Vertebrogenic Lumbar Back Pain (vLBP) is a specific, MRI-identifiable subset of chronic Low Back Pain (cLBP), associated with Modic Type 1 changes at the vertebral endplate adjacent to a degenerate lumbar disc. Modic changes are visible on magnetic resonance imaging (MRI) as a sign of vertebral bone and marrow degeneration, and patients with vLBP typically suffer moderate to severe, persistent pain and disability that does not respond to standard of care.

Microbiology studies suggest that approximately 50% of spinal discs with adjacent Modic changes are infected with bacteria, with Cutibacterium acnes (C. acnes) responsible for 80% of these infections. Infection can occur during the healing process after disc herniation or injury, as the area becomes vascularised to support repair. During this phase, bacteria may infiltrate the disc, leading to a chronic, low-grade infection that causes inflammation and bone degradation, resulting in the vertebral oedema observed as Modic changes (figure 1).

Pioneering research by Persica’s founders linked this bacterial infection to Modic changes and, in turn, to vLBP. Two randomised controlled trials have demonstrated that high-dose, prolonged oral antibiotics significantly reduce pain and disability in patients with vLBP. However, effective antibiotic delivery to the infected disc is challenging due to its limited blood supply. As a result, treatment response is slow, requiring long-term antibiotic use, which can lead to side effects, compliance challenges, and concerns around antibiotic stewardship.

Persica is addressing these challenges through the development of PP353, a targeted, non-opioid intradiscal therapy delivered directly to the site of disease. Designed to achieve superior local exposure with just two injections, PP353 addresses an underlying cause of vLBP, rather than only managing its symptoms, offering patients an alternative to long-term analgesic use, including opioids.

Preclinical and first-in-human data for PP353 was published in the peer-reviewed JOR Spine in November 2024.

The Phase 1b Modic Trial completed in Q1 2025.

Results from the Phase 1b trial:

• The PP353 clinical trial met its primary endpoint, demonstrating statistically significant and clinically meaningful results in patients with vLBP (Modic Type 1 changes), with a 3.4-point (50%) within-group reduction in pain from baseline and a 1.4-point (30%) between-group reduction versus placebo at 12 months in the Full Analysis Set.
• The PP353 group reported clinically meaningful reductions in pain from baseline from 3 months onwards, continuing to improve at 12 months. The placebo group did not achieve clinically meaningful change from baseline.
• The PP353 group also reported statistically significant and clinically meaningful reductions in disability, with a within-group reduction of 9.4 points (63%) and a between-group reduction of 3.9 points (39%) versus placebo in the Full Analysis Set at 12 months.
• The PP353 group reported clinically meaningful reductions in disability from baseline from 1 month onwards, continuing to improve at 12 months. The placebo group did not achieve clinically meaningful change from baseline until 6 months.
• Reduced analgesic use, including a notable decrease in opioid use from 25% at baseline to 11% at 12 months.
• Greater outcomes were observed in the Per Protocol Set.
• PP353 was well tolerated, with no limiting gastrointestinal side effects observed.
• The Modic Trial enrolled 44 patients across 4 countries and followed patients for 12 months. Patients had experienced vLBP for more than 6 months (mean duration of 5.5 years) and had not been helped by existing non-surgical treatments.

References:
Hagger G, Guest S, Birchall S, et al. Preclinical development and characterisation of PP353, a formulation of linezolid for intradiscal administration. JOR Spine. 2024; 7(4):e70010.

Tripathi SS, Sneath R, Golash A, et al. Pharmacokinetics of PP353, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first-in-human, Phase 1b, open-label, single-dose study. JOR Spine. 2024; 7(4):e70009.

Michael R. Lassen, Matthew Scarborough, Nigel Gilchrist et al. Intradiscal linezolid (PP353) treatment for chronic low back pain associated with Modic change type 1: an international, first-in-human, randomised, sham procedure-controlled, double-blind, phase 1b clinical trial