Scholar Rock

Scholar Rock is a clinical-stage biotechnology that develops antibodies targeting growth factors such as the transforming growth factor beta (TGFβ) superfamily in their latent (inactive precursor) form, which they claim yields a high level of selectivity, maximizing efficacy and potentially minimizing adverse effects.

Directly in the context of aging, Scholar Rock is developing a drug to inhibit excessive TGFβ signalling to potentially suppress the development of fibrosis, the result of imperfect repair, in multiple organs. They are also actively developing other drugs that tackle signalling relating to cancer, spinal muscular atrophy, and iron-restricted anemias.

SRK-373
TGFβ and some members of its superfamily play a key role in age-related inflammation and impair tissue regeneration, leading to fibrosis, but inhibiting them nonselectively and directly in the form of ALK5 inhibitors resulted in severe heart valve lesions in rodent and nonhuman primate models.

Scholar Rock says that SRK-373 “targets latent TGFβ1 associated with latent TGFβ-binding proteins (LTBPs), which enables specific inhibition of TGFβ1 in fibrotic tissue. This is a unique strategy that specifically blocks latent TGFβ1 activation within the extracellular matrix [ECM], the primary location of fibrosis, but has no effect on latent TGFβ1 present on the surface of immune cells.”

Scholar Rock’s pipeline page indicates that SRK-373 is in preclinical development, and their main page for the antibody says that they are advancing it into IND-enabling studies. This paper seems to be an animal study of SRK-373 under the name LTBP-49247. As intended, it bound to latent TGFβ-binding proteins in the ECM, but not to either of the two transmembrane proteins present on immune cells. LTBP-49247 ameliorated fibrosis in a rat model of Alport syndrome and an adenine model of of chronic kidney disease kidney fibrosis, but did not cause the cardiac valve toxicity seen with classial TGFβ inhibitors. They say that their “preclinical studies have demonstrated that preventing TGFβ1 activation can offer a powerful new approach to treating fibrosis in multiple organs.”

Apitegromab (SRK-015 or SRK-439)
Myostatin, also known as Growth Differentiation Factor 8 (GDF8), is a paracrine signaling  molecule produced by skeletal muscle that limits skeletal muscle growth.  Like others of Scholar Rock’s targets, myostatin is a  member of the TGFβ protein family. Myostatin is released into the local environment when the myostatin precursors promyostatin and latent myostatin are activated by sequential proteolysis.

Apitegromab is a fully human monoclonal antibody that specifically binds to promyostatin and latent myostatin, thereby inhibiting the formation of the mature form. It is in most advanced development for Spinal Muscular Atrophy, for which the Phase II TOPAZ trial and Phase III SAPPHIRE trial have reported back positive results.

Of greater potential relevance to its possible use as a longevity therapeutic, in June 2025 SR reported that the Phase 2 EMBRAZE proof-of-concept trial found that adding apitegromab to tirzepatide over 24 weeks of treatment resulted in a 54.9% greater retention of lean mass relative to tirzepatide alone in subjects who were obese or who were  overweight with one or more adiposity-related comorbidities.

One year prior, the company had reported that it helps preserve lean mass and attenuate regain of adipose tissue following withdrawal of semaglutide in a mouse model of diet-induced obesity; in an associated press release, the company stated that it was more effective in this regard after than an anti-ACTRII antibody (such as bimagrumab), but this was not reported in the study abstract.

SRK-439, which the company inconsistently equates with apitegromab, is also said to be in preclinical development for additional, unspecified rare neuromuscular disorders, with an anticipated IND filing in 2H 2025.

Linavonkibart (SRK-181)
Linavonkibart is another fully human IgG4 monoclonal antibody that selectively inhibits latent latent TGFβ1; it is not clear how it differs from SRK-373. It is currently in Phase I trials in combination with the anti-PD-(L)1 immunotherapy pembrolizumab (Keytruda) for treatment of patients with advanced solid tumors that are anti-PD1-resistant. TGFβ1 is a logical target in such patients: it inhibits immune surveillance of cancer by impairing the infiltration of the tumor by T-cells, reducing antigen presentation, and inhibiting T-cell cytotoxicity.

SR-affiliated scientists reported in 2021 that linavonkibart was well-tolerated in an initial group of 25 subjects as monotherapy and in combination, with one RECIST1.1 partial response in a patient with renal cell carcinoma at the 800 mg dose. An expansion phase of this trial ws presented at a scientific conference in May 2024; it reported additional adverse reactions, but also an increase in partial responses, a decrease circulating myeloid-derived suppressor cells, and an increase in CD8+ T-cell infiltration into tumors of several types.

SRK-256
SRK-256 is in development for iron-restricted anemia (also known as functional anemia), in which a person has too little iron available in circulation despite adequate cellular iron availability. Iron-restricted anemia is caused by abnormally high levels of hepcidin, a protein that enhances cellular iron uptake and inhibits its release; as a result, iron remains locked inside a person’s liver and other cells, which leaves insufficient iron available for the production of red blood cells.