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PDSP Technology

PDSP regenerative peptide technology

BRIM’s core technology platform is based on the Pigment epithelium-derived factor (PEDF)-Derived Short Peptides, PDSP. This technology was licensed from Mackay Memorial Hospital in 2015. Within 18 months after the technology transfer, BRIM completed the preclinical development of BRM421, an innovative first-in-class therapy for dry eye disease and subsequently filed an IND application. In 2017, the US FDA approved BRM421 to initiate its first-in-human (FIH) clinical trial directly as a Phase 2 study, bypassing Phase 1. Following continuous efforts and optimization, BRIM has completed dose adjustment for BRM421 and submitted a new clinical trial application to the US FDA for a dose-ranging study. Based on the study results, the optimal dose will be selected to plan and conduct a second Phase 3 trial in the United States.

 

In parallel, BRIM is actively exploring PDSP applications beyond ophthalmology. Building on the achievements of its Taiwan R&D team, BRIM has established a global patent strategy to expand its innovative drug pipeline and strengthen its intellectual property portfolio. This approach not only creates value for the company but also aims to deliver high-quality, safe, effective, and affordable new therapies for patients with limited treatment options.

PEDF protein structure and functional domain

The function of 34-mer peptide region (ASp44-Asn 77) : anti-angiogenesis, pro-apoptotic tumor cells (anti-tumor)
The function of 44-mer peptide region (Val78-Thr121, BRM421 (29-mer) is Ser 93-Thr 121) : neurotrophy, neuroprotective activity, stem cell regeneration, anti-inflammation

Pigment epithelium-derived factor (PEDF) is a multifunctional secretory protein, originally identified in the retinal pigment epithelium (RPE), and is broadly expressed in human tissues. It promotes neuronal growth, survival, and differentiation, and is therefore classified as a neurotrophic factor.

Among PEDF’s functional domains, the 44-amino acid region (Val78–Thr121 ; red region in the figure above) possesses neurotrophic, stem-cell-activating, and anti-inflammatory properties.

Building on these biological functions, BRIM has optimized a 29-amino acid sequence within the 44-mer region (Ser93–Thr121) to establish its PDSP regenerative peptide technology platform, which supports the development of innovative therapeutics across multiple indications.

Unique features and advantages of PDSP

  • Promotes the proliferation and differentiation of stem cells and then repairs damaged tissues
  • Early-onset potential in various disease animal models
  • Low immunogenicity due to short peptides with natural sequence
  • Low cost drug substance produced by solid-phase peptide synthesis (SPPS) with low-cost and no endotoxin risk
  • High pharmaceutical stability with eye drop formula optimized with over 2-years of shelf life

Limbus regeneration by PDSP

Limbal stem cells (LSCs), located at the limbus —the epithelial cell layer at the junction of the cornea, conjunctiva, and sclera—are the key to maintaining the normal function of the cornea. Corneal homeostasis and repair mainly depend on the proliferation and differentiation of LSCs.

 

Studies have shown that PDSP promotes the growth and self-renewal of LSCs. In a rabbit model involving extensive limbus resection, just two weeks of PDSP treatment effectively regenerated the limbal region and restored its corneal repair function. In contrast, in the vehicle-treated group that underwent two sequential 50% limbal resections, there was a large number of new blood vessels in the limbus and the boundary between the cornea and the sclera was lost. During the corneal repair challenge, the corneal damage failed to heal within 7 days, indicating a complete loss of limbal function.

 

The functions of PEDF have been well documented in numerous studies.  PEDF promotes the growth and differentiation of neurons and various stem cells. In animal disease models, PEDF has been shown to activate myoblasts, retinal precursor cells, and stem cells from the liver, hair follicles, and nerve, leading to enhanced tissue regeneration. These effects contribute to wound healing, corneal repair, and recovery from degenerative or traumatic conditions such as age-related macular degeneration, muscle, liver, and nerve injuries. Therefore, PEDF is a potential new drug candidate for treating various diseases. However, compared to PDSP, the full-length PEDF protein presents challenges in tissue permeability, long-term storage stability, and manufacturing cost. Therefore, BRIM identified and extracted the functional domain of PEDF to develop the 29-mer PDSP as the active pharmaceutical ingredient (API) for new drug development.

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