Tarveda Therapeutics Announces Results from Phase 1 Study of PEN-221 Presented at the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting

-- Evidence of antitumor activity observed --

-- Phase 2a study enrolling patients --

Watertown, MA, June 4, 2018 – Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing Pentarins™ as a new class of potent and selective medicines to treat a wide range of cancers, today announced Phase 1 results that were presented at the American Society for Clinical Oncology (ASCO) Annual Meeting from an ongoing Phase 1/2a study of PEN-221 in patients with somatostatin receptor 2 (SSTR2)-expressing neuroendocrine tumors (NET) or small cell lung cancer (SCLC). The results presented had a data cutoff date of February 23, 2018. As of April 11, 2018, four patients remained on study.

“PEN-221, our lead Pentarin miniature drug conjugate, is designed to rapidly penetrate deep into solid tumors where it is highly selective for the somatostatin receptor 2 and accumulates its potent DM1 payload,” said Richard Wooster, Ph.D., President of Research and Development and Chief Scientific Officer at Tarveda. “Based on the safety results and encouraging signs of antitumor activity seen in our Phase 1 dose escalation and safety study for PEN-221, 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."

The Phase 1 portion of the study was designed as a dose escalating study to assess safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PEN-221 in patients with SSTR2-expressing advanced neuroendocrine or small cell lung cancers. The results show that PEN-221 appears to be well-tolerated with evidence of antitumor activity seen in multiple patients. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) was established as 18mg and will be further evaluated in the Phase 2a portion of the study.

“There is a very real need for new treatment options for patients living with neuroendocrine tumors and small cell lung cancer,” said Melissa Johnson, M.D., Associate Director, Lung Cancer Research Program at Sarah Cannon Research Institute. “PEN-221, an SSTR2 directed drug conjugate linked to a DM1 cytotoxic payload, is an exciting and novel approach to treating patients with SSTR2 expressing tumors identified using biomarker imaging agents OctreoScan or Gallium-68 DOTATATE PET. PEN-221 was well tolerated by patients in this clinical trial. In addition, the encouraging signals of antitumor activity and prolonged stable disease further supports continuation of the study of PEN-221 in the Phase 2a trial.”

Phase 1 Trial Design

PEN-221 was administered as a one-hour, intravenous infusion once every three weeks to escalating cohorts of two to six patients with SSTR2 expressing advanced solid tumors including advanced gastroenteropancreatic, lung, thymus or other neuroendocrine tumors or small cell lung cancers or large cell neuroendocrine tumors of the lung. Safety was assessed by vital sign measurements, physical examinations, neurological examinations, ECOG performance status, documentation of adverse events, clinical laboratory tests, and electrocardiography. Disease response was assessed by duration of response and standard RECIST criteria.

Safety Data

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.

The majority of treatment-related/treatment-emergent adverse events were mild (Grade 1) to moderate (Grade 2) with the most common being fatigue (48%), nausea (48%), diarrhea (44%), and peripheral neuropathy (26%). There were single reports of Grade 3 peripheral neuropathy, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase and constipation at the 25mg dose. One patient at the 25mg dose experienced a Grade 3 drug induced liver injury.

The Maximum Tolerated Dose and Recommended Phase 2 Dose of PEN-221 is 18mg administered once every 3 weeks.

Efficacy data

There was preliminary evidence of antitumor activity:

• 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.
• Target lesion shrinkage leading to minor responses at the time of this data review were observed in 3/7 patients who had either a GI or pancreatic NET (dose range 8-18 mg).
• The only SCLC patient had SD for 12 weeks.

As of April 11, 2018, four patients remained in the Phase 1 portion of the study with stable disease of 5, 7, 12, 14 months respectively.

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 midgut neuroendocrine tumors, pancreatic neuroendocrine tumors, and small cell lung cancer (ClinicalTrials.gov Identifier: NCT02936323).

About Pentarins™
Tarveda is developing Pentarins™, potent and selective miniature drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cancer cell killing agent through a tuned chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for rapid and deep penetration into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell killing payload inside the cancer cells for efficacy.

About Tarveda Therapeutics, Inc.

Tarveda Therapeutics, Inc. discovers and develops Pentarins™, a new class of potent and selective miniature drug conjugates with enhanced targeting capabilities for the treatment of a wide range of solid tumor cancers. Tarveda’s lead Pentarin drug candidate, PEN-221, is a miniature drug conjugate that targets the somatostatin receptor 2 (SSTR2) for treatment of patients with neuroendocrine, small cell lung, prostate, and other cancers that express SSTR2. 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, the highly potent active metabolite of irinotecan. Tarveda’s strategy includes developing its own proprietary Pentarins as well as applying the Pentarin platform to enhance the effectiveness of the targeting moieties and novel payloads of pharmaceutical collaborators. www.tarveda.com