Tarveda Therapeutics Presents Promising Phase 2 Data of PEN-221 in Gastrointestinal Mid-gut Neuroendocrine Tumors

Results presented at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting

PEN-221 to be further evaluated in a randomized trial in patients with gastrointestinal neuroendocrine tumors

Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin^® miniature drug conjugates, today announced data from the gastrointestinal (GI) mid-gut neuroendocrine tumors (NETs) cohort of its Phase 2 clinical trial of PEN-221, presented at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting.

"The results presented at ASCO from the gastrointestinal mid-gut neuroendocrine cohort of the PEN-221 trial show that PEN-221 was well tolerated and demonstrated efficacy exceeding its clinical efficacy goals with a clinical benefit rate of 88.5% and median progression-free survival of 9 months," said Jeffrey Bloss, M.D., Chief Medical Officer of Tarveda. "We are encouraged by the safety and efficacy shown by PEN-221 in GI mid-gut NETs and are developing a randomized trial to further evaluate PEN-221 in this patient population."

"Gastrointestinal neuroendocrine tumors are a disease with a significant unmet need. While targeting SSTR2 receptors has been an effective strategy in treating GI NETs, there remains a need for additional therapies which delay disease progression and prolong patients' lives," said Daniel M Halperin, M.D., Assistant Professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "PEN-221 selectively binds with high affinity to SSTR2 expressed on neuroendocrine tumors, where it releases its DM1 payload directly into the tumor cells, causing cell cycle arrest and apoptosis. This approach demonstrated encouraging efficacy results in the GI mid-gut NET cohort of the Phase 2 trial and was well tolerated by patients."

The results presented had a data cutoff of July 31, 2020 and five patients remained on study at the time of the cutoff. Of the 32 patients included in these results, the first nine were treated at the Phase 1 determined maximum tolerated dose of 18 mg. After review of the safety, tolerability, and pharmacokinetic data, the regimen was amended to 8.8 mg/m2 for all subsequent patients to achieve more uniform exposures across all patients and reduce toxicity in patients with lower body-surface-area (BSA).

Trial Design

PEN-221 was administered as a one-hour intravenous infusion once every three weeks to patients with advanced SSTR2+ GI mid-gut NETs with documented radiographic progression within the six months prior to enrollment. Preliminary efficacy was assessed using RECIST 1.1. A clinically meaningful efficacy result was defined as a clinical benefit rate (CBR) > 75% and a median progression-free survival (mPFS) > 8 months.

Safety Data

A safety analysis of 32 patients demonstrated that PEN-221 was well tolerated when dosed at 8.8 mg/m2. The most frequent treatment related adverse events of any Grade were fatigue (39%), nausea (38%), diarrhea (35%), decreased appetite (30%), infusion reaction (24%), aspartate transaminase (AST)/alanine transaminase (ALT)/alkaline phosphatase (Alk Phos) increase (24%), and peripheral neuropathy (21%). 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%).

Efficacy Data

PEN-221 demonstrated efficacy at 8.8 mg/m2 with a CBR of 88.5% and mPFS of 9 months. Of the 26 patients who were evaluable for response, 23 (88.5%) had stable disease (SD) reported as their best response and target lesion shrinkage was observed in 10 (38%) patients.

A randomized trial of PEN-221 in GI mid-gut NET patients is now in development.

The poster presentation is available on demand on the ASCO website beginning on June 4, 2021 at 9:00 AM ET. Details of the poster presentation are as follows:

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.

Abstract Number: 4110

About PEN-221

PEN-221 is a miniature drug conjugate consisting of a peptide ligand, that is highly selective in targeting SSTR2, joined through a cleavable linker to the potent cytotoxic payload DM1. SSTR2 is overexpressed on the cell surface of a range of solid tumors including neuroendocrine tumors and small cell lung cancers. In non-clinical experiments, PEN-221 binds with high affinity and selectivity to SSTR2. On binding, PEN-221 triggers SSTR2 internalization resulting in the accumulation of the DM1 payload in tumor cells followed by cell cycle arrest and apoptosis.

PEN-221 is being evaluated in Phase 2a expansion cohorts enrolling patients with mid-gut neuroendocrine tumors, pancreatic neuroendocrine tumors, and small cell lung cancer (ClinicalTrials.gov Identifier: NCT02936323).

About Tarveda Therapeutics^®, Inc.

Tarveda Therapeutics is a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin^® miniature drug conjugates, for the treatment of patients with various solid tumor malignancies. Tarveda's Pentarin^® miniature drug conjugates are designed to deeply penetrate solid tumors, selectively bind to the desired tumor targets and accumulate their anti-cancer payloads directly in tumor cells. The payload is retained and then released over time causing the anti-cancer payload to become active in the tumor.

Tarveda currently has two Pentarin^® miniature drug conjugates in clinical trials. Its first clinical program, PEN-866, is the initial candidate from its Heat Shock Protein 90 ("HSP90") binding miniature drug conjugate platform. HSP90 is a molecular chaperone that is highly activated in the harsh tumor environment, but which remains relatively dormant in normal tissue. Up to 75% of solid tumors have activated HSP90, and small molecule drugs that target activated HSP90 have desirable binding properties in solid tumors. PEN-866 is a miniature drug conjugate that selectively binds to the activated form of HSP90 linked to a topoisomerase 1 inhibitor (SN-38), a potent anti-cancer payload. PEN-866 has commenced its Phase 2a trial in various types of solid tumors. In addition to PEN-866, Tarveda is developing additional miniature drug conjugates on its HSP90 binding miniature drug conjugate platform to target other promising anti-cancer payloads such as kinase inhibitors and radioisotopes to solid tumors. Tarveda's second clinical program, PEN-221, is a Pentarin^® miniature drug conjugate currently in clinical evaluation for the treatment of patients with certain neuroendocrine solid tumors expressing SSTR2 on the cell surface. PEN-221 is a miniature drug conjugate consisting of a peptide ligand, that is highly selective in targeting SSTR2, joined through a cleavable linker to the potent cytotoxic payload DM1. PEN-221 is currently progressing through its Phase 2a trial. For more information regarding Tarveda, go to: http://www.tarvedatx.com.

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