Technology


Technology

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SILK DERIVED PROTEIN-4 (SDP-4)

Designed to treat the signs & symptoms of Dry Eye Disease (DED)

SDP-4 offers a novel biotherapeutic approach as it is naturally derived from silk protein, and is designed to treat DED through a dual-mechanism of action that inhibits inflammation while physically improving tear film stability.

Novel biologic drug with a dual mechanism of action

SDP-4 inhibits the activation of the NF-κB gene transcription pathway, which reduces the production of known pro-inflammatory DED mediators. In addition, SDP-4’s inherent protein nature allows it to act like a mucin-replacement by enhancing the spreading and wetting properties of an impaired ocular epithelial surface.

NF-kB Driven DED

NF-κB activation is known to play a role in DED as the inflammatory pathway can be stimulated through a number of different biological stimuluses. Signaling antagonist can include numerous growth factors, microbial byproducts, multiple cytokines, and UV irradiation. When activated, the NF-κB transcription factor enters the cell nucleus and drives production of additional inflammatory mediators such as MMP-9, multiple interleukin cytokines, and TNF-α.

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SILK DERIVED PROTEIN-4 (SDP-4)

Designed to treat the signs & symptoms of Dry Eye Disease (DED)

SDP-4 offers a novel biotherapeutic approach as it is naturally derived from silk protein, and is designed to treat DED through a dual-mechanism of action that inhibits inflammation while physically improving tear film stability.

Novel biologic drug with a dual mechanism of action

SDP-4 inhibits the activation of the NF-κB gene transcription pathway, which reduces the production of known pro-inflammatory DED mediators. In addition, SDP-4’s inherent protein nature allows it to act like a mucin-replacement by enhancing the spreading and wetting properties of an impaired ocular epithelial surface.

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NF-κB Driven DED Inflammation


NF-κB activation is known to play a role in DED as the inflammatory pathway can be stimulated through a number of different biological stimuluses. Signaling antagonists can include numerous growth factors, microbial byproducts, multiple cytokines, and UV irradiation. When activated, the NF-κB transcription factor enters the cell nucleus and drives production of additional inflammatory mediators such as MMP-9, various interleukin cytokines, and TNF-α.

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PRE-CLINICAL STUDY RESULTS


Recent studies have shown that SDP-4 works to inhibit the ability of IκB kinase to activate the NF-κB transcription factor, thereby preventing it from translocating into the nucleus to produce pro-inflammatory drivers of DED.

In vitro results

The SDP-4 drug candidate was found to reduce DED-related inflammatory gene transcription factors within the NF-κB cell signaling pathway using human corneal cell cultures and validated bioassay models [1]. In addition, further work demonstrated SDP-4 enhanced pro-healing effects in various human corneal cell culture models [2].

In vivo results

SDP-4’s biotherapeutic activity was further demonstrated in vivo within a corneal model where it caused a substantial reduction in the presence of the DED pro-inflammatory marker MMP-9, while simultaneously increasing pro-healing indicators [3]. Further safety data has shown the drug candidate to be non-toxic and non-immunogenic on both the ocular surface and within the body systemically.

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PRE-CLINICAL STUDY RESULTS


Recent studies have shown that SDP-4 works to inhibit the ability of IκB kinase to activate the NF-κB transcription factor, thereby preventing it from translocating into the nucleus to produce pro-inflammatory drivers of DED.

In vitro results

The SDP-4 drug candidate was found to reduce DED-related inflammatory gene transcription factors within the NF-κB cell signaling pathway using human corneal cell cultures and validated bioassay models [1]. In addition, further work demonstrated SDP-4 enhanced pro-healing effects in various human corneal cell culture models [2].

In vivo results

SDP-4’s biotherapeutic activity was further demonstrated in vivo within a corneal model where it caused a substantial reduction in the presence of the DED pro-inflammatory marker MMP-9, while simultaneously increasing pro-healing indicators [3]. Further safety data has shown the drug candidate to be non-toxic and non-immunogenic on both the ocular surface and within the body systemically.

Dose Dependent & Non-Toxic

Potency bioassay results demonstrate that SDP-4 reduces NF-κB activity dose dependently by over 20-fold when compared to controls, with a maximal dose response at a 1% concentration. In vivo, pre-clinical safety studies indicate that SDP-4 is well tolerated both in the ocular environment and systemically with a negligible toxicity and immunogenicity profile within clinically relevant concentration ranges.

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