvement. No patients in the control group showed 1- or 2-step improvement at the same time point. No patients in the AXPAXLI group experienced any worsening in DRSS. 1 of 8 (12.5%) in the control group experienced worsening in the DRSS at 40 weeks. Durability of Effect: A single injection of AXPAXLI provided durable DRSS improvement up to 40 weeks Rescue medication: No patients in either arm received rescue medication Next Steps: Positive HELIOS results support decision to move directly to a Phase 3 study with AXPAXLI in patients with NPDR, pending discussions with the FDA Data Release: Ocular plans to present topline results from the HELIOS study at a future meeting “We are pleased to announce positive topline data for AXPAXLI in patients with diabetic retinopathy. In an effort to get AXPAXLI to patients as quickly as possible, we unmasked this study, and based on the observed safety, efficacy results and durable treatment effect, we have decided to accelerate the DR program to Phase 3. We look forward to providing additional information on our timeline for next steps, including our plans to present these results at an upcoming meeting in the coming months,” said Jeffrey S. Heier, Chief Scientific Officer (CSO) of Ocular Therapeutix. “It is promising that the efficacy signals seen to date in this Phase 1 study consistently favor AXPAXLI. These data demonstrated DRSS improvements and durability for up to 40 weeks,” said Dilsher Dhoot, MD. “In addition, these results, combined with the results in the AMD studies of AXPAXLI, make me even more enthusiastic to be a principal investigator in the SOL-1 study.” Dr. Dhoot, of California Retina Consultants, is an internationally recognized key opinion leader in retinal diseases. About the HELIOS study The Phase 1 HELIOS study is a multi-center, double-masked, randomized 2:1, parallel group clinical trial conducted at 10 centers in the U.S. The data set reported here is based on 21 evaluable subjects (one patient of the 22 enrolled subjects died from an unrelated event). The study was designed to evaluate the safety, tolerability and efficacy of AXPAXLI compared to a sham control in subjects with moderately severe to severe NPDR without Diabetic Macular Edema (DME). The primary endpoint of the study is frequency of treatment emergent adverse events (TEAEs). Secondary study endpoints include changes in the DRSS, changes in best corrected visual acuity (BCVA), changes in central subfield thickness compared to baseline, and the portion of subjects receiving rescue therapy. About AXPAXLI™ AXPAXLI 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 AMD, DR and other retinal diseases. AboutOcularTherapeutix,Inc. Ocular Therapeutix, Inc. is a biopharmaceutical company committed to enhancing people’s vision and quality of life through the development and commercialization of innovative therapies for wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), and other diseases and conditions of the eye. AXPAXLI™ (axitinib intravitreal implant, also known as OTX-TKI), Ocular’s product candidate for retinal disease, is based on its ELUTYX™ proprietary bioresorbable hydrogel-based formulation technology. AXPAXLI is currently in the first of two planned pivotal Phase 3 trials for wet AMD, the SOL-1 trial, and a Phase 1 clinical trial for the treatment of NPDR. The clinical portfolio also includes PAXTRAVA™ (travoprost intracameral implant, also known as OTX-TIC), currently in a Phase 2 clinical trial for the treatment of primary open-angle glaucoma or ocular hypertension. Ocular’s expertise in the formulation, development and commercialization of innovative therapies of the eye and the ELUTYX platform supported the development and launch of its first commercial drug product, DEXTENZA®, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery and ocular itching associated with allergic conjunctivitis. ELUTYX is also the foundation for two other clinical-stage assets, 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, as well as several preclinical programs. Follow us on our website, LinkedIn or X. DEXTENZA® is a registered trademark of Ocular Therapeutix, Inc. AXPAXLI™, PAXTRAVA™, and ELUTYX™ and Ocular Therapeutix™ are trademarks of Ocular Therapeutix, Inc. 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, design, and enrollment of the Company’s Phase 3 trials of AXPAXLI (also called OTX-TKI) for the treatment of wet AMD and the Company’s planned Phase 3 clinical development program of AXPAXLI for the treatment of diabetic retinopathy; the Company’s plans to advance the development of AXPAXLI, PAXTRAVA and its other product candidates; the potential utility of any of the Company’s product candidates; the 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; the ability to retain regulatory approval of DEXTENZA or any product or product candidate that receives regulatory approval; the initiation, design, timing, conduct and outcomes of clinical trials, including the SOL-1 trial, the HELIOS trial, and the planned Phase 3 clinical development program of AXPAXLI for diabetic retinopathy as well as the Company’s other ongoing clinical trials; the risk that the FDA will not agree with the Company’s interpretation of the written agreement under Special Protocol Assessment for the SOL-1 trial; the risk that even though the FDA has agreed with the overall design of the SOL-1 trial, the FDA may not agree that the data generated by the SOL-1 trial supports potential 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 or utilize a different formulation than the earlier trials, or whether preliminary or interim data from a clinical trial will be predictive of final data from such trial; 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; the 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 Joyce Allaire LifeSci Advisors jallaire@lifesciadvisors.com