locnartecan (PEN-866) / Tarveda Therap, Madrigal Pharma, SciClone, National Cancer Institute - Bethesda - LARVOL DELTA

Vincristine and Temozolomide in Combination With PEN-866 for Adolescents and Young Adults With Relapsed or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=64 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Ewing Sarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • UGT1A1

First in human phase I/IIa study of PEN-866, a heat shock protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumours: Phase I results (ESMO 2019) - P1/2; "PEN-866 appears well tolerated with an expected adverse event profile and preliminary evidence of antitumor activity. PEN-866 will be evaluated in phase 2a expansion cohorts (NCT03221400). Clinical trial identification: NCT03221400 July 18, 2017."

Clinical • P1/2 data

PEN-866 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=340 | Recruiting | Sponsor: Tarveda Therapeutics | Trial completion date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2021 ➔ Jan 2023

Trial completion date • Trial primary completion date • Anal Carcinoma • Cervical Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer • HSP90AA1

[VIRTUAL] Characterization of PEN-866, a Heat Shock Protein 90 (HSP90) binding conjugate of SN-38, in patient plasma and tumors from the first in human study (AACR-I 2020) - "PEN-866 has an extended plasma half-life in patients with advanced solid malignancies and showed good stability in circulation with limited plasma exposure of the payload SN-38. Analysis of tumor biopsies up to 6 days after dosing demonstrated significant accumulation and extended exposures of PEN-866 and SN-38 within the tumor tissue that exceed plasma exposures."

Clinical • P1 data • HSP90AA1

[VIRTUAL] Pen-866, a miniature drug conjugate of a heat shock protein 90 (HSP90) ligand linked to SN38 for patients with advanced solid malignancies: Phase I and expansion cohort results. (ASCO 2020) - P1/2 | "PEN-866 was well tolerated and demonstrated preliminary evidence of antitumor activity. PEN-866 will be evaluated in Phase 2a expansion cohorts enrolling multiple solid tumors (NCT03221400). Research Funding: Tarveda Therapeutics, Inc."

Clinical • P1 data • Anal Carcinoma • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Solid Tumor • Squamous Cell Carcinoma • HSP90AA1

Tarveda Therapeutics and SciClone Pharmaceuticals Expand Partnership by Entering into a License Agreement for HSP90-PI3K Miniature Drug Conjugates in Greater China (Businesswire) - "Tarveda Therapeutics...announced that the company has entered into a collaboration and license agreement with SciClone Pharmaceuticals (Holdings) Limited ('SciClone'). Pursuant to the license agreement, Tarveda has granted an exclusive license permitting SciClone to develop, manufacture and commercialize a preclinical-stage product portfolio of miniature drug conjugates that consist of a phosphoinositide 3-kinase (PI3K) inhibitor (undisclosed) payload moiety, a linker and a heat shock protein 90 (HSP90) binding moiety in Greater China, including Mainland China, Hong Kong, Macau and Taiwan....This license agreement builds on Tarveda and SciClone’s existing exclusive licensing agreement signed in March 2020 to partner in Greater China for PEN-866...in solid tumors."

Licensing / partnership • Oncology • Solid Tumor

Sarah Cannon to present latest cancer research insights at ASCO20 Virtual Meeting (Businesswire) - "Sarah Cannon announced that it will present its latest cancer research insights at the American Society of Clinical Oncology’s (ASCO®) Annual Meeting being held virtually May 29 – 31, 2020. This year, Sarah Cannon’s drug development and research expertise is featured through more than 110 abstracts and presentations, including data from more than 50 phase 1 studies....Jesus Berdeja, MD...is the discussant on the plenary session focused on 'Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide, and Dexamethasone for Initial Therapy of Newly Diagnosed Multiple Myeloma' on Sunday, May 31 from 12-2:30 PM CT. Dr. Berdeja will also highlight data in an oral presentation on 'Update of CARTITUDE-1: A Phase Ib/II Study of JNJ-4528, a B-Cell Maturation Antigen-Directed CAR-T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma.' (Abstract 8505)."

Clinical data • Breast Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Indolent Lymphoma • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Rectal Cancer • Small Cell Lung Cancer • Solid Tumor

Vincristine and Temozolomide in Combination With PEN-866 for Adolescents and Young Adults With Relapsed or Refractory Solid Tumors (clinicaltrials.gov) - P1/2; N=64; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • Combination therapy • New P1/2 trial • Ewing Sarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • UGT1A1

PEN-866 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2; N=150; Recruiting; Sponsor: Tarveda Therapeutics

Clinical • New P1/2 trial • Anal Carcinoma • Cervical Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer • HSP90AA1

PEN-866 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2; N=260; Recruiting; Sponsor: Tarveda Therapeutics; N=150 ➔ 260

Clinical • Enrollment change • Anal Carcinoma • Cervical Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Thoracic Cancer • Vulvar Cancer • HSP90AA1

PEN-866 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2; N=150; Recruiting; Sponsor: Tarveda Therapeutics; Trial completion date: Jun 2020 ➔ Jun 2022; Trial primary completion date: Dec 2019 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Anal Carcinoma • Cervical Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer • HSP90AA1

Combination of the miniature drug conjugate PEN-866 with PARP inhibitors as a rational approach to overcoming limitations of PARP inhibitor monotherapy (AACR 2018) - "PEN-866 is a novel miniature drug conjugate comprised of a Heat Shock Protein 90 (HSP90) targeting ligand attached through a cleavable linker to SN-38, the active metabolite of the approved topoisomerase I inhibitor, irinotecan. These data demonstrate that combination of PEN-866 and PARP inhibitors provide greater efficacy than single agent activity alone, including BRCA wildtype tumors, and support the evaluation of such combinations in the clinical setting. The authors acknowledge David Proia, Weiwen Ying and others from Synta Pharmaceuticals who contributed to this work."

BRCA Biomarker • Monotherapy • PARP Biomarker • Ovarian Cancer

Tarveda Therapeutics reports complete data from phase 1 portion of phase 1/2a study of PEN-866 to be presented at the ASCO20 virtual scientific program (Businesswire) - P1/2, N=260; NCT03221400; Sponsor: Tarveda Therapeutics; "PEN-866 was well-tolerated, demonstrated a high therapeutic index, and showed evidence of anti-tumor activity across multiple tumors and dose ranges (wide therapeutic range), including one partial response. The data also confirm the favorable pharmacokinetic profile of PEN-866 and its ability to engage with its intended target and concentrate delivery of its toxic SN-38 payload intra-tumorally. The full results of the Phase 1 portion of the Phase 1/2a study will be presented at the American Society for Clinical Oncology’s ASCO20 Virtual Scientific Program..."

P1 data • Oncology • Solid Tumor

Tarveda Therapeutics to present data from first in human study of PEN-866 at the 2020 AACR Virtual Annual Meeting (Businesswire) - “Tarveda Therapeutics, Inc…announced that the company will present data from its first in human study of PEN-866 at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting, occurring April 27-28, 2020. PEN-866 is the initial clinical program from Tarveda’s HSP90 binding miniature drug conjugate platform, which is designed to bind to activated Heat Shock Protein 90 (HSP90) to accumulate and release its potent topoisomerase 1 inhibitor (SN-38) payload in solid tumors.”

P1 data • Oncology • Solid Tumor

Tarveda Therapeutics presents pharmacokinetic and tumor biopsy data from first in human study of PEN-866 at the 2020 AACR virtual annual meeting (Businesswire) - P1/2, N=260; NCT03221400; Sponsor: Tarveda Therapeutics; "Tarveda Therapeutics...presented new pharmacokinetic and target engagement data from its Phase 1 study of PEN-866 in patients with solid tumor malignancies at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting...The poster...showcased confirmatory pharmacokinetics of PEN-866 in patient plasma and highlighted data from two patient biopsies, which confirmed higher concentrated levels of the PEN-866 conjugate and SN-38 payload in tumor relative to plasma."

P1 data • PK/PD data • Oncology • Solid Tumor

Tarveda Therapeutics and SciClone Pharmaceuticals International Establish licensing agreement for PEN-866 in Greater China (Businesswire) - "Tarveda Therapeutics...which it refers to as Pentarin® miniature drug conjugates, for the treatment of patients with various solid tumor malignancies, and SciClone Pharmaceuticals International Ltd., ('SciClone') today announced that they have entered into a licensing agreement for PEN-866, the initial clinical program from Tarveda’s HSP90 binding miniature drug conjugate platform, which is designed to bind to the activated form of Heat Shock Protein 90 (HSP90) to accumulate and release its potent topoisomerase 1 inhibitor (SN-38) payload in solid tumors."

Licensing / partnership

"#TarvedaTherapeutics and #SciClonePharmaceuticals International Establish Licensing Agreement for #PEN866 in Greater China https://t.co/ORR5i7b8IQ" (@1stOncology)

M&A

Tarveda Therapeutics presents data from the phase 1 portion of a phase 1/2a study of PEN-866 at the European Society for Medical Oncology (ESMO) Congress 2019 (Businesswire) - P1/2a, N=150; NCT03221400; Sponsor: Tarveda Therapeutics; "'Investigating new treatment options for patients who are not responding to standard therapies is central to our research efforts,' said Johanna Bendell, M.D...Results of the study show that PEN-866 was well tolerated with no dose limiting toxicities (DLTs) in the first four cohorts (30-240 mg). One DLT was observed in cohort 5 (360 mg) and was resolved with dose reduction. 2 DLTs were observed in cohort 7 (200 mg/m2). One fatal event of dehydration occurred 11 days following the last dose of PEN-866."

P1/2 data

Tarveda Therapeutics to present at upcoming conferences (Businesswire) - "At ESMO, Johanna Bendell will present results from an ongoing Phase 1 study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of PEN-866 in patients with progressive, advanced solid malignancies. At the time of this reporting, a number of patients remain on the study, therefore this does not represent the final data set."

P1 data

Tarveda Therapeutics to present at upcoming conferences (Businesswire) - P1/2, N=150; NCT03221400; Sponsor: Tarveda Therapeutics; “Tarveda Therapeutics®, Inc….announced that the company will present results from the Phase 1 portion of a Phase 1/2a study of PEN-866 in patients with advanced solid malignancies at the European Society for Medical Oncology (ESMO) Congress 2019, occurring September 27 – October 1, in Barcelona, Spain.”

P1/2 data

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."