Triphase Accelerator Announces Positive Updated Phase 1 Data with TRPH-222 in Non-Hodgkin’s Lymphoma

• High response rates: ORR of 54% and a CR rate of 38%
• Durable responses: ~25 months median duration of response
• Favourable safety profile: AEs predominantly low grade, tolerable, easily managed, and reversible
• Easily administered in the community setting

TORONTO and SAN DIEGO, Feb. 22, 2022 (GLOBE NEWSWIRE) — Triphase Accelerator, a private drug development company dedicated to advancing novel compounds through clinical proof-of-concept, today announced updated results from its Phase 1 multi-center, open-label, monotherapy study of TRPH-222 in heavily pre-treated patients with relapsed and/or refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). This investigational antibody-drug conjugate (ADC) was designed to deliver the microtubule-inhibiting payload maytansine to CD22-expressing cells and employs a novel third-generation stable linker-conjugation technology (SMARTag^®).

This first in human study was designed to evaluate the safety, tolerability, and pharmacokinetics of TRPH-222 monotherapy. As of January 7, 2022, 32 patients with R/R NHL had been enrolled: 15 indolent (14 follicular lymphoma (FL) and 1 marginal zone lymphoma (MZL)), and 17 aggressive histologies (15 diffuse large B-cell lymphoma (DLBCL), 1 transformed follicular lymphoma (TFL), and 1 mantle cell lymphoma (MCL)), with a median of 4 (1-9) prior lines of therapy. 22 patients were enrolled in dose-escalating cohorts of TRPH-222 (0.6 mg/kg to 10 mg/kg), and 10 patients in the dose-expansion cohort (7.5 mg/kg TRPH-222). Adverse events were more prevalent at doses ≥7.5 mg/kg and less prevalent at lower doses.  There was also a trend to higher grade adverse events in patients with aggressive histologies, compared to indolent ones.  The most frequent (≥ 5%) treatment-emergent related adverse events (Grade ≥3) included thrombocytopenia (34%), neutropenia (22%), ALT/AST elevation (6%), dry eye (6%) and blurred vision (6%). Cytopenias were non-febrile, infrequent, late onset, asymptomatic and resolved without significant intervention. Ocular findings were consistent with known epithelial keratopathy of ADCs and were generally low grade. Overall, TRPH-222 has a favourable safety profile with most AEs being predominantly low grade, tolerable, easily managed, and reversible.

Preliminary efficacy results in the trial suggest evidence of anti-tumor activity, most notably in patients with R/R FL. Of the 13 response-evaluable FL patients, 5 complete responses (CR) and 2 partial responses (PR) were observed, with an overall response rate (ORR) of 54% and a complete response rate (CRR) of 38%. Responses were generally early, durable and CRs were maintained off-therapy, with a median duration of response (mDOR) of 24.9 months (95% CI: 2.2, NR) in R/R FL. Beyond FL, CRs were also observed in 1 DLBCL patient and in 1 MCL patient.

“TRPH-222 is a novel CD22-targeting antibody drug conjugate with a unique efficacy and safety profile that has successfully passed the Phase 1 test. It demonstrated robust clinical activity in NHL, with durable complete responses that were enriched in FL patients.  I particularly liked that my patients who achieved remissions with TRPH-222 were able to discontinue study drug and remain in remission for extended periods of time. The durable complete responses and minimal toxicity profile associated with TRPH-222 highlight its potential to be widely integrated into current treatment regimens” stated Dr. Hernandez-Ilizaliturri, MD, Chief of the Lymphoma Section at Roswell Park, and lead investigator for the TRPH-222-100 study.

Dr. Kuruvilla, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, one of the primary investigators on the TRPH-222-100 study added, “My experience with TRPH-222 is that it is a highly active drug, is well tolerated and has a good fit in FL. It was straightforward to administer to patients, with little concern for adverse events and no need for continual close monitoring. In sequencing treatments pre or post CAR-T therapy, I would choose a CD22-targeted ADC over CD19-targeted therapies prior to a CD19 CAR-T regimen due to CD19 antigen shedding. An agent like TRPH-222 could easily be incorporated into CD19 CAR-T treatment algorithms”.

Key Results:

• TRPH-222 monotherapy is well tolerated up to 10 mg/kg, with a low incidence of AEs commonly associated with ADCs, such as thrombocytopenia, neutropenia and liver transaminase increases. Most AEs seen with TRPH-222 were predominantly low grade, tolerable, easily managed and reversible.
• Seven complete responses (CR: 5 FL, 1 DLBCL, 1 MCL) and three partial responses (PR: 2 FL, 1 TFL) have been observed at doses from 0.6 to 10 mg/kg. Five patients with metabolic CRs that were confirmed after 3 additional cycles are now off treatment and continue in CR; 3 patients remain in CR with responses maintained for up to 25 months.
• The observed data support further clinical studies of TRPH-222, including combinations with other anti-tumor agents in B-cell lymphoma patients. Triphase is preparing for upcoming conversations with regulatory agencies on a Phase 2 study plan.

More information about this study can be found at www.clinicaltrials.gov, identifier NCT03682796.

Triphase also announced that Dr. Niclas Stiernholm, the former president and CEO of Trillium Therapeutics, which was recently acquired by Pfizer Inc., has joined the company as a senior advisor. “We are pleased to have Niclas join us during this next stage of growth.  We will benefit from his experience with Trillium”, commented Triphase’s Executive Chair, Dr. Ilse Treurnicht. “There are obvious parallels between Trillium and Triphase, both homegrown Toronto biotech companies with strong local support from academic stakeholders. We look forward to advancing TRPH-222 in the clinic, as well as to growing our pipeline over the next few years”.

About TRPH-222

TRPH-222 is a novel antibody-drug conjugate (ADC), composed of an anti-CD22 monoclonal antibody modified to allow site-specific conjugation of a maytansine payload via a non-cleavable linker. The drug, formerly called CAT-02-106, was developed by Catalent Biologics using its proprietary SMARTag^® technology and was licensed to Triphase Accelerator. CD22 is a cell surface protein expressed across all subtypes of B-cell lymphomas. The approval of Besponsa in 2017, an anti-CD22 ADC for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (B-ALL), supports the rationale for CD22 targeting in these B-cell diseases. Triphase holds exclusive global rights to develop and commercialize TRPH-222.

About Triphase Accelerator

Triphase Accelerator is a private drug development company with a primary focus on oncology and operations in Toronto and San Diego. Triphase Accelerator is dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies using a unique, science-based model that is faster and more cost-effective than traditional pharmaceutical and biotech industry drug development approaches. Triphase Accelerator was founded by the Ontario Institute for Cancer Research (OICR) and FACIT, in partnership with Toronto Innovation Acceleration Partners (TIAP) and MaRS. For more information, visit www.triphaseco.com.

CONTACT: Grant Gibson, CPA
Chief Financial Officer
Triphase Accelerator
grant.gibson@triphaseco.com