Lutetium-177 PNT6555 / Eli Lilly - LARVOL DELTA

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER) (clinicaltrials.gov) - P1 | N=20 | Terminated | Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company | Trial completion date: Dec 2026 ➔ Oct 2024 | Active, not recruiting ➔ Terminated; Business decision

Trial completion date • Trial termination • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company | N=10 ➔ 24

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

FRONTIER: FAPi Radioligand OpeN-label, phase 1 study to evaluate safety, Tolerability and dosImetry of [Lu-177]-PNT6555; a dose Escalation study for tReatment of patients with select solid tumors (SNMMI 2024) - P1 | "Normal organ dosimetry and the safety profile from FRONTIER clearly demonstrate the potential of FAP-targeted radioligand therapy as a precision treatment modality capable of minimal off-target effects. However, the low absorbed tumor doses observed suggest tumor retention time was limited, in sharp contrast to the observations in preclinical models. Improved preclinical approaches may be needed to successfully translate this promising treatment modality to the clinic."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genetic Disorders • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs • FAP

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER) (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: POINT Biopharma | Recruiting ➔ Active, not recruiting | N=30 ➔ 10

Enrollment change • Enrollment closed • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

POINT Biopharma Reports Second Quarter 2023 Financial Results and Provides Business Highlights (GlobeNewswire) - "Enrollment in PNT2002's phase 3 SPLASH trial (NCT04647526) is complete and topline data is expected in the fourth quarter of 2023. Six trial sites remain open for recruitment to complete a separate pharmacokinetic sub-study....In May 2023, enrollment in cohort 3 of the phase 1 FRONTIER trial (NCT05432193) began, and a total of seven participants have been dosed with 177Lu-PNT6555 to date. We continue to anticipate data from the full FRONTIER study to be available in the first half of 2024....PNT2001: 225Ac-labelled next-generation PSMA-targeted radioligand therapy...We anticipate a health authority submission in the fourth quarter of 2023, and expect the first patient dosed in this trial to be in the first quarter of 2024."

P1 data • P3 data: top line • Regulatory • Trial status • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

POINT Biopharma Expands Its Research with Next-Generation Isotopes, Publishing New Preclinical Data at SNMMI’s Annual Congress (GlobeNewswire) - "POINT Biopharma Global Inc...announced the publication of preclinical data from their pan-cancer, fibroblast activation protein-α (FAP)-targeted program, PNT2004, at the 2023 Annual Meeting of the Society of Nuclear Medicine & Molecular Imaging (SNMMI), taking place June 24-27, 2023, in Chicago, IL. PNT6555, the lead candidate in the PNT2004 program, led to complete and durable tumor regression and improved survival in HEK-mFAP tumor-bearing mice when chelated to any one of the three radioisotopes studied: lutetium-177 (177Lu), actinium-225 (225Ac), and terbium-161 (161Tb). Additionally, 177Lu-PNT6555 in combination with anti-PD-1 checkpoint blockade was assessed in the aggressive, immunocompetent CT26-mFAP mouse model and demonstrated a significant survival benefit compared to either treatment alone."

Preclinical • Oncology • Solid Tumor

FRONTIER: FAPi radioligand open-label, phase 1 study to evaluate safety, tolerability and dosimetry of [Lu-177]-PNT6555—A dose escalation study for treatment of patients with select solid tumors. (ASCO 2023) - P1 | "Pre-clinical characterization of the novel fibroblast activation protein (FAP) targeting ligand PNT6555 for the imaging and therapy of cancer. Presented at SNMMI Annual Meeting April 2022; Vancouver, BC, Canada.Clinical trial information: NCT05432193."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genetic Disorders • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • FAP

POINT Biopharma Announces FRONTIER Trial-in-Progress Poster Presentation at ASCO (GlobeNewswire) - "POINT Biopharma Global...announced an upcoming poster presentation for the Company’s ongoing phase 1, pan-cancer, fibroblast activation protein-α (FAP-α)-targeted trial, FRONTIER (NCT05432193), at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place June 2-6, 2023, in Chicago, IL. The Trial-in-Progress poster will include trial background information, study design considerations, and a cohort enrollment status update."

Trial status • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

POINT Biopharma Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Highlights (GlobeNewswire) - "Enrollment in cohort 2 of FRONTIER began in December 2022 and we expect enrollment in cohort 3 to begin in the second quarter of 2023. A total of six participants have been dosed with 177Lu-PNT6555 to date. We anticipate data from the full FRONTIER study to be available in the first half of 2024."

Enrollment status • P1 data • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

POINT Biopharma Releases New Preclinical Data Supporting the Combination of 177Lu-PNT6555 with Immunotherapy (GlobeNewswire) - "POINT Biopharma Global...released new preclinical data from the Company’s pan-cancer fibroblast activation protein-α (FAP-α) targeted program, PNT2004. The preclinical study focused on assessing the potential of the lead candidate in the PNT2004 clinical program, 177Lu-PNT6555, in combination with anti-PD-1 immunotherapy. The CT26-mFAP tumor model used expresses low levels of FAP, grows aggressively, and is insensitive to anti-PD-1 immunotherapy. The study found that combination treatment with 177Lu-PNT6555 and anti-PD-1 resulted in a significant survival benefit, as compared to either treatment independently."

Preclinical • Oncology

Lantheus and POINT Biopharma Announce Strategic Collaboration and Exclusive License Agreements for the Commercialization of PNT2002 & PNT2003 (GlobeNewswire) - "'We are excited to continue developing and scaling our manufacturing capabilities to support the PNT2002 and PNT2003 launches and continue development of PNT2004, our pan-cancer FAP-α program, which is currently in Phase 1, and PNT2001, our actinium-225 next-generation PSMA program which is expected to begin Phase 1 in 2023'."

Launch • New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

POINT Biopharma Reports Third Quarter 2022 Financial Results and Announces Strategic Collaboration and Exclusive License Agreements with Lantheus Holdings (GlobeNewswire) - "FRONTIER is evaluating PNT6555 (the lead candidate of PNT2004) in approximately 30 patients in five FAP-avid cancer indications: colorectal, pancreatic, esophageal, melanoma, and soft tissue sarcomas....Phase 1 data from FRONTIER is expected in H1 2024."

P1 data • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: POINT Biopharma | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: POINT Biopharma

New P1 trial • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

POINT Biopharma Reports First Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "The Company filed a clinical trial application (CTA) with Health Canada at the end of the first quarter of 2022 for PNT6555, the lead of the pan-cancer PNT2004 fibroblast activation protein-alpha (FAP-alpha) targeted program. The clinical trial for PNT2004 is expected to first initiate in Canada in summer 2022....The Company remains on track to launch its in-house n.c.a. 177Lu manufacturing program in 2023."

Canadian regulatory • Commercial • Oncology • Solid Tumor

POINT Biopharma Unveils FRONTIER: A Pan-Cancer FAP-α Targeted Clinical Program (GlobeNewswire) - "A No-Objection Letter from Health Canada has been received, enabling the initiation of PNT2004’s Phase 1 therapeutic trial using 68Ga-PNT6555 for imaging and 177Lu-PNT6555 for therapy...POINT Biopharma Global Inc...announced details of the initial clinical trial in the Company’s pan-cancer Fibroblast Activation Protein-α (FAP-α) targeted program PNT2004, FRONTIER...The Phase 1 clinical trial is expected to commence in summer 2022 in Canada and will use a gallium-68 (68Ga)-based PNT6555 molecular imaging agent to select patients to receive a no-carrier-added (n.c.a.) lutetium-177 (177Lu)-based PNT6555 therapeutic agent...The Phase 1 clinical protocol will evaluate PNT6555 in ~30 patients in five FAP-avid cancer indications: colorectal, pancreatic, esophageal, melanoma, and soft tissue sarcoma....The company expects to present initial imaging and dosimetry data in early 2023."

Clinical protocol • New P1 trial • P1 data • Trial initiation date • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

POINT Biopharma to Present on its Pan-Cancer FAP-Alpha Targeted Program at the AACR Annual Meeting (GlobeNewswire) - "POINT Biopharma Global...will present a poster on its FAP-Alpha targeted program PNT2004 at the American Association for Cancer Research (AACR) 2022 Annual Meeting....Efficacy studies with 177Lu-PNT6555 or 225Ac-PNT6555 demonstrate compelling and dose-responsive inhibition of HEK-mFAP tumor growth....In animal studies, PNT6555 has successfully delivered large doses of radiation to tumors with limited uptake observed in non-target tissues."

Preclinical • Oncology • Solid Tumor

POINT Biopharma Provides Early-Stage Program Updates (GlobeNewswire) - "The Company recently completed a pre-CTA (Clinical Trial Application) meeting with Health Canada regarding the development pathway and clinical study design for the upcoming Phase 1 trial, and expects to file a CTA with Health Canada at the end of Q1 2022. The clinical trial is expected to commence in summer 2022 in Canada and will use a gallium-68 (Ga-68)-based PNT6555 molecular imaging agent to select patients to receive a no-carrier-added (n.c.a.) lutetium-177 (Lu-177)-based PNT6555 therapeutic agent. Additional preclinical studies in syngeneic and PDX models for monotherapy and combination treatment are in development and include other therapeutic isotopes such as actinium-225 (Ac-225)."

Canadian regulatory • New P1 trial • Preclinical • Oncology