Adipose Tissue_Appetite_and Obesity

SAT-716 - Preclinical Efficacy and Safety of A Therapeutic FSH-Blocking Antibody in Obesity and Alzheimer'S Disease Models

Saturday, June 13, 2026

9:30 AM - 4:30 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

Satish Rojekar, PhD

Assistant Professor
Icahn School of Medicine at Mount Sinai
Jersey City, NJ, United States

Co-Author(s)

AP

Anusha Pallapati, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
Steven Sims, MS (he/him/his)

Institute for Translational Medicine and Pharmacology
Icahn School of Medicine at Mount Sinai
New York, NY, United States
JG

Judit Gimenez-Roig, MSc

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
FK

Funda Korkmaz, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
AM

Anurag Misra, PhD

Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
San Antonio, Texas, United States
FS

Farhath Sultana, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
UC

Uliana Cheliadinova, MD

Instructor
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
New York, NY, United States
AG

Anisa Gumerova, MD, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
DV

Darya Vasilyeva, MD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
AM

Anne Macdonald, BA

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
SH

Susan Hutchison, BS

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
OB

Orly Barak, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
RP

Rukmani Pandey, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
OM

Ofer Moldavski, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
AT

Abraham J.P. Teunissen, PhD

BioMedical Engineering and Imaging Institute
NEW YORK, New York, United States
SK

Se-Min Kim, MD (he/him/his)

Associate Professor
Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
SA

Susan Elizabeth Appt, DVM

Professor
Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Winston-Salem, North Carolina, United States
SH

Shozeb Haider, PhD

School of Pharmacy, University College London, London, United Kingdom
London, England, United Kingdom
TF

Tal Frolinger, PhD (she/her/hers)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States
Vitaly Ryu, Ph.D. (he/him/his)

Associate Professor
Mount Sinai
New York, NY, United States
RL

Rauf Latif, PhD

Associate Professor
Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, New York, United States
CR

Clifford J. Rosen, MD

Maine Health Institute for Research, Scarborough, Maine, USA
Scarborough, Maine, United States
DL

Daria Lizneva, MD, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States
YG

Yogesh K. Gupta, PhD

Associate Professor
University of Texas at San Antonio Health Science Center, San Antonio, TX, USA
San Antonio, Texas, United States
TY

Tony Yuen, PhD

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
NEW YORK, New York, United States

Senior Author/Primary Investigator(s)

MZ

Mone Zaidi, MD, PhD (he/him/his)

Institute for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
New York, NY, New York, United States

Disclosure(s):

Satish Rojekar, PhD: No financial relationships to disclose

Steven Sims, MS: No financial relationships to disclose

Uliana Cheliadinova, MD: No financial relationships to disclose

Vitaly Ryu, PhD: No financial relationships to disclose

Background: Follicle-stimulating hormone (FSH) directly regulates bone, adipose tissue, and brain function. Inhibition of FSH action using FSH-blocking antibodies has been shown to prevent osteoporosis, obesity, and Alzheimer’s disease (AD) in mouse models. To achieve clinical efficacy through subcutaneous delivery, a high-concentration formulation of the antibody with preserved stability and functional integrity is required. Here, we describe the formulation development, biophysical evaluation, and preclinical validation of our humanized FSH-blocking monoclonal antibody MS-Hu6 and its murine surrogate Hf2 in obesity and AD animal models.

Methods: The crystal structure of MS-Hu6 was solved at atomic resolution. MS-Hu6 and Hf2 were formulated at 100 mg/mL using FDA-approved excipients under 21CFR58-compliant GLP conditions. Biophysical characterization included protein thermal shift, size-exclusion chromatography, and dynamic light scattering. Pharmacokinetics and biodistribution were assessed in male and female C57BL/6 mice using 89Zr-labeled MS-Hu6. Since mice develop anti-drug antibodies against MS-Hu6, subsequent efficacy studies were performed with Hf2. Metabolic efficacy of Hf2 (200 μg, i.p., 5x weekly, 16 weeks) was evaluated in ovariectomized C57BL/6 mice on a high-fat diet, while cognitive effects were assessed in OVX 3xTg and APP/PS1 AD mice. Safety studies were conducted in African green monkeys receiving MS-Hu6 (8 mg/kg, i.v. and s.c., monthly, 5 months).

Results: MS-Hu6 binds to FSH with high precision, confirmed by crystallographic and docking analyses. Formulated antibodies demonstrated excellent thermal and colloidal stability, monomer purity (>99.6%), and monomer retention (>98%) after 4 freeze–thaw cycles and 90 days of storage at 4°C or 25°C. 89Zr-MS-Hu6 exhibited β phase serum half-life of up to 132 h with sustained tissue presence in Tg32 FcRn-humanized mice. In high-fat-fed ovariectomized mice, Hf2 induced dose-dependent reductions in body weight (13.2%) and fat mass (24%) by week 5, with sustained effects 20 weeks post-treatment. Mesenteric white adipose tissue declined by 35%, whereas lean mass and food intake remained unchanged. Hf2 improved recognition and spatial memory in 3xTg and APP/PS1 mice, and 24-week Hf2 administration further improved spatial memory acquisition (Morris Water Maze). MS-Hu6 was well tolerated in monkeys, which showed normal vital and biochemical indices during the 5-month study.

Conclusions: MS-Hu6 constitutes a GLP-compliant, structurally defined, ultra-high-concentration FSH-blocking antibody platform showing long-lasting metabolic and cognitive efficacy with favorable safety in nonhuman primates. These findings provide comprehensive IND-enabling data supporting advancement of MS-Hu6 to first-in-human evaluation.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*