UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 7, 2023
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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Item 7.01 Regulation FD Disclosure.
On August 7, 2023, Keros Therapeutics, Inc. (the “Company”) updated its corporate presentation for use in meetings with investors, analysts and others. The presentation is available through the Company’s website and a copy is attached as Exhibit 99.1 to this Current Report on Form 8-K.
The information under Item 7.01 in this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section. Such information and the accompanying Exhibit 99.1 are not incorporated by reference in any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
During a conference call and webcast scheduled to be held at 8:00 a.m. Eastern time on August 8, 2023, the Company’s management will provide an overview of TROPOS, its global Phase 2 clinical trial to evaluate KER-012 in combination with background therapy in patients with pulmonary arterial hypertension. A copy of the presentation for the conference call and webcast is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit | ||||||||
| No. | Description | |||||||
| 104 | Cover Page Interactive Data File (the cover page XBRL tags are embedded within the Inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| KEROS THERAPEUTICS, INC. | ||||||||
| By: | /s/ Jasbir Seehra | |||||||
Jasbir Seehra, Ph.D. Chief Executive Officer | ||||||||
Dated: August 7, 2023
August 2023 Corporate Presentation
Corporate Presentation 2 Statements contained in this presentation 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, expected results and timing of its preclinical studies and clinical trials for KER-050, KER-047, KER-012 and KER-065; and the potential of Keros’ proprietary discovery approach. 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, KER-012 and KER-065; 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 August 7, 2023, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation 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. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third -party sources. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. The trademarks included in this presentation are the property of the owners thereof and are used for reference purposes only. Disclaimer
KER-065 therapeutic protein P R E C L I N I C A L Corporate Presentation 3 Focused on Transforming the Lives of Wide Range of Patients with Disorders Linked to Dysfunctional TGF-β Superfamily Signaling We believe our product candidates have the potential to unlock the full therapeutic benefits of modulating the TGF-β superfamily and provide disease-modifying benefit to patients P H A S E 3P R E C L I N I C A L P H A S E 1 P H A S E 2 KER-050 therapeutic protein KER-047 small molecule KER-050 therapeutic protein H E M A T O L O G Y KER-012 therapeutic protein P U L M O N A R Y & C A R D I O V A S C U L A R Myelodysplastic Syndromes (MDS) Myelofibrosis (MF) Functional Iron Deficiency (FID)-Anemia in MDS and MF Pulmonary Arterial Hypertension Duchenne Muscular Dystrophy Musculoskeletal 4KER-012 therapeutic protein N E U R O M U S C U L A R Chronic Heart Failure with Preserved Ejection Fraction/Reduced Ejection Fraction Keros is a clinical-stage biopharmaceutical company Developing potentially differentiated product candidates designed to alter transforming growth factor-beta (TGF-β) signaling and target pathways critical for the growth, repair and maintenance of a number of tissue and organ systems Undisclosed Assets
B Hematology Franchise Corporate Presentation 4
5 TGF-b Superfamily Plays a Critical Role in the Maintenance of the Bone Marrow Microenvironment Hematopoiesis, the process by which blood cells are produced in the bone marrow, requires the coordinated control of cell division, differentiation and production of the specialized cellular machinery for each cell type ▸ Ineffective hematopoiesis is the failure of immature blood cells to properly develop into mature cells, and may lead to low levels of circulating red blood cells (anemia), white blood cells (neutropenia) or platelets (thrombocytopenia) TGF-β superfamily signaling regulates many processes in the bone marrow microenvironment, including: ▸Differentiation and maturation of hematopoietic cells ▸ Iron homeostasis ▸ Bone turnover ▸ Pro-inflammatory signaling ▸Motility of malignant cells Keros is developing product candidates with the potential to address ineffective hematopoiesis and functional iron deficiency: ▸KER-050: Modified activin receptor IIA (ActRIIA) ligand trap designed to bind to and inhibit signaling of select TGF-β ligands, including activin A, activin B, GDF8 and GDF11, to promote growth and differentiation of erythroid cells and platelets ▸KER-047: Small molecule product candidate designed to inhibit activin receptor-like kinase-2 (ALK2) to suppress hepcidin expression and mobilize iron for incorporation into hemoglobin Corporate Presentation
B KER-050 6 Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelodysplastic Syndromes Ongoing Phase 2 Clinical Trial of KER-050 for the Treatment of Anemia in Patients with Very Low-, Low- or Intermediate-Risk Myelodysplastic Syndromes Corporate Presentation
BCorporate Presentation 7 MDS MDS is a collection of bone marrow disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Clinical Consequences The clinical consequences of MDS include anemia, bleeding, iron overload, cardiovascular disease and progression to acute myeloid leukemia (AML). Survival Ranges Median survival ranges from approximately nine years for very low-risk patients to less than a year for high-risk patients. Scope In the United States, there are 60,000 to 170,000 patients living with MDS and 15,000 to 20,000 new cases of MDS reported each year. Clinical Consequences of Ineffective Hematopoiesis Myelodysplastic Syndromes (MDS)
8Corporate Presentation Current treatment options for symptomatic anemia includes red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs) and Reblozyl® ▸ RBC transfusions provide symptomatic relief of anemia, but are also associated with iron overload which can increase risk of AML and reduce overall survival ▸ ESAs’ benefit is limited to patients with low transfusion burden and low endogenous erythropoietin levels ▸ Reblozyl® approved for treatment of anemia in RS+ patients requiring transfusions who have failed prior ESA treatment ▸ Similar to ESAs, benefit primarily in low transfusion burden (LTB) patients. Only 20% of high transfusion burden (HTB) patients achieved 8-week transfusion independence with Reblozyl® versus 4% with placebo We believe KER-050 has the potential to improve the bone marrow and restore normal hematopoiesis by targeting multiple cell lineages in MDS ▸ Based on data from our completed Phase 1 clinical trial of KER-050 and multiple preclinical studies, we believe KER-050 has the potential to increase red blood cell and platelet production by acting across the spectrum of cellular differentiation and maturation in hematopoiesis while also improving bone health RS+: patients that have ring sideroblasts. Novel Treatment Options are Needed to Address Unmet Need of Patients Living with MDS
B ▸ KER-050 administered subcutaneously once every four weeks (Q4W) Primary Objective: ▸ Assess safety and tolerability of KER-050 Select Efficacy Endpoints: ▸ IWG 2006 Hematological improvement-erythroid (HI-E): ▸ Hemoglobin increase of ≥1.5 g/dL for 8 weeks (in NT and LTB patients) ▸ Reduction of ≥4 RBC units transfused over 8 weeks compared to baseline (in HTB patients) ▸ Transfusion independence (TI) for at least 8 weeks in patients who require ≥ 2 RBC units transfused at baseline Ongoing Trial – Status as of April 3, 2023: ▸ Part 1 Dose Escalation (N=31; completed) ▸ RP2D: 3.75 mg/kg with the ability to titrate to 5 mg/kg Q4W ▸ RP2D Experienced Patients: N=59 ▸ 25 patients from Part 1 ▸ 34 patients from Part 2 Corporate Presentation 9 Amended Phase 2 Clinical Trial Design and Dose Levels Data are presented as of a data cutoff date of April 3, 2023. RP2D = Recommended Part 2 Dose; CMML: chronic myelomonocytic leukemia; high transfusion burden (HTB): ≥4 units of RBC/8 weeks for hemoglobin (Hgb) ≤9 g/dL; low transfusion burden (LTB): 1-3 units of RBC/8 weeks for Hgb ≤9 g/dL; non-transfused (NT): Hgb ≤10 g/dL; non-RS: patients that did not have ring sideroblasts. Part 1: Dose Escalation Cycle 5 to Cycle 24 of Study Drug Part 1 - Extension Dose Escalation Cohort 1 0.75 mg/kg N=6 Cohort 2 1.5 mg/kg N=6 Cohort 3 2.5 mg/kg N=6 Cohort 4 3.75 mg/kg N=6 Cohort 5 5 mg/kg N=6 Part 2: Dose Confirmation Dose Confirmation Cohort C NT (RS+ & Non-RS) N=10 Cohort B LTB/HTB Non-RS N=30 Cohort A LTB/HTB RS+ N=30 Cohort D CMML – 0 N=10 Cohort E Iron overload on iron chelation N=15 Cohort F Iron overload without iron chelation N=15 Ongoing Phase 2 Clinical Trial of KER-050 for the Treatment of Anemia in Patients with Very Low-, Low- or Intermediate-Risk MDS
10Corporate Presentation Baseline Characteristics RP2D dataset (n=59) Age, years, median (range) 74.0 (53-89) Male, n (%) 34 (57.6) RBC transfusion status, units per 8 weeks, n (%) Non-transfused (NT), 0 units 12 (20.3) Low Transfusion Burden (LTB), <4 units 16 (27.1) High Transfusion Burden (HTB), ≥4 to <8 units 31 (52.5) HTB, ≥8 units 12 (20.3) Ring Sideroblast status, n (%) RS+ 42 (71.2) Non-RS 17 (28.8) IPSS-R Risk Category, n (%) Very Low 8 (13.6) Low 29 (66.1) Intermediate 11 (18.6) Missing 1 (1.7) MDS WHO 2016 classification, n (%) MDS 2 (3.4) MDS-MLD 12 (20.3) MDS-RS-MLD 29 (49.2) MDS-RS-SLD 5 (8.5) Missing 11 (18.6) Prior ESA therapy, n (%) 13 (22.0) Iron chelator therapy, n (%) 17 (28.8) In June 2023, we presented data from 59 patients receiving the RP2D as of the April 3, 2023 data cut-off date ▸ 59 patients were evaluable for safety ▸ 37 patients were evaluable for efficacy Most patients required transfusions at baseline ▸ Over half were high transfusion burden (HTB; ≥4 RBC units/8 wks) ▸ Among HTB patients, 12/31 (38.7%) received ≥8 RBC units/8 wks ▸ Majority were ring sideroblast positive (RS+) ▸ Majority had multi-lineage dysplasia (MLD) Exposure of overall MDS RP2D population ▸ Mean duration of treatment was 225 days as of the data cut-off date (≈32 weeks) ▸ Range 6 to 649 days (≈1 to 93 weeks) ▸ Median doses received = 6 ▸ Range 1 to 22 ▸ 14 (23.7%) patients received ≥12 doses ▸ 15 (25.4%) patients received <3 doses Data are presented as of a data cutoff date of April 3, 2023. Enrolled Patient Population Included Difficult-to-Treat Patients With High Disease Burden
11Corporate Presentation Category RP2D dataset (n=59) Any TEAE, n (%) 53 (89.8) Any treatment related TEAE 19 (32.2) Any TE serious AE (TESAE) 20 (33.9) Any treatment-related TESAE 1 (1.7) Any TEAE leading to death 2 (3.4) Any TEAE leading to IMP Discontinuation1 6 (10.2) Data are presented as of a data cutoff date of April 3, 2023. 1 Related TEAEs leading to IMP discontinuation = injection site reaction; unrelated TEAEs = nodular melanoma, COPD and cardiac failure congestive (both in 1 patient), dyspnea, cardiac failure, and myocardial infarction KER-050 generally well-tolerated at RP2D of 3.75 to 5.0 mg/kg ▸Most frequent treatment-emergent adverse events (TEAEs) that occurred (in ≥15% patients) regardless of causality were: ▸ Fatigue (22%), nausea (18.6%), diarrhea (18.6%), epistaxis (16.9%), COVID-19 (15.3%) and dyspnea (15.3%) ▸ 6 TEAEs led to treatment discontinuation: ▸ Related TEAEs: Injection-site reaction (Grade 2) ▸Unrelated TEAEs: Nodular melanoma; dyspnea; chronic obstructive pulmonary disease and cardiac failure congestive (both in one patient), cardiac failure and myocardial infarction ▸ 2 fatal TEAEs (cardiac failure and myocardial infarction) determined to be unrelated to study treatment by the investigator TEAE = Treatment Emergent Adverse Event TESAE = Treatment Emergent Serious Adverse Event IMP = Investigational Medicinal Product AML = Acute Myeloid Leukemia No patients progressed to AML KER-050 Was Generally Well-Tolerated
12Corporate Presentation Data are presented as of a data cutoff date of April 3, 2023. *Percentage based on 34 patients who had at least 24 weeks of treatment or discontinued AND had both baseline and 8weeks of post-baseline platelet data. Response Summary RP2D Patients1 All evaluable patients HTB evaluable patients Overall Erythroid Response (HI-E or TI), n (%) 19/37 (51.4) 11/22 (50) IWG 2006 HI-E, n (%) 19/37 (51.4) 11/22 (50) TI ≥8 weeks2, n (%) 11/26 (42.3) 9/22 (40.9) RS+, n (%) 8/19 (42.1) 6/17 (35.3) Non-RS, n (%) 3/7 (42.9) 3/5 (60) 1 Includes data for weeks 0-24 in RP2D patients with ≥24 weeks of treatment or who discontinued 2 TI-evaluable patients received at least 2 RBC units in the 8 weeks prior to treatment initiation • Similar rates of HI-E and TI observed regardless of transfusion burden or RS status • 44.1%* of patients show a ≥30 x 109/L increase from baseline in platelet count sustained over at least 8 weeks KER-050 Treatment Resulted in Hematological Response Across a Broad Population of Patients with Lower-Risk MDS
13Corporate Presentation Data are presented as of a data cutoff date of April 3, 2023. 1. 2 patients discontinued with insufficient data to determine 8-week transfusion reduction, and are not included in this plot; 2. Baseline hemoglobin calculated as average over 8-week pre-treatment period. Hemoglobin values within 14 days following a transfusion censored except for pre-transfusion values. Per protocol, KER-050 dose must be held at hemoglobin levels ≥12 g/dL. KER-050 treatment led to reductions in transfusion burden1 ▸ Reduced transfusion burden observed in majority of LTB and HTB patients ▸ TI observed in both RS+ and non-RS patients ▸ TI achieved in patients with baseline transfusion burden ranging from 2 to 11 units/8 weeks Patient Weeks KER-050 treatment demonstrated sustained increases in hemoglobin observed over 6 months2 ▸ 8/15 (53.3%) NT and LTB patients with ≥6 months of treatment (or discontinued) achieved HI-E response in first 24 weeks of treatment ▸Observed sustained increases in hemoglobin support durable response with KER-050 N= Observed Mean Hemoglobin Value By Visit NT and LTB HI-E Responders M e a n ± S E M ( g /d L ) 8 8 8 6 4 8 5 8 6 7 4 78 0 4 8 12 16 20 24 8 9 10 11 12 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 -100 -75 -50 -25 0 HTB LTB Non-RS Reductions in Transfusion Burden and Sustained Increases in Hemoglobin Observed with KER-050 Treatment 2 2 9 9 4 3 4 3 8 6 7 5 13 9 6 4 8 5 4 2 8 4 9 4 8 2 2 0 2 0 4 0 4 0 4 0 5 0 5 0 8 0 8 0 11 0 6 0
14Corporate Presentation Data are presented as of a data cutoff date of April 3, 2023. 19 patients achieved HI-E or TI ▸During weeks 0-24 in RP2D patients with ≥24wk of treatment or who discontinued Median duration of response was 42.4 weeks 10/19 patients (52.6%) had ongoing response at time of data cutoff ▸ Patients with ongoing response censored at time of data cutoff, denoted by vertical Data Suggest KER-050 Elicited a Durable Response
B KER-050 15 Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelofibrosis Ongoing Phase 2 Open-Label Clinical Trial to Evaluate the Safety and Efficacy of KER-050 as Monotherapy or in Combination with Ruxolitinib in Participants with Myelofibrosis Corporate Presentation
BCorporate Presentation 16 MF MF is a rare cancer of the bone marrow in which the marrow is replaced by scar tissue and is not able to produce healthy blood cells Clinical Consequences MF is characterized by ineffective hematopoiesis, an enlarged spleen, bone marrow fibrosis and shortened survival. Patients often experience multiple disease-associated and treatment-emergent cytopenias, including anemia and thrombocytopenia Current Treatments Currently, there are limited therapeutic options to address the MF- associated cytopenias. Within a year of diagnosis, 26% of patients with MF will develop thrombocytopenia and 51% will develop anemia. Additionally, within a year of diagnosis, 38% of patients with MF are RBC transfusion dependent Scope In the United States, there are 16,000 to 18,500 patients living with MF and approximately 3,000 newly diagnosed each year Myelofibrosis (MF)
BCorporate Presentation 17 Data are presented as of a data cutoff date of October 1, 2022. Primary Objective: ▸ Part 1: Assess safety and tolerability of KER-050 ▸ Part 2: Confirm safety and tolerability of the dose(s) selected from Part 1 Secondary Endpoints include: ▸ Evaluate the pharmacokinetics, pharmacodynamics and efficacy of KER-050 administered with or without ruxolitinib KER-050 was generally well tolerated at 0.75mg/kg: ▸No dose-limiting toxicities ▸Most frequent TEAEs reported by ≥ 2 patients were diarrhea (25.0%) and fatigue, dyspnea and COVID-19 (16.7% each) ▸ 1 TEAE led to KER-050 dose modification: amyloidosis (unrelated) ▸No TEAEs led to either study treatment or study discontinuation Ongoing Phase 2 Clinical Trial to Evaluate KER-050 as Monotherapy or in Combination with Ruxolitinib in Patients with MF
BCorporate Presentation 18 Change by Study Arm Change by Transfusion Status NTD: Non–transfusion dependent Although variability was observed amongst the patients, treatment with KER-050 at the lowest dose in this trial (0.75 mg/kg) resulted in increased reticulocytes and platelets on aggregate, both as monotherapy and in combination with ruxolitinib, and regardless of transfusion status ▸ This is consistent with prior preclinical and clinical findings on the pharmacodynamic effects of KER-050 These data support the potential of KER-050 to promote differentiation of erythroid and megakaryocytic precursors and ameliorate anemia and thrombocytopenia in patients with MF KER-050 Treatment Increased Reticulocytes and Platelets in Patients with MF Data are presented as of a data cutoff date of October 1, 2022.
BCorporate Presentation 19 Case Study of Patient on KER-050 Monotherapy Treatment at 0.75mg/kg Q4W ▸ 60-year-old non-transfusion dependent female with primary MF ▸ Treatment with KER-050 increased hematopoiesis ▸A robust increase in reticulocytes observed after a single dose of KER-050 was followed by a sustained increase in hemoglobin (≥1.5 g/dL over baseline) and corresponding decrease in ferritin and erythropoietin with continued dosing ▸An increase in platelets was also observed Observed Increases in RBC Parameters and Platelets in a Patient with KER-050 Treatment (Monotherapy) Data are presented as of a data cutoff date of October 1, 2022.
B KER-047 20 A Novel Product Candidate Designed to Treat Functional Iron Deficiency That is a Consequence of Elevated ALK2 Signaling Corporate Presentation
BCorporate Presentation 21 ALK2 signaling controls hepcidin expression, a hormone that controls iron homeostasis Hepcidin is the master regulator of iron flux into and out of storage tissues ▸ The body responds to demands for iron by increasing or reducing the production of hepcidin, which leads to a reduction or increase in iron availability, respectively. Elevated hepcidin is observed in chronic inflammation, iron overload or results from mutations in the regulatory proteins that control hepcidin expression Functional iron deficiency is a condition when the body has adequate iron in the body, but the iron cannot be mobilized out of storage tissues and incorporated into RBCs, resulting in anemia ▸ RBC transfusions, which are used to treat anemia, can lead to iron overload and toxicity in cardiovascular and other tissues Modulating ALK2 signaling will normalize high hepcidin levels, restore serum iron and ameliorate anemia in functional iron deficiency Increased Hepcidin Expression Leads to Functional Iron Deficiency
BCorporate Presentation 22 KER-047 is a novel, oral, investigational small molecule inhibitor of ALK2 with low nanomolar IC50 PK/ADME: Suitable for 1x daily oral dosing There were no serious adverse events reported in the randomized, double-blind, placebo-controlled two-part Phase 1 clinical trial of KER-047 in healthy volunteers -100 -50 0 50 100 MAD: Hepcidin Percent Change from Baseline at Day 7, 8 hrs Post-Dose H e p ci d in (% C h a n g e f ro m B a se li n e ± SE M ) Placebo 50mg 100mg 200mg 1 4 7 11 30 30.0 31.0 32.0 33.0 34.0 35.0 Mean Reticulocyte Hemoglobin at each visit Visit R e ti cu lo cy te H e m o gl o b in ( p g, ± S E M ) Placebo 50 mg 100 mg 200 mg 350 mgDays on drug ▸ Consistent with ALK2 inhibition, decreases in serum hepcidin were observed in Cohorts 1 through 3 of Part 2 of the trial ▸ Treatment related decreases in hepcidin were associated with increased serum iron ▸An increase in reticulocyte hemoglobin was observed in Cohorts 1 through 4 of Part 2 of the trial, starting on Day 4 of treatment ▸ Pronounced increase in reticulocyte hemoglobin observed in cohorts with lower baseline reticulocyte hemoglobin KER-047 Treatment Reduced Hepcidin Levels and Increased Hemoglobin Content in Reticulocytes in a Phase 1 Clinical Trial
BCorporate Presentation 23 KER-047 Treatment of One IRIDA Patient Resulted in a Decrease in Hepcidin and an Increase in Reticulocyte Hemoglobin Laboratory Results Before, During, and After Administration of KER-047 for the First Low-Dose Cohort (n=1) In December 2022, we presented data from one patient enrolled in our open label, two-part, dose-escalation and dose-expansion Phase 2 clinical trial to evaluate KER-047 in patients with iron-refractory iron deficiency anemia (IRIDA). The patient completed 14 days of treatment with KER-047 (25mg once daily) and a 14 day-follow up ▸ A dose of 25mg once daily was generally well tolerated; no serious adverse events or dose limiting toxicities were observed during treatment ▸ Consistent with results from our Phase 1 clinical trial of KER047 in healthy volunteers, we observed decreases in hepcidin and serum ferritin as well as increases in reticulocyte hemoglobin We are conducting an open label, two-part Phase 2 clinical trial to evaluate response-guided dose titration of KER-047 in MDS and MF patients with functional iron deficiency. The primary objectives of this trial are to assess the safety and tolerability of KER-047. The secondary objectives of this trial are to evaluate the pharmacokinetics, pharmacodynamics and preliminary efficacy of KER-047. We terminated this trial early, having observed data in the one patient enrolled that we believe is suggestive of proof of mechanism. The early termination was not on the basis of any safety concerns
Pulmonary and Cardiovascular Franchise Corporate Presentation 24
KER-012 Corporate Presentation 25 Investigational Treatment for Pulmonary Arterial Hypertension (PAH) and for Cardiovascular Disorders Ongoing Randomized, Phase 2, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of KER-012 in Combination with Background Therapy in Adult Participants with Pulmonary Hypertension
Corporate Presentation 26 Thickened Vasculature Pulmonary Arterial Hypertension Pa PVR Myogenic & Fibrogenic Differentiation PAH is a debilitating disorder characterized by elevated pulmonary vascular resistance due to increased vascular smooth muscle cell proliferation and inflammation ▸ This results in diminished oxygenation, impaired cardiac output, and right ventricle (RV) overload ▸ Patients experience shortness of breath, fatigue, fainting, chest pain, palpitations and swelling of extremities and abdomen. Despite current treatment options, the 5-year survival remains only slightly above 50% ▸ PAH is associated with imbalanced TGF-β superfamily signaling, including insufficient bone morphogenic protein (BMP) signaling and increased signaling by activins and GDFs KER-012 is a modified activin receptor IIB ligand trap ▸Designed to rebalance TGF-β superfamily signaling ▸ Being developed for the treatment of pulmonary and cardiovascular disorders, including PAH ▸ KER-012 is designed to preferentially inhibit select ligands (activin A, activin B, GDF 8 and GDF 11) to potentially rebalance TGF-β superfamily signaling without a dose-limiting increase in RBCs Imbalances in TGF-b Superfamily Signaling Underlies Vascular Remodeling in PAH
1. K. Babbs, et al. Am J Respir Crit Care Med 2022;205:A5776; 2. Babbs K, et al. Am Heart Association Scientific Sessions 2021; RKER-012 = Research KER-012 fused with Fc region of murine IgG1 0.0 0.2 0.4 0.6 0.8 Fulton Index R V /( L V + S ) -15.7% -28.0% ✱ ✱ ✱ ✱ ns ✱ ✱ ns 0 20 40 60 80 100 Pulmonary Artery Pressure s P A P ( m m H g ) -27.5% -44.5% ✱ ✱ ✱ ✱ ns ✱ ✱ ns One way ANOVA followed by Sidak post-hoc test. Ns – not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. Percent change compared to hypoxia + vehicle rats. Hypoxia/PAH Hypoxia/PAH Sugen-Hypoxia Model of PAH1 Pulmonary Artery Banding2 (Direct Cardiac Effects) Cardiac Fibrosis S ham P A B + V eh ic le P A B + R K E R -0 12 0 5 10 15 20 25 F ib ro ti c t is s u e ( % ) -38.9% ✱✱✱✱ ✱✱ 27Corporate Presentation RKER-012 Reduced Pulmonary Arterial Pressure, Right Ventricle Hypertrophy and Cardiac Fibrosis Observed in Rodent PAH Models
PAH Domain Preclinical Data Phase 1 Clinical Trial1,2 MOA & Ligand Specificity: • Strong activin/GDF binding observed • Observed to be BMP-sparing vs. ActRIIA-Fc • We believe PD data support potential for maximal target engagement with doses in Phase 2 Fibrosis & Inflammation: Inflammation Fibrosis Pro-inflammatory biomarkers Anti-inflammatory biomarkers Pro-fibrotic biomarkers Anti-fibrotic biomarkers CV & Hemodynamics: Smooth muscle hypertrophy Pulmonary arterial pressure Right ventricular hypertrophy Cardiac fibrosis (direct) Ventricular dysfunction biomarkers Ventricular dysfunction biomarkers Remodeling biomarkers Erythropoiesis (Hb/RBCs): • No increase observed • No clinically meaningful changes observed Safety & Tolerability: N/A • Generally well tolerated up to 4.5 mg/kg (multiple doses) in Part 2 of the trial • AEs generally mild Corporate Presentation 28 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 volunteers. ▸ The primary objectives of this trial were safety, tolerability and pharmacokinetics. 1. Natarajan H., et al. American Society for Bone and Mineral Research 2022 Annual Meeting; 2. Natarajan H., et al. 2023 American Thoracic Society International Conference Observed KER-012 Profile Supports Therapeutic Rationale in PAH
Corporate Presentation 29 Primary Objective: ▸ To evaluate the effect of KER-012 on hemodynamics compared to placebo in participants on background PAH therapy Primary Endpoint: ▸ Change from baseline in pulmonary vascular resistance (PVR) at Week 24 Key Secondary Objective: ▸ To evaluate the effect of KER-012 on exercise capacity compared to placebo in participants on background PAH therapy Key Secondary Endpoint: ▸ Change from baseline in 6-minute walk distance at Week 24 1.5 mg/kg KER-012 (Q4W) (n=20) 3.0 mg/kg KER-012 (Q4W) (n=20) 4.5 mg/kg KER-012 (Q4W) (n=20) 3.0 mg/kg KER-012 (Q4W)Placebo (Q4W) (n=30) N=90 Stratified Randomization 2:2:2:3* 8 Weeks Post Last Dose OR 4 Weeks Post End of Extension Period (as applicable) 24-Week Treatment Period Double-Blind, Placebo-Controlled 72-Week Extension Period Double-Blind, All Active Safety Follow-Up (End of Trial) Final Analysis Extension Analysis *Approximately 90 patients diagnosed with PAH and on stable PAH background therapy will be randomized and assigned in a 2:2:2:3 ratio to the 1.5 mg/kg, 3.0 mg/kg, and 4.5 mg/kg KER-012 doses and placebo treatment arms. TROPOS Trial: Global Phase 2 Clinical Trial of KER-012 in Patients with PAH
Neuromuscular Franchise Corporate Presentation 30
KER-065 Corporate Presentation 31 Designed to Address Neuromuscular Diseases, with an initial focus on Duchenne Muscular Dystrophy (DMD)
Corporate Presentation 32 KER-065 is a selective activin receptor ligand trap ▸Designed to inhibit the biological effects of myostatin and activin to increase skeletal muscle and bone mass, increase fat metabolism and reduce fibrosis ▸ Being developed for the treatment of neuromuscular diseases, with an initial focus on DMD In preclinical studies, KER-065 showed high affinity for and potent inhibition of ligands involved in the regulation of muscle and bone homeostasis. Additionally, in preclinical studies, the research form of KER-065 (RKER-065): ▸ Increased muscle mass, muscle function and bone mass in wild-type mice ▸ Increased muscle mass, grip strength and trabecular bone in a mouse model of DMD We expect to initiate a randomized, double-blind, placebo-controlled, two-part Phase 1 clinical trial to evaluate the safety and tolerability of single and multiple ascending doses of KER-065 in healthy volunteers in Q1 2024 KER-065 Overview
Corporate Presentation 33 ▸KER-050 ▸Complete enrollment in transfusion-dependent cohorts in Phase 2 MDS trial H2 2023 ▸Announce additional data from Part 2 of Phase 2 MDS trial H2 2023 ▸Announce dose escalation data from Phase 2 MF trial H2 2023 ▸Initiate Part 2 of Phase 2 MF trial H2 2023 ▸KER-047 ▸Announce initial data from Phase 2 FID (MDS and MF) trial H1 2024 ▸KER-012 ▸Initiate Phase 2 open-label biomarker trial in patients with chronic heart failure H2 2023 with preserved ejection fraction and in such patients with reduced ejection fraction ▸KER-065 ▸Commence Phase 1 healthy volunteer trial Q1 2024 Anticipated Key Milestones
August 8, 2023 KER-012 Update
KER-012 Update 2 Disclaimer Statements contained in this presentation 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, expected results and timing of its preclinical studies and clinical trials for KER-050, KER-047, KER-012 and KER-065; and the potential of KER-012 to treat diseases such as pulmonary arterial hypertension without a dose-limiting red blood cell effect (including with respect to the TROPOS trial). 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, KER-012 and KER-065; 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 August 7, 2023, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation 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. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third -party sources. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. The trademarks included in this presentation are the property of the owners thereof and are used for reference purposes only.
KER-012 Update 3 Agenda Topic Discussant(s) Welcome and Introduction Jasbir Seehra PAH Overview and Unmet Medical Needs Mardi Gomberg-Maitland KER-012 Predicted MoA & Differentiation Simon Cooper KER012 Phase 2 PAH (TROPOS) Trial Rationale, Design Mardi Gomberg-Maitland Anticipated Key Milestone Jasbir Seehra Q&A Open Panel Closing Remarks & Adjourn Jasbir Seehra
KER-065 therapeutic protein P R E C L I N I C A L KER-012 Update 4 We believe our product candidates have the potential to unlock the full therapeutic benefits of modulating the TGF-β superfamily and provide disease-modifying benefit to patients P H A S E 3P R E C L I N I C A L P H A S E 1 P H A S E 2 KER-050 therapeutic protein KER-047 small molecule KER-050 therapeutic protein H E M A T O L O G Y KER-012 therapeutic protein P U L M O N A R Y & C A R D I O V A S C U L A R Myelodysplastic Syndromes (MDS) Myelofibrosis (MF) Functional Iron Deficiency (FID)-Anemia in MDS and MF Pulmonary Arterial Hypertension Duchenne Muscular Dystrophy Musculoskeletal 4KER-012 therapeutic protein N E U R O M U S C U L A R Chronic Heart Failure with Preserved Ejection Fraction/Reduced Ejection Fraction Keros is a clinical-stage biopharmaceutical company Developing potentially differentiated product candidates designed to alter transforming growth factor-beta (TGF-β) signaling and target pathways critical for the growth, repair and maintenance of a number of tissue and organ systems Undisclosed Assets Focused on Transforming the Lives of Wide Range of Patients with Disorders Linked to Dysfunctional TGF-β superfamily signaling
KER-012 Update 5 Director of the Pulmonary Hypertension Program at The George Washington University Heart and Vascular Institute. Over 150 publications, including, CHEST, Circulation, Circulation Heart Failure, European Respiratory Journal, Journal of American College of Cardiology (JACC), JACC Heart Failure, JAMA-Internal Medicine, and the New England Journal of Medicine. Past Chair of the Pulmonary Hypertension Council at the International Society of Heart and Lung Transplantation, Vice-Chair of the Education Committee at the International Society of Heart and Lung Transplantation, Section Editor at Journal of American College of Cardiology, and an Associate Editor at both CHEST and the European Respiratory Journal. Mardi Gomberg-Maitland, MD, MSC TROPOS Steering Committee Chair
Pulmonary Arterial Hypertension Overview KER-012 Update 6
KER-012 Update 7 Normal/Healthy PAH/Diseased Vascular Smooth Muscle Pathology: • Pulmonary Smooth Muscle & Endothelial Cell Proliferation • Inflammation • Vasoconstriction mPAP PVR RV Remodeling & Failure Humbert M, et al. Euro Resp J 2019;53 (1801887) 1-14; mPAP=mean pulmonary arterial pressure; PVR=pulmonary vascular resistance ; RV=right ventricle PAH is Characterized by Vascular Remodeling and Dysfunction Leads to Hemodynamic Abnormalities, Disease Progression, and Severe Morbidity
8 Bluish lips and skin Fatigue & Weakness Angina (chest pain) Fluttering Chest Sensation Dyspnea (shortness of breath) Dizziness & Fainting Dry Coughing Abdominal Bloating Peripheral Edema (Swelling) Decreased Work Productivity Diminished Functional Capacity Poor Quality of Life Anxiety & Depression KER-012 Update Pulmonary Arterial Hypertension is All Encompassing Symptoms and Complications Negatively Impact Most Aspects of Patients’ Lives
KER-012 Update 9 Epidemiology: ~40,000 addressable PAH patients in U.S. (~59-81% Female1) Reported average age at diagnosis: 36-71 years2 Cause & Prognosis: ~50-60% idiopathic origin (U.S./Europe)1 Slightly above 50% survival at 5 years • Current standard of care (SOC) for PAH is the use of drugs that promote vasodilation • Currently available treatments do not correct the underlying biology Pulmonary Arterial Hypertension at a Glance A Rare, Progressive and Debilitating Disease Resulting in Significant Health and Economic Burden 1. Hoeper MM, et al. Lancet Resp Med DOI:https://doi.org/10.1016/S2213-2600(15)00543-3; 2. Rothbard N, et al. Cardiol J. 2020; 27(2):184-193.
KER-012 MOA and Differentiation in PAH KER-012 Update 10
KER-012 Update 11 KER-012 is a modified activin receptor IIB ligand trap ▸Designed to rebalance TGF-β superfamily signaling ▸ Being developed for the treatment of pulmonary and cardiovascular disorders, including PAH ▸ KER-012 is designed to preferentially inhibit select ligands (activin A, activin B, GDF 8 and GDF 11) to potentially rebalance TGF-β superfamily signaling without a dose-limiting increase in RBCs Cellular Signaling Defects: • Increased Activin Signaling • Reduced BMP Signaling Normal/Healthy PAH/Diseased BMPTGF-b GDF Activin Pro-Proliferative Anti-Proliferative TGF-b Signaling Balanced BMP TGF-b GDF Activin Pro-Proliferative Anti-Proliferative TGF-b Signaling Imbalanced Vascular Smooth Muscle Pathology: • Pulmonary Smooth Muscle & Endothelial Cell Proliferation • Inflammation • Vasoconstriction Humbert M, et al. Euro Resp J 2019;53 (1801887) 1-14; GDF=growth differentiation factors; BMP=bone morphogenic proteins PAH Pathophysiology and Disease Progression Characterized by TGF-b Signaling Imbalance in Pulmonary Artery Vascular Wall (and Endothelial Cells)
KER-012 is designed to inhibit select TGF-β superfamily ligands to: • Inhibit pro-proliferative activins and GDFs without increasing RBCs • Spare BMP binding to permit anti-proliferative BMP signaling KER-012 Structure TGF-b TGF-b GDF Activin Pro-Proliferative Anti-Proliferative TGF-b Signaling Imbalanced PAH Activin BMP GDF Activin Pro-Proliferative Normalized Anti-Proliferative Normalized TGF-b Signaling Rebalanced KER-012 TGF-b BMP KER-012 Update 12 KER-012 A Novel, Investigational Activin Receptor Type IIB Ligand Trap
Activin/GDF Ligand Binding BMP Ligand Binding ActRIIA-Fc KER-012 (Modified ActRIIB-Fc) ActRIIA-Fc KER-012 (Modified ActRIIB-Fc) Activin A Strong Strong BMP-2 Semi-Weak Weak Activin B Strong Strong BMP-3 Weak Weak Activin C Weak Weak BMP-4 Semi-Weak Weak BMP-5 Strong Semi-Strong GDF-8 Strong Strong BMP-6 Strong Weak GDF-11 Strong Strong BMP-7 Strong Semi-Strong BMP-9 Semi-Weak Weak BMP-10 Strong Strong In Vitro Ligand Binding Affinity Strong Semi-Strong Semi-Weak Weak • KER-012 affinity for SMAD2/3 ligands is comparable to ActRIIA • KER-012 had lower affinity for multiple BMPs compared to ActRIIA 13 Gudelsky A et al American Thoracic Society 2023 Annual Meeting. Am J Respir Crit Care Med 2023;207:A378 KER-012 vs. Native ActRllA In Vitro Binding Studies Support Comparable Activin/GDF Specificity and Greater BMP-Sparing of KER-012 KER-012 Update
Activin/GDF Ligand Binding BMP Ligand Binding ActRIIA-Fc KER-012 (Modified ActRIIB-Fc) ActRIIA-Fc KER-012 (Modified ActRIIB-Fc) Activin A Strong Strong BMP-2 Semi-Weak Weak Activin B Strong Strong BMP-3 Weak Weak Activin C Weak Weak BMP-4 Semi-Weak Weak BMP-5 Strong Semi-Strong GDF-8 Strong Strong BMP-6 Strong Weak GDF-11 Strong Strong BMP-7 Strong Semi-Strong BMP-9 Semi-Weak Weak BMP-10 Strong Strong In Vitro Ligand Binding Affinity Strong Semi-Strong Semi-Weak Weak 14KER-012 Update Gudelsky A et al American Thoracic Society 2023 Annual Meeting. Am J Respir Crit Care Med 2023;207:A378 • KER-012 affinity for SMAD2/3 ligands is comparable to ActRIIA • KER-012 had lower affinity for multiple BMPs compared to ActRIIA KER-012 vs. Native ActRllA In Vitro Binding Studies Support Comparable Activin/GDF Specificity and Greater BMP-Sparing of KER-012
1. K. Babbs, et al. Am J Respir Crit Care Med 2022;205:A5776; 2. Babbs K, et al. Am Heart Association Scientific Sessions 2021; RKER-012 = Research KER-012 fused with Fc region of murine IgG1 0.0 0.2 0.4 0.6 0.8 Fulton Index R V /( L V + S ) -15.7% -28.0% ✱ ✱ ✱ ✱ ns ✱ ✱ ns 0 20 40 60 80 100 Pulmonary Artery Pressure s P A P ( m m H g ) -27.5% -44.5% ✱ ✱ ✱ ✱ ns ✱ ✱ ns One way ANOVA followed by Sidak post-hoc test. Ns – not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. Percent change compared to hypoxia + vehicle rats. Hypoxia/PAH Hypoxia/PAH Sugen-Hypoxia Model of PAH1 Pulmonary Artery Banding2 (Direct Cardiac Effects) Cardiac Fibrosis S ham P A B + V eh ic le P A B + R K E R -0 12 0 5 10 15 20 25 F ib ro ti c t is s u e ( % ) -38.9% ✱✱✱✱ ✱✱ 15KER-012 Update RKER-012 Preclinical Data Reduced Pulmonary Arterial Pressure, Right Ventricle Hypertrophy, and Cardiac Fibrosis Observed in Rodent PAH Models
PAH Domain Preclinical Data Phase 1 Clinical Trial1,2 MOA & Ligand Specificity: • Strong activin/GDF binding observed • Observed to be BMP-sparing vs. ActRIIA-Fc • We believe PD data support potential for maximal target engagement with doses in Phase 2 Fibrosis & Inflammation: Inflammation Fibrosis Pro-inflammatory biomarkers Anti-inflammatory biomarkers Pro-fibrotic biomarkers Anti-fibrotic biomarkers CV & Hemodynamics: Smooth muscle hypertrophy PAP RVH Cardiac fibrosis (direct) Ventricular dysfunction biomarkers Ventricular dysfunction biomarkers Remodeling biomarkers Erythropoiesis (Hb/RBCs): No increase observed No clinically meaningful changes observed Safety & Tolerability: N/A • Generally well tolerated up to 4.5 mg/kg (multiple doses) in Part 2 of the trial • AEs generally mild KER-012 Update 16 ▸ 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 volunteers. ▸ The primary objectives of this trial were safety, tolerability and pharmacokinetics. 1. Natarajan H., et al. American Society for Bone and Mineral Research 2022 Annual Meeting; 2. Natarajan H., et al. 2023 American Thoracic Society International Conference; PAP=pulmonary arterial pressure; RVH=right ventricular hypertrophy Observed KER-012 Profile Supports Therapeutic Rationale in PAH
Rationale of TROPOS Trial in PAH KER-012 Update 17 Mardi Gomberg-Maitland, MD, MSc George Washington University School of Medicine and Health Sciences
18 • Sotatercept is an investigational activin receptor llA-Fc (native ActRIIa fused to Fc region of IgG1) ligand trap • A third-party Phase 3 clinical trial of sotatercept1 demonstrated the importance of the TGF-β superfamily in patients with PAH • Improved 6-minute walking distance (6MWD) along with hemodynamics, biomarkers, World Health Organization Functional Class, Risk Scores, delayed time to clinical worsening, and improved 2 of 3 quality of life domains was reported in this trial1 • Adverse events that occurred more frequently with sotatercept than with placebo in that Phase 3 trial included increased hemoglobin levels, epistaxis and telangiectasia1 1. Hoeper M, et al. New Eng J Med 2023; 388 (16):1478-90 KER-012 Update Targeting the TGF-b Superfamily in PAH Phase 3 STELLAR Trial Presented at American College of Cardiology 2023 Scientific Sessions
19 • Maximum dose in PAH limited to 0.7 mg/kg in the clinical trial due to increased hemoglobin observed in earlier-phase clinical trials1,2 1. Sherman et al 2013 J. Clin Pharmacol 53(11) 1121–1130; 2. Humbert M et al, New Engl J Med 2023; 384:1204-15; 3. Cappellini MD et al. Haematologica 2019; 104(3) 477-484 Sherman et al 2013 (Phase 1) Humbert et al 2021 (Phase 2 PAH) Cappellini et al 2019 (Phase 2 b-thalassemia) KER-012 Update Sotatercept Dosing in PAH Limited Due to On-Target AEs Doses between 0.3 mg/kg and 0.7 mg/kg administered every 21 days
KER-012 Update 20 • BMP-sparing ligand trap has the potential to reduce bleeding risk Loss of BMP Signaling Impairs Endothelial Function and Vascular Integrity
KER-012 Update 21 A Randomized, Phase 2, Double-blind, Placebo-controlled Trial to Investigate the Safety and Efficacy of KER-012 in Combination with Background Therapy in Adult Participants with Pulmonary Arterial Hypertension Planning for ~60 sites TROPOS is a Global Phase 2 Clinical Trial in PAH
22 WHO/NYHA FC II or III symptoms Stable PAH-specific background therapy (ERA/PDE5-I/sGC stimulator/prostacyclin analogue or receptor agonist). Six-minute walk distance (6MWD) ≥ 150 and ≤ 500 meters ▸Note: Right-heart catheterization will be performed during Screening Adult patients ≥ 18 years of age. Primary diagnosis of symptomatic PAH (WHO Group 1) in subgroups: ▸ Idiopathic ▸Heritable ▸Drug or toxin-induced ▸ PAH associated with: ▸ Connective tissue disease, ▸ Congenital systemic-pulmonary intracardiac shunt ▸Hemodynamic parameters consistent with PAH diagnosis: ▸Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND ▸ Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND ▸ Pulmonary vascular resistance (PVR) ≥ 5 Wood Units (400 dyn·sec·cm−5). KER-012 Update Key Eligibility Criteria for Participation
23 • Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease • Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease • Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after • Has uncontrolled systemic hypertension • Hemoglobin < 9 g/dL at screening • Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment KER-012 Update • Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis • Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to baseline or planned initiation during the study • Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept) • Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to screening, whichever is longer. Key Exclusion Criteria
KER-012 Update 24 Approximately 90 patients diagnosed with PAH and on stable PAH background therapy will be randomized and assigned in a 2:2:2:3 ratio to the 1.5 mg/kg, 3.0 mg/kg, and 4.5 mg/kg KER-012 doses and placebo treatment arms. 1.5 mg/kg KER-012 (Q4W) (n=20) 3.0 mg/kg KER-012 (Q4W) (n=20) 4.5 mg/kg KER-012 (Q4W) (n=20) 3.0 mg/kg KER-012 (Q4W)Placebo (Q4W) (n=30) N=90 Stratified Randomization 2:2:2:3 8 Weeks Post Last Dose OR 4 Weeks Post End of Extension Period (as applicable) 24-Week Treatment Period Double-Blind, Placebo-Controlled 72-Week Extension Period Double-Blind, All Active Safety Follow-Up (End of Trial) Final Analysis Extension Analysis TROPOS Trial Design
KER-012 Update 25 Primary Objective Primary Endpoint To evaluate the effect of KER-012 on hemodynamics compared to placebo in participants on background PAH therapy Change from baseline in pulmonary vascular resistance (PVR) at Week 24 Key Secondary Objective Key Secondary Endpoint To evaluate the effect of KER-012 on exercise capacity compared to placebo in participants on background PAH therapy Change from baseline in 6MWD at Week 24 TROPOS Primary & Key Secondary Objective & Endpoint Pooled-Arm KER-012 Hemodynamics and Exercise Capacity Evaluated vs. Placebo over a 24-week Treatment Period
KER-012 Update 26 Secondary Objective Secondary Endpoint To evaluate the safety and tolerability of KER-012 Incidence of treatment-emergent AEs, treatment related AEs and discontinuation due to AEs; change from baseline in clinical lab values, vital signs and ECG; Incidence of ADA To evaluate the effects of KER-012 on hemodynamics Change from baseline in mPAP, CO, CI, PAWP, mRAP, SvO2, SV, SVI and PAC at Week 24 and Week 96 To evaluate the effects of KER-012 on NT-proBNP Change from baseline in NT-proBNP by visit To evaluate improvement in functional class of KER-012 compared to placebo Proportion of participants who achieved improvement from baseline in NYHA FC/WHO by visit ECG=electrocardiogram; CO=carbon monoxide; CI=cardiac index; mRAP=; Sv02=venous oxygen saturation;SV=stroke volume; SVI=stroke volume index; PAC=premature atrial contractions; NT-proBNP=n-terminal pro-b-type natriuretic peptide TROPOS Secondary Objectives and Endpoints Evaluated vs. Placebo over a 24-week Treatment and 72-week Extension Period
KER-012 Update 27 Exploratory Objectives Exploratory Endpoints To evaluate physical activity Change from baseline in overall activity as measured by actigraphy To evaluate improvement in additional risk stratification measures Proportion of patients who achieve improvement in REVEAL Lite 2 and COMPERA 2.0 by visit To evaluate the effect of KER-012 on clinical worsening Incidence of and time to first clinical worsening To evaluate the PD effect of KER-012 on biomarkers Change from baseline in PAH-related biomarkers and other biomarkers by visit To evaluate the HRQoL Change from baseline in HRQoL measures by visit (PAH-SYMPACT and emPHasis-10) HRQoL=health-related quality of life TROPOS Exploratory Objectives and Endpoints Evaluated vs. Placebo over a 24-week Treatment and 72-week Extension Period
KER-012 Update 28 ▸KER-050 ▸Complete enrollment in transfusion-dependent cohorts in Phase 2 MDS trial H2 2023 ▸Announce additional data from Part 2 of Phase 2 MDS trial H2 2023 ▸Announce dose escalation data from Phase 2 MF trial H2 2023 ▸Initiate Part 2 of Phase 2 MF trial H2 2023 ▸KER-047 ▸Announce initial data from Phase 2 FID (MDS and MF) trial H1 2024 ▸KER-012 ▸Initiate Phase 2 open-label biomarker trial in patients with chronic heart failure H2 2023 with preserved ejection fraction and in such patients with reduced ejection fraction ▸KER-065 ▸Commence Phase 1 healthy volunteer trial Q1 2024 Anticipated Key Milestones
Questions & Answers KER-012 Update 29