LEXINGTON, Mass., Sept. 12, 2022 (GLOBE NEWSWIRE) — Keros Therapeutics, Inc. (“Keros”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for patients with hematological, pulmonary and musculoskeletal disorders with high unmet medical needs, announced today that it has presented preliminary clinical data from the multiple escalating dose (“MAD”) part 2 of its trial Phase 1 clinical trial of KER-012 in healthy postmenopausal women at the 2022 Annual Meeting of the American Society of Bone and Mineral Research on Sunday, September 11, 2022. In addition, Keros also announced preclinical data evaluating the bone anabolic activity of RKER-050, a research form of KER-050, in a mouse model of myelodysplastic syndromes (“MDS”).
“We have reported data from Part 2 of our Phase 1 clinical trial of KER-012, which continues to support the potential of KER-012 to correct dysfunctional activin signaling in multiple diseases,” said Jasbir S. Seehra, Ph.D., President and CEO of Keros. “We observed evidence of maximal inhibition of activin signaling, as evidenced by reduced follicle-stimulating hormone as well as increased levels of bone-specific alkaline phosphatase, which is a marker of osteoblast activity. Importantly, no clinically significant changes were observed in hemoglobin or red blood cells. We believe these results support the potential of KER-012 to treat diseases such as pulmonary arterial hypertension and bone disorders characterized by increased activin signaling. With the completion of this Phase 1 clinical trial, we are preparing to initiate a Phase 2 clinical trial in early 2023 evaluating KER-012 in patients with pulmonary arterial hypertension.
- KER-012, a modified ActRIIB ligand trap, administered to healthy postmenopausal women was generally well tolerated and increased biomarkers of bone formation, supporting a bone anabolic mechanism
This Phase 1 clinical trial was a randomized, double-blind, placebo-controlled, two-part trial to evaluate the safety, tolerability, and pharmacokinetics of KER-012. Preliminary data from the first part of the trial involving single ascending dose (“SAD”) were reported in May 2022. In part 2 of the trial, subjects received three subcutaneous doses of 0. 75, 1.5 or 4.5 mg/kg KER-012 or placebo given 28 days apart with a 16 week safety follow-up. A total of 26 subjects were enrolled in three sequential cohorts of multiple ascending dose escalation, with eight subjects in the 0.75 mg/kg cohort and six subjects in each of the 1.5 mg/kg and 4, 5 mg/kg receiving KER-012. Six subjects enrolled in Part 2 of this trial received doses of placebo.
As of the August 4, 2022 data cutoff, KER-012 was generally well tolerated at all doses tested. One subject discontinued after receiving two doses of placebo due to a serious unrelated adverse event. Another subject withdrew consent after receiving two 1.5 mg/kg doses of KER-012. There were no discontinuations due to treatment-related adverse events, and the majority of observed adverse events were mild in severity and resolved.
Preliminary results from Part 2 of this trial include the following:
- Maximum target engagement was observed in the 4.5 mg/kg dose cohort, with a mean (standard deviation, “SD”) reduction of 52.0 (19.32)% in the hormone follicle-stimulating (“FSH”). Five of six subjects who received a 4.5 mg/kg dose of KER-012 achieved a >40% reduction in serum FSH levels from baseline.
- Robust, dose-dependent and sustained increases in markers of bone formation were observed:
- Dose-dependent increases in serum levels of bone-specific alkaline phosphatase (“BSAP”), a marker of osteoblast activity, were observed from the lowest dose of 0.75 mg/kg. The greatest increase in BSAP was observed in the 4.5 mg/kg dose cohort, with mean (SD) maximum increases of 76.5 (20.33)% from baseline.
- Repeated administration of KER-012 at 28-day intervals resulted in an increase in BSAP after each dose, which is favorable for osteoblast activation after each dose, potentially due to increased signaling of bone morphogenic proteins.
- Treatment with three doses of KER-012 at 28-day intervals caused no changes in hemoglobin or red blood cells in any of the multiple-dose cohorts evaluated in Part 2 of this trial.
- RKER-050, a Novel Activin Type II Receptor Ligand Trap, Improved Bone Loss in a Murine Model of Myelodysplastic Syndrome
A research form of KER-050 (“RKER-050”) was tested in a mouse model of MDS. Male MDS mice received either vehicle or 7.5 mg/kg RKER-050 once weekly for six weeks. Healthy male mice received vehicle only.
Vehicle-treated MDS mice had reduced bone volume, lower bone volume fraction, increased trabecular separation, and reduced trabecular count compared to healthy controls. However, treatment with RKER-050 prevented loss of bone volume, bone volume fraction, and trabecular count and reduced trabecular separation in MDS mice compared to vehicle-treated MDS mice.
These data suggest that KER-050 has the potential to restore hematopoiesis and bone health, which may lead to the regeneration of a healthier bone marrow microenvironment in patients with MDS.
KER-012 is designed to bind and inhibit the signaling of transforming growth factor-beta (“TGF-β”) ligands that suppress bone growth, including activin A and activin B. Keros believes that KER -012 has the potential to increase bone morphogenic protein (“BMP”) pathway signaling through this inhibition of activin A and activin B signaling, and therefore treat diseases such as pulmonary arterial hypertension (“PAH”) which are associated with reduced BMP signaling due to inactivating mutations in the BMP receptor. KER-012 is being developed for the treatment of PAH and for the treatment of disorders associated with bone loss, such as osteogenesis imperfecta and osteoporosis.
Keros’ lead protein therapeutic product candidate, KER-050, is an engineered ligand trap composed of a modified ligand-binding domain of the TGF-β receptor known as the activin type IIA receptor that is fused to the part of the human antibody known as the FC Domain. KER-050 is being developed for the treatment of low blood counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients with hematological, pulmonary and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the TGF-β family of proteins, which are master regulators of red blood cell and platelet production as well as the growth, repair and maintenance of muscles and muscles. bone. Keros’ lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis. Keros’ lead small molecule product candidate, KER-047, is being developed for the treatment of anemia resulting from iron imbalance. Keros’ third product candidate, KER-012, is being developed for the treatment of PAH and for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta.
Caution Regarding Forward-Looking Statements
Statements in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “plans”, “believes”, “expects”, “intends”, “plans”, “potential”, “projects”, “would” and “future” or similar expressions are intended to identify forward-looking statements. Examples of such forward-looking statements include statements regarding: Keros’ expectations regarding its growth, strategy, progress and the design, goals and timing of its clinical trials for KER-012; the potential of KER-012 to correct dysfunctional activin signaling in multiple diseases; the potential of KER-012 to treat diseases such as PAH and bone disorders characterized by increased activin signaling; and the potential of KER-050 to restore hematopoiesis and bone health, leading to the regeneration of a healthier bone marrow microenvironment in patients with MDS. Because these statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by these forward-looking statements. These risks and uncertainties include, among others: K the limited operating history and historical losses of eros; Keros’ ability to raise additional funds to complete the development and any commercialization of its product candidates; Keros’ dependence on the success of its lead product candidates, KER-050, KER-012 and KER-047; that Keros may be delayed in initiating, enrolling or completing any clinical trial; competition from third parties developing products for similar uses; Keros’ ability to obtain, retain and protect its intellectual property; Keros’ reliance on third parties for manufacturing, clinical trials and preclinical studies; and risks related to the impact on our business of the COVID-19 pandemic or similar public health crises.
These and other risks are described in greater detail in Keros’ filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of the company’s Quarterly Report on Form 10-Q. , filed with the SEC on August 4, 2022, and its other documents subsequently filed or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Keros undertakes no obligation to update these statements to reflect events that occur or circumstances that exist after the date on which they were made.