New Research Reveals PC111's Potential to Revolutionize Pemphigus and SJS/TEN Treatment

Image Credit: © dermnetnz.org

Scinai Immunotherapeutics has just published a peer-reviewed article in the Journal of Dermatological Treatment highlighting its novel drug, PC111.¹ The publication, which was authored by Roberta Lotti, PhD, and a team from the University of Modena and PincellSrl, explores the potential of the first-in-class human anti-Fas Ligand monoclonal antibody.² PC111 has a unique, non-immunosuppressive mode of action, acting locally at the keratinocyte level and downstream of the immune system.

In the study, it was found that PC11 prevented blister formation in in vitro, ex vivo, and in vivo humanized models of pemphigus vulgaris through the targeting of soluble Fas Ligand (sFasL). It also showed potential for life-saving treatment of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, preventing FasL-mediated keratinocyte apoptosis and ocular damage. Both of these severe diseases have a high unmet need with limited effective treatments.

Pemphigus is an autoimmune blistering disorder in which autoantibodies (PVIgG) attack desmogleins(Dsg1 and Dsg3) in keratinocytes, disrupting cell adhesion and leading to blister formation. Traditional treatments rely heavily on broad immunosuppressants, such as corticosteroids and rituximab, which are effective but carry substantial risks, including infections and relapse. Emerging data reveal that keratinocyte apoptosis, mediated by sFasL, plays a critical role in disease pathogenesis.

PC111 specifically neutralizes human sFasL, thereby preventing keratinocyte apoptosis and subsequent acantholysis. In both keratinocyte cultures and human skin organ cultures, PC111 inhibited PVIgG-induced acantholysis. In a humanized FasL mouse model, PC111 significantly reduced blister formation and disease severity. These effects were achieved rapidly and without affecting systemic immune function, positioning PC111 as a non-immunosuppressive, targeted therapy that acts downstream of autoantibody production.

In contrast to rituximab, which takes months to reach efficacy and often requires repeated dosing, PC111’s localized and fast action offers the potential for earlier clinical remission, fewer adverse effects, and long-term disease control. It may also be used as a bridge therapy or in combination with immunosuppressants, allowing for dose reduction and better patient outcomes.

The article also highlights the therapeutic potential of PC111 in Stevens-Johnson syndrome and Toxic Epidermal Necrolysis, acute life-threatening skin reactions that are typically triggered by drugs. In these conditions, sFasL levels are markedly elevated early in the disease course and contribute to widespread keratinocyte apoptosis and epidermal detachment. PC111 effectively blocked keratinocyte death in vitro when exposed to Stevens-Johnson syndrome/Toxic Epidermal Necrolysis patient serum and protected ocular tissue in a preclinical mouse model.

"This new publication further validates our conviction that PC111 has the potential to transform the treatment landscape for pemphigus and SJS/TEN," Amir Reichman, CEO of Scinai, said in the press release. "The scientific leadership and development expertise of the Pincell's team have been instrumental, and with their expected integration into Scinai upon exercise of the option, we are well positioned to advance PC111. With strong science, regulatory clarity, and substantial market potential, we believe PC111 can deliver life-changing benefits to patients, and meaningful value to shareholders."¹

The drug has already been granted orphan drug designation in Europe, with the company looking to make similar strides in the US. With accelerated approval pathways, the company aims to have PC111 enter the market within the next 3 to 4 years. Future clinical trials are planned for both indications of PC111.

References

1. Scinai Announces New Peer-Reviewed Publication Supporting PC111 as a Disease-Modifying Therapy for Pemphigus and SJS/TEN. News release. PR Newswire. July 29, 2025. Accessed July 30, 2025. https://www.prnewswire.com/news-releases/scinai-announces-new-peer-reviewed-publication-supporting-pc111-as-a-disease-modifying-therapy-for-pemphigus-and-sjsten-302516002.html

2. Lotti R, Amato A, Bennett B, Zanocco-Marani T, Marconi A, Pincelli C. Treatment of pemphigus and other neglected skin conditions with PC111, a human anti-Fas Ligand monoclonal antibody: a potential disease modifier. J Dermatolog Treat. 2025;36(1):2526075. doi:10.1080/09546634.2025.2526075