at Harvard Medical School
Glyka Athanasiadou Q-FASTR Fund
November 2026
November 2026
Dear Christy and Andreas,
The Glyka Athanasiadou Q-FASTR Fund supported two projects on the Harvard Medical School Quadrangle this year. I’m pleased to share their early results in the following pages.Q-FASTR supports projects at the point where there is a clear idea but not yet the data that agencies and companies require before they will commit, which is the stage at which funding is hardest to secure.
Philanthropy has made Q-FASTR a truly catalytic engine for translational research at Harvard Medical School. Your latest gift filled an immediate gap and reinforced a culture here that values translational boldness and impact. The progress described in this report is positioning both teams to advance to the next stage of research and to build momentum for future funding and collaborations.
I am deeply grateful for your support of this work.
Mark Namchuk, PhD
Sincerely,
Mark Namchuk, PhD
Puja and Samir Kaul Professor of the Practice of
Biomedical Innovation and Translation
Executive Director of Therapeutics Translation,
Harvard Medical School
Relaxin Family Peptide Receptor 2 Modulators as Therapeutics
Andrew Kruse, PhD, Professor of Biological Chemistry and Molecular Pharmacology
Xunan Wang, Graduate Student
Elizabeth Wren, Research Assistant
Goal: To develop two protein-based therapeutic candidates targeting the relaxin family peptide receptor 2 (RXFP2)—one that switches the receptor on, one that blocks it—and advance both to the point of a clinical development candidate.
Abstract: RXFP2 is a cell-surface receptor switched on by the peptide hormone INSL3, and together the pair helps govern two distinct systems: bone turnover and male reproductive physiology. When RXFP2 signals in bone, the osteoblasts that build new bone proliferate and mineralization increases. In sperm, the same signal suppresses apoptosis and promotes survival. Because the receptor sits at the center of both processes, the team is building molecules that work in opposite directions: agonists that activate it and antagonists that block it. In preliminary studies, the team has engineered an INSL3-based agonist that potently activates RXFP2 signaling, and a chimeric INSL3/5 hormone that competes with the natural hormone to block activation. An RXFP2 agonist could treat osteoporosis, which affects more than 10 million people in the United States alone. Side effects and poor adherence limit current osteoporosis drugs; a long-acting, once-monthly agonist could improve on both. An RXFP2 antagonist could also serve as a male contraceptive, with monthly dosing setting it apart from existing options in both duration and reversibility.
Update: The team has designed and optimized both the agonist and the antagonist and has completed pharmacokinetic studies—how long each molecule persists in the body—for each.
In vivo assessment of the agonist is the next step. The team’s collaborator Marc Wein, MD, PhD, an endocrinologist in the Endocrine Unit at Massachusetts General Hospital, will have his lab dose mice with the agonist, as well as negative and positive controls, for four weeks, followed by micro-computed tomography (microCT) and other analyses to look at bone density. The team will also check serum from these mice for anti-drug antibodies, which would signal an immune reaction against the molecule itself.
Testing of the antagonist, the contraceptive candidate, in isolated tissue is still in the planning stage.
Andrew Kruse, PhD
Xunan Wang
Elizabeth Wren
Development of Targeted Ectodomain Shedding Molecules
Stephen Blacklow, MD, PhD, Gustavus Adolphus Pfeiffer Professor of Biological Chemistry and Molecular Pharmacology
Rhiannon Moss, PhD, Research Fellow
Goal: To develop biologic drugs that cut a target protein’s extracellular domain—the portion that projects outside the cell—free from the cell membrane.
Abstract: Because the approach is not tied to any one protein, it could apply broadly: a disease-driving protein whose extracellular domain is shed loses its activity at the cell surface. The long-term plan is to extend the technology to switch off a wide range of target proteins.
Update: The team tested several designs for knob-in-hole bispecific antibodies—engineered antibodies whose two arms bind different targets, held together by a complementary pair of mutations—and settled on a commercial bispecific-antibody platform, the Zymeworks framework, for building them.
They have now produced a bispecific antibody with one arm against ADAM10, the enzyme that does the cutting, and one against FLAG, a short peptide tag used as a laboratory handle. To test the concept, they are making a FLAG-tagged version of LAG-3, an immune checkpoint protein on T cells, to see whether the bispecific can bring ADAM10 to LAG-3 and trigger its cleavage.
In parallel, they are preparing ADAM10 antigens for a nanobody campaign—a search for a small, single-domain antibody against ADAM10 that could replace the 11G2 antibody now used for the ADAM10 arm.
Rhiannon Moss, PhD
Stephen Blacklow, MD, PhD
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