Mesoblast to Meet With FDA Next Month to Discuss Rexlemestrocel-L and Opioid Cessation

Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that the U.S. Food & Drug Administration (FDA) has scheduled a meeting in early December to discuss Mesoblast's data on opioid reduction and cessation from its first Phase 3 study (MSB-DR003) of rexlemestrocel-L in patients with chronic low back pain (CLBP).

In Mesoblast's first randomized controlled Phase 3 trial of 404 patients, 168 of whom were taking opioids at baseline, more than 3-fold higher numbers of patients treated with a single intra-discal injection of rexlemestrocel-L + HA were able to cease use of all opioids by 36 months compared with saline-treated controls (p=0.008).

In light of the devastating opioid crisis that continues to rage in the US, in September 2025 FDA provided new Guidance to Industry on Development of Non-Opioid Agents for Treatment of Chronic Pain. ¹ Since CLBP is the principal cause of chronic prescription opioid use, there is a significant need for a safe, effective, and durable opioid-sparing treatment in patients with CLBP associated with degenerative disc disease.

Mesoblast Chief Executive Silviu Itescu said: "FDA has emphasized the importance of developing non opioid treatments for chronic pain, and we look forward to discussing plans for rexlemestrocel-L as an agent that may result in both amelioration of CLBP as well as opioid reduction or cessation."

Rexlemestrocel-L has received Regenerative Medicine Advanced Therapy (RMAT) designation for treatment of CLBP due to degenerative disc disease, a serious condition that is a major contributory factor to the nation's opioid crisis. Mesoblast is seeking FDA approval based on reduction in CLBP through 12 months and is actively recruiting a 300-patient confirmatory Phase 3 trial across 40 sites in the US, with enrollment expected to be completed in the coming quarter.

About Rexlemestrocel-L for Chronic Low Back Pain associated with Degenerative Disc Disease
The 300-patient randomized controlled confirmatory Phase 3 trial of Mesoblast's second generation allogeneic, STRO3-immunoselected, and industrially manufactured stromal cell product candidate rexlemestrocel-L in combination with hyaluronic acid (HA) as delivery agent for injection into the lumbar disc is actively enrolling in patients with chronic low back pain (CLBP) due to inflammatory degenerative disc disease (DDD) of less than five years duration at multiple sites across the U.S.

FDA has previously agreed on the design of this 300-patient randomized, placebo-controlled confirmatory Phase 3 trial, and the 12-month primary endpoint of pain reduction as an approvable indication. This endpoint was successfully met in Mesoblast's first Phase 3 trial. Key secondary measures include improvement in quality of life and function.

A particular focus is on treatment of patients on opioids, since discogenic back pain accounts for approximately 50% of prescription opioid usage in the US. Significant pain reduction and opioid cessation were observed in Mesoblast's first Phase 3 trial.

FDA has designated rexlemestrocel-L a Regenerative Medicine Advanced Therapy (RMAT) for the treatment of chronic low back pain. RMAT designation provides all the benefits of Breakthrough and Fast Track designations, including rolling review and eligibility for priority review on filing of a Biologics License Application (BLA).

About Chronic Low Back Pain
Back pain is the leading cause of disability in Americans under 45 years, ² with an annual prevalence in the general US adult population of 10-30%. ³ CLBP caused by inflammation and degenerative disc disease (DDD) is a serious condition with a prevalence of over 7 million people in the US alone. ^4,5 CLBP due to DDD is a leading cause of disability, and is associated with impaired quality of life, severe limitations in ability to perform activities of daily living, reduced ability to work, and negative impacts on mental health. CLBP accounts for approximately 50% of prescription opioid usage in the US, ⁵ making the condition a significant contributor to the opioid epidemic.

About Mesoblast
Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The therapies from the Company's proprietary mesenchymal lineage cell therapy technology platform respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process.

Mesoblast's Ryoncil ^® (remestemcel-L-rknd) for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months and older is the first FDA-approved mesenchymal stromal cell (MSC) therapy. Please see the full Prescribing Information at www.ryoncil.com .

Mesoblast is committed to developing additional cell therapies for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Ryoncil ^® is being developed for additional inflammatory diseases including SR-aGvHD in adults and biologic-resistant inflammatory bowel disease. Rexlemestrocel-L is being developed for heart failure and chronic low back pain. The Company has established commercial partnerships in Japan, Europe and China.

About Mesoblast intellectual property: Mesoblast has a strong and extensive global intellectual property portfolio, with over 1,000 granted patents or patent applications covering mesenchymal stromal cell compositions of matter, methods of manufacturing and indications. These granted patents and patent applications provide commercial protection extending through to at least 2044 in all major markets.

About Mesoblast manufacturing: The Company's proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com , LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

References / Footnotes

1. United States Food & Drug Administration. Development of Non-Opioid Analgesics for Chronic Pain Guidance for Industry. Draft Guidance. September 2025
2. American Academy of Pain Medicine - Get the Facts on Pain. The American Academy of Pain Medicine. http://www.painmed.org/patientcenter/facts-on-pain/ Accessed on June 28, 2017.
3. Urits I, Burshtein A, Sharma M, et al. Low Back Pain, a Comprehensive Review: Pathophysiology, Diagnosis, and Treatment. Current Pain and Headache Reports. 2019;23(3):1-10. doi:10.1007/s11916-019-0757-1.
4. Navigant: Commercial Assessment for a Proprietary Cell-Based Therapy for DDD in the U.S. and the EU3 – August 2014.
5. Decision Resources: Chronic Pain December 2015.
   

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