Syntimmune Announces Positive Preliminary Results from Clinical Proof-of-Concept Trial of SYNT001 in Pemphigus Vulgaris and Foliaceus

May 17, 2018 |

5 min read

Favorable safety and tolerability profile consistent with Phase 1a data SYNT001 treatment resulted in clinical improvement as measured by Pemphigus Disease Area Index (PDAI) score, with clinical effect persisting beyond the treatment period Rapid reductions in total IgG and circulating immune complex (CIC) levels

BOSTON--(BUSINESS WIRE)-- Syntimmune, Inc., a clinical-stage biotechnology company developing antibody therapeutics targeting FcRn, today announced positive preliminary results from its Phase 1b proof-of-concept trial of SYNT001 in patients with pemphigus vulgaris and pemphigus foliaceus. The data showed clinically meaningful benefit of SYNT001, with a favorable safety and tolerability profile similar to that observed in the Phase 1a study.

“There remains a clear unmet need for a safe and fast-acting treatment for patients with pemphigus, who face serious symptoms and complications associated with their disease,” said Donna Culton, M.D., Ph.D., an assistant professor at the University of North Carolina School of Medicine. Culton presented preliminary results of the Phase 1b study at the International Investigative Dermatology conference being held on May 16-19, 2018 in Orlando, FL. “These preliminary data demonstrate safety as well as a rapid reduction in PDAI scores and lowering of IgG levels with treatment of SYNT001, which support further studies of this drug as a potential new therapeutic option,” Culton said.

Trial Design

SYNT001-103 is an ongoing, multi-center, open-label Phase 1b study evaluating the safety and clinical effect of SYNT001 in patients with active pemphigus vulgaris (PV) or pemphigus foliaceus (PF). SYNT001 will be studied in three successive dosing cohorts, each treated with five weekly doses of SYNT001 administered intravenously (IV), with dose escalation between cohorts up to a maximum of 45 mg/kg. The study observation period covers 16 weeks, including an active treatment period from day 0-28 and follow-up through day 112. The primary endpoint of the study is safety and tolerability. Secondary endpoints include PDAI, total IgG, CIC and serum anti-desmoglein IgG (anti-DSG1 and anti-DSG3) levels. The results reported in this press release include data from seven patients (six with PV and one with PF) enrolled in the first cohort who received five weekly infusions of 10 mg/kg SYNT001 and are in varying stages of follow-up.

Results from First Cohort

Primary endpoint analysis revealed SYNT001 to be well tolerated in treated patients, with all study drug-related adverse events (AEs) characterized as mild or moderate. No severe or serious study drug-related AEs were reported.

The secondary endpoint measures showed a reduction in mean PDAI score from severe to moderate, with clinical effect persisting beyond the treatment period. Rapid and clinically meaningful reductions in pharmacodynamic biomarkers were observed in all patients. At nadir, mean total IgG levels were reduced by 59% (day 30), mean CIC levels were reduced by 50% (day 33), mean anti-DSG1 levels were reduced by 22% (day 14) and mean anti-DSG3 levels were reduced by 24% (day 33).

“We believe that effective reduction in PDAI scores at this lowest dose indicates the potential for a greater magnitude and duration of response at higher doses. In individual patients, we saw reductions of up to 67% in total IgG, 71% in CIC, 65% in anti-DSG1 and 61% in anti-DSG3. These results strengthen our conviction that reducing pathogenic autoantibodies and blocking key inflammatory functions of FcRn may offer an innovative approach to treat pemphigus and could give rise to therapeutic benefits in a wide range of autoimmune diseases that are similarly mediated,” said Jean-Paul Kress, M.D., president and CEO of Syntimmune. “We see tremendous promise for SYNT001, which we are also currently evaluating in an ongoing clinical proof-of-concept trial in warm autoimmune hemolytic anemia. We look forward to initiating additional studies in other indications and realizing the broad potential of SYNT001.”

Syntimmune is conducting an additional ongoing Phase 1b trial of SYNT001 in warm autoimmune hemolytic anemia (WAIHA). Interim data for the WAIHA trial are expected in the second half of 2018.

About SYNT001

Syntimmune is developing SYNT001, an investigational humanized IgG4 monoclonal antibody optimized to inhibit FcRn binding to IgG at both neutral and acidic pH. Studies have shown that SYNT001 rapidly facilitates clearance of IgG and IgG circulating immune complexes (CICs), with the potential to block innate immune responses induced by IgG and CIC, as well as inhibit T cell and B cell activation in response to CIC. Additionally, studies suggest that SYNT001 accomplishes its effects on IgG without destroying immune cells or impacting other types of immunoglobulin. SYNT001 has the potential to exert a rapid therapeutic effect in a wide range of IgG-mediated autoimmune diseases.

About Syntimmune

Founded in 2013, Syntimmune is a clinical-stage biotechnology company developing differentiated drug candidates in a wide range of autoimmune diseases. Drawing on the pioneering research of its scientific founders, the company is advancing novel therapies based on its deep expertise in the biology of the neonatal Fc receptor (FcRn) and its complex role in the pathogenesis of IgG-mediated autoimmune diseases. Syntimmune’s lead candidate, SYNT001, is a monoclonal antibody that specifically blocks FcRn-IgG interactions and is being studied in multiple Phase 1b/2a trials for the treatment of IgG-mediated autoimmune diseases. Syntimmune is also developing SYNT002, which targets FcRn-albumin interactions to facilitate the clearance of albumin-bound toxins. Headquartered in Boston, Mass., Syntimmune has raised $78 million in private financing from leading life sciences investors led by Apple Tree Partners. Investors also include Partners Innovation Fund, FMB Research, and AFB Fund. For more information on Syntimmune, please visit the company’s website at www.syntimmune.com.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Syntimmune’s development of its product candidates, including SYNT001 and SYNT002, the timing of receipt and announcement of data from its clinical trials and studies, and the potential benefits to patients of the product candidates. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. All information in this press release is as of the date of the release, and Syntimmune undertakes no duty to update this information unless required by law.