Vascarta Outlines Proposed Mechanistic Link Between VAS-101's (Vasceptor®) Vascular and Red Blood Cell Effects in Sickle Cell Disease

Company connects new preclinical microcirculation findings with prior low-dose sublingual clinical data to propose how Vasceptor® (VAS-101) may improve red blood cell sickling kinetics without requiring direct, high-concentration inhibition of hemoglobin S polymerization

SUMMIT, N.J., Aug. 20, 2026 /PRNewswire/ -- Vascarta Inc., a clinical-stage biopharmaceutical company advancing transdermal curcuminoid therapeutics for pain, inflammation, and sickle cell disease (SCD), today outlined a proposed mechanistic framework connecting two recent findings on Vasceptor® (VAS-101): a newly published preclinical study demonstrating preservation of tissue oxygenation and microvascular perfusion, and previously reported clinical results showing improved red blood cell (RBC) sickling kinetics in SCD patients treated with a low-dose sublingual formulation.

Two Complementary Findings

• Preclinical microcirculation study: In a rat model of acute sickle vaso-occlusive episode (VOE), topical pretreatment with VAS-101 preserved interstitial tissue oxygenation, arteriolar diameter, and mean arterial pressure following exchange transfusion with human sickle (HbSS) red blood cells, while untreated animals developed progressive tissue hypoxia and vasoconstriction [1].
  
  
  
  
• Clinical sublingual pilot: In a Phase I pilot study of five SCD patients treated sublingually with minimal-dose VAS-101 (0.1 mL, twice weekly for 29 days), red blood cells drawn from patients showed measurable improvement in ex vivo sickling kinetics, including a delayed morphological point of sickling, reduced rate of sickling, and decreased area under the sickling curve (AUC10) [2].

The Open Question

The preclinical study evaluated the effect of VAS-101 on the host vasculature; the red blood cells used in that model were unexposed donor sickle cells, so the study was not designed to determine whether Vasceptor® also changes the intrinsic sickling behavior of red blood cells themselves. The clinical pilot, by contrast, measured exactly that — but at a curcuminoid dose well below the concentration generally understood to be required for curcumin to directly and stoichiometrically inhibit hemoglobin S polymerization [3]. This raised the question of what could account for improved RBC sickling kinetics at a dose too low for a direct hemoglobin-binding effect.

A Proposed Explanatory Framework

A mechanism for inhibiting RBC sickling through repeated, low-dose transdermal or transmucosal curcumin most likely proceeds through pathways that reduce oxidative damage to the red blood cell itself, rather than through direct binding to hemoglobin. Oxidative damage to RBC proteins and lipids is a well-established driver of increased sickling propensity in sickle cell disease [4,5]. This creates a destructive feedback loop: oxidative stress promotes cell dehydration and membrane rigidity, which in turn directly drives hemoglobin S (HbS) polymerization and cell deformation. Viewed this way, each of the mechanisms below — with the exception of direct curcumin binding to hemoglobin — converges on a common endpoint: reducing the oxidative burden borne by the red blood cell, thereby lowering the probability of sickling.

• Reduced hypoxia/reoxygenation cycling burden: By preserving tissue oxygenation and microvascular perfusion in vivo, Vasceptor® may reduce the frequency and severity of the deoxygenation/reoxygenation cycles known to progressively and irreversibly damage sickle red blood cells over their circulatory lifespan [1,6,7]. A less hypoxic vascular environment could yield a circulating RBC population with less cumulative sickling-related oxidative injury, independent of any direct drug effect on hemoglobin.
  
  
  
  
• Catalytic membrane and antioxidant stabilization: Curcuminoids delivered transdermally or sublingually are absorbed into red blood cells, where they act as antioxidants and membrane stabilizers during each brief intracellular residence, then are exported and redistributed as the cell recirculates. Repeated, low-level exposure over many circulatory passes may meaningfully slow the accumulation of oxidative membrane injury that predisposes cells to sickle more readily, without requiring a single high-concentration exposure [8].
  
  
  
  
• RBC-intrinsic nitric oxide signaling: Curcuminoids are reported to activate endothelial nitric oxide synthase (eNOS) both in the vascular endothelium and within red blood cells themselves, an erythrocrine function increasingly recognized as relevant to RBC physiology [9]. Nitric oxide generated within RBCs may influence membrane deformability and oxygen affinity through pathways distinct from hemoglobin S polymerization chemistry, while also limiting the oxidative conditions that promote sickling.
  
  
  
  
• Reduced systemic inflammatory and oxidative burden: Preclinical data have shown VAS-101 reduces hemolysis, circulating inflammatory markers, and downstream oxidative stress to RBCs in a humanized sickle cell mouse model [10]. Lower systemic inflammation and oxidative stress may reduce upstream injury to red blood cells generally, an effect that would manifest in ex vivo sickling assays without implicating direct hemoglobin binding.

Vascarta emphasizes that this framework is a scientific hypothesis intended to guide future investigation, not a proven mechanism. Neither the preclinical microcirculation study nor the sublingual clinical pilot was designed to isolate these pathways directly, and dedicated mechanistic studies — including chronic sickle cell disease models and RBC-specific oxidative-damage biomarker assays — will be needed for confirmation.

Leadership Perspectives

Dr. Bjorn Song, Chief Executive Officer of Song Biotechnologies and Study Director, commented: "Vasceptor's (VAS-101) ability to improve tissue oxygenation goes beyond Sickle Cell Disease into numerous pathologies mediated by hypoxia. As a topical/transdermal treatment, its accessibility affords high treatment compliance and avoids use complications that come with oral and intravenous routes of administration."

Dr. Joel Friedman, Vascarta Scientific Founder & Chief Science Officer, commented: "What's compelling about placing these two datasets side by side is that they point to the same underlying biology from two different vantage points. The rat model tells us Vasceptor® can protect the vasculature and preserve oxygen delivery during a simulated crisis. The sublingual pilot tells us that, over time, patients' own red blood cells appear to sickle more slowly. Neither result alone proves the connection, but together they support a working hypothesis: that Vasceptor® may be interrupting the feed-forward cycle between hypoxia and sickling upstream of the hemoglobin molecule itself, rather than only acting on it directly. That has real implications for how we think about dosing and endpoints going forward."

Dr. Richard Prince, Vascarta Chairman, CEO & President, commented: "These findings, taken together, reinforce our conviction in Vasceptor's potential across the full arc of sickle cell disease care — from protecting tissue during an acute event to potentially improving the underlying health of red blood cells with sustained, low-dose use. We believe this kind of mechanistic clarity strengthens both our clinical development plan and our IND submission later this year, and we look forward to testing this hypothesis directly in future studies."

About VAS-101 (Vasceptor®)

VAS-101 is a topical curcumin formulation employing a patented transdermal delivery technology designed to increase bioavailability. Curcumin possesses anti-sickling, anti-inflammatory, antioxidant, and vasoactive properties, but its translational potential has historically been constrained by limited oral bioavailability. VAS-101 is being clinically evaluated in sickle cell disease and other chronic inflammatory indications.

About Vascarta

Vascarta is a clinical-stage pharmaceutical company exploring efficient transdermal delivery of pharmaceuticals to address inflammation and pain, with an initial focus on sickle cell disease and osteoarthritis. More information can be found at www.vascarta.com.

Media & Investor Contact

Dr. Richard Prince, Chairman, CEO & President — rprince@vascarta.com

References

1. Nugent WH, Prince R, Friedman J, Song BK. Transdermal curcumin gel (VAS-101 drug candidate) improves the microcirculation and tissue oxygenation in a rat model of sickle cell vaso-occlusive episode. J Sickle Cell Dis. 2026;3(1):yoag034. https://doi.org/10.1093/jscdis/yoag034

2. Vascarta Inc. Vascarta Announces Phase I Results of VAS-101 Administered Sublingually in Sickle Cell Disease Patients. PR Newswire. June 24, 2026. https://www.prnewswire.com/news-releases/vascarta-announces-phase-i-results-of-vas-101-administered-sublingually-in-sickle-cell-disease-patients-302809748.html

3. Metaferia B, Cheng X, Kaur H, et al. Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease. Proc Natl Acad Sci U S A. 2022;119(40):e2210779119. https://doi.org/10.1073/pnas.2210779119

4. Wang Q, Zennadi R. The role of RBC oxidative stress in sickle cell disease: from the molecular basis to pathologic implications. Antioxidants (Basel). 2021;10(10):1608. https://doi.org/10.3390/antiox10101608

5. Vona R, Sposi NM, Mattia L, Gambardella L, Straface E, Pietraforte D. Sickle cell disease: role of oxidative stress and antioxidant therapy. Antioxidants (Basel). 2021;10(2):296. https://doi.org/10.3390/antiox10020296

6. Du E, Dao M. Faster sickling kinetics and sickle cell shape evolution during repeated deoxygenation and oxygenation cycles. Exp Mech. 2019;59(3):319-325. https://doi.org/10.1007/s11340-018-00444-5

7. Ballas SK, Mohandas N. Sickle red cell microrheology and sickle blood rheology. Microcirculation. 2004;11(2):209-225. https://doi.org/10.1080/10739680490279410

8. Hicks W, Jana S, Kassa T, et al. Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation. Sci Rep. 2024;14(1):31441. https://doi.org/10.1038/s41598-024-82943-1

9. Cortese-Krott MM, Kelm M. Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol. 2014;2:251-258. https://doi.org/10.1016/j.redox.2013.12.027

10. Goel Y, Arellano MA, Fouda RT, et al. Targeting sickle cell pathobiology and pain with novel transdermal curcumin. PNAS Nexus. 2025;4(2):pgaf053. https://doi.org/10.1093/pnasnexus/pgaf053

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SOURCE Vascarta Inc.