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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. It was licensed from the Mackay Memorial Hospital in 2015, and BRIM completed the IND filing for BRM421 treating dry eye disease within 18 months after the technology transfer was completed. BRM421 is the first-in-class innovative drug that the US FDA agreed the first-in-human study to be a phase 2 clinical trial design to skip the phase 1 trial. Now, the planning of the second phase 3 trial of BRM421 is underway.

Besides in ophthalmology, PDSP can also be used in other indications. Through the efforts of our RD team, BRIM is actively developing additional applications for PDSP to expand the pipeline and global patent portfolio. In the hope of creating value with new drug development, BRIM strives to provide high-quality, safe, effective, and affordable medicines for patients in need.

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), which is ubiquitous in human tissues, is a multifunctional secretory protein. It was first discovered to be secreted by the retinal pigment epithelium (RPE), a layer of cells that supports the retina. PEDF can promote nerve growth, survival, and differentiation, so it is called a neurotrophic factor.

Among PEDF’s functional domains, the 34-amino acid functional domain (34-mer) has anti-angiogenesis and tumor-inhibiting functions. There is also a 44-amino acid functional domain (44-mer) that has neurotrophic functions, stem cell activation, and anti-inflammatory effects.

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

The first PDSP is a short peptide (Ser93-Thr121) consisting of 29 amino acid sequences from the 44-mer region and has the same functional characteristics as the 44-mer:

  1. Activating stem cells: promote stem cell proliferation and differentiation to repair damaged tissues, including limbal stem cells for cornea, mesenchymal stem cells for cartilage and tendons, and skin hair follicle stem cells for hair growth and wound healing.
  2. Early onsets: different animal disease models and human trials of dry eye disease showed early onset efficacy.
  3. Low immunogenicity: the 29-mer peptide sequence is natural and short, so it is not easy to induce an immune response to affect the long-term efficacy.
  4. Low cost: the API is synthesized by solid-phase peptide synthesis (SPPS). The cost is low and has a low risk of endotoxin contamination.
  5. High stability: the current eye drop is stable over two years with an optimized formulation.

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. The homeostasis and repair of the cornea mainly rely on the proliferation and differentiation of LSCs.

Literature shows that PDSP can promote the growth and self-renewal of LSCs. In a rabbit model with extensive limbus resection, only two weeks of PDSP treatment can effectively regenerate the limbus and restore its function of repairing the cornea. Compared with the vehicle group, after two times 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 cornea damage can not be repaired within 7 days, indicating a complete loss of limbal function.

The function of PEDF has been demonstrated in numerous literatures that it can promote the growth and differentiation of neurons and stem cells. In animal disease models, PEDF has been shown to activate myoblasts, retinal precursor cells, and various stem cells including the liver, hair follicles, and nerve. The growth, differentiation, and self-renewal of the stem cells can then repair damaged tissues, affecting wound healing, corneal repair, age-related macular degeneration, muscle, liver, and nerve damage, etc. Therefore, PEDF is a potential new drug candidate for treating various diseases.

However, compared to PDSP, PEDF as a protein will raise concerns regarding its tissue permeability, long-term storage stability, and manufacturing cost. Therefore, BRIM only took the functional domain of PEDF and derived a 29-mer PDSP as the active pharmaceutical ingredient (API) for new drug development.

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