BioOra scaling up manufacturing to support the Malaghan Institute’s phase 2 trial to register CD19-specific CAR T
BioOra scaling up manufacturing to support the Malaghan Institute’s phase 2 trial to register CD19-specific CAR T
Phase 1 trial (ENABLE-1) completed enrolment of 30 subjects with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) who received T cells expressing a CD19-specific chimeric antigen receptor (CAR) known as WZTL-002
ENABLE-1 established safety, demonstrated efficacy including durable responses, and established the recommended phase 2 dose (RP2D) with results presented at the 66th Annual American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, CA
Phase 2 trial (ENABLE-2) is now enrolling patients with the goal of registering this CAR T cell product for r/r B-NHL in New Zealand
BioOra Limited is the exclusive manufacturing partner to the Malaghan Institute of Medical Research in support of ENABLE-1 and ENABLE-2 clinical trials
Image: The BioOra Limited Team
Wellington, January 28th, 2025 /-- BioOra Limited, a biotech company based in New Zealand, announces the scale-up of their program in support of New Zealand’s first CAR T for cancer immunotherapy. Having recently completed a pre-Series A equity funding round, BioOra is increasing their team and capacity in preparation for the next step in the Malaghan Institute’s ENABLE-2 trial, the expansion from one trial site in Wellington to three locations with the addition of Christchurch and Auckland. The goal of ENABLE-2 (clinicaltrials.gov NCT06486051) is to enrol 60 adults with r/r large B-NHL with the goal of registering WZTL-002 for commercialisation.
The ENABLE-2 trial follows ENABLE-1 trial (clinicaltrials.gov NCT04049513) run by the Malaghan Institute that completed enrolment in 2024, in which 30 patients in New Zealand with r/r B-NHL received WZTL-002, comprising autologous T-cells expressing a third generation CAR signalling through CD28, Toll-like receptor 2, and CD3-zeta.
Commercial second-generation CAR-T cells directed against CD19 and incorporating CD28 co-stimulation are standard care for r/r B-NHL but are associated with cytokine release syndrome (CRS) in up to 85%, immune effector cell-associated neurotoxicity syndrome (ICANS) in up to 50%, and late ≥ effector cell-associated hematotoxicity (ICAHT) in 60% of patients. These toxicities contribute to healthcare costs and limit availability of treatment.
Results of the ENABLE-1 dose escalation (n = 21) and dose expansion (n= 9) cohorts were revealed at ASH on Saturday December 7, 2024 by the Malaghan Institute’s Clinical Director Dr Robert Weinkove, the principal investigator (abstract #2067). Dr Weinkove presented efficacy (3-month complete response, CR) of 52% and 56% in the two cohorts, including some durable responses (3+ years). Seventeen subjects (57%) had CRS of grades 1 or 2, none had severe CRS (grade ≥3) and only a single ICANS episode (grade 1, self-resolving) occurred. Four subjects (13%) had late ICAHT of grade 3 – 4. Twenty-one subjects were treated within RP2D range (0.5 – 1x 106 CAR+ T-cells/kg). All patients in the dose expansion cohort were managed as outpatients, and seven received CAR-T manufactured using an automated process based on the Cocoon® Platform.
“The efficacy and safety data from ENABLE-1 are highly encouraging given that subjects had progressed after multiple prior therapies and many were at risk of complications”, says Dr Weinkove. “Compared to the leading approved CD28-costimulated CAR T-cell product Yescarta®, the ENABLE-1 trial suggests improved safety as measured by CRS and ICANS rate, and similar efficacy at a late line of therapy. This improved safety profile could facilitate outpatient management and lower the overall costs of CAR T-cell therapy. ENABLE-2 will provide additional efficacy and safety data in the large B-cell lymphoma population.”
John Robson, Managing Director of BioOra, says these clinical data support BioOra’s increased investment to commercialise the CAR-T developed with the Malaghan Institute. “With successful completion of ENABLE-1, we are focused on ENABLE-2 with a view to registering WZTL-002, with subjects cared for as outpatients and receiving CAR-T cells manufactured using our cost-effective automated process.” says Robson.
“We are delighted by these clinical results,” says Dr Laurence Cooper, Director and Chair of the Medical Advisory Board at BioOra. “The clinical data presented at ASH are a credit to the Malaghan Institute and affirm our commitment at BioOra to broadening the reach of CAR-T to New Zealand and beyond.”
BioOra are opening their Series A funding round in early 2025 to deliver commercial CAR-T at the conclusion of the multi-centre ENABLE-2 trial.
BioOra Ltd
BioOra is a privately held joint venture between the Malaghan Institute of Medical Research and Bridgewest Ventures NZ LP. In partnership with Callaghan Innovation, the company is commercialising CAR-T, beginning with WZTL-002. WZTL-002 was licensed from Wellington Zhaotai Therapies Ltd. MIMR is the sponsor for ENABLE-1 and ENABLE-2.
Patient and provider contact (Malaghan)
Brittany Lavender
Tel: +64 4 499 6914 or clinicaltrialmanagement@malaghan.org.nz
Media contact (BioOra)
John Robson
Tel: +64 21 842 960 or john.robson@bioora.com
Media contact (Malaghan)
Gail Marshall
Tel: +64 21 360 432 or gmarshall@malaghan.org.nz