Mirum Pharmaceuticals Announces Positive Results from Cohort 2 of the Pivotal PROGRESS Study of ATEBRIOZ™ (zilurgisertib) in Pediatric Patients Aged 6 to <12 Years with Fibrodysplasia Ossificans Progressiva

Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM), a leading rare disease company, today announced positive results from Cohort 2 of the pivotal PROGRESS study of ATEBRIOZ™ (zilurgisertib), an oral activin receptor-like kinase 2 (ALK2) inhibitor, in pediatric patients aged 6 to <12 years with fibrodysplasia ossificans progressiva (FOP). At Week 24, zilurgisertib reduced total heterotopic ossification (HO) lesion volume and improved clinician-assessed joint mobility. No zilurgisertib-treated patients developed new HO lesions.

The results build on data from PROGRESS Cohort 1, which supported the U.S. Food and Drug Administration (FDA) approval of ATEBRIOZ in September 2026 for adult and pediatric patients aged 12 years and older with FOP. Mirum plans a supplemental New Drug Application (sNDA) submission in H1 2027 to expand the indication to pediatric patients aged 6 to <12 years.

“These results represent an important advance for younger children living with FOP,” said Rob Myers, M.D., Chief Medical Officer of Mirum. “The reduction in total HO volume and absence of new lesions seen with zilurgisertib build on the positive results previously observed in adolescents and adults in Cohort 1 of PROGRESS. We look forward to discussing these findings with the FDA to expand access to ATEBRIOZ for younger children living with this debilitating disease.”

“FOP is a devastating genetic disease that leads to progressive loss of mobility, independence, quality of life, and shortened lifespan,” said Frederick S. Kaplan, M.D., Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine at the University of Pennsylvania Perelman School of Medicine. “Childhood is a critical window in FOP, so a therapy targeting the underlying cause of the disease is especially important for this young age group. Results such as these offer hope that we may be able to slow disease progression in children before its most serious consequences arise.”

PROGRESS Cohort 2 Results

Cohort 2 of the PROGRESS study enrolled 25 pediatric patients aged 6 to <12 years with FOP. Patients were randomized 1:1 to receive once-daily oral zilurgisertib 75 mg (n=12) or placebo (n=13) during a 24-week double-blind period, followed by an open-label extension. The mean age at baseline was 8.3 years, with a mean of 5.0 years since initial diagnosis. All patients completed the double-blind period and entered the open-label extension.

At Week 24, mean total HO lesion volume decreased by 8.09 cm³ in patients receiving zilurgisertib, compared with an increase of 9.14 cm³ in patients receiving placebo (nominal p=0.003). No zilurgisertib-treated patients developed new HO lesions.

Improvements in clinician-assessed joint mobility were also observed. Joint mobility was assessed using the Cumulative Analogue Joint Involvement Scale (CAJIS), a validated measure of physical function in FOP scored from 0 (no impairment) to 30 (maximum impairment). At Week 24, CAJIS scores improved by a mean of 0.80 points in patients receiving zilurgisertib, compared with 0.09 points in patients receiving placebo. In untreated patients with FOP, CAJIS scores are reported to worsen by approximately 0.5 points per year.¹ Key efficacy data from Cohort 2 are shown below in the Efficacy Results table.

Efficacy Results

Zilurgisertib was generally well tolerated, with a safety profile consistent with that observed in PROGRESS Cohort 1. No new safety signals were identified. No patients discontinued treatment during the double-blind period, and no zilurgisertib-treated patients experienced growth plate closure. Additional safety findings included:

• Most adverse events were mild or moderate in severity.

• Serious adverse events and Grade ≥3 adverse events were infrequent and occurred less frequently in patients receiving zilurgisertib than in those receiving placebo.

• Adverse events occurring in more than 10% of zilurgisertib-treated patients and at a higher frequency than with placebo included arthralgia, cough, pyrexia, and vomiting (3 subjects each), and alopecia, epistaxis, fall, iron deficiency, and nasopharyngitis (2 subjects each).

ATEBRIOZ is approved by the U.S. FDA to reduce the volume of total new HO in adult and pediatric patients aged 12 years and older with FOP. Total new HO lesion volume includes expansion of baseline HO lesion burden as well as any new discrete HO that developed during the 24-week double-blind period.

Full Cohort 2 results will be presented at an upcoming medical meeting. Cohort 3 of the PROGRESS study, which is evaluating zilurgisertib in pediatric patients aged 2 to <12 years, is currently enrolling.

ATEBRIOZ is available in the U.S. through Mirum Access Plus (MAP), a patient support program designed to help patients, families, and healthcare providers navigate treatment access. MAP provides insurance coverage and access support, financial assistance for eligible patients, personalized patient support, and educational resources for patients and caregivers. Eligible patients can pay as little as $0 per month. To learn more, call 855-MRM-4YOU (1-855-676-4968) or visit atebrioz.com.

About ATEBRIOZ™ (zilurgisertib) tablets

ATEBRIOZ™ (zilurgisertib) tablets are a once-daily oral activin receptor-like kinase 2 (ALK2) inhibitor approved by the U.S. Food and Drug Administration (FDA) to reduce the volume of total new heterotopic ossification in adult and pediatric patients aged 12 years and older with Fibrodysplasia Ossificans Progressiva (FOP). In people living with FOP, pathogenic variants in the ACVR1 gene result in abnormal activation of ALK2, leading to the formation of bone in muscles, tendons, ligaments and other soft tissues through a process known as heterotopic ossification (HO). For more information, please visit atebrioz.com.

Mirum Pharmaceuticals, Inc. licensed zilurgisertib from Incyte for worldwide development and commercialization.

IMPORTANT SAFETY INFORMATION

ATEBRIOZ is contraindicated in pregnancy. ATEBRIOZ can cause fetal harm based on data from animal studies. Patients of reproductive potential should use effective contraception and should immediately discontinue ATEBRIOZ and contact their healthcare provider if pregnancy occurs.

US Prescribing Information

About the PROGRESS Study

PROGRESS is a global, randomized, double-blind, placebo-controlled Phase 2 study evaluating the efficacy and safety of zilurgisertib in patients with fibrodysplasia ossificans progressiva (FOP). PROGRESS Cohort 1 enrolled 63 patients 12 years of age and older who were randomized 1:1 to receive zilurgisertib 100 mg once daily or placebo during a 24-week double-blind treatment period, followed by an open-label extension. Results from Cohort 1 have been reported through Week 48.

The PROGRESS study is also evaluating the safety and efficacy of zilurgisertib in younger patients with FOP. Cohort 2 enrolled 25 patients aged 6 to <12 years who were randomized 1:1 to receive zilurgisertib 75 mg once daily or placebo during a 24-week double-blind treatment period, followed by an open-label extension. Cohort 3, which is evaluating zilurgisertib in patients aged 2 to <12 years, is currently enrolling.

About Fibrodysplasia Ossificans Progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, progressive genetic disease affecting approximately 300 people in the United States and 900 worldwide. FOP is characterized by heterotopic ossification (HO), a process in which bone forms in muscles, tendons, ligaments and other soft tissues. Symptoms typically become apparent in early childhood, and the number and volume of HO lesions increase over time, progressively restricting movement and limiting mobility, daily function, and independence.

About Mirum Pharmaceuticals

Mirum Pharmaceuticals (NASDAQ: MIRM) is a leading rare disease company with a global footprint of approved products and a broad pipeline of investigational medicines. Purpose-built to bring forward breakthrough medicines for people with overlooked conditions, Mirum focuses on rare liver and rare genetic diseases, where it has built deep expertise and strong connections to patient communities. The company’s commercial portfolio includes LIVMARLI® (maralixibat) for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), ATEBRIOZ™ (zilurgisertib) for fibrodysplasia ossificans progressiva (FOP), CHOLBAM® (cholic acid) for bile-acid synthesis disorders and CTEXLI® (chenodiol) for cerebrotendinous xanthomatosis (CTX).

Mirum’s clinical-stage pipeline includes volixibat, an IBAT inhibitor in late-stage development for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), brelovitug, a fully human monoclonal antibody in late-stage development for chronic hepatitis delta virus (HDV) and MRM-3379, a PDE4D inhibitor being evaluated for Fragile X syndrome (FXS).

Mirum’s success is driven by a team dedicated to advancing high impact medicines through strategic development, disciplined execution and purposeful collaboration across the rare disease ecosystem. Learn more at https://mirumpharma.com/ and follow Mirum on Facebook, LinkedIn, Instagram and X.

Mirum Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, expectations regarding the timing, enrollment or results of clinical trials for zilurgisertib, the potential benefit of zilurgisertib in real world settings versus clinical trial settings, including the potential to slow disease progression in children before FOP’s most serious consequences arise, the timing of regulatory engagement with the FDA and any resulting submission of an sNDA for ages 6 to <12, the importance of ATEBRIOZ™ as an additional therapy for the treatment of FOP, the potential presentation of zilurgisertib clinical results at an upcoming medical meeting, cost to patients and methods of availability. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plan,” “may,” “expected,” “will,” “could,” “would,” “guidance,” “potential,” “continue” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with the development of investigational medicines generally, including the failure of future studies to generate the same or similar data as prior studies, risks inherent in the regulatory submission process in the U.S., risks and uncertainties associated with Mirum’s business in general, the impact of geopolitical and macroeconomic events, and the other risks described in Mirum’s Quarterly Report for the quarter ended June 30, 2026, filed with the Securities and Exchange Commission on August 5, 2026, and subsequent filings with the Securities and Exchange Commission, which are available at www.sec.gov. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Mirum and the Mirum logo are trademarks of Mirum Pharmaceuticals, Inc.

References

¹Pignolo RJ, et al. Orphanet J Rare Dis. 2019;14:113.

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