Actinium-225 DOTATATE (RYZ101) / BMS, RayzeBio - LARVOL DELTA

RYZ101 (225Ac-DOTATATE) + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor Expressing Extensive-Stage Small-Cell Lung Cancer (IASLC-WCLC 2024) - P1 | "Preliminary pharmacokinetic findings indicate clearance and half-life comparable to previous studies of RYZ101 and 177 Lu-DOTATATE. Conclusions : There were no DLTs reported at DL1 (6.5 MBq) and the dose of RYZ101 has been escalated to the next dose level. The study is actively enrolling patients to receive RYZ101 at DL2 (8.3 MBq) and additional safety data will be presented once mature."

Back Pain • Cardiovascular • Fatigue • Heart Failure • Hematological Disorders • Infectious Disease • Influenza • Lung Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

RYZ101 (225Ac-DOTATATE) + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor-Expressing Extensive-Stage SCLC (IASLC-WCLC 2025) - P1 | "Conclusions : There were no DLTs reported at DL1 (6.5 MBq) or DL2 (8.3 MBq) and the RYZ101 dose was escalated to DL3 (10.2 MBq) with six patients dosed to date; the study has completed enrollment for dose escalation and is proceeding to dose expansion. Updated data will be presented."

Back Pain • CNS Disorders • Depression • Eosinophilia • Fatigue • Heart Failure • Immunology • Infectious Disease • Influenza • Lung Cancer • Musculoskeletal Pain • Neutropenia • Pneumonia • Psychiatry • Respiratory Diseases • Rheumatology • Septic Shock • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

Phase 1b portion of the ACTION-1 phase 1b/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177 Lu somatostatin analogue (SSA) therapy: Safety and efficacy findings. (ASCO-GI 2025) - P3 | "RYZ101 was well tolerated, and a fixed dose of 10.2 MBq was declared the recommended phase 3 dose. Initial data suggest promising efficacy and a manageable safety profile. Part 2 (phase 3) of the ACTION-1 trial is enrolling and will compare RYZ101 at 10.2 MBq every 8 weeks for 4 cycles with standard of care in patients with advanced SSTR2+ GEP-NETs progressing after 177Lu-labeled SSAs."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR • SSTR2

A phase 1 first-in-human, dose-escalation and -expansion study of RYZ401, a novel radiopharmaceutical therapy (RPT) labeled with actinium-225 (225Ac), in patients with neuroendocrine tumors (NETs) and other solid tumors expressing somatostatin receptors (SSTRs). (ASCO-GI 2026) - P1 | "Use of the α-emitter 225Ac as the radioactive component has shown promising results in clinical studies: initial data from ACTION-1 suggest promising efficacy for RYZ101, a first-in-class, highly potent α-emitting RPT, in patients with SSTR+ GEP-NETs progressing after 2–4 cycles of 177Lu-somatostatin analogs. RYZ401 dosimetry will be evaluated in a sub-study of 10−16 patients. Enrollment is ongoing in the USA."

Clinical • First-in-human • P1 data • Gastrointestinal Cancer • Oncology • Solid Tumor • SSTR

TRACY-1: Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: RayzeBio, Inc. | Trial completion date: Jan 2033 ➔ Nov 2033

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • SSTR

Dosimetry Results from the Phase 1b/3 ACTION-1 Trial of [225Ac]Ac-DOTATATE (RYZ101) in Patients with Somatostatin Receptor-Expressing, Well-Differentiated GEP-NETs. (PubMed, J Nucl Med) - P3 | "The 213Bi daughter mostly remained with DOTATATE in tumors, decaying at the same location as 221Fr. The favorable tumor-to-normal tissue absorbed dose ratio of [225Ac]Ac-DOTATATE supports its use in patients with SSTR-expressing GEP-NETs."

Journal • P1 data • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR • SSTR2

RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Joshua Palmer | Suspended ➔ Recruiting

Enrollment open • Brain Cancer • Meningioma • Oncology • Solid Tumor

RYZ101-101: Study of RYZ101 in Combination With SoC in Subjects With SSTR+ ES-SCLC (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: RayzeBio, Inc. | N=49 ➔ 21 | Trial completion date: Mar 2029 ➔ Jul 2027 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1 • SSTR

RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma (clinicaltrials.gov) - P1/2 | N=30 | Suspended | Sponsor: Joshua Palmer | Recruiting ➔ Suspended

Trial suspension • Brain Cancer • Meningioma • Oncology • Solid Tumor

ACTION-1: Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy (clinicaltrials.gov) - P3 | N=338 | Recruiting | Sponsor: RayzeBio, Inc. | Trial completion date: Jul 2028 ➔ Dec 2030

Trial completion date • Carcinoid Tumor • Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

TRACY-1: Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: RayzeBio, Inc. | Recruiting ➔ Active, not recruiting | N=124 ➔ 16

Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • SSTR

ACTION-1: Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy (clinicaltrials.gov) - P3 | N=288 | Recruiting | Sponsor: RayzeBio, Inc. | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Carcinoid Tumor • Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Solid Tumor • SSTR

RYZ101 (225Ac-DOTATATE) + carboplatin + etoposide + atezolizumab in treatment-naïve patients with somatostatin receptor-expressing (SSTR2+) extensive-stage small-cell lung cancer (ES-SCLC) (ESMO Asia 2025) - P1 | "The preliminary safety profile of RYZ101 + SoC for first-line treatment of patients with ES-SCLC was favorable, with no treatment discontinuations due to AEs and no DLTs. The RP2D was 10.2 MBq. Dose expansion has begun."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Joshua Palmer | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Meningioma • Oncology • Solid Tumor

RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Joshua Palmer

New P1/2 trial • Brain Cancer • Meningioma • Oncology • Solid Tumor

BMS, RayzeBio launch radiopharmaceutical manufacturing site in Indianapolis (Fierce Pharma) - "Bristol Myers Squibb has opened its radiopharmaceutical manufacturing facility in Indianapolis, which played a major role in the company’s $4.1 billion acquisition of RayzeBio in December 2023. The isotope and drug production plant is now fully operational, BMS said on Friday. CEO Chris Boerner helped cut the ribbon on the $160 million, 77,000-square foot complex, which is equipped to produce next-generation radiopharmaceutical cancer treatments based on the alpha-emitting isotope actinium-225 (Ac225)....RayzeBio’s top radiopharmaceutical candidate, RYZ101, is in phase 3 testing for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and early-stage development for small cell lung cancer. Last year, because of a shortage of actinium, RayzeBio halted enrolment in the phase 3 trial."

Commercial • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Small Cell Lung Cancer

RYZ101 (225Ac-DOTATATE) in patients with estrogen receptor-positive, human epidermal growth factor receptor 2–negative, locally advanced and unresectable, or metastatic breast cancer progressing after prior therapy: The phase 1b/2 TRACY-1 study. (ASCO 2025) - P1/2 | "Concomitant amino acid IV infusions (containing L-arginine and L-lysine) will be co-infused with RYZ101 for renal protection. The study is ongoing and enrolling patients in the USA."

Clinical • Metastases • P1/2 data • Breast Cancer • Endocrine Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • ER • HER-2 • SSTR • SSTR2

Study of RYZ101 in Combination With SoC in Subjects With SSTR+ ES-SCLC (clinicaltrials.gov) - P1 | N=49 | Recruiting | Sponsor: RayzeBio, Inc. | N=31 ➔ 49 | Trial primary completion date: Mar 2027 ➔ Jun 2027

Enrollment change • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1 • SSTR

Alpha radioligand therapy in neuroendocrine neoplasms: current landscape and spotlight on RYZ101. (PubMed, Future Oncol) - "While the advent and regulatory approval of beta emitting RLT such as 177Lu-DOTATATE has offered a valuable therapeutic option for patients with NETs, there is still very significant room to tap the maximal therapeutic potential of RLT. Yet, other alpha RLT agents are currently being investigated in both RLT-naïve as well-pre-treated patient populations. While long-term safety and efficacy data are awaited, alpha RLT agents such as RYZ101 offer a unique opportunity to enhance the therapeutic promise of RLT in NETs."

Journal • Review • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Study of RYZ101 in Combination with SoC in Subjects with SSTR+ ES-SCLC (clinicaltrials.gov) - P1 | N=31 | Recruiting | Sponsor: RayzeBio, Inc. | Trial completion date: Dec 2026 ➔ Mar 2029 | Trial primary completion date: Mar 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1 • SSTR

AcTRESS: A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients with Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Jules Bordet Institute | N=30 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Hematological Malignancies • Multiple Myeloma • Oncology

ACTION-1: Study of RYZ101 Compared with SOC in Pts W Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy (clinicaltrials.gov) - P3 | N=288 | Recruiting | Sponsor: RayzeBio, Inc. | Trial primary completion date: Jul 2025 ➔ Dec 2025

Trial primary completion date • Carcinoid Tumor • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

TRACY-1: Trial of 225Ac-DOTATATE (RYZ101) in Subjects with ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: RayzeBio, Inc. | Trial completion date: Jul 2029 ➔ Jan 2033 | Trial primary completion date: May 2028 ➔ Oct 2028

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

RYZ101 (225Ac-DOTATATE) ± pembrolizumab in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced and unresectable or metastatic breast cancer progressing after prior therapy: the phase 1b/2 TRACY-1 study (SABCS 2024) - "Concomitant amino acid IV infusions (containing L-arginine and L-lysine) will be co-infused with RYZ101 for renal protection. The study is expected to begin enrolment in July 2024."

IO biomarker • Metastases • P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • SSTR • SSTR2

ACTION-1 phase Ib/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors progressing after 177Lu somatostatin analogue therapy: Phase 1b safety/efficacy (NANETS 2024) - P3 | "Longer-term safety and efficacy data will be presented. Part 2 (phase 3) is enrolling and will compare RYZ101 at 10.2 MBq every 8 weeks for 4 cycles with standard of care in patients with advanced SSTR2+ GEP-NETs progressing following prior 177Lu-labeled SSAs."

Clinical • P1 data • Endocrine Cancer • Fatigue • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR • SSTR2