SL-172154 / Shattuck - LARVOL DELTA

Phase Ib trial of SL-172154, a bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, in combination with mirvetuximab soravtansine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. (PubMed, Br J Cancer) - P1 | "Combination of SL172154 with MIRV did not improve upon the previously reported ORR for MIRV, while the combination with PLD resulted in a higher ORR than reported for PLD, albeit in a small number of patients. Limited tumor penetration of SL-172154, lack of durable CD47 blockade, inability to overcome T cell exhaustion and other mechanisms of resistance may explain these findings. Trial register number: NCT05483933."

Journal • P1 data • Platinum resistant • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • CD40 • FOLR1

Phase Ib trial of SL-172154, a bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, in combination with mirvetuximab soravtansine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer (Nature, Br J Cancer) - "65 patients (60% folate receptor alpha (FRα) high and 40% medium/low) were enrolled in the MIRV cohort and 21 patients in the PLD cohort. Most common TEAEs ( > 40%) in the MIRV cohort were blurred vision, nausea, infusion related reaction, transaminase increase, diarrhea, and in the PLD cohort, nausea, constipation, neutropenia and fatigue. The objective response rate in the MIRV cohort was 33% (95% CI, 19%, 50%) for FRα high subgroup, and 15% (95% CI, 4%, 35%) for FRα medium/low subgroup, and in the PLD cohort was 20% (95% CI, 6%, 44%)."

P1 data • Platinum resistant • Ovarian Cancer

Phase Ib trial of SL-172154, a bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, in combination with mirvetuximab soravtansine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer (Nature, Br J Cancer) - "65 patients (60% folate receptor alpha (FRα) high and 40% medium/low) were enrolled in the MIRV cohort and 21 patients in the PLD cohort. Most common TEAEs ( > 40%) in the MIRV cohort were blurred vision, nausea, infusion related reaction, transaminase increase, diarrhea, and in the PLD cohort, nausea, constipation, neutropenia and fatigue. The objective response rate in the MIRV cohort was 33% (95% CI, 19%, 50%) for FRα high subgroup, and 15% (95% CI, 4%, 35%) for FRα medium/low subgroup, and in the PLD cohort was 20% (95% CI, 6%, 44%)."

P1 data • Platinum resistant • Ovarian Cancer

SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov) - P1 | N=106 | Terminated | Sponsor: Shattuck Labs, Inc. | Completed ➔ Terminated; Development discontinued

Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • TP53

Safety, Pharmacodynamic, and Anti-Tumor Activity of SL-172154 As Monotherapy and in Combination with Azacitidine (AZA) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) Patients (pts) (ASH 2023) - "The median number of prior lines of AML therapy was 2 [range 1-4]; 25 (93%) had received venetoclax (VEN) and 23 (85%) had received a hypomethylating agent (HMA). SL-172154 was well tolerated up to 3 mg/kg as monotherapy and in combination with AZA. Preliminary efficacy signals were detected in UnTx TP53m-MDS and R/R AML. A response to SL-172154 monotherapy, dose-dependent increases in serum cytokines and accumulation of mature myeloid cells in BM suggest a potential role for CD40 stimulation."

Clinical • Combination therapy • IO biomarker • Monotherapy • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD36 • CD40LG • CXCL8 • IL10 • ITGAM • SCARB1 • SIRPA • TP53

SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects with MDS or AML (clinicaltrials.gov) - P1 | N=106 | Completed | Sponsor: Shattuck Labs, Inc. | Active, not recruiting ➔ Completed | N=160 ➔ 106 | Trial completion date: Nov 2024 ➔ Feb 2025 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • TP53

SL03-OHD-105: Phase 1b Study of SL-172154 Administered with Combination Agent(s) in Subjects with Ovarian Cancers (clinicaltrials.gov) - P1 | N=86 | Completed | Sponsor: Shattuck Labs, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Nov 2024 ➔ Feb 2025 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Trial completion • Trial completion date • Trial primary completion date • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • FOLR1

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer. (PubMed, J Immunother Cancer) - P1 | "SL-172154 was tolerable as monotherapy and induced, dose-dependent, and cyclical immune cell activation, increases in multiple serum cytokines, and trafficking of CD40-positive B cells and monocytes following each infusion. The safety, PK, and PD activity support 3.0 mg/kg as a safe and pharmacologically active dose."

Journal • P1 data • Oncology • Ovarian Cancer • Solid Tumor • CD40 • CD40LG • CD8 • IL12A • SIRPA

SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects with MDS or AML (clinicaltrials.gov) - P1 | N=160 | Active, not recruiting | Sponsor: Shattuck Labs, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Nov 2024 | Trial primary completion date: Apr 2025 ➔ Nov 2024

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Oncology • TP53

Top-line Phase 1B SL-172154 Clinical Trial Results (GlobeNewswire) - P1a/1b | N=160 | NCT05275439 | Sponsor: Shattuck Labs, Inc. | "Top-line Phase 1B SL-172154 Clinical Trial Results - HR-MDS: Interim Overall Survival (OS) analysis was completed on September 3, 2024. Overall Survival: Current median OS of 15.6 months. The median survival for patients with TP53m HR-MDS is currently 10.6 months and will not improve beyond 13.1 months with subsequent data cuts; TP53m AML: Interim OS analysis was completed on September 3, 2024. Overall Survival: Current median OS is 10.5 months and will not improve beyond 11.7 months with subsequent data cuts. Benchmark Data: Benchmark median OS of approximately 5-8 months for TP53m AML patients treated with azacitidine alone."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

SL03-OHD-105: Phase 1b Study of SL-172154 Administered with Combination Agent(s) in Subjects with Ovarian Cancers (clinicaltrials.gov) - P1 | N=86 | Active, not recruiting | Sponsor: Shattuck Labs, Inc. | Trial completion date: Apr 2025 ➔ Nov 2024

Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • FOLR1

Shattuck Labs Provides Company Update… (GlobeNewswire) - "Shattuck Labs, Inc...announced a strategic pipeline prioritization to include the discontinuation of its clinical program, SL-172154....On September 30, 2024, Shattuck and Ono Pharmaceutical Co., Ltd. (Ono) mutually agreed to terminate the Collaboration and License Agreement dated February 13, 2024 (Collaboration Agreement)....Following the mutual termination, Shattuck is no longer required to satisfy any remaining performance obligations and will not receive any future research activity reimbursements or upfront, milestone, or royalty payments from Ono."

Discontinued • Licensing / partnership • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

SL03-OHD-105: Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers (clinicaltrials.gov) - P1 | N=86 | Active, not recruiting | Sponsor: Shattuck Labs, Inc. | Trial primary completion date: Jul 2024 ➔ Dec 2024

Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • FOLR1

Shattuck Labs Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML: Initiated enrollment of the Part D cohort, a randomized, controlled Phase 1B dose-expansion cohort in frontline HR-MDS patients. Approximately 60 patients will be randomized in a 1:1:1 ratio to receive SL-172154 at 3mg/kg in combination with AZA, SL-172154 at 1mg/kg in combination with AZA, or AZA as monotherapy."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Shattuck Labs Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Phase 1B Trial of SL-172154 in Platinum-Resistant Ovarian Cancer (PROC): Completed enrollment for the cohort combining SL-172154 with Elahere....Shattuck continues to follow patients for progression free survival and overall survival and, should such results mature favorably in either PROC cohort, will evaluate further development in PROC at that time."

Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer

Shattuck Labs Announces Addition to Russell 2000 and Russell 3000 Indexes (GlobeNewswire) - "Shattuck Labs, Inc...announced its addition to the Russell 2000 and Russell 3000 Indexes at the conclusion of the 2024 Russell U.S. Indexes annual reconstitution. Shattuck’s addition will be effective today when the U.S. equity markets open....'We are pleased to be included in the Russell Indexes, which is reflective of the continued progress that we’ve made in 2024, including the rapid advancement of SL-172154 in HR-MDS and TP53m AML'..."

Financing • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

PHASE 1B STUDY OF SL-172154, A BI-FUNCTIONAL FUSION PROTEIN TARGETING CD47 AND CD40, WITH AZACITIDINE IN PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA AND HIGHER-RISK MYELODYSPLASTIC SYNDROMES (EHA 2024) - "The combination of 3 mg/kg 154+AZA showed an acceptable safety profile. Preliminary efficacy results suggest that the combination of 154+AZA provides encouraging CR rates inpreviously untreated HR-MDS and TP53m AML pts and successfully bridged responding TP53m AML pts toHCT."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myocardial Infarction • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • CD40 • CD40LG • SIRPA • TP53

Shattuck Labs Announces Updated Positive Interim Data from the Phase 1B Dose Expansion Clinical Trial of SL-172154 in Combination with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients (GlobeNewswire) - P1b | N=34 | NCT04406623 | Sponsor: Shattuck Labs, Inc | "Interim efficacy results as of April 23, 2024, showed four of 21 (19%) treated patients in our Phase 1B study of SL-172154 in combination with PLD have achieved partial responses. The Javelin-200 study reported an ORR of 4% with PLD alone. Two additional patients with stable disease showed maximum tumor reductions of 17% and 27% and were continuing on study. The Company is continuing to follow patients for progression free survival and overall survival....Both of these combinations, SL-172154 combined with PLD and SL-172154 combined with Elahere, have shown an acceptable safety profile with IRRs as the most common treatment emergent AE as of the data cutoff."

P1 data • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Shattuck Labs Announces Updated Positive Interim Data from the Phase 1B Dose Expansion Clinical Trial of SL-172154 in Combination with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients (GlobeNewswire) - P1 | N=160 | NCT05275439 | Sponsor: Shattuck Labs, Inc. | "Shattuck Labs, Inc...announced updated interim data from the Phase 1B dose expansion clinical trial of SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML patients....Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML: HR-MDS: As of the data cut-off date of April 23, 2024, in 24 treated patients (21 had TP53m, 16 had complex karyotype, and seven had therapy-related MDS), the ORR was 67%. Ten (42%) patients achieved a CR with 3.6 months as the median time to CR....TP53m AML: As of the data cut-off date of June 4, 2024, in 21 treated patients (all 21 had TP53 mutations or deletion, 19 had a complex karyotype, and 14 had secondary AML) the ORR was 43%."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Shattuck Labs Announces Updated Positive Interim Data from the Phase 1B Dose Expansion Clinical Trial of SL-172154 in Combination with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients (GlobeNewswire) - "Shattuck will host a conference call today at 7:30 a.m. ET...to discuss the data from the poster presentation featured at the EHA 2024 Congress, including an interim safety and efficacy update from the frontline expansion cohorts in HR-MDS and TP53m AML."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Shattuck Labs Announces Orphan Drug Designation Granted by the U.S. Food and Drug Administration (FDA) for SL-172154 for the Treatment of Acute Myeloid Leukemia (AML) (GlobeNewswire) - "Shattuck Labs, Inc...announced that the U.S. FDA has granted orphan drug designation (ODD) to lead clinical candidate SL-172154 for the treatment of AML...'we look forward to presenting additional data from the Phase 1B dose expansion clinical trial of SL-172154 with azacitidine in frontline higher-risk myelodysplastic syndromes and TP53m AML patients during a poster presentation at the European Hematology Association 2024 Congress'."

Orphan drug • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Orphan Designation: Treatment of acute myeloid leukemia (FDA) - Date Designated: 06/07/2024

Orphan drug • Acute Myelogenous Leukemia

Shattuck Labs to Host Investor Call and Webcast on Additional Interim Data Presented at the European Hematology Association (EHA) 2024 Congress from the Phase 1B Dose Expansion Clinical Trial of SL-172154 with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients (GlobeNewswire) - "Conference call and webcast to be held June 14, 2024 at 7:30 a.m. ET featuring lead investigator...Shattuck Labs, Inc...announced that it will host an investor call for an interim safety and efficacy update from the Phase 1B dose expansion clinical trial of SL-172154 with AZA in HR-MDS and TP53m AML, being presented at the EHA 2024 Congress. The event will feature lead investigator, Dr. Naval G. Daver, from The University of Texas MD Anderson Cancer Center."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers (clinicaltrials.gov) - P1 | N=86 | Active, not recruiting | Sponsor: Shattuck Labs, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • FOLR1

Shattuck Labs to Present Additional Data from the Phase 1B Dose Expansion Clinical Trial of SL-172154 with Azacitidine (AZA) in Frontline Higher-Risk Myelodysplastic Syndromes (HR-MDS) and TP53 mutant (TP53m) Acute Myeloid Leukemia (AML) Patients at the European Hematology Association (EHA) 2024 Congress (GlobeNewswire) - P1a/1b | N=160 | NCT05275439 | Sponsor: Shattuck Labs, Inc. | "Shattuck Labs...announced the presentation of additional data from the Phase 1B dose expansion clinical trial of SL-172154 with AZA in frontline HR-MDS and TP53m AML patients...HR-MDS: In 23 evaluable patients (20 had TP53m, 21 had complex karyotype, and seven had therapy-related MDS), the objective response rate (ORR) was 65%. Nine patients achieved a CR within 16 weeks as the median time to CR. None of the patients with CR progressed as of the data cutoff...TP53m AML: In 14 evaluable patients (11 of whom had secondary AML) the ORR was 36%. A total of 21 patients will be included in the final pre-conference data cutoff. Two patients achieved a CR, the median time to CR was 8.7 weeks. Another patient achieved a CR with incomplete hematologic recovery (CRi) and two patients achieved a partial response (PR). None of the responders progressed as of the data cutoff."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome