About Us | ScientistKROS Keros Therapeutics Inc.
Upcoming Catalysts
| Drug | Stage | Catalyst Date |
|---|---|---|
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KER-050
Myelodysplastic syndromes
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Phase 2
Phase 2
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Drug Pipeline
| Drug | Stage | Notes |
|---|---|---|
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KER-047
Anemia
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Phase 2
Phase 2
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Phase 2 trials to commence 2H 2021.
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KER-012
Osteoporosis
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Phase 1
Phase 1
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Phase 1 trial to be initiated 2H 2021.
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Latest News
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LEXINGTON, Mass., June 22, 2021 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. ("Keros") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced preliminary results from Cohorts 1 and 2 of its Phase 2 clinical trial evaluating KER-050 for the treatment of anemia and thrombocytopenia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes ("MDS") who either have ring sideroblasts ("RS positive") or do not have ring sideroblasts ("non-RS") and who either have or have not previously received treatment with an erythroid stimulating agent.
The ongoing trial is designed as an open-label, two-part, multiple ascending dose trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of KER-050 in patients with MDS. As of May 14, 2021 (the "data cut-off date"), 12 patients had received at least one dose of KER-050, nine of whom had completed eight weeks of treatment. Patients in Cohort 1 and 2 received 0.75 mg/kg and 1.5 mg/kg doses of KER-050, respectively, once every four weeks for 12 weeks. Preliminary results from Cohorts 1 and 2 of the trial, as of the data cut-off date, include:
- Five patients that completed eight weeks of treatment with KER-050 as of the data cut-off date met at least one of the following endpoints:
- Increase in hemoglobin ≥ 1.5 g/dL for eight weeks, or
- 50% reduction in transfusion requirements over eight weeks, or
- Transfusion independence for at least eight weeks.
- Observed increases in reticulocytes, hemoglobin and platelets.
- Observed clinically meaningful reductions in transfusion burden in both RS positive and non-RS patients that required transfusions at baseline (≥2 red blood cell units over eight weeks).
- Three patients that completed eight weeks of treatment with KER-050 as of the data cut-off date achieved transfusion independence for at least eight weeks.
As of the data cut-off date, KER-050 was well tolerated in Cohorts 1 and 2 of this trial. No drug-related serious adverse events ("SAEs") were reported. There were four treatment-emergent SAEs reported, all of which were deemed unrelated to study drug, including anemia, febrile illness, pneumonia and death. Two patients withdrew from the trial prior to completing eight weeks of treatment with KER-050, one due to death deemed unrelated to study drug and one patient withdrew consent. There was one observed treatment-related adverse event of maculopapular rash that was moderate in severity.
"These preliminary results are encouraging, as we observed increases in hematological parameters in the two lowest Part 1 dose cohorts, dosed monthly, in both RS positive and non-RS patients with MDS," said Jasbir S. Seehra, Ph.D., Chief Executive Officer of Keros. "We believe these initial results demonstrate proof-of-concept of KER-050 in patients with very low-, low- to intermediate-risk MDS, and support the potential of KER-050 as a treatment for diseases associated with ineffective hematopoiesis."
Following Safety Review Committee recommendation, dosing for Cohort 3 of the trial was initiated at 2.5 mg/kg of KER-050, to be administered once every four weeks for 12 weeks. Keros expects to report additional Part 1 data and initiate Part 2 of the trial by the end of 2021.
Additionally, based on these preliminary results as of the data cut-off date, Keros plans to extend the treatment duration of the trial from 12 weeks to up to two years to define response rate following six months of treatment with KER-050 and to confirm durability of response. Keros also intends to update the protocol to increase the size of Part 2 of the trial to confirm response rates and to help guide the design of the expected registration program. Keros expects to share the Part 2 trial design by the end of 2021.
Conference Call and Webcast
Keros will host a conference call and webcast on Wednesday, June 23, 2021 at 8:00 AM EDT to review the preliminary results from the KER-050 Phase 2 clinical trial. The conference call will be webcast live at https://edge.media-server.com/mmc/p/pnjzf86g. The live teleconference may be accessed by dialing (833) 528-0563 (domestic) or (830) 221-9673 (international) and entering conference ID: 1889520. An archived version of the call will be available in the Investors section of the Keros website at https://ir.kerostx.com/ for 90 days following the conclusion of the call.
About KER-050
Keros' lead protein therapeutic product candidate, KER-050, is an engineered ligand trap comprised of a modified ligand-binding domain of the Transforming Growth Factor-Beta receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. KER-050 is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes, or 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 suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the Transforming Growth Factor-Beta family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros' lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes 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, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros' third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
Cautionary Note Regarding Forward-Looking Statements
Statements contained 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 "anticipates," "believes," "expects," "intends," "plans," "potential," "projects," "would" and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros' expectations regarding its growth, strategy, progress and the design, objectives and timing of its clinical trials for KER-050; and the potential of KER-050 to treat patients with MDS and diseases associated with ineffective hematopoiesis. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros' limited operating history and historical losses; Keros' ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros' dependence on the success of its lead product candidates, KER-050 and KER-047; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros' ability to obtain, maintain and protect its intellectual property; Keros' dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; and risks relating to the impact on our business of the COVID-19 pandemic or similar public health crises.
These and other risks are described more fully 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 May 6, 2021, and its other documents subsequently filed with 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 such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Mike Biega
[email protected]
617-921-966
- Five patients that completed eight weeks of treatment with KER-050 as of the data cut-off date met at least one of the following endpoints:
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- Multiple poster presentations demonstrate that ALK2 inhibition lowered hepcidin levels and improved iron homeostasis in preclinical models of anemia and iron overload.
- Poster presentation demonstrates that KER-050 had effects on multiple stages of erythroblast maturation (both early- and late-stage) and increased circulating erythropoietin in preclinical models. The observed rapid and durable effects on erythropoiesis provide continued support for KER-050 as a potential treatment for ineffective hematopoiesis in myelodysplastic syndromes ("MDS") and myelofibrosis.
LEXINGTON, Mass., June 11, 2021 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. ("Keros") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today presented data from the ALK2 and KER-050 hematology programs at the European Hematology Association EHA2021 Virtual Congress held from June 9 through June 17, 2021.
"We are pleased to be able to present multiple posters at this year's EHA2021 Virtual Congress. Our preclinical studies continue to elucidate the relationship between ALK2 inhibition, hepcidin and serum iron. These data support that ALK2 inhibition may be a potential treatment option for indications associated with high hepcidin, including anemia of inflammation ("AI") and iron refractory iron-deficiency anemia ("IRIDA"). In addition, the data suggests that ALK2 inhibition has the potential to mobilize and reduce tissue iron in diseases of iron overload," said Jasbir S. Seehra, Ph.D., Chief Executive Officer of Keros. "We also presented new preclinical data for KER-050 that demonstrated its rapid and durable effects on erythropoiesis and increases in circulating erythropoietin, which we believe provides a strong rationale for investigating KER-050 as a treatment for ineffective hematopoiesis in MDS and myelofibrosis."
Details of the presentations are as follows:
Inhibition of ALK2 Through Administration of a Small Molecule Inhibitor Decreased Hepcidin, Increased Serum Iron and Ameliorated Anemia in an Induced Model of Anemia of Inflammation
- ALK2 is a potential therapeutic target in anemia resulting from chronic inflammation - Abstract Number: EP839
To induce a model of chronic kidney disease ("CKD"), mice were dosed daily for six weeks with 50 mg/kg of adenine, leading to iron deficiency anemia (37.6% decrease in serum iron; p<0.0001), associated with increased circulating interleukin-6 ("IL6") (2.42-fold; p<0.05) and hepcidin (3.49-fold; p<0.01). After completing the six weeks of adenine-administration, we administered 5 mg/kg of either a selective small molecule ALK2 kinase inhibitor ("KTI-2338"), or vehicle daily for 10 days in the CKD mice, and observed a reversal of the CKD-related changes in the KTI-2338-treated mice. We observed an increase in serum iron (108.2%; p<0.0001), decrease in hepcidin (85.4%; p<0.0001) and improvements in red blood cell ("RBC") count (7.2%; ns), hemoglobin ("HGB") (10.9%; p<0.0001) and hematocrit (10.3%; p<0.05) compared to vehicle. Reticulocyte hemoglobin ("RET-HGB") content, a measure of the incorporation of iron into hemoglobin, increased 9.9% (p<0.01) with KTI-2338 compared to vehicle-treated CKD mice, normalizing to baseline levels.
These data demonstrate that inhibition of ALK2 improved hematological markers of anemia, serum hepcidin and serum iron levels in a mouse model of AI resulting from chronic kidney disease characterized by elevated IL6, suggesting that targeting ALK2 inhibition could potentially treat anemia arising from high hepcidin.
Administration of an ALK2 Inhibitor in a Mouse Model of Iron Overload Resulted in Significant Reductions in Liver Non-Heme Iron
- ALK2 inhibition, a novel therapeutic approach to iron overload - Abstract Number: EP842
Administration of KTI-2338 reduced circulating hepcidin levels and increased serum iron in wild-type mice after three days of daily dosing. Specifically, we observed a reduction in hepcidin as soon as four hours post the third administration of KTI-2338, which was sustained through 12 hours post-administration, as well as an increase in serum iron eight hours post-administration, which peaked at 16 hours post-administration.
Mice were dosed daily with 100 mg/kg of iron dextran to induce iron overload and subsequently dosed with either KTI-2338 (5 mg/kg) or vehicle. Mice dosed with iron dextran became iron overloaded and exhibited a substantial 47-fold increase in hepatic iron compared to mice that received vehicle (p<0.0001). Our initial results indicated that, after 63 hours of dosing with KTI-2338, there were significant reductions in liver non-heme iron content (62%). Subsequent analysis using a more selective iron assay confirmed that treatment with KTI-2338 reduced non-heme iron (13.4%) compared to vehicle treated mice (p<0.006).
These data suggest that, in conditions with iron overload, ALK2 inhibition may potentially be used to remove excess iron from the liver, potentially improving the effectiveness of chelation therapy and excretion.
Treatment with ALK2 Antibodies to Neutralize the ALK2 Receptor Reduced Serum Hepcidin and Increased Circulating Iron in Non-Human Primates, a Preclinical Model Highly Representative of Human Biology
- Administration of ALK2 neutralizing antibodies to cynomolgus monkeys led to a sustained decrease in hepcidin, increase in circulating iron and increase in erythrocyte hemoglobin - Abstract Number: EP840
Keros has developed two fully human antibodies, KTI-016 and KTI-018, that are designed to specifically bind to and neutralize the ALK2 receptor. To determine the pharmacokinetic and pharmacodynamic properties of these antibodies, female cynomolgus monkeys received a single subcutaneous dose (3 mg/kg) of either antibody. Serum drug concentrations and indices of iron and hematology were assessed intermittently over an 8-week period. KTI-016 and KTI-018 were both rapidly absorbed, reached Cmax within 48 hours and had half-lives of 49.1 hours and 33.9 hours, respectively.
Six hours after administration, KTI-016 and KTI-018 reduced serum hepcidin by 50.3% and 55.6%, respectively. The reduction in hepcidin peaked starting at 48 hours post-administration, at 77.8% in the KTI-016-treated group and 77.2% in the KTI-018-treated group. These decreases remained through day 10 before returning to baseline by day 14. A corresponding increase in circulating iron occurred starting at 24 hours following administration, peaking at 63.9% (p<0.01) and 72.4% (p<0.001) in the KTI-016- and KTI-018-treated groups, respectively. This response was also sustained through day 10, returning to baseline by day 14.
KTI-016 and KTI-018 were also observed to have comparable effects on increasing RET-HGB, red blood cell hemoglobin ("RBC-HGB") and mean corpuscular hemoglobin concentration ("MCHC") (data from the two antibodies were combined). RET-HGB increased by 4.9% (p<0.001) at 3 days post-dose and remained elevated for at least 10 days. Increases in RBC-HGB content were observed initially at 35 days post-dose, with a 4.2% increase (p<0.0001) at day 56. We also observed increases in MCHC starting at 42 days post-dose, with a 3.7% increase (p<0.001) at day 56.
We believe iron mobilized by treatment with KTI-016 and KTI-018 was incorporated into hemoglobin, as evidenced by the observed increases in RET-HGB, RBC-HGB and MCHC. Accordingly, these data demonstrate that these antibodies may be a potential treatment for anemias arising from elevated hepcidin, such as IRIDA and AI.
Preclinical Study of KER-050 Demonstrated Effects on Multiple Stages of Erythroblast Maturation and Increased Circulating Erythropoietin
- KER-050, an inhibitor of TGF-β superfamily signaling, observed to have a rapid, dynamic, and durable effect on erythropoiesis - Abstract Number: EP758
Mice treated with a single dose of a research form of KER-050 ("RKER-050") showed rapid and sustained increases in RBCs and HGB, observed from 12 hours (RBCs +8%; p<0.001 and HGB +9%; p<0.005) through day 51 (RBCs + 8% p<0.001), compared to vehicle-treated mice.
Treatment with RKER-050 also resulted in a dynamic mobilization of erythroblasts from the bone marrow into circulation. At 12 hours post-administration, we observed a 20% reduction in bone marrow ("BM") proerythroblasts that corresponded to a 37% increase in erythroblasts at 24 hours post-administration, which we believe indicates that early progenitors were differentiating into erythroblasts. We also observed an increase in mature erythroblasts, which suggests the differentiation of late-stage progenitors. This maturation of erythroblasts corresponded to an increase in circulating reticulocytes ("RETs") at 12 hours post-administration (+18%; p<0.05), as well as to an increase in RBCs observed at 48 hours post-dose (+8% p<0.0001).
The initial increase in RETs observed at 12 hours post-administration was reduced (-15%; p<0.05) at 24 hours post-administration, which we believe indicates that RETs matured to RBCs. At 48 hours post-administration, RET numbers returned to vehicle-comparable levels, which we believe indicates that the RET pool was replenished. This data potentially demonstrates that there was a continued progression of erythroblasts through maturation. This increased differentiation and maturation of erythroblast contributed to a sustained upregulation of erythropoiesis at day 14 post-dose.
In the RKER-050-treated mice, erythropoietin upregulation was not observed until day 4. However, erythropoietin was significantly increased from day 7 (+68%, p<0.0001) through day 37 (4-fold increase, p<0.05) which potentially indicates that erythropoietin has a contributing role in sustaining the RKER-050-mediated increase in RBCs and HGB, compared to vehicle, through at least day 51.
We believe the observed rapid and durable effect on erythropoiesis via multiple stages of erythroblast maturation (both early- and late-stage) as well as the observed increase in circulating erythropoietin provides a strong rationale for investigating KER-050 as a potential treatment for ineffective erythropoiesis in MDS and myelofibrosis.
About KER-050
Keros' lead protein therapeutic product candidate, KER-050, is an engineered ligand trap comprised of a modified ligand-binding domain of the Transforming Growth Factor-Beta receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. KER-050 is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes, or MDS, and in patients with myelofibrosis. In October 2020, Keros announced the dosing of the first two participants in its Phase 2 clinical trial evaluating KER-050 for the treatment of anemia and thrombocytopenia in very low-, low-, or intermediate-risk MDS. Keros expects to report initial data from Part 1 of this trial by the end of June 2021. Additionally, Keros plans to commence an open-label Phase 2 clinical trial evaluating KER-050 for the treatment of patients with myelofibrosis-associated cytopenias in the third quarter of 2021 and expects to report initial data from this trial in 2022.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the Transforming Growth Factor-Beta family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros' lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes 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, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros' third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
Cautionary Note Regarding Forward-Looking Statements
Statements contained 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 "anticipates," "believes," "expects," "intends," "plans," "potential," "projects," "would" and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros' expectations regarding its growth, strategy, progress and timing of its clinical trials for KER-050; the potential of KER-050 to treat diseases that exhibit defects in different stages of erythropoiesis, including MDS and myelofibrosis; the potential of ALK2 inhibition to treat a variety of indications, including iron overload and anemias that arise from elevated hepcidin, such as IRIDA and AI; and the potential of ALK2 inhibition to improve the effectiveness of chelation therapy and excretion. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros' limited operating history and historical losses; Keros' ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros' dependence on the success of its lead product candidates, KER-050 and KER-047; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros' ability to obtain, maintain and protect its intellectual property; Keros' dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; and risks relating to the impact on our business of the COVID-19 pandemic or similar public health crises.
These and other risks are described more fully 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 May 6, 2021, and its other documents subsequently filed with 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 such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Julia Balanova
646-378-2936
- Multiple poster presentations demonstrate that ALK2 inhibition lowered hepcidin levels and improved iron homeostasis in preclinical models of anemia and iron overload.
-
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LEXINGTON, Mass., May 27, 2021 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. ("Keros") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced that Keros' President and Chief Executive Officer Jasbir S. Seehra, Ph.D., will present at the Jefferies Virtual Healthcare Conference on Tuesday, June 1 at 2:00 PM EST.
The fireside chat presentation will be webcast live at https://wsw.com/webcast/jeff174/kros/1876041 and archived in the Investors section of the Keros website at https://ir.kerostx.com/. A replay will be available for 90 days following the conclusion of the event.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the transforming growth factor-Beta, or TGF-ß, family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros' lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes 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, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros' third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
Investor Contact:
Julia Balanova
[email protected]
646-378-2936 -
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LEXINGTON, Mass., May 25, 2021 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. ("Keros") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced that the United States Patent and Trademark Office ("USPTO") has issued U.S. Patent No. 11,013,785 ("the '785 patent"). The '785 patent is a composition of matter patent directed to novel therapeutic proteins, including KER-050. The '785 patent contains 20 claims and expires no earlier than November 2037.
"We are very pleased to have this foundational patent issued, which is the first for the Company's wholly-owned internal programs and is a validation of the differentiated approach that we are taking to develop new product candidates," said Jasbir S. Seehra, Ph.D., Chief Executive Officer of Keros. "We will continue to strengthen our patent portfolio to support our discovery efforts and protect our expanding pipeline of wholly-owned assets for the treatment of hematological and musculoskeletal diseases."
Keros has an extensive intellectual property portfolio covering KER-050, KER-047 and KER-012, in addition to multiple preclinical assets in the Company's pipeline.
About KER-050
Keros' lead protein therapeutic product candidate, KER-050, is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-β receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. KER-050 is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes, or 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 suffering from hematologic 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 of the growth, repair and maintenance of muscle and bone. Keros' lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes 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, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros' third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
Cautionary Note Regarding Forward-Looking Statements
Statements contained 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 "anticipates," "believes," "expects," "intends," "plans," "potential," "projects," "would" and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros' expectations regarding its ability to strengthen its patent portfolio to support its discovery efforts and protect its expanding pipeline. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros' limited operating history and historical losses; Keros' ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros' dependence on the success of its lead product candidates, KER-050 and KER-047; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros' ability to obtain, maintain and protect its intellectual property; Keros' dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; and risks relating to the impact on our business of the COVID-19 pandemic or similar public health crises.
These and other risks are described more fully 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 May 6, 2021, and its other documents subsequently filed with 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 such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Julia Balanova
[email protected]
646-378-2936
-
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LEXINGTON, Mass., May 14, 2021 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. ("Keros" or the "Company") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced results from a preclinical study of KER-012 on pulmonary and cardiac dysfunction in an established rodent model of pulmonary arterial hypertension ("PAH") at the virtual American Thoracic Society International Conference held May 14 through 19, 2021. Additional data from a previously conducted nonclinical study in cynomolgus monkeys was also included in the presentation.
KER-012 prevented markers of inflammation and fibrosis, and vascular remodeling in a rodent PAH model and did not alter red blood cell number in rats or non-human primates.
- RKER-012, a Novel Activin Receptor Type IIB (ActRIIB) Ligand Trap, Reduced Cardiopulmonary Pathology in a Rodent Model of Pulmonary Arterial Hypertension
Keros combined administration of SUGEN5416, a tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1/2, with exposure to chronic hypoxia to recapitulate the biology in PAH. A research form of KER-012 ("RKER-012") was tested in this SUGEN/hypoxia ("SH") rat model of PAH. Adult male rats were subjected to SH and received either vehicle or 10 mg/kg RKER-012 twice weekly for four weeks. Rats maintained under normal oxygen conditions ("normoxic controls") received only vehicle.
Consistent with enhanced pulmonary vascular remodeling and cardiac fibrosis, vehicle-treated SH rats showed significantly greater right ventricle plasminogen activator inhibitor-1 ("PAI-1") expression (+236.7%; p<0.05), α-smooth muscle actin ("α-SMA") expression (+255.4%; p<0.05) and increased arterial wall thickness (+43.8%, p<0.001), relative to normoxic controls. Treatment with RKER-012 reduced heart PAI-1 expression and lung α-SMA to levels equivalent to normoxic controls and reduced arterial wall thickness, which Keros believes suggests that KER-012 could potentially prevent the progression of PAH.
Additionally, vehicle-treated SH rats had significantly greater neutrophil number (+139.2%; p<0.01) relative to normoxic controls. Treatment with RKER-012 reduced neutrophils to levels of normoxic controls, indicating a reduction in PAH-associated inflammation. There was no effect of SH or RKER-012 on either white blood cells or lymphocytes.
Finally, vehicle-treated SH rats had significantly greater Fulton index, which measures enlargement of the right ventricle (+21.7; p<0.0001), as well as trends for increased atrial natriuretic peptide ("ANP") (+172.8%; p=0.18) and B-type natriuretic peptide ("BNP") (+38.7%; p=0.057), relative to normoxic controls. Treatment with RKER-012 reduced Fulton Index to control levels, and reduced ANP and BNP expression to levels below controls, which Keros believes indicates that KER-012 could potentially reduce PAH-induced damage to the heart.
RKER-012 did not increase red blood cell number in the SH rats, relative to either vehicle-treated SH rats or normoxic controls. Similarly, KER-012 did not increase red blood cells in healthy naïve non-human primates, a model highly translatable to humans.
"The Keros team is presenting exciting data on our KER-012 program at ATS. PAH is associated with imbalanced signaling in the transforming growth factor-beta ("TGF-ß") pathway, and the results of this study suggest that KER-012 prevented disease progression in this PAH model, which we believe supports our hypothesis that rebalancing signaling by inhibiting certain ligands may provide benefit in PAH," said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. "Additionally, treatment with KER-012 did not increase red blood cells in both rats and nonhuman primates, which can result from inhibition of this pathway. We believe that the current study supports that KER-012 has the potential to treat PAH in patients without dose-limiting increases in red blood cells."
About KER-012
KER-012 is designed to bind to and inhibit the signaling of TGF-ß ligands, including activin A and activin B, which are key regulators of bone remodeling that act to suppress bone growth. Keros believes that KER-012 has the potential to increase the signaling of bone morphogenic protein ("BMP") pathways through this inhibition of activin A and activin B signaling, and consequently treat diseases such as PAH that are associated with reduced BMP signaling due to inactivating mutations in the BMP receptors. KER-012 is being developed for the treatment of disorders associated with bone loss, such as osteogenesis imperfecta and osteoporosis, and for the treatment of PAH.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the Transforming Growth Factor-Beta family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros' lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes 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, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros' third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
Cautionary Note Regarding Forward-Looking Statements
Statements contained 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 "anticipates," "believes," "expects," "intends," "plans," "potential," "projects," "would" and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: the potential of KER-012 to treat diseases such as PAH without dose-limiting increases in red blood cells. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros' limited operating history and historical losses; Keros' ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros' dependence on the success of its lead product candidates, KER-050 and KER-047; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros' ability to obtain, maintain and protect its intellectual property; Keros' dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; Keros' ability to enter into new collaborations; and risks relating to the impact on our business of the COVID-19 pandemic or similar public health crises.
These and other risks are described more fully 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 May 6, 2021, and its other documents subsequently filed with 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 such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Julia Balanova
[email protected]
646-378-2936 - RKER-012, a Novel Activin Receptor Type IIB (ActRIIB) Ligand Trap, Reduced Cardiopulmonary Pathology in a Rodent Model of Pulmonary Arterial Hypertension