Everest Medicines announces FDA grants our Partner Calliditas Therapeutics Accelerated Approval of TARPEYO™ (budesonide) to Reduce Proteinuria in IgA Nephropathy

Everest Medicines Limited (HKEX 1952.HK) today reported that Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) ("Calliditas") announced that the US Food and Drug Administration (FDA) has approved TARPEYOTM (budesonide) delayed release capsules 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) ≥1.5g/g. This indication is approved under accelerated approval. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.1

"We are very excited to bring the first and only FDA-approved treatment to reduce proteinuria in IgAN to market," said Renée Aguiar-Lucander, Chief Executive Officer of Calliditas. "TARPEYO represents an FDA approved product to help these patients who are at risk of rapid disease progression."

"The FDA approval of Calliditas' novel formulation of budesonide, which we are advancing in our territory under the development name 'NEFECON', marks a major step forward for IgAN treatment," said Kerry Blanchard, MD, PhD, CEO of Everest Medicines. "We congratulate our partner Calliditas on its expedited global clinical and regulatory advancements to make this first-in-disease therapy available to patients in need. At Everest, we look forward to progressing development of this important therapy for patients in Greater China and other parts of Asia, where there is a high prevalence of IgAN."

TARPEYO is approved under accelerated approval based on achieving its primary endpoint of  reduction in proteinuria in Part A of the NeflgArd pivotal Phase 3 study, an ongoing, randomized, double-blind, placebo-controlled, multicenter study conducted to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN1. The effect of TARPEYO was assessed in patients with biopsy-proven IgAN, eGFR ≥35 mL/min/1.73 m2, and proteinuria (defined as either ≥1 g/day or UPCR ≥0.8 g/g) who were on a stable dose of maximally-tolerated RAS inhibitor therapy.

Patients taking TARPEYO (n=97) showed a statistically significant 34% reduction in proteinuria from baseline vs 5% with RASi alone (n=102) at 9 months. The treatment effects for the primary endpoint of UPCR at 9 months were consistent across key subgroups, including key demographic and baseline disease characteristics.1 The most common adverse reactions (≥5%) in this study were hypertension, peripheral edema, muscle spasms, acne, dermatitis, weight increase, dyspnea, face edema, dyspepsia, fatigue, and hirsutism.

Richard Lafayette M.D., Professor of Medicine at Stanford University and the Director of the Stanford Glomerular Disease Center commented, "IgAN is a tough diagnosis for many patients, and it can progressively lead to the need for dialysis and/or kidney transplantation. The FDA approval of TARPEYO now offers disease-specific treatment for patients with this complicated disease."

Richard Philipson, Calliditas Chief Medical Officer added, "TARPEYO was developed to target a root cause of IgAN. The FDA's approval of TARPEYO demonstrates our unwavering dedication to patients suffering from IgAN. We would like to thank the patients, researchers and clinical staff who participated in the studies of TARPEYO."

Bonnie Schneider, Director and Co-Founder of the IGA Nephropathy Foundation of America commented," It has been a difficult journey not only for our family but for all the IgA nephropathy patients we serve. Having this disease specific option has our community very excited."

For more information, please see Calliditas press release on this announcement

About NEFECON

NEFECON (approved in the United States under accelerated approval under the trade name TARPEYOTM) is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. NEFECON was designed as a 4 mg delayed release capsule and is enteric coated so that it would 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 NEFECON's efficacy is mediated via local effects in the ileum vs systemic effects. In June 2019, Everest Medicines entered into an exclusive, royalty-bearing license agreement with Calliditas, which gives Everest Medicines exclusive rights to develop and commercialize NEFECON in Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China, Taiwan, China and Singapore.

About the NeflgArd Study

The global clinical trial NeflgArd is an ongoing Phase 3, randomized, double-blind, placebo- controlled, multicenter study to evaluate the efficacy and safety of NEFECON once daily vs placebo in adult patients with primary IgAN (N=360) as an addition to optimized RASi 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, a confirmatory validation study in which no NEFECON treatment will be administered, will assess eGFR at two years.

The trial met its primary objective in Part A of demonstrating a statistically significant reduction in urine protein creatinine ratio, UPCR or proteinuria, after 9 months of treatment with 16 mg once daily of NEFECON compared to placebo. Patients taking NEFECON plus RASi (n=97) showed a statistically significant 34% reduction from baseline vs 5% with RASi alone (n=102) at 9 months, resulting in UPCR reduction of 31% (16% to 42%) p=0.0001.

About Primary Immunoglobulin A Nephropathy

Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger's Disease) is a  progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 are recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney.4,5 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.5,6

About Everest Medicines

Everest Medicines is a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record of high-quality clinical development, regulatory affairs, CMC, business development and operations both in China and with leading global pharmaceutical companies. Everest Medicines has built a portfolio of ten potentially global first-in-class or best-in-class molecules, many of which are in late-stage clinical development. The Company's therapeutic areas of interest include oncology, autoimmune disorders, cardio-renal diseases and infectious diseases. For more information, please visit its website at www.everestmedicines.com.

About Calliditas

Calliditas Therapeutics is a biopharma company headquartered in Stockholm, Sweden, focused on identifying, developing, and commercializing novel treatments in orphan indications, with an initial focus on renal and hepatic diseases with significant unmet medical needs. Calliditas is listed on Nasdaq Stockholm (ticker: CALTX) and the Nasdaq Global Select Market (ticker: CALT). Visit www.calliditas.com for further information.

1. TARPEYOTM (budesonide) [prescribing information]. Stockholm, SE: Calliditas Therapeutics AB; 2021

2. Fellstrom BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. May 27, 2017;389(10084):2117-2127. https://doi:10.1016/S0140-6736(17)30550-0

3. Hastings, M. C., Bursac, Z., Julian, B. A., Villa Baca, E., Featherston, J., Woodford, S. Y., Bailey, L., & Wyatt, R. J. (2018). Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep, 3(1), 99-104. https://doi.org/10.1016/j. ekir.2017.08.008

4. Barratt, J., & Feehally, J. (2005). IgA nephropathy. J Am Soc Nephrol, 16(7), 2088-2097. https://doi.org/10.1681/ASN.2005020134

5. Barratt, J., Rovin, B. H., Cattran, D., et al. (2020). Why Target the Gut to Treat IgA Nephropathy? Kidney Int Rep, 5(10), 1620-1624. https://doi.org/10.1016/j.ekir.2020.08.009

6. Jarrick, S., Lundberg, S., Welander, A., et al. (2019). Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study. J Am Soc Nephrol, 30(5), 866-876. https://doi.org/10.1681/ASN.2018101017

Source: Everest Medicines