ACVR2A x ACVR2B

Medicxi co-led Company's US$70 million Series A less than 2 years ago Third Medicxi portfolio exit to US biopharma in last 12 months LONDON, GENEVA and JERSEY, British Isles, July 14, 2023 /PRNewswire/ -- Medicxi, a leading European life sciences investment firm, announces that its portfolio company, Versanis Bio, a private clinical-stage biopharmaceutical company focused on the development of new medicines for the treatment of cardiometabolic diseases, has entered into a definitive agreement to be acquired by Eli Lilly and Company (NYSE: LLY). Under the terms of the agreement, which is subject to customary conditions, Versanis shareholders would receive up to $1.925 billion USD in cash, inclusive of an upfront payment and subsequent payments upon achievement of certain development and sales milestones. Versanis was founded in 2021 by biotech investment firm Aditum Bio to develop bimagrumab for the treatment of metabolic diseases and obesity following its in-licensing from Novartis. Medicxi invested in the company in August 2021 when it co-led a $70 million Series A financing with Atlas Venture. Nick Williams, Partner at Medicxi, led the investment and is a member of the Versanis Board of Directors. Versanis' lead asset is bimagrumab, a first-in-class, fully human monoclonal antibody to activin type II receptors that blocks binding of ligands including myostatin, activins, and GDF11. Bimagrumab is currently being assessed in the BELIEVE Phase 2b study alone or in combination with semaglutide in adults living with overweight or obesity. Combining incretins with bimagrumab has the potential to improve the quality and durability of weight loss, with the goal of achieving better outcomes for people living with obesity and obesity-related complications. Nick Williams, Partner at Medicxi, said: "The acquisition of Versanis reinforces our belief in the importance of body composition when considering the therapeutic management of obesity. Bimagrumab exhibits a differentiated clinical profile, with the potential to achieve meaningful body fat loss whilst at the same time increasing muscle mass. This single-asset exit further strengthens our belief in delivering value via investing in focused, asset-driven companies. We are extremely excited to be partnering with an experienced organisation like Lilly that will continue to develop bimagrumab in combination with its portfolio of incretins to improve patient outcomes in cardiometabolic diseases." Notes to Editors About Medicxi Medicxi is a healthcare-focused investment firm with the mission to create and invest in companies across the full drug development continuum. Leveraging deep expertise in drug development and company creation spanning over two decades, Medicxi invests in early and late-stage therapeutics with a product vision that can fulfill a clear unmet medical need. For more information, please visit: About Versanis Versanis is a privately held, clinical-stage biopharmaceutical company bringing transformational treatments to people living with cardiometabolic disease. The company's lead asset, bimagrumab, is being advanced in the BELIEVE Phase 2b study as a novel treatment to help adults achieve and maintain both fat loss and a healthy body composition, with additional indications to follow. Versanis was founded in 2021 by Aditum Bio. For more information, please visit . SOURCE Medicxi

LEXINGTON, Mass., May 22, 2023 (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, pulmonary and cardiovascular disorders with high unmet medical need, today announced that it presented additional biomarker data from its completed Phase 1 clinical trial of KER-012 in healthy post-menopausal women at the American Thoracic Society (“ATS”) 2023 International Conference, held from May 19 through May 24, 2023. In addition, Keros presented preclinical data showing the potential of a research form of KER-012 (“RKER-012”) to improve left ventricular function in a mouse model of left ventricular pressure overload, as well as preclinical data evaluating transforming growth factor-beta (“TGF-β”) signaling in two major cell types involved in the dysregulated vascular remodeling in pulmonary arterial hypertension (“PAH”), and KER-012’s effect on this ligand-induced signaling. “We are pleased to present clinical and preclinical data from our KER-012 program at the ATS conference this year. The preclinical presentations demonstrate observed ligand selectivity of KER-012 and changes in inflammation and fibrosis in models of PAH and cardiovascular diseases. From our completed Phase 1 clinical trial of KER-012 in healthy post-menopausal women, we presented new data with observed sustained changes in serum biomarkers of cardiac dysfunction, inflammation and fibrosis,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. “We believe these data support the potential of KER-012 to treat fibrosis and inflammation in patients with PAH and in patients with cardiovascular disease.” Clinical Presentation Administration of KER-012, a Modified Activin Receptor IIB Ligand Trap, Led to Changes in Biomarkers of Cardiovascular Health in a Ph1 Study Conducted in Healthy Post-Menopausal Women This Phase 1 clinical trial was a randomized, double-blind, placebo-controlled, two-part trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of KER-012. Keros reported preliminary topline data from the Part 1 single ascending dose portion of the trial in May 2022, and additional preliminary clinical data from the Part 2 multiple ascending dose portion of the trial in September 2022. The following data from the subjects enrolled in the highest dose cohort (4.5 mg/kg) from Part 2 of this trial were presented at ATS 2023: Serum proteins associated with inflammation and structural remodeling pathways were altered following one dose of 4.5 mg/kg of KER-012 versus placebo, which Keros believes is consistent with the predicted mechanism of action of KER-012: Decreases in markers of fibrosis, as indicated by changes in matrix metalloproteinases (MMP-7 and 10) and collagen fragments, were observed;Reductions in pro-inflammatory cytokines (IL-6 and IL-11) were observed; andIncreases in anti-inflammatory cytokines (IL-4 and IL-35) and markers of macrophage polarization (MARCO and sCD163) were also observed. Sustained reductions in a biomarker of cardiac dysfunction (serum N-terminal pro-brain natriuretic peptide) were observed in subjects administered 4.5 mg/kg of KER-012 versus placebo. Preclinical Presentations RKER-012, a Novel Modified ActRII Ligand Trap, Attenuated Cardiac Remodeling and Fibrosis in a Transverse Aortic Constriction Model of Heart Failure Keros used a transverse aortic constriction (“TAC”) model of left ventricle overload to evaluate whether RKER-012 could prevent or treat cardiac remodeling and fibrosis in mice. Mice either underwent sham or TAC surgery. Following these procedures, sham mice received vehicle and TAC mice received either vehicle (“TAC-vehicle”) or 10 mg/kg of RKER-012 (“TAC-RKER-012”) twice weekly, starting from the first day (“TAC-RKER-012 Group 1”) or fourteenth day (“TAC-RKER-012 Group 2”) after surgery. Eight weeks post-surgery, mice were assessed for associated cardiac pathologies. Relative to sham mice, TAC-vehicle mice had increased heart weight, left ventricular posterior wall thickness, interventricular septal end diastole, left ventricular fibrosis and elevated tissue remodeling markers, indicating that the TAC surgery worked as intended. TAC-RKER-012 Group 1 mice had significantly reduced heart weight, left ventricular posterior wall thickness, interventricular septal end diastole and left ventricular fibrosis compared to TAC-vehicle mice. TAC-RKER-012 Group 2 mice had significantly reduced left ventricular posterior wall thickness and interventricular septal end diastole compared to TAC-vehicle mice, while heart weight and left ventricular fibrosis trended towards a decrease. These data demonstrate that RKER-012 lessened the severity of cardiac fibrosis and remodeling, leading to an improvement in left ventricular function, which Keros believes supports the potential of KER-012 to benefit heart failure patients as a preventative or treatment option. RKER-012, a Novel Activin Receptor Type IIB (ActRIIB) Ligand Trap, Inhibited Mediators of Dysregulated Vascular Remodeling in Pulmonary Endothelial and Smooth Muscle Cells This preclinical study evaluated TGF-β ligand signaling in human pulmonary arterial endothelial cells (“HPAECs”) and smooth muscle cells (“HPASMCs”), which are two major cell types involved in the dysregulated vascular remodeling in PAH, and KER-012’s effect on this ligand-induced signaling. HPAECs and HPASMCs were treated with activin A, GDF11, or bone morphogenetic protein 9 (“BMP9”) in the presence of KER-012. KER-012 treatment reduced activin A and GDF11-induced SMAD 2/3 signaling in the HPAECs and HPASMCs, but did not inhibit BMP9-induced pSMAD1 signaling. Separately, pulmonary arterial cells cultured in normoxia or hypoxia for 48 hours to mimic conditions in PAH were evaluated with RKER-012. Keros observed increases in activin A induced by hypoxia in HPAECs, but not in HPASMCs, which is consistent with the role of endothelial dysfunction in PAH and suggests that activin A may be released from endothelial cells during vascular remodeling. RKER-012 was able to reduce SMAD2 activation in hypoxic endothelial cells back to normoxic levels by binding endogenously upregulated activin A in an in vitro model replicating hypoxia in PAH. These data from this in vitro model suggest that KER-012 can potentially correct imbalanced SMAD signaling in PAH, partially by inhibiting activin A, a key pathogenic driver of PAH. About the Completed Phase 1 Clinical Trial of KER-012 in Healthy Volunteers In September 2022, Keros completed a randomized, double-blind, placebo-controlled, two-part Phase 1 clinical trial to evaluate single and multiple ascending doses of KER-012 in healthy post-menopausal women. The primary objectives of this trial were to evaluate the safety and tolerability of escalating doses of KER-012 administered as single and multiple subcutaneous doses in healthy post-menopausal women. In Part 1 of this trial, 32 subjects received either a single 0.75, 1.5, 3 or 5 mg/kg dose of KER-012 and eight subjects received a single dose of placebo, each administered subcutaneously with an eight-week safety follow-up. The subjects were enrolled in sequential single-ascending dose escalation cohorts of ten subjects each. In Part 2 of the trial, subjects received three subcutaneous doses of either 0.75, 1.5 or 4.5 mg/kg of KER-012 or placebo administered 28 days apart with a 16-week safety follow-up. A total of 26 subjects were enrolled in three sequential multiple-ascending dose escalation cohorts, 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 cohorts receiving KER-012. Six subjects enrolled in Part 2 of this trial received placebo doses. About KER-012 KER-012 is designed to bind to and inhibit the signaling of TGF-β ligands that suppress bone growth, including activin A and activin B. 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 PAH and for the treatment of cardiovascular disorders. 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 hematological, pulmonary and cardiovascular 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 a number of tissues, including blood vessels and heart tissue. 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 functional iron deficiency. Keros’ third product candidate, KER-012, is being developed for the treatment of PAH and for the treatment of cardiovascular disorders. 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 "believes," "intends," “potential” and "suggest" 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-012; the potential of KER-012 to treat fibrosis and inflammation in patients with PAH and in patients with cardiovascular disease; the potential of KER-012 to benefit heart failure patients as a preventative or treatment option; and the potential of KER-012 to correct imbalanced SMAD signaling in PAH. 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 product candidates, KER-050, KER-047 and KER-012; 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; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies. 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 4, 2023, 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: Justin Frantzjfrantz@soleburytrout.com617-221-9100

LEXINGTON, Mass., May 04, 2023 (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, pulmonary and cardiovascular disorders with high unmet medical need, today provided a business update and reported financial results for the quarter ended March 31, 2023. “We are on track to report additional data from multiple clinical trials this year, including our two Phase 2 clinical trials of KER-050, one in patients with myelodysplastic syndromes ("MDS") and one in patients with myelofibrosis,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer. “We believe these data readouts, combined with the planned commencement of our Phase 2 clinical trial of KER-012 in patients with pulmonary arterial hypertension in the first half of this year, position Keros for a year of important clinical milestones.” Recent Corporate Highlights Cash position strengthened: The Company has utilized its existing at the market offering to sell additional shares of common stock, which strengthened its cash position. The Company expects that its cash and cash equivalents as of March 31, 2023 will enable the Company to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025.Strengthened leadership with board appointment: In May 2023, Keros appointed Dr. Alpna Seth, Ph.D., to its board of directors. Recent Program Highlights KER-012 for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders Keros will present three poster abstracts from its KER-012 program at the American Thoracic Society (“ATS”) 2023 International Conference, to be held from May 19 through May 24, 2023. The following abstracts were posted to the ATS conference website on March 2, 2023: Clinical Presentation: “Administration of KER-012, a Modified Activin Receptor IIB Ligand Trap, Led to Changes in Biomarkers of Cardiovascular Health in a Ph1 Study Conducted in Healthy Post-Menopausal Women” Session Name: A26: Precision-Based Approaches to Pulmonary Vascular DiseaseDate and Presentation Time: May 21, 2023; 9:00 a.m. - 11:00 a.m. Eastern time Preclinical Presentation: “RKER-012, a Novel Modified ActRII Ligand Trap, Attenuated Cardiac Remodeling and Fibrosis in a Transverse Aortic Constriction Model of Heart Failure” Session Name: A71: Matters of the Heart: Studies on Cardiopulmonary Vascular DiseaseDate and Presentation Time: May 21, 2023; 11:30 a.m. - 1:15 p.m. Eastern time Preclinical Presentation: “RKER-012, a Novel Activin Receptor Type IIB (ActRIIB) Ligand Trap, Inhibited Mediators of Dysregulated Vascular Remodeling in Pulmonary Endothelial and Smooth Muscle Cells” Session Name: B59: Breaking Bad: New Drugs and Formulations for Pulmonary Hypertension and RV FailureDate and Presentation Time: May 22, 2023; 11:30 a.m. - 1:15 p.m. Eastern time First Quarter 2023 Financial Results Keros reported a net loss of $35.8 million in the first quarter of 2023 as compared to a net loss of $24.2 million in the first quarter of 2022. The increase of $11.6 million for the first quarter was largely due to increased research and development efforts as well as additional investments to support the achievement of Keros' clinical and corporate goals. Research and development expenses were $31.1 million for the first quarter of 2023 as compared to $18.1 million for the same period in 2022. The increase of $13.0 million was primarily due to additional research and development efforts, manufacturing activities and personnel expenses to support the advancement of Keros’ pipeline. General and administrative expenses were $7.8 million for the first quarter of 2023 as compared to $6.0 million for the same period in 2022. The increase of $1.7 million was primarily due to increase in personnel expenses and other external expenses to support Keros' organizational growth. Keros’ cash and cash equivalents as of March 31, 2023 was $351.4 million compared to $279.0 million as of December 31, 2022. Keros expects that the cash and cash equivalents it had on hand at March 31, 2023 will enable Keros to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025. 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 hematological, pulmonary and cardiovascular 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 a number of tissues, including blood vessels and heart tissue. 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 MDS and in patients with myelofibrosis. Keros’ lead small molecule product candidate, KER-047, is being developed for the treatment of functional iron deficiency. Keros’ third product candidate, KER-012, is being developed for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders. 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 “believe,” “enable,” “expects,” “plans,” “progress” and “will” 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, KER-047 and KER-012; and Keros’ expected cash runway. 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 product candidates, KER-050, KER-047 and KER-012; 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; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies. 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 Annual Report on Form 10-K, filed with the SEC on March 3, 2023, 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: Justin Frantzjfrantz@soleburytrout.com617-221-9100 KEROS THERAPEUTICS, INC. Condensed Consolidated Statements of Operations (In thousands, except share and per share data) (Unaudited) THREE MONTHS ENDED MARCH 31, 2023 2022 REVENUE: License revenue$— $— Total revenue — — OPERATING EXPENSES: Research and development (31,091) (18,078)General and administrative (7,778) (6,048)Total operating expenses (38,869) (24,126)LOSS FROM OPERATIONS (38,869) (24,126)OTHER INCOME (EXPENSE), NET Interest expense, net — (1)Other income (expense), net 3,065 (59)Total other income (expense), net 3,065 (60)Net loss$(35,804) $(24,186)Net loss attributable to common stockholders—basic and diluted$(35,804) $(24,186)Net loss per share attributable to common stockholders—basic and diluted$(1.26) $(1.01)Weighted-average common stock outstanding—basic and diluted 28,369,453 23,993,698 KEROS THERAPEUTICS, INC.Condensed Consolidated Balance Sheets (In thousands, except share and per share data) (Unaudited) MARCH 31,2023 DECEMBER 31,2022ASSETS CURRENT ASSETS: Cash and cash equivalents351,429 279,048 Prepaid expenses and other current assets10,793 6,719 Total current assets362,222 285,767 Operating lease right-of-use assets16,364 15,548 Property and equipment, net2,933 2,021 Restricted cash1,327 1,327 Other long-term assets1,590 2,118 TOTAL ASSETS384,436 306,781 LIABILITIES AND STOCKHOLDERS' EQUITY CURRENT LIABILITIES: Accounts payable4,682 3,339 Current portion of operating lease liabilities— 455 Accrued expenses and other current liabilities10,776 12,753 Total current liabilities15,458 16,547 Operating lease liabilities, net of current portion13,994 12,811 Total liabilities29,452 29,358 STOCKHOLDERS' EQUITY: Common stock, par value of $0.0001 per share; 200,000,000 shares authorized as of March 31, 2023 and December 31, 2022, respectively; 29,548,649 and 27,543,453 shares issued and outstanding as of March 31, 2023 and December 31, 2021, respectively3 2 Additional paid-in capital619,219 505,855 Accumulated deficit(264,238) (228,434)Total stockholders' equity354,984 277,423 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY384,436 306,781