Could Inhaled Cell Therapy Change the Course of COPD?

Investigational cell therapies are raising questions about whether treatment could influence the underlying course of chronic obstructive pulmonary disease (COPD), rather than provide short-term improvements alone. For a therapy designed to stimulate endogenous lung repair, the evidence would need to extend beyond an early change in symptoms or lung function to demonstrate durable clinical benefit.

Nebulized delivery introduces another question: Can a familiar respiratory device reliably administer a living-cell product? SMSbiotech is investigating Small Mobile Stem (SMS) cells, a proprietary, blood-derived cell population intended for allogeneic administration. The proposed mechanism involves interactions with cells involved in lung repair, but whether those interactions produce meaningful benefit in patients with COPD remains unestablished.

In an interview with Pharmacy Times, Abdulkader Rahmo, PhD, co-founder, president, and chief science officer at SMSbiotech, discusses the proposed biology of SMS cells, how early clinical findings could inform dose selection, and what evidence would distinguish disease modification from a transient treatment effect. He also explains how pharmacists could help coordinate the handling of a living-cell product intended for nebulized delivery and why device familiarity alone would not make this approach ready for routine care.

Rahmo is a co-founder and executive of the company developing SMS cells. Product characteristics and early clinical observations discussed below are developer-reported. SMS cells are investigational and are not FDA-approved for COPD; their safety and efficacy have not been established. Permission to proceed with a clinical trial does not constitute FDA approval of a treatment.

Responses have been edited for clarity.

Pharmacy Times: What are SMS cells, and how does their proposed mechanism differ from that of mesenchymal stromal cells or other cell-based therapies previously investigated for COPD?

Abdulkader Rahmo, PhD: Small Mobile Stem cells are a proprietary population of adult, blood-derived stem cells being developed as an investigational regenerative cell therapy. The key distinction is how the cells are proposed to produce their regenerative effect.

For SMS cells, the proposed mechanism is primarily cell-to-cell selective binding and direct signaling rather than replacement of damaged lung cells. SMS cells are reported to bind selectively to lung cells involved in repair—including alveolar type 2 progenitor cells and mesenchymal cells—and to induce changes in gene expression and proliferation.

Mesenchymal stromal/stem cells, or MSCs, have been extensively investigated in COPD and other inflammatory diseases. Their proposed therapeutic effects have generally centered on paracrine and immunomodulatory signaling—for example, secretion of cytokines, growth factors, extracellular vesicles, and other factors that can modulate inflammation and tissue responses. MSCs are therefore also largely thought to act through signaling rather than simply replacing damaged tissue.

For other cell therapies, depending on the cell type, approaches have attempted to provide anti-inflammatory effects, deliver trophic factors, replace damaged cells, or stimulate endogenous repair. SMS cells are being positioned as a multitarget regenerative signaling cell rather than primarily as a replacement cell.

The claimed differentiator is therefore not simply that SMS cells “replace tissue,” but that they may physically engage several endogenous regenerative cell populations and alter their gene activity, potentially coordinating several components of lung repair at once. Preclinical reports describe interactions with alveolar progenitor cells, mesenchymal cells, and endothelial cells, together with angiogenic and extracellular-matrix effects.

Furthermore, SMS cells are substantially smaller than MSCs and naturally derived from circulating blood. The proposed advantage is that their size and mobility allow them to move through the pulmonary microcirculation without the vascular trapping associated with larger cells. Their small size and stability also make nebulized delivery to the lungs feasible, as SMS cells retain viability and potency after nebulization.

That creates an important conceptual distinction. In the MSC approach, cells are administered and release immunomodulatory or trophic factors that modify the local environment.

In the proposed SMS approach, small circulating cells are administered and selectively bind to endogenous repair cells. Alterations in gene activity and proliferation, together with vascular and extracellular-matrix effects, are intended to stimulate coordinated tissue regeneration.

One particularly important nuance is that SMS cells are not necessarily an alternative to MSC biology: SMS cells can interact with and stimulate mesenchymal cells. In other words, the hypothesis is that SMS cells could activate the patient’s endogenous MSC or progenitor compartment rather than simply supplying another population of MSCs.

In addition, SMS cells have the ability to be expanded to large scales while maintaining their potency over multiple proliferation cycles. This stability is further demonstrated by their ability to withstand refrigerated storage for several weeks without significant loss of viability or potency.

Pharmacy Times: What scientific and technical considerations led SMSbiotech to pursue nebulized delivery, and how does the platform maintain cell viability, dosing consistency, and lung deposition during administration?

Rahmo: The scientific rationale for nebulized delivery is closely tied to the proposed biology and physical characteristics of SMS cells. The cells are unusually small and resilient, allowing them to be nebulized while maintaining viability and potency. The company therefore pursued inhalation as a way to deliver the cells directly to the diseased lung rather than relying on systemic administration and subsequent trafficking to the lung.

Several scientific and technical considerations informed the choice of nebulization.

Direct access to the target organ is one consideration. COPD pathology is concentrated in the airways, alveoli, and pulmonary microenvironment. Nebulization provides a noninvasive route for placing the investigational cells directly into the respiratory tract. This could offer an advantage over systemic cell administration, where cells may target organs other than those intended.

Another consideration is compatibility with repeatable, off-the-shelf treatment. The cells are being developed as an allogeneic product rather than a patient-specific therapy. The company’s manufacturing platform is intended to support large-scale production and consistent dosing.

The native robustness of SMS cells is the central enabling characteristic rather than a special protective formulation. SMS cells retain viability and potency following nebulization and are sufficiently resilient to tolerate physical and environmental stresses associated with administration.

Furthermore, SMS cells can be stored at 2 to 8 °C for more than 3 weeks. This stability simplifies handling compared with conventional cryopreserved cell therapies that require frozen storage and thawing immediately before administration.

SMSbiotech’s manufacturing strategy is designed around ex vivo expansion of SMS cells while retaining potency, allowing the company to manufacture standardized allogeneic batches rather than relying on a new donor-derived preparation for each patient. The process supports extensive proliferation and uses functional assays to assess SMS-cell quality and potency.

For the clinical COPD program, SMS cells are being administered in ascending-dose cohorts, providing an opportunity to characterize tolerability and dosing before later-stage efficacy studies.

The intended mechanism for deposition is aerosol-mediated deposition in the respiratory tract using an established nebulization device. The rationale is that inhaled aerosol droplets, approximately 5 µm in size, carry viable SMS cells into the lungs, where the cells can interact with endogenous cells involved in tissue repair.

SMS cells can selectively interact with mesenchymal and progenitor cells in the lung using what we call Targeted Multi-Gene Activity Modulation, or TMAM. SMSbiotech has conducted in silico SMS-cell deposition research for the process of nebulization and inhalation into the human lung.

The development logic is that small size and physical resilience support compatibility with nebulization, which enables direct pulmonary administration and potential interactions with endogenous lung repair cells.

The delivery technology and proposed mechanism are closely connected. Nebulization is not merely a convenient route of administration; it is intended to place viable cells at the anatomical site where their proposed regenerative interactions occur.

Pharmacy Times: How will findings from the ongoing Australian study inform the US phase 1b trial, particularly its dose-escalation decisions, safety monitoring, and selection of a dose for further study?

Rahmo: The Australian study is positioned to provide the first human dose-response and safety information that can guide the US phase 1b program. The Australian trial is an ascending-dose phase 1b study, and the first cohort has completed its protocol-specified 28-day safety-monitoring period without therapy-related adverse events. Dose escalation is underway. The FDA has subsequently cleared the US phase 1b study to proceed.

The most immediate use of the Australian data will be to establish whether escalation to the next SMS-cell dose is supported by the observed safety profile. The Australian study is evaluating 3 ascending doses, so observations from each cohort can provide information on tolerability before exposing additional participants to higher doses.

For the US study, the relevant information would include treatment-emergent and treatment-related adverse events, pulmonary symptoms or changes in respiratory status, and laboratory and other safety findings. The severity, duration, and reversibility of adverse events would also be important, as would whether any safety signal appears dose related.

The Australian experience can therefore help establish whether the proposed US dose levels and escalation sequence are appropriate.

Because this is a novel inhaled cell therapy, the Australian study also provides practical information about the administration procedure itself, not just the cells. This includes tolerability of nebulized administration and whether unexpected pulmonary or systemic reactions emerge following dosing.

The first 2 Australian participants were treated as sentinel patients and underwent close observation before the program progressed. Both completed their scheduled dosing and observation periods without drug-related adverse effects.

As additional cohorts are treated, the accumulated safety dataset should provide a better understanding of whether monitoring needs to focus on particular pulmonary, inflammatory, immunologic, or systemic events.

An important point is that the highest tolerated dose is not necessarily the dose that should automatically be taken forward. The Australian study can provide an initial view of the relationship between dose, safety, and biological or clinical signals.

SMSbiotech’s Australian protocol includes exploratory measures of potential efficacy, including lung-function measures, exacerbation frequency, and patient-reported outcomes, although the phase 1 study is principally a safety and tolerability study.

The emerging data could help distinguish among different possibilities. A lower dose could show adequate tolerability with an early biological or clinical signal. An intermediate dose could have an acceptable safety profile with stronger evidence of biological activity. A higher dose could produce additional exposure without a commensurate increase in observed activity, or with increasing tolerability concerns.

The objective would be to identify a dose or dose range with a favorable balance of safety and evidence of biological activity rather than simply selecting the maximum dose administered.

The US program is particularly important to SMSbiotech because the FDA has reviewed the investigational new drug application and issued a “Study May Proceed” notification. The US study is a phase 1b trial, with first-patient dosing targeted for the fourth quarter of 2026.

Consequently, the Australian trial can function as an important clinical learning dataset for the US program. It can provide early human experience with nebulized SMS cells, identify administration-related or cell-related safety signals, and provide preliminary information about dose selection.

The Australian study is intended to establish the initial human safety and dose-exposure experience with nebulized SMS cells. Those findings can inform the US phase 1b dose-escalation strategy, refine safety monitoring, and help identify the dose or dose range that provides the most appropriate balance between tolerability and preliminary evidence of biological activity.

Pharmacy Times: Beyond short-term safety and tolerability, what biological markers or clinical outcomes would provide credible evidence that SMS cells affect the underlying course of COPD rather than only its symptoms?

Rahmo: For SMS cells, the strongest evidence of a disease-modifying effect in COPD would be a convergent pattern showing not merely that patients feel better or breathe better temporarily, but that the underlying structural and functional abnormalities of the lung are changing.

This would be particularly important given the proposed regenerative mechanism of SMS cells.

Useful measures could include quantitative CT findings showing reduced progression of emphysema, increased preservation or restoration of functional lung tissue, and potentially changes in low-attenuation volume.

Imaging or other validated measures suggesting preservation or restoration of alveolar architecture would also be useful. Evidence of improved pulmonary vascular density or perfusion could be relevant if that is part of the proposed mechanism. Sustained improvement in diffusing capacity of the lungs for carbon monoxide, or DLCO, could provide complementary evidence of improved gas-exchange capacity.

A convincing result would be particularly interesting if structural improvement correlated with functional improvement rather than occurring independently.

Forced expiratory volume in 1 second, or FEV₁, is already recognized by the FDA as a surrogate end point that has been used for COPD drug approvals. However, for a regenerative therapy, the trajectory could be more informative than a short-term increase.

For example, a symptomatic effect could involve FEV₁ increasing shortly after treatment and subsequently returning toward baseline. Potential disease modification could involve FEV₁ improving and remaining improved, or its subsequent rate of decline being meaningfully reduced compared with an appropriate control group.

Other useful measures would include forced vital capacity, residual volume or hyperinflation, and DLCO. These should be assessed longitudinally rather than interpreted from a single posttreatment measurement.

A durable reduction in moderate and severe COPD exacerbations would be clinically meaningful because exacerbations are directly related to morbidity and disease burden. FDA materials have used annualized moderate-to-severe exacerbation rate as a COPD clinical-trial end point.

For SMS cells, the most informative finding would be a sustained reduction in exacerbation frequency and severity, particularly if accompanied by objective evidence of preserved lung structure or function.

Evidence of the proposed regenerative biology would also be important for establishing why SMS cells might work.

If the proposed mechanism involves interaction with endogenous progenitor, mesenchymal, endothelial, or epithelial cells, studies could look for changes in markers of alveolar epithelial regeneration, type II alveolar epithelial-cell activity, extracellular-matrix remodeling, and angiogenesis or pulmonary vascular repair.

Other measures could include inflammatory and fibrotic signaling, cell-to-cell signaling pathways predicted to be affected by SMS cells, and potentially gene-expression signatures consistent with activation of endogenous repair pathways.

Ideally, these biomarkers would be mechanistically linked to the proposed SMS-cell mechanism and demonstrate a dose-response relationship.

Ultimately, structural and molecular findings need to translate into meaningful patient benefit. Useful measures include sustained improvement in dyspnea and exercise capacity, such as 6-minute-walk distance. Physical activity, health-related quality of life, exacerbation-free time, and COPD-related hospitalization would also be useful.

The FDA specifically emphasizes that clinical outcomes—whether patients feel, function, or survive better—are the most direct measures of clinical benefit.

For SMS cells, I would look for concordance across 3 levels.

At the mechanistic level, changes in regenerative or progenitor-cell, inflammatory, vascular, or matrix biomarkers would indicate that the proposed biology is occurring.

At the structural and functional level, sustained FEV₁ or DLCO improvement, reduced hyperinflation, and favorable quantitative CT changes would suggest that the lung itself is changing.

At the clinical level, fewer exacerbations, improved exercise capacity, and durable quality-of-life improvement would demonstrate that the biological changes matter to patients.

The most persuasive result would be longitudinal rather than simply a before-and-after improvement. For example, evidence that SMS treatment produces a sustained structural change in emphysematous lung accompanied by preservation or improvement of lung function and fewer exacerbations.

Conversely, a short-lived improvement in FEV₁, oxygenation, or symptoms, without evidence of structural or biological change, would be much harder to interpret as regeneration rather than a transient physiological or anti-inflammatory effect.

Pharmacy Times: If nebulized cell therapies advance into clinical practice, what requirements could they introduce for product storage, preparation, device compatibility, administration, and patient monitoring—and where would pharmacists fit within that workflow?

Rahmo: If nebulized SMS cells or another living-cell aerosol therapy eventually becomes a routine clinical product, the operational model would probably look less like conventional inhaled medication and more like a cell-therapy product integrated with respiratory drug delivery.

The exact requirements would depend on the final product, formulation, labeling, and device. If the refrigerated stability and scalability described are demonstrated, they could offer an operational advantage over cell therapies requiring cryopreservation. A product that arrives refrigerated and remains stable for a defined period would still require product-specific procedures rather than assumptions based on conventional nebulizer practice.

The first question would be the product’s validated storage condition and shelf life.

For a cell therapy, the site would need documented controls for storage temperature and excursions, product identification and lot or batch traceability, expiration dating, transport and chain of custody, and inventory management.

Procedures would also be needed for quarantining damaged product or product exposed to temperature excursions, as well as reconciling administered, unused, and discarded doses.

These are already recognized issues in cell-therapy logistics. The International Society for Cell & Gene Therapy, or ISCT, specifically identifies storage, shipping, primary-container selection, stability, and poststorage analytics as important components of cell-therapy supply chains.

If SMS cells’ reported refrigerated stability ultimately becomes part of an approved product’s specifications, that could substantially simplify the workflow compared with therapies requiring deep cryogenic storage.

The preparation step could become particularly important because cells are living products.

A pharmacy or cell-therapy service might need to verify the correct patient and product or lot, product release status and expiration, storage history and temperature-excursion status, and any required equilibration or preparation time.

Verification would also include cell concentration and intended dose, whether dilution or other preparation is permitted, compatibility of the nebulizer and materials, and the maximum allowable time between preparation and administration.

The final product would ideally have a highly standardized procedure.

The FDA’s current cell and gene therapy framework emphasizes product-specific chemistry, manufacturing, and controls and validation over the product life cycle, including appropriate release criteria and manufacturing or process controls.

Device compatibility is one of the differences from conventional cell therapy. With an ordinary drug, nebulizers may affect aerosol performance. With a living-cell aerosol, the device could potentially affect the product itself.

SMSbiotech’s development program establishes key parameters of the selected nebulizer devices, such as cell viability before and after nebulization, cell recovery from the device, and cell concentration delivered per unit time.

Other parameters include aggregation or cell retention within the device, aerosol particle or droplet characteristics, emitted dose, residual dose in the nebulizer, the effects of nebulization duration and flow rate, and whether cells retain their intended biological potency after aerosolization.

In other words, the cell product, formulation, designated nebulizer, and administration procedure may need to be treated as an integrated delivery system.

A practical administration protocol could begin with the pharmacy or cell-therapy service verifying and preparing the product, followed by transfer to the treatment area, device setup, and nebulization. Disposal, reconciliation, and documentation would complete the process.

Staff would be provided with standardized procedures for assembling and checking the nebulizer, minimizing interruptions during administration, and confirming the prescribed dose.

Procedures would also address incomplete doses or device malfunction, documentation of actual administration time and product lot, and handling of biological waste.

The administration environment might also need to accommodate immediate observation because the consequences of an unexpected pulmonary reaction could be different from those associated with an ordinary inhaled medication.

Monitoring would probably have 2 layers.

During and shortly after administration, clinicians could monitor oxygen saturation, respiratory rate, heart rate, and blood pressure. They could also assess wheezing, bronchospasm or dyspnea, cough and other airway reactions, and hypersensitivity or infusion-like reactions, if relevant to the product.

The precise observation period would depend on clinical-trial and ultimately labeling requirements.

Because this is a living-cell therapy intended to potentially alter tissue biology, follow-up could extend considerably beyond the administration visit.

Depending on the demonstrated mechanism and risks, this could include pulmonary-function testing, exacerbation surveillance, adverse-event monitoring, and immunologic assessments. Imaging where scientifically justified, biomarkers of biological activity, and longer-term follow-up for unexpected effects could also be included.

The monitoring program would be driven by the actual clinical evidence and regulatory risk assessment rather than simply by the fact that the product is a cell therapy.

Pharmacists could become central coordinators of the product workflow, particularly if the therapy is distributed through hospital or specialty pharmacies.

Before treatment, the role could span ordering and scheduling, product procurement, storage and inventory, lot and expiration verification, temperature-excursion management, and review of the prescription and patient-specific dose.

At preparation, pharmacists could verify the product, prepare it according to approved instructions, document the dose and lot, ensure device and product compatibility, and coordinate with respiratory therapy or nursing.

During administration, they could confirm that the correct product reaches the correct patient, support troubleshooting and deviation management, and ensure documentation and dose reconciliation.

After administration, they could document administration and product disposition, report suspected adverse events, maintain traceability, and participate in pharmacovigilance and quality investigations.

AABB’s first Cell and Gene Therapy Standards for Pharmacy, effective October 1, 2025, specifically address pharmacy management of the receipt, storage, handling, and dispensing of approved cell and gene therapies.

If SMS cells ultimately demonstrate the refrigerated stability and scalability described by the developer, they could have an operational advantage over cell therapies requiring cryopreservation. A product that arrives refrigerated, remains stable for a defined period, and can be administered directly through a standardized nebulizer could fit into a specialty-pharmacy and respiratory-care workflow rather than requiring a highly specialized cellular-therapy infusion center.

Pharmacists could occupy an unusually important position at the intersection of cell-therapy quality control, medication distribution, device coordination, and patient-specific dosing. AABB’s current pharmacy standards and ISCT’s cell-therapy handling frameworks suggest that this type of specialized pharmacy infrastructure is already emerging for other cellular therapies.

Pharmacy Times: Looking beyond this specific investigational product, how could delivering complex therapies through familiar devices such as nebulizers change where and by whom treatment is administered, and what barriers must be resolved before that model becomes clinically practical?

Rahmo: Beyond any one product, using a familiar device such as a nebulizer could shift complex biologic therapies out of highly specialized infusion or cellular-therapy centers and toward pulmonary clinics, outpatient treatment centers, and specialty pharmacies.

The key is that familiarity of the device does not by itself make the therapy simple: a living-cell product introduces requirements that conventional inhaled drugs do not.

Today, many complex cell therapies require specialized facilities because the product may have stringent storage, preparation, chain-of-identity, and administration requirements. AABB’s current standards distinguish pharmacy management of cell and gene therapies from the clinical administration of cellular therapies, reflecting the specialized infrastructure involved.

A stable, ready-to-administer cell product delivered through a standardized nebulizer could move treatment from a specialized cellular-therapy center to a hospital, outpatient infusion or pulmonary center, and eventually a community specialty clinic.

A nebulizer is already familiar to respiratory clinicians and many patients. If a complex therapy could be delivered reproducibly through one, several components of the treatment pathway could become more conventional.

Respiratory therapists could administer the treatment, and pharmacists could manage product receipt, storage, preparation, and dispensing. Pulmonary clinics could incorporate administration into existing COPD workflows. Patients might avoid intravenous access and prolonged infusion-center visits, and specialty pharmacies could become part of the distribution network.

This direction is consistent with the broader evolution of cell-therapy pharmacy infrastructure. AABB’s 2025 Cell and Gene Therapy Standards for Pharmacy specifically address receipt, storage, handling, and dispensing of these products, including chain of identity and custody, staff competency, and quality oversight.

The most important milestone would be demonstrating an end-to-end process that is as predictable as conventional drug administration. That would require a stable product, simple preparation, a validated device, a reproducible viable dose, predictable lung deposition, manageable monitoring, and reliable documentation and traceability.

If those conditions can be met, the significance of nebulized cell therapy would extend beyond the particular cell product. It could create a new model in which the delivery technology becomes the bridge between sophisticated biologic therapies and ordinary outpatient respiratory care.

The critical test is whether the entire therapy, device, and workflow system can be standardized sufficiently that moving treatment closer to the patient does not compromise product quality, dose accuracy, safety, or clinical benefit.