Shape Pharmaceuticals Provides Update on SHP-141 Topical HDAC Inhibitor Clinical Development for Cutaneous T Cell Lymphoma

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Shape Pharmaceuticals today provided an update on the clinical development of SHP-141, its novel, topically administered histone deacetylase inhibitor (HDACi) for the treatment of cutaneous T cell lymphoma (CTCL).

“There is a strong rationale for investigating SHP-141 in clinical trials based on its validated mechanism of action and preclinical data suggesting potent activity. SHP-141, as a topical agent, is characterized by lower toxicity than systemic agents in this class”

SHP-141 is currently undergoing a multi-center, randomized, placebo-controlled Phase 1b clinical trial to evaluate the safety and tolerability of the compound at escalating doses in patients with Stage 1A, 1B or 2A CTCL. The trial is also evaluating the effect of the compound on skin lesions in these patients. Two of the study’s three dose escalating cohorts have been treated, and the study is proceeding on track.

Michael Krathen, MD, Clinical Assistant Professor of Dermatology at Stanford University, noted the ongoing clinical trial during a presentation at the annual meeting of the American Academy of Dermatology titled, "Case Based Discussions in Cutaneous Lymphomas: Treating early stage mycosis fungoides." “There is a strong rationale for investigating SHP-141 in clinical trials based on its validated mechanism of action and preclinical data suggesting potent activity. SHP-141, as a topical agent, is characterized by lower toxicity than systemic agents in this class,” said Dr. Krathen. “This study is providing an initial opportunity to assess SHP-141’s safety profile and its anti-CTCL activity.” Dr. Krathen is an investigator in the Phase 1b clinical trial.

The emergence of systemically administered HDACi inhibitors has proven to be a significant advance in the treatment of CTCL, particularly for patients with more advanced disease. However, systemic toxicity of these agents has limited their use in patients during the earlier stages of the disease. SHP-141 is a novel, small molecule, “soft-drug” HDACi that is chemically designed to act directly on the skin and then break down into an inactive form as it is absorbed, and thereby preventing systemic exposure. Preclinical studies have demonstrated that topical application of SHP-141 produces substantial HDAC inhibition in the skin, no detectable systemic exposure of SHP-141 or systemic toxicity, even at maximum feasible dose levels.

“SHP-141 represents an important innovative approach that could eventually treat all patients with CTCL, with special benefit for approximately 70 percent of CTCL patients with earlier stage disease who do not receive HDACi’s today,” said Steven Landau, MD, Director of Scientific Evaluation at HealthCare Ventures and Chief Medical Officer for Shape Pharmaceuticals. “The clinical program is aimed at building on the strong results in preclinical studies and demonstrating proof-of concept in humans.”

About Cutaneous T-Cell Lymphoma

Cutaneous T-Cell Lymphoma (CTCL) is a rare, life-altering, and life-threatening form of Non-Hodgkin’s lymphoma (NHL) which initially presents in the skin. CTCL is a heterogeneous group of malignant lymphomas that are more common in men, occur most often in people older than 55, and affect twice as many African-Americans as Caucasians. CTCL patients typically present with skin symptoms and lesions, including follicular papules, erythematous patches, elevated plaques, alopecia, pendulous slack skin, pustular lesions and subcutaneous nodules. Lesions of this lymphoma may remain as patches or plaques confined to the skin for many years prior to the development of cutaneous tumors or visceral disease. Patients with later stages of CTCL currently have a median survival of five years.

About Shape Pharmaceuticals

Shape Pharmaceuticals, Inc. is developing SHP-141, a novel, topical, “soft-drug” HDAC inhibitor for the treatment of patients with cutaneous T cell lymphoma (CTCL) and psoriasis. Shape has an ongoing Phase 1b clinical study in CTCL patients and has completed a Phase 1b clinical study in psoriasis patients. The development of SHP-141 is being supported through a Therapeutic Accelerator Program partnership with the Leukemia & Lymphoma Society, which is providing funding of up to $3.3 million. Shape is a HealthCare Ventures funded Focused Company founded by James E. Bradner, M.D. of Dana-Farber Cancer Institute and Ralph Mazitschek, Ph.D. of Massachusetts General Hospital.