Pipeline

A defining feature of our discovery research is understanding immunologic mechanisms as they relate to dermatology and translating these learnings into empowering solutions for patients.

Diversified dermatology and immunology portfolio—charting new territories

Preclinical
Phase 1
Phase 2
Phase 3

A-101 45%

Topical

ATI-502
JAK1/JAK3 Inhibitor

Topical

ATI-502
JAK1/JAK3 Inhibitor

Topical

ATI-502
JAK1/JAK3 Inhibitor

Topical

ATI-502
JAK1/JAK3 Inhibitor

Topical

ATI-501
JAK1/JAK3 Inhibitor

Oral

ATI-450
MK2 Pathway Inhibitor

Oral
Potential in Rheumatoid arthritis, Psoriasis, Hidradenitis suppurativa, Cryopyrin-associated periodic syndromes, Pyoderma gangrenosum

ATI-1777
JAK1/JAK3 Inhibitor

Soft Topical
Potential in Atopic dermatitis, Vitiligo, Alopecia areata

ITK/JAK3 Inhibitor

Soft Topical
Potential in Psoriasis, Inflammatory dermatoses

ITK/JAK3 Inhibitor

Oral
Potential in Psoriasis, Inflammatory dermatoses

ITK/JAK3 Inhibitor

Oral (gut restricted)
Potential in Inflammatory bowel disease

MK2 Pathway Inhibitor

Oral
Potential in Oncology

Diversified dermatology and immunology portfolio—charting new territories

Program
Therapeutic Indication
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

A-101 45%

Topical
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ATI-502
JAK1/JAK3 Inhibitor

Topical
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ATI-501
JAK1/JAK3 Inhibitor

Oral
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ATI-450
MK2 Pathway Inhibitor

Oral
Potential in Rheumatoid arthritis, Psoriasis, Hidradenitis suppurativa, Cryopyrin-associated periodic syndromes, Pyoderma gangrenosum
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ATI-1777
JAK1/JAK3 Inhibitor

Soft Topical
Potential in Atopic dermatitis, Vitiligo, Alopecia areata
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ITK/JAK3 Inhibitor

Soft Topical
Potential in Psoriasis, Inflammatory dermatoses
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ITK/JAK3 Inhibitor

Oral
Potential in Psoriasis, Inflammatory dermatoses
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

ITK/JAK3 Inhibitor

Oral (gut restricted)
Potential in Inflammatory bowel disease
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

MK2 Pathway Inhibitor

Oral
Potential in Oncology
Discovery
Lead Optimization
IND Enabling
Phase 1
Phase 2
Phase 3

The role of the JAK pathway in alopecia areata

Aclaris is focused on developing JAK1/JAK3 inhibitors to interfere with the signals that result in generation of mature killer T cells and subsequent death of the hair follicle (steps 4-7).

1. The skin is made up of several layers. The cells responsible for skin pigmentation, called melanocytes, reside in the top layer of skin called the epidermis. Beneath this layer is the dermis, where the hair follicle resides.

2. A type of immune cell, called T cells, can be found in the dermis. In certain autoimmune conditions, such as alopecia areata, T cells mistake self-antigens presented by the hair follicle cells as foreign antigens that need to be destroyed.

3. When the T cell is activated by this antigen, it produces an inflammatory signaling molecule, known as a cytokine, called interferon gamma (IFN-γ)

4. Receptors on the hair follicle cells bind to IFN-γ. JAK1/JAK2 proteins pass this signal inside of the cell to STAT proteins, which translocate to the nucleus and regulate gene expression.

5. JAK/STAT signaling in the hair follicle cell results in the production of the cytokine IL-15. Then, IL-15 signals through JAK1/JAK3 in the T cell to produce more inflammatory cytokines. This also drives the T cell to become a “killer T cell” which can attack and damage hair follicle cells expressing self-antigens.

6. IFNγ produced by the T cell and IL-15 produced by the hair follicle establishes a feedback loop, which maintains the killer T cells in an activated state. This leads to damage to the hair follicle and reduced hair growth.

7. Once a follicle cell has been damaged, the T cell is released to initiate the destructive process with another hair follicle cell.