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Arcutis Is Building a Robust Dermatology Pipeline

At Arcutis, we are focused on filling the innovation gap in medical dermatology drug development by applying our deep clinical, product development, and commercial expertise in dermatology to develop best-in-class therapies against biologically validated targets. Our vision is to revitalize the standard of care for dermatological diseases and conditions through novel therapies that simplify disease management for physicians and eliminate the need to compromise between drug safety, efficacy, and tolerability for patients.

PDE4 Inhibitor

PDE4 Inhibitor molecular compound.
  • Topical roflumilast is a selective, highly potent, once-daily, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor being investigated for the once-daily treatment of chronic plaque psoriasis, atopic dermatitis, seborrheic dermatitis, and scalp psoriasis
  • Inhibition of PDE4 has been validated for oral psoriasis therapy1 but is a novel formulation for many topical dermatologic conditions
  • Topical roflumilast is being developed as a cream and foam formulation. Topical roflumilast is a highly potent, anti-inflammatory PDE4 inhibitor reformulated from an oral product that was approved by the US Food and Drug Administration in 2011 to treat patients with severe chronic obstructive pulmonary disease1

PDE4 plays a key role in immunodermatology1

PDE4 is an enzyme that contributes to immunodermatologic conditions.

3 Icons showing roles of PDE4: increases inflammatory mediators, disrupts skin barrier balance, and increases inflammatory response.

Inhibition of PDE4 modulates the immune response in the skin1

Inhibition of PDE4 modulates the immune response by downregulating inflammatory cytokines, restoring the skin barrier balance, and decreasing inflammatory response.

3 icons with text: down regulates inflammatory cytokines, restores skin barrier balance, decreases inflammatory response.

Roflumilast is a PDE4 inhibitor being developed in topical cream and foam formulations

JAK1 Inhibitor

  • ARQ-252 is a selective, highly potent, topical Janus kinase 1 (JAK1) inhibitor being investigated as a cream for the treatment of hand eczema and vitiligo
  • ARQ-252 demonstrates greater potency in vitro for JAK1 than JAK2,2 which may avoid the hematologic adverse effects typically associated with inhibition of JAK23
  • JAK inhibitors in development have demonstrated treatment efficacy for inflammatory conditions such as rheumatoid arthritis, Crohn’s disease, psoriasis, and atopic dermatitis4
  • ARQ-255, a formulation of ARQ-252 modified to deliver the drug deeper into the dermis, is being investigated for the treatment of alopecia areata
JAK1 Inhibitor molecular compound.

Role of JAK1 in immunomodulation

JAK-dependent cytokines contribute to immunodermatologic conditions5,6

The role of JAK 1 immunomodulation.

Selective in vitro inhibition of JAK1 modulates immunodermatology pathways

Selective in vitro inhibition of JAK1 modulates or reduces the activity of specific cytokines while maintaining other JAK-dependent immunomodulatory pathways, with the potential for fewer adverse effects than pan-JAK inhibitors5

Selective in vitro inhibition of JAK1 modulates immunodermatology pathways.

ARQ-252 and ARQ-255 are the same investigational JAK1 inhibitor, with ARQ-252 being investigated as a topical cream and ARQ-255 as a suspension

References

1. Li et al. Front Pharmacol. 2018;9:1048. 2. Data on file, Arcutis Biotherapeutics. 3. Biggioggero et al. Drugs Context. 2019;8:212595. 4. Damsky and King. J Am Acad Dermatol. 2017;76:736-744. 5. Schwartz et al. Nat Rev Drug Discov. 2017;17:78. 6. Fragoulis et al. Rheumatology (Oxford). 2019;58:i43-i54.

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