nendratareotide uzatansine (PEN-221) / Tarveda Therap - LARVOL DELTA

CS5005: A novel SSTR2-targeted antibody-drug conjugate (ADC) with robust antitumor activity in preclinical studies (AACR 2025) - "In SCLC, SSTR2-targeted therapies, including RAZ101 (225Ac bearing RDC), PEN221 (peptide drug conjugate) etc., have shown encouraging clinical results. CS5005 represents a promising SSTR2-targeted ADC for the treatment of advanced solid tumors. The preclinical findings support further IND-enabling studies and clinical investigations of CS5005 as a novel therapeutical option."

Preclinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

SSTR2 as an anatomical imaging marker and a safety switch to monitor and manage CAR T cell toxicity. (PubMed, Sci Rep) - "Treatment with PEN-221 rapidly reduced the abundance of CAR T cells, decreasing the severity of xenogeneic graft-versus-host disease (GvHD), and prolonged survival. Our study supports the development of SSTR2 as a single genetic marker for CAR T cells that is readily applicable to humans both for anatomical detection of T cell distribution and an image-guided safety switch for rapid elimination of CAR T cells."

CAR T-Cell Therapy • Journal • Graft versus Host Disease • Immunology • Oncology • Solid Tumor • ICAM1 • IL12A • SSTR • SSTR2

[VIRTUAL] The safety and efficacy of PEN-221 somatostatin analog (SSA)-DM1 conjugate in patients (PTS) with advanced GI mid-gut neuroendocrine tumor (NET): Phase 2 Results (NANETS 2021) - "PEN-221 appears well tolerated at 8.8 mg/m2 q 3 weeks and has demonstrated efficacy exceeding its clinical efficacy goals with a CBR of 88.5% and a mPFS of 9 months."

Clinical • P2 data • Anemia • Endocrine Cancer • Fatigue • Hematological Disorders • Lung Cancer • Neuroendocrine Tumor • Oncology • Pain • Small Cell Lung Cancer • Solid Tumor • ALK • SSTR2

"PEN-221 Demonstrates Clinical Benefit in Gastrointestinal NETs @MDAndersonNews #NANETSGoesVirtual2021 #NANETS2021 https://t.co/s9Fi69ORg3" (@OncLive)

Clinical • Gastrointestinal Disorder

Epigenetic modulation of SSTR2 expression provides the potential to broaden PEN-221 treatment population (AACR 2019) - P1/2; "In addition, a pharmacodynamic assessment of epigenetic modulator treatment on SSTR2 expression levels was performed. These data demonstrate that combination of PEN-221 and epigenetic modulators provide greater efficacy than single agent activity alone and support the evaluation of such combinations in the clinical setting."

Clinical

First in human phase 1/2a study of PEN-221 somatostatin analog (SSA)-DM1 conjugate for patients (PTS) with advanced neuroendocrine tumor (NET) or small cell lung cancer (SCLC): Phase 1 results. (ASCO 2018) - P1/2; "PEN-221 appears well tolerated with preliminary evidence of antitumor activity."

Clinical • P1/2 data • Neuroendocrine Tumor • Small Cell Lung Cancer

[VIRTUAL] The safety and efficacy of PEN-221 somatostatin analog (SSA)-DM1 conjugate in patients (PTS) with advanced GI mid-gut neuroendocrine tumor (NET): Phase 2 results. (ASCO 2021) - P1/2 | "PEN-221 appears well tolerated at 8.8 mg/m2 q 3 weeks and has demonstrated efficacy exceeding its clinical efficacy goals with a CBR of 88.5% and a mPFS of 9 months . A randomized trial of PEN-221 in GI mid-gut NET patients is now in development."

Clinical • P2 data • Endocrine Cancer • Fatigue • Lung Cancer • Neuroendocrine Tumor • Oncology • Pain • Small Cell Lung Cancer • Solid Tumor • 5-Hydroxyindoleacetic Acid • ALK • CGA, CHGA • CTCs • ENO2 • SSTR2

Tarveda Therapeutics Presents Promising Phase 2 Data of PEN-221 in Gastrointestinal Mid-gut Neuroendocrine Tumors (Businesswire) - P1/2a, N=89; NCT02936323; Sponsor: Tarveda Therapeutics; "A safety analysis of 32 patients demonstrated that PEN-221 was well tolerated when dosed at 8.8 mg/m2...Only 14 (10%) of these events were Grade 3 or greater. Grade 3 treatment related adverse events, which were reported in two or more patients, included fatigue (7.6%), ALT/AST/Alk Phos increase (7.6%), and peripheral neuropathy (3%)....PEN-221 demonstrated efficacy at 8.8 mg/m2 with a CBR of 88.5% and mPFS of 9 months."

P2 data • Neuroendocrine Tumor • Oncology

Tarveda Therapeutics to Present Data from Phase 2 Study of PEN-221 at 2021 ASCO Annual Meeting (Businesswire) - "Tarveda Therapeutics, Inc....announced that the company will present data from its Phase 2 clinical trial of PEN-221 at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting occurring virtually June 4-8, 2021....Title: The safety and efficacy of PEN-221 somatostatin analog (SSA)-DM1 conjugate in patients (PTS) with advanced GI mid-gut neuroendocrine tumor (NET): Phase 2 results."

P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers (clinicaltrials.gov) - P1/2; N=89; Completed; Sponsor: Tarveda Therapeutics; Active, not recruiting ➔ Completed

Clinical • Trial completion • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SSTR

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. (PubMed, Nat Commun) - P=N/A | "Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival."

Journal • Epstein-Barr Virus Infection • Head and Neck Cancer • Infectious Disease • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer. (PubMed, Mol Cancer Ther) - "The unique attributes of the miniaturized drug conjugate allowed for deep tumor penetration and limited plasma exposure that may enable long-term dosing, resulting in durable tumor control. Collectively, these data suggest potential for antitumor activity of PEN-221 in patients with SSTR2-positive SCLC."

Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers (clinicaltrials.gov) - P1/2; N=90; Active, not recruiting; Sponsor: Tarveda Therapeutics; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Thoracic Cancer

Tarveda Therapeutics to present data from phase 1 study of PEN-221 at the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting (Businesswire) - P1/2a, N=90; NCT02936323; Sponsor: Tarveda Therapeutics; "Tarveda Therapeutics, Inc....announced that it will present [Title: First in human phase 1/2a study of PEN-221 somatostatin analog (SSA)-DM1 conjugate for patients (PTS) with advanced neuroendocrine tumor (NET) or small cell lung cancer (SCLC): Phase 1 results.] Phase 1 results from a Phase 1/2a study of PEN-221 in patients with neuroendocrine tumors or small cell lung cancer at the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting occurring June 1-5, 2018 in Chicago IL."

P1 data • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Tarveda Therapeutics announces results from phase 1 study of PEN-221 presented at the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting (Businesswire) - P1, N=23; NCT02936323; Sponsor: Tarveda Therapeutics; "we have initiated the Phase 2a portion of our Phase 1/2a trial of PEN-221 to explore its potential in treating patients with gastrointestinal midgut and pancreatic neuroendocrine tumors as well as small cell lung cancer...A safety analysis of all 23 patients demonstrated that PEN-221 was well-tolerated with no dose limiting toxicities up to 18mg. Two of three patients administered 25mg of PEN-221 experienced dose limiting toxicities that rapidly and fully resolved following treatment discontinuation....Among 15 NET patients who were evaluable for response, 11 had stable disease (SD) at 9 weeks, of whom 8 were sustained for 18–45 weeks, including 2 ongoing patients with SD for 44 and 45 weeks at the time of this data review."

P1 data • Trial status • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Discovery of an SSTR2-targeting maytansinoid conjugate (PEN-221) with potent activity in vitro and in vivo. (PubMed, J Med Chem) - "PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 is currently under evaluation in human clinical trials."

Journal • Preclinical

Tarveda Therapeutics publishes results of preclinical studies evaluating PEN-221 as a treatment for small cell lung cancer in Molecular Cancer Therapeutics (Businesswire) - “Tarveda Therapeutics®, Inc….announced the publication of several preclinical studies evaluating PEN-221 as a novel therapeutic for the treatment of small cell lung cancer (SCLC). The publication, ‘Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer,’ was published in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research….We were encouraged by these results and initiated the Phase 2a portion of the study, which is currently enrolling patients with results expected in 2020.’”

P2 data • Preclinical

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers (clinicaltrials.gov) - P1/2; N=90; Recruiting; Sponsor: Tarveda Therapeutics; Trial completion date: Dec 2019 ➔ Dec 2020; Trial primary completion date: Jun 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date

Tarveda Therapeutics, Inc Company Presentation (BIO 2019) - "PEN-221 comprises a highly selective peptide for SSTR2 conjugated to the potent cytotoxic payload, DM1, through a tuned cleavable linker. Tarveda is also advancing its Pentarin HSP90 drug conjugate platform with lead drug candidate PEN-866, which is a miniature drug conjugate that selectively binds to the intracellular target, Heat Shock Protein 90 (HSP90), and is linked to the payload SN-38, a potent topoisomerase I inhibitor."

Tarveda Therapeutics to present nonclinical data on PEN-221 in combination with epigenetic modulation at the 2019 AACR Annual Meeting (Businesswire) - “Tarveda Therapeutics…announced that the company will present nonclinical data on PEN-221 at the 2019 American Association for Cancer Research (AACR) Annual Meeting, occurring March 29 – April 3, 2019 in Atlanta, GA…The data show that an HDAC inhibitor increases the tumor expression of SSTR2 with synergy of efficacy."

Preclinical