About vertebrogenic lumbar back pain (vLBP) and PP353

What is vertebrogenic lumbar back pain (vLBP)?

Vertebrogenic lumbar back pain (vLBP) is chronic Low Back Pain (cLBP) associated withModic changes on MRI. Modic changes are MRI defined abnormalities in the vertebral endplates and adjacent bone marrow which are associated with low-burden indolent bacterial infection of the disc causing inflammation and oedema and/or fatty infiltration. vLBPaccounts for approximately 15% of all cLBP patients, is often severely disabling, and responds poorly to standard care; around 80% of vLBP patients are refractory to conservative treatment and approximately 30% use opioids. vLBP now has its own ICD-10 diagnostic code (CM-54.51) in the USA.

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vLBP associated Modic changes are classified as Type 1 (reflecting active inflammation or bone oedema), Type 2 (reflecting fatty marrow replacement), or mixed Type 1 and Type 2. Both types are included in the vLBP population that PP353 will target in Phase 3 development. The presence of Modic changes is identifiable with a standard MRI scan, making patient identification and selection straightforward for clinicians.

What is PP353?

PP353 is a transformative, non-opioid intradiscal therapy in development for vLBP, a precisely defined condition affecting approximately 15% of all cLBP patients (an estimated 10 million patients in the US and Europe). PP353 is uniquely formulated to deliver linezolid, a well-characterised antibiotic, directly into the affected disc. Two administrations of PP353, four days apart, provide the necessary antibiotic exposure within the disc in order to target the low-bioburden bacterial infection and treat the underlying cause of vLBP.^1,2

Who is PP353 designed for?

PP353 is designed to treat patients with vLBP, cLBP with Modic changes (Type 1, Type 2, or mixed Type 1 and Type 2) confirmed on MRI, who have had inadequate relief from conservative standard of care. PP353 is being developed as the first targeted treatment option after failure of conservative treatment approaches, before more invasive interventions such as Basivertebral Nerve Ablation (BVNA) or surgery.

Why does PP353 use an antibiotic?

High-quality microbiology studies show that bacteria are associated with approximately 50% of painful discs in vLBP patients, with around 80% of infections caused by Cutibacteriumacnes.³ This low-burden, indolent bacterial infection results in inflammation and pain and Modic changes on MRI. PP353 delivers linezolid directly into the infected disc, achieving high local concentrations of the antibiotic and treating the infection.

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Linking bacterial infection to Modic changes and vLBP is supported by multiple lines of evidence: histological studies have visualised bacteria embedded in micro-colonies deep within disc tissue, ruling out contamination;^4,5 animal models show that inoculation of C. acnes into disc tissue reproduces Modic-like changes;^6–8 and three independent randomised controlled trials have now demonstrated clinical benefit from antibiotic therapy in patients with cLBP and Modic changes.^9–11  Approximately 200 patients have been treated in antibiotic RCTs for cLBP and Modic changes with demonstrated clinical benefit.

PP353 clinical development

What clinical evidence supports PP353?

• PP353 has been evaluated in an international, randomised, double-blind, sham-controlled Phase 1b trial (MODIC trial) which has been published in eClinicalMedicine (The Lancet) in February 2026.¹¹ The MODIC trial data were also presented at the American Society of Interventional Pain Physicians (ASIPP) 2026 Annual Meeting, receiving a Top Abstract Award.¹²
• Patients receiving PP353 showed statistically significant and clinically meaningful improvements in all key endpoints compared with placebo at 12 months.
• The primary endpoint revealed a 3.4-point reduction in pain scores for the PP353 group versus 2.0 points for placebo (p=0.028), representing a 30% between-group difference.
• Over 60% of PP353 participants achieved clinically meaningful pain and disabilityreductions of ≥50% at 12 months.
• PP353 participants experienced substantial reductions in disability scores: 63% improvement on the Roland Morris Disability Questionnaire and 51% on the Oswestry Disability Index, both significantly superior to placebo.
• Reduced analgesic use was observed in patients treated with PP353. Furthermore, at the 12month assessment, patients treated with PP353 showed a significantly greater reduction in opioid use than those receiving placebo. Based on opioid use recorded during the 7 days before each study visit, opioid use declined from a mean of 4.94 days at baseline to 0.30 days at 12 months, corresponding to a 4.13 day reduction versus placebo (p<0.01).
• The treatment was well-tolerated with no increase in the number of adverse events or the severity compared to the group receiving sham injections.

More detail
Full citation: Lassen MR, Scarborough M, Gilchrist N, et al. Intradiscal linezolid (PP353) treatment for chronic low back pain associated with Modic change type 1. eClinicalMedicine 2026;92:103764. doi:10.1016/j.eclinm.2026.103764.

How does PP353 compare with existing treatments for vLBP?

Nearly all patients with vLBP will initially be treated with physical therapy such as physiotherapy and simple analgesics such as non-steroidal anti-inflammatory drugs and paracetamol. These treatments do not provide much benefit to patients who have vLBP and so these patients are then generally referred to a spine / pain specialist. Other available treatment options such as epidural injections and steroid injections only offer transient relief.

The only treatment option which has been shown to work in vLBP is a new procedure called Basivertebral Nerve Ablation (BVNA). BVNA is a current treatment option for vLBP but is limited by its complex and invasive nature and addresses the symptoms rather than the underlying cause. The efficacy of PP353 in the Phase 1b trial was comparable to BVNA, and Key Opinion Leader research supports positioning PP353 as the preferred first-line treatment after failure of conservative care, before considering BVNA or surgical interventions, because it targets the underlying pathology rather than just controlling pain perception.

What is Persica’s development pathway for PP353?

PP353 is Phase 3-ready with plans to conduct two randomised, sham-controlled trials in the US/EU and China. Persica is seeking a partner or investment to enable execution of the planned registrational studies.

PP353 versus oral antibiotics for vLBP

How is PP353 different from oral antibiotics for vLBP?

PP353 differs from published data for oral antibiotic regimens in two fundamental ways:

1. Route of delivery: PP353 delivers antibiotic directly into the intervertebral disc via intradiscal injection, achieving high local concentrations where needed while minimising systemic exposure.
2. Treatment duration and systemic exposure: PP353 requires just two administrations over four days, resulting in a 99.9% reduction in systemic antibiotic exposure compared with oral regimens that typically span 90-100 days.

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The intervertebral disc is poorly vascularized, meaning that oral antibiotics reach it only indirectly fromsystemic circulation, achieving modest local concentrations. In oral antibiotic trials, up to 300g are given over 100 days whereas in the PP353 trial 0.3g is given over approximately one week.

What should be taken into consideration when comparing published data from oral antibiotics trials to the PP353 trial?

Several critical factors must be considered when comparing data from oral antibiotic studies to PP353 data:

• Antibiotic exposure: While oral regimens deliver hundreds of grams systemically over months, PP353 delivers 0.3 grams directly to the target tissue over days. What matters for efficacy is the local concentration achieved at the site of pathology, not total systemic dose.Oral antibiotic studies use a range of potentially sub-optimal dose regimens which may explain different outcomes. For example, the Norwegian AIM study (Braten et al, 2019¹⁰) used an intermediate oral dose of amoxicillin, 2.25g per day over 90 days, which was lower than the high-dose arm in the earlier Albert et al study (3g per day).¹³
  Exposure-response analyses, recently presented at ASPN, provide compelling evidence that the difference in outcomes between the Albert and Braten studies may be explained by dose.¹⁴ This dose and intradiscal exposure-response relationship across the oral antibiotic literature supports the view that achieving adequate antibiotic exposure at the disc is the critical factor. Intradiscal delivery, which achieves local concentrations above that which any oral regimen can deliver, addresses that limitation directly.
• Population differences:PP353 specifically targets the subset of patients with vLBP(cLBP with Modic changes), without other obvious current causes of cLBP e.g. current herniation – a precisely defined population.Other studies e.g. Cicuttini et al enrolled patients with current herniation regardless of their Modic changes.¹⁵ These patients were excluded from most oral antibiotic studies,and the study results should not be compared.

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For example, the Cicuttini et al study enrolled patients with current disc herniation and used a low-dosesystemic oral regime of 0.5g twice a day.¹⁵ These design differences define an entirely different clinical question. The study does not address the potential of locally delivered intradiscal therapy in a precisely selected vLBP population.

What benefits are there with an intradiscal formulation to treat vLBP?

Intradiscal drug exposure: The poorly vascularized disc presents a pharmacological challenge. Direct intradiscal delivery achieves therapeutic concentrations at the target site that systemic dosing cannot match without prohibitive systemic exposure.

Tolerability and side effects: In published oral antibiotic trials, patients reported gastrointestinal adverse events.^9,10 In the PP353 Phase 1b trial, treatment-related adverse events occurred at similar or lower frequency in the PP353 group compared to the sham procedure group, with no severe or disabling adverse events.¹¹ Furthermore, no treatment-related gastrointestinal side-effects were reported in the PP353 group.

Antibiotic resistance and stewardship: Prolonged systemic antibiotic courses (90-100 days) carry substantial risks for resistance development and disruption of the microbiome. PP353’s targeted approach dramatically reduces systemic exposure and treatment duration, potentially offering a more responsible stewardship profile.

Clinical appropriateness: PP353’s approach – precise patient selection via the Modic biomarker, targeted delivery, and minimal systemic exposure – represents a fundamentally different therapeutic strategy.

Antibiotic Stewardship

How does treatment with PP353 align with antibiotic stewardship principles? 

Responsible antibiotic stewardship was central to Persica’s founding mission. PP353 reduces antibiotic exposure by 99.9% compared to published oral data (0.3g vs 300g), achieves higher exposures at the infection site, is restricted to patients with confirmed Modic changes on MRI, and is administered in just two doses over four days. It is precisely the kind of targeted, localised, minimal-duration intervention that stewardship frameworks are designed to support.

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Estimates suggest that even with widespread adoption, PP353 would increase total systemic linezolid use by less than 0.2% by weight.¹¹ The low systemic exposure from intradiscal administration means plasma concentrations are likely to remain below the threshold that confers selective advantage for resistant variants, minimising resistance risk. This is a fundamentally different stewardship profile to the published prolonged high-dose oral courses, with their well-documented gastrointestinal burden and resistance concerns.