Triphase Accelerator Initiates Phase 1 Clinical Trial of TRPH-222 in B-cell Lymphoma

Triphase Accelerator Corporation, a company dedicated to acquiring and developing novel therapeutics for the treatment of cancer, and Catalent, the leading global provider of advanced delivery technologies and development solutions for drugs, biologics, and consumer health products, recently announced that Triphase Accelerator’s TRPH-222, an anti-CD22 antibody-drug conjugate (ADC) for the treatment of patients with lymphoma, has been dosed in the first patient in a Phase 1 clinical trial.

TRPH-222 was originally developed by Catalent’s subsidiary Redwood Bioscience, Inc. using the proprietary SMARTag platform, which provides optimized site-specific protein-modification and linker technologies. Triphase Accelerator obtained the worldwide rights to further develop this program and subsequently announced that Celgene had obtained the option to acquire all rights to the program as part of an expanded strategic collaboration.

The Phase 1 clinical trial is a multi-center, open-label study of TRPH-222 monotherapy in subjects with relapsed and/or refractory B-cell non-Hodgkin lymphoma (NHL), which will be conducted in two stages, dose-escalation and dose-expansion. The study is currently enrolling patients at sites in the US and Canada, including Roswell Park Cancer Center, University of Pennsylvania, Ohio State University, Sarah Cannon Research Institute, Princess Margaret Cancer Centre and Jewish General Hospital. Additional sites are planned to support the dose-expansion stage. More information about this study can be found at www.clinicaltrials.gov, Identifier NCT03682796.

“We are thrilled to advance the first SMARTag ADC into human clinical trials and evaluate its potential for better tolerability and an expanded therapeutic index as compared to conventional ADCs” said Dr. Mathias Schmidt, Executive Vice President and Head of Research & Development of Triphase Accelerator. “We look forward to assessing the potential clinical benefit of TRPH-222 in patients with relapsed/refractory B-cell lymphoma and remain convinced that this molecule can play an important role in the future treatment of lymphoma.”

“We are excited to see Triphase Accelerator reach this important milestone with TRPH-222,” added Mike Riley, Vice President and General Manager, Catalent Biologics. “The SMARTag technology has the potential to create ADCs with significantly higher tolerability and expanded therapeutic index. The improved conjugate stability and biophysical characteristics of TRPH-222 has translated to improved tolerability in preclinical testing, and we look forward to further validation in the clinic.”

TRPH-222 is a novel, site-specific antibody-drug conjugate (ADC) targeting CD22, a B-cell-restricted sialo-glycoprotein that is an important modulator of B-cell signaling and survival, and is expressed on nearly all B-cell malignancies. CD22 is a clinically validated ADC target with potential in Non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). The compound itself combines a humanized antibody, modified for site-specific conjugation to a cytotoxic payload using Hydrazino-Pictet-Spengler (HIPS) chemistry and a proprietary linker. Pre-clinical data have shown that this optimization of payload placement and linker composition, combined with the stability afforded by HIPS chemistry, leads to better tolerability and expanded therapeutic index.

Triphase Accelerator is a private drug development company with a primary focus on oncology and with 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), in partnership with MaRS Innovation and MaRS. It has a strategic relationship with Celgene for oncology-focused drug development opportunities. In 2016, Celgene acquired the company’s assets related to its proteasome inhibitor, marizomib (MRZ), which is currently in Phase 3 development for glioblastoma. For more information, visit www.triphaseco.com.

Catalent’s proprietary SMARTag platform, which provides site-specific protein-modification and linker technologies, was developed by Redwood Bioscience, Inc. to enable the generation of homogenous bioconjugates engineered to enhance potency, safety and stability. The aldehyde tag technology employs natural co-translational modifications found in human cells to create one or more attachment sites at designated positions on protein molecules. These chemical “handles’’ are then stably conjugated to payloads (eg, cytotoxic or effector) to prevent their systemic release. The SMARTag platform provides precise payload positioning, stable, site-specific conjugation, and defined stoichiometry of drug–protein ratios. The control afforded by the technology enables identification of superior drugs from libraries of differentially designed conjugates. Catalent acquired Redwood Bioscience, Inc. in 2014.

Catalent is the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products. With more than 85 years serving the industry, Catalent has proven expertise in bringing more customer products to market faster, enhancing product performance and ensuring reliable clinical and commercial product supply. Catalent employs over 11,000 people, including over 1,800 scientists, at more than 30 facilities across five continents, and in fiscal year 2018 generated approximately $2.5 billion in annual revenue. Catalent is headquartered in Somerset, New Jersey. For more information, visit www.catalent.com.