Chickenpox

-- Zero shingles cases after 18.8 months follow-up in 619 patients receiving any dose of amezosvatein, a development-stage adjuvanted subunit vaccine -- Ten shingles cases would have been expected absent vaccination -- Updated data will be featured in an oral presentation at the World Vaccine Congress Barcelona, 31 October 2024, in Theatre 5 at 13:30 CEST SEATTLE, Oct. 31, 2024 (GLOBE NEWSWIRE) -- Curevo Vaccine (Curevo), a privately-held clinical-stage biotechnology company dedicated to developing varicella zoster virus (VZV) vaccines with improved tolerability and accessibility, today announced an upcoming oral presentation at the World Vaccine Congress currently underway in Barcelona of shingles case outcomes data from an 876-patient Phase 2 trial of amezosvatein (a non-mRNA, adjuvanted subunit vaccine also known as CRV-101) head-to-head versus Shingrix® in participants aged 50 years and older. There were zero confirmed cases of herpes zoster (shingles) in the amezosvatein arm of participants, regardless of dose, after mean follow-up of 18.8 months in this post-hoc analysis of the Phase 2 trial. Based on the shingles incidence rate from the placebo arm North American cohort of ZOSTER-006, a Phase 3 trial of Shingrix, 10 of the 876 participants in the Phase 2 trial should have been diagnosed with a confirmed shingles case absent effective vaccination.1 There were also no shingles cases in the Shingrix arm of this Phase 2 trial. “With the duration of follow-up in our Phase 2 trial now sufficient for comparison, we are excited to report zero shingles cases for amezosvatein,” said Dr. Guy De La Rosa, Curevo’s Chief Medical Officer. “These data provide outcomes-based confirmation of the non-inferiority immunogenicity data we reported earlier.” “These data support our efforts to bring a new shingles vaccine to global markets,” stated George Simeon, Curevo’s Chief Executive Officer. “Though somewhat unsurprising, given amezosvatein also showed non-inferior immunogenicity to Shingrix at day 84 in this trial, these longer-term data represent additional de-risking for the program.” About the Phase 2 trialThe Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix on an identical two-dose, two months apart schedule. 876 participants were randomized to receive one of four different amezosvatein doses or Shingrix. The mean follow-up of the 619 participants receiving amezosvatein was 18.8 months. Mean follow-up of the 257 participants who received Shingrix was 21.5 months. The co-primary endpoint of the Phase 2 trial was anti-gE antibody humoral immune responses one month after the second vaccine dose (Day 84). The randomized, observer-blind, and active-controlled trial was conducted at multiple centers in the USA. All suspected cases of shingles were confirmed by either PCR test or, if PCR testing was inconclusive or unavailable, by a blinded panel of shingles experts – a system similar to one used in multiple prior shingles vaccine pivotal studies. As presented earlier in the month at the IDWeek scientific conference, this co-primary immunogenicity endpoint was met in the highest amezosvatein dose studied (100 μg gE plus 15 μg SLA-SE) as participants’ immune responses to amezosvatein were non-inferior to participants’ immune responses to Shingrix. High-dose amezosvatein and Shingrix generated similar serum neutralizing antibodies to the varicella zoster virus (VZV) and T-cell responses specific for the gE antigen. Vaccines are studied for both safety and reactogenicity/tolerability. Data on the reactogenicity/tolerability of amezosvatein and Shingrix were collected via a participant diary filled out for the seven days after each injection. Participants were asked to grade the tolerability of each vaccine on a scale of Grade 1 to Grade 3. Grade 1 represents what are considered normal reactions to an active vaccine that do not interfere or prevent daily activity. Grade 2 represents reactogenicity events interfering with daily activities. Grade 3 represents reactogenicity events preventing daily activities. Amezosvatein and Shingrix demonstrated comparable safety in this Phase 2 trial. However, the highest dose of amezosvatein demonstrated a clinically-meaningful and statistically-significant improvement for Grade 2 and Grade 3 reactogenicity versus Shingrix. Just 7.3% of participants in the trial receiving the highest dose of amezosvatein reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event compared to 33.3% of participants receiving Shingrix. This result was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons). Reactogenicity events were broken down between local reactions (injection site pain, redness, or swelling) and systemic reactions (fever, headache, fatigue, myalgia/muscle pain, chills). Just 3.6% of high-dose amezosvatein participants had a Grade 2 or Grade 3 local reactogenicity event compared to 25.3% of Shingrix participants. For systemic reactogenicity events, 5.5% of high-dose amezosvatein participants had a Grade 2 or Grade 3 event versus 19.1% for Shingrix. Both results were statistically significant (p=0.0002 and p=0.0139, respectively, in a post hoc analysis unadjusted for multiple comparisons). No Grade 3 reactogenicity events were reported for amezosvatein. About amezosvatein‘Amezosvatein’ is the assigned non-proprietary name for CRV-101, a non-mRNA adjuvanted subunit vaccine under investigation by Curevo. Like Shingrix, amezosvatein uses a subunit protein antigen called glycoprotein ‘E’ (gE). Targeting the gE antigen is proven to elicit a long-term, protective immune response to prevent shingles. Also like Shingrix, amezosvatein uses an adjuvant targeting the TLR4 pathway to boost the immune response to the gE antigen. Amezosvatein was engineered to have a best-in-class safety profile in addition to manufacturing advantages to improve vaccine accessibility. The SLA-SE adjuvant formulation was developed at Seattle-based Access to Advanced Health Institute (AAHI) and amezosvatein was licensed from the Mogam Institute for Biomedical Research, a research institute funded by South Korea’s GC Biopharma. About shinglesAlso called ‘herpes zoster’, shingles occurs when the varicella zoster virus causing childhood chickenpox re-emerges from sensory ganglion nervous system cells where the virus lies dormant after initial exposure. Virtually all adults have been exposed to the varicella zoster virus and around 30% will develop shingles at least once in their lifetime. The blistering skin rash accompanying shingles also causes severe pain, with both pain and rash lasting up to four weeks. Between 10-18% of those who get shingles develop post-herpetic neuralgia (PHN), a condition marked by debilitating nerve pain lasting over six months and often beyond one year. There is no approved treatment for PHN. Shingles may also affect the eyes, potentially causing loss of vision. Contracting shingles has also been linked with increased risk of heart attack, stroke, and dementia/Alzheimer’s disease. About CurevoCurevo is a privately held, clinical-stage biotechnology company based near Seattle dedicated to reducing the burden of infectious disease by developing vaccines with improved tolerability and accessibility. Curevo’s lead product is amezosvatein, a non-mRNA sub-unit vaccine to prevent shingles, a serious medical condition involving a painful, blistering skin rash where 10-18% of people also develop serious, long-lasting nerve pain. The current $4+ billion shingles vaccine market is characterized by accessibility issues and vaccine hesitancy/dose avoidance related to vaccine tolerability. Curevo is also developing a non-live, non-mRNA subunit chickenpox vaccine intended to reduce or eliminate barriers to immunizing immunocompromised children. For more information visit https://curevovaccine.com/. 1. Lal, et al. New England Journal of Medicine, May 2015. Shingrix® is a registered trademark of GlaxoSmithKline, PLC.

STOCKHOLM, Sweden, Oct. 16, 2024 (GLOBE NEWSWIRE) -- Calliditas Therapeutics AB (Nasdaq Stockholm: CALTX) (“Calliditas”), today announced upcoming presence and data presentations at the American Society of Nephrology Kidney Week 2024 in San Diego, California on October 23 – 27, 2024. Presentations will highlight an open-label extension study of the efficacy and safety of Nefecon (TARPEYO® (budesonide) delayed release capsules)) in patients with primary immunoglobulin A nephropathy (IgAN), results from a real-world case series of IgAN patients, and additional insights from biomarker analysis. “We look forward to attending ASN Kidney Week and sharing additional data that reinforce Nefecon as a cornerstone treatment in IgAN,” said Richard Philipson, Chief Medical Officer at Calliditas. "This conference offers a great opportunity to exchange scientific knowledge with leading experts in nephrology and contribute to discussions around innovative treatments, including our potentially disease-modifying option." The oral presentation and poster presentation details are below. Following the meeting, they will be available on the Presentations and Publications page on Calliditas’ corporate website. Oral Presentation Details: Title: “NeflgArd Open-Label Extension: Efficacy and Safety of Nefecon in Patients with IgAN Who Completed the 2-Year Phase 3 Trial”Date and Time: October 25, 2024 from 4:40 PM to 4:50 PM PTLocation: Room 6D, Convention Center Poster Presentation Details: Title: “Results from a real-world case series of IgAN patients who received at least 9 months of Tarpeyo”Date and Time:Location: October 25, 2024 from 10:00 AM to 12:00 PM PT Title: Specificity of Nefecon in Targeting Pathogenic IgA in IgA Nephropathy While Preserving Systemic Humoral ImmunityDate and Time: October 25, 2024 from 10:00 AM to 12:00 PM PT Title: Impact of Nefecon on Complement Pathways in IgA Nephropathy: An Analysis of Lectin, Alternative, and Terminal PathwaysDate and Time: October 25, 2024 from 10:00 AM to 12:00 PM PT For more information, visit booth 1920 or visit the ASN Kidney Week 2024 website here. 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 PRECAUTIONSHypercorticism 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). Immunosuppression and Increased Risk of Infection: Corticosteroids, including TARPEYO, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: reduce resistance to new infections, exacerbate existing infections, increase the risk of disseminated infections, increase the risk of reactivation or exacerbation of latent infections, and mask some signs of infection. Corticosteroid-associated infections can sometimes be serious. Monitor for infection and consider TARPEYO withdrawal as needed. Avoid corticosteroid therapy, including TARPEYO, in patients with active or quiescent tuberculosis or hepatitis B infection; untreated fungal, bacterial, systemic viral, or parasitic infections; ocular herpes simplex; or Kaposi’s sarcoma. Avoid exposure to active, easily-transmitted infections (e.g., chickenpox, 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 POPULATIONSPregnancy: 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 TARPEYOTARPEYO 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 Primary Immunoglobulin A NephropathyPrimary 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. About Calliditas Calliditas Therapeutics is a biopharma company headquartered in Stockholm, Sweden, focused on identifying, developing, and commercializing novel treatments in orphan indications with significant unmet medical needs. Visit Calliditas.com for further information. For further information, please contact:Emma Santosegsantos@lifescicomms.com The information was sent for publication, through the agency of the contact persons set out above, on October 16, 2024, at 14.00 p.m. CET.

-- Positive data from 876-patient head-to-head trial versus Shingrix ® shows amezosvatein elicits robust humoral and cellular immune responses with comparatively lower reactogenicity -- Amezosvatein met both primary endpoints of immunogenicity non-inferiority and safety -- Updated data will be presented on poster #597, available October 17 th from 12:15 to 1:30pm PDT in Hall J & K SEATTLE, Oct. 16, 2024 (GLOBE NEWSWIRE) -- Curevo Vaccine (Curevo), a privately-held clinical-stage biotechnology company dedicated to developing varicella zoster virus (VZV) vaccines with improved tolerability and accessibility, today announced the upcoming presentation of data from an 876-patient Phase 2 trial of amezosvatein (a non-mRNA, adjuvanted subunit vaccine also known as CRV-101) head-to-head versus Shingrix in participants aged 50 years and older at the ID Week 2024 conference under way in Los Angeles. Amezosvatein met all primary endpoints in the randomized, active-controlled, and observer-blind Phase 2 trial, including demonstrating non-inferiority to Shingrix as measured by humoral immune response. Amezosvatein also exhibited improved tolerability, with lower rates of solicited local and systemic adverse events in this Phase 2 trial. Based upon these results, Curevo will advance amezosvatein into global Phase 3 trials in 2025 to address a market for shingles vaccination currently exceeding $4 billion annually. Amezosvatein and Shingrix are adjuvanted recombinant protein subunit vaccines targeting glycoprotein E (gE), the most abundant glycoprotein expressed on the surface of the varicella zoster virus responsible for shingles. Each vaccine is administered in a two-dose series two months apart. Both vaccines include toll-like receptor 4 (TLR-4) agonists to activate immune response. Amezosvatein contains the SLA adjuvant formulated in a stable emulsion with squalene oil, which differs from the adjuvant formulation in Shingrix combining MPL with saponin. Additionally, SLA was specifically engineered to target the human TLR-4 receptor. SLA is created via chemical synthesis rather than the complex biological process used to create MPL. The co-primary endpoint of the Phase 2 trial was anti-gE antibody humoral immune responses one month after the second vaccine dose (Day 84). This co-primary immunogenicity endpoint was met in the highest amezosvatein dose studied (100 μg gE plus 15 μg SLA-SE) as participants’ immune responses to amezosvatein were non-inferior to participants’ immune responses to Shingrix. The geometric mean fold-rise in anti-gE antibodies from baseline to Day 84 in the amezosvatein high-dose arm was 47.45x versus 47.93x for Shingrix. The ability of both vaccines to generate a serum neutralizing antibody response to VZV was also studied. The highest dose of amezosvatein had a geometric mean fold rise in anti-VZV neutralizing antibodies from baseline to Day 84 of 13.78x versus 10.62x for Shingrix. T-cell responses specific for the gE antigen were also measured by looking at a panel of four markers of T-cell activation, similar to the analysis completed in prior Shingrix trials. The highest dose of amezosvatein had a geometric mean fold rise of T-cells expressing two or more activation markers from baseline to Day 84 of 64.62x versus 42.05x for Shingrix. Vaccines are studied for both safety and reactogenicity/tolerability. Data on the reactogenicity/tolerability of amezosvatein and Shingrix were collected via a participant diary filled out for the seven days after each injection. Participants were asked to grade the tolerability of each vaccine on a scale of Grade 1 to Grade 3. Grade 1 represents what are considered normal reactions to an active vaccine that do not interfere or prevent daily activity. Grade 2 represents reactogenicity events interfering with daily activities. Grade 3 represents reactogenicity events preventing daily activities. Amezosvatein and Shingrix demonstrated comparable safety in this Phase 2 trial. However, the highest dose of amezosvatein demonstrated a clinically-meaningful and statistically-significant improvement for Grade 2 and Grade 3 reactogenicity versus Shingrix. Just 7.3% of participants in the trial receiving the highest dose of amezosvatein reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event compared to 33.3% of participants receiving Shingrix. This result was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons). Reactogenicity events were broken down between local reactions (injection site pain, redness, or swelling) and systemic reactions (fever, headache, fatigue, myalgia/muscle pain, chills). Just 3.6% of high-dose amezosvatein participants had a Grade 2 or Grade 3 local reactogenicity event compared to 25.3% of Shingrix participants. For systemic reactogenicity events, 5.5% of high-dose amezosvatein participants had a Grade 2 or Grade 3 event versus 19.1% for Shingrix. Both results were statistically significant (p=0.0002 and p=0.0139, respectively, in a post hoc analysis unadjusted for multiple comparisons). No Grade 3 reactogenicity events were reported for amezosvatein. If confirmed in a Phase 3 trial, this reactogenicity advantage could represent a significant advantage for amezosvatein since higher-grade reactogenicity events interfering or preventing daily activities are of particular concern to those considering being vaccinated for shingles. “Around 30% of people don’t go back for their second dose of Shingrix within the label-recommended window, and not receiving the second dose greatly reduces the protective effect of the vaccine. 1 Recently-presented survey data 2 indicate reactogenicity fears are the number one cited reason given for this second-dose avoidance,” said Dr. Guy De La Rosa, Curevo’s Chief Medical Officer. “Reactogenicity concerns are similarly the top cited reason given by responders in the research project for avoiding Shingrix vaccination altogether. Amezosvatein’s advantages in reactogenicity seen in this Phase 2 trial were exciting, particularly in the context of the potent humoral and cellular immune responses demonstrated.” “Shingrix is widely available in the USA and elsewhere, but clinicians like myself often have difficulty convincing our patients to take the vaccine due to its widely-known reputation of being a difficult vaccine to tolerate,” stated Dr. William Smith with the Alliance for Multispecialty Research, the primary investigator on this Phase 2 trial and a board-certified physician who has been involved in more than 1,900 clinical trials over the last 35 years. “Shingles is a very serious disease with effects often outlasting the painful rash. If these amezosvatein data are confirmed in Phase 3 trials and the vaccine is approved, I expect its lower reactogenicity rates will help get more people protected against shingles.” “The entire Curevo team is focused on starting our global Phase 3 program next year,” noted George Simeon, Curevo’s Chief Executive Officer. “If these results are confirmed in our registrational trials, we hope a vaccine like amezosvatein with non-inferior immunogenicity, improved reactogenicity, and more streamlined manufacturing can address current barriers to shingles vaccination.” About the Phase 2 trial The Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix on an identical two-dose, two months apart schedule. 257 participants received Shingrix and 619 participants across five arms received amezosvatein. Amezosvatein achieved both primary endpoints in the trial, Day 84 safety/tolerability and Day 84 humoral immune response as measured by the geometric mean concentration of anti-gE antibodies to both vaccines. The trial enrolled participants at over a dozen sites across the USA. About amezosvatein ‘Amezosvatein’ is the assigned non-proprietary name for CRV-101, a non-mRNA adjuvanted subunit vaccine under investigation by Curevo. Like Shingrix, amezosvatein uses a subunit protein antigen called glycoprotein ‘E’ (gE). Targeting the gE antigen is proven to elicit a long-term, protective immune response to prevent shingles. Also like Shingrix, amezosvatein uses an adjuvant targeting the TLR4 pathway to boost the immune response to the gE antigen. Amezosvatein was engineered to have a best-in-class safety pro addition to manufacturing advantages to improve vaccine accessibility. The SLA-SE adjuvant formulation was developed at Seattle-based Access to Advanced Health Institute (AAHI) and amezosvatein was licensed from the Mogam Institute for Biomedical Research, a research institute funded by South Korea’s GC Biopharma. About shingles Also called ‘herpes zoster’, shingles occurs when the varicella zoster virus causing childhood chickenpox re-emerges from sensory ganglion nervous system cells where the virus lies dormant after initial exposure. Virtually all adults have been exposed to the varicella zoster virus and around 30% will develop shingles at least once in their lifetime. The blistering skin rash accompanying shingles also causes severe pain, with both pain and rash lasting up to four weeks. Between 10-18% of those who get shingles develop post-herpetic neuralgia (PHN), a condition marked by debilitating nerve pain lasting over six months and often beyond one year. There is no approved treatment for PHN. Shingles may also affect the eyes, potentially causing loss of vision. Contracting shingles has also been linked with increased risk of heart attack, stroke, and dementia/Alzheimer’s disease. About Curevo Curevo is a privately held, clinical-stage biotechnology company based near Seattle dedicated to reducing the burden of infectious disease by developing vaccines with improved tolerability and accessibility. Curevo’s lead product is amezosvatein, a non-mRNA sub-unit vaccine to prevent shingles, a serious medical condition involving a painful, blistering skin rash where 10-18% of people also develop serious, long-lasting nerve pain. The current $4+ billion shingles vaccine market is characterized by accessibility issues and vaccine hesitancy/dose avoidance related to vaccine tolerability. Curevo is also developing a non-live, non-mRNA subunit chickenpox vaccine intended to reduce or eliminate barriers to immunizing immunocompromised children. For more information visit . (1) Zerbo, et al. “Effectiveness of a recombinant zoster vaccine against herpes zoster in a real-world-setting.” Annals of Internal Medicine , January 2024. (2) Wagner, et al. “Challenges in shingles vaccination update in the United States: The role of concerns about adverse events”, presented at the International Herpesvirus Workshop, July 2024. Shingrix ® is a registered trademark of GlaxoSmithKline, PLC. CONTACT: Contacts David Miller Sr. Director of Strategic Communications pr@curevovaccine.com