Three CAR-T cell therapy studies announced from UK start-up Autolus

Clinical-stage, biopharmaceutical start-up company, Autolus, steps into the chimeric antigen receptor (CAR)-T cell therapy fray with three new studies looking at the treatment of various cancers.

The three studies comprise AMELIA and ALEXANDER for AUTO3 — a Phase I/II study in paediatric acute lymphoblastic leukaemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) — as well as the APRIL study of AUTO2 — a Phase I/II study of patients with multiple myeloma.

AUTO2 and AUTO3 are both dual targeting CAR-T cell therapies. The announcement of the trials evaluating these two therapies comes on the back of the recent FDA approval of Novartis’ CAR-T cell therapy, and Gilead’s proposed acquisition of Kite Pharma for its CAR-T programme.

“Our approach at Autolus is to understand how tumours defend against T-cells and then design and programme CAR-T cell products which specifically address those defence and escape mechanisms,” stated Dr Martin Pule, Autolus’ Founder and chief scientific officer.

AUTO2 targets both B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). The APRIL study will involve dose-escalation in participants to determine the maximum tolerated dose and establish a recommended dose. This will then be extended to further evaluate the safety, tolerability and clinical activity at this recommended dose.

“BCMA CAR-T cell therapies have shown considerable promise in early clinical studies,” explained Dr Jesus G. Berdeja, director of Myeloma Research & Senior Investigator, Hematologic Malignancies, Sarah Cannon Research Institute. “A dual-targeted approach may minimise the risk for antigen negative escape and extend CAR-T treatment to patients with low density of BCMA antigen on the surface their cancer cells.”

“Breaking the defence mechanisms of cancers against T-cells is key to unlocking the curative potential of CAR-T cell therapies,” added Dr Christian Itin, Autolus’ CEO. “AUTO2 is a first example of Autolus’ approach to specifically re-programme the patient’s own T-cells to minimise the risk of the cancer cells escaping treatment. With the start of the APRIL study we have transitioned to a clinical stage company; an important step on our path to build a fully integrated autologous CAR-T cell company with a portfolio of differentiated therapies for the treatment of patients with cancer.”

AUTO3 is an autologous T-cell product, genetically modified to express two separate CARs which recognise CD19 and CD22. “The AUTO3 programme seeks to overcome two limitations of current therapies by introducing dual targeting CARs and addressing checkpoint mediated inhibition,” asserted Pule.

The two studies evaluating AUTO3 — AMELIA and ALEXANDER — will also be dose-escalating studies initially focussed on finding the maximum tolerated dose and establish a recommended dose. These will also then be extended to further evaluate the safety, tolerability and clinical activity at this recommended dose. Additionally, AUTO3 will be evaluated as a standalone therapy and in combination with a checkpoint inhibitor in ALEXANDER.

“The advent of CD19 CAR-T cell based therapy is an exciting and revolutionary advancement in the treatment of children with relapsed ALL,” commented Professor Persis Amrolia, Professor of Transplantation Immunology, Great Ormond Street Hospital, London. “However, in approximately a third of the patients the disease reoccurs by losing CD19 antigen. AUTO3, a dual targeting CAR, addresses this challenge by independently targeting CD19 and CD22 antigen, which has the promise of reducing antigen escape.”

“CD19-directed CAR-T cell therapies already offer the possibility of an important new treatment option for patients with relapsed and refractory DLBCL. AUTO3 is a novel approach which simultaneously targets a second clinically relevant antigen, CD22,” summarised Dr Anas Younes, Chief, Lymphoma Service at Memorial Sloan Kettering Cancer Center, New. “The field is looking forward to seeing how patients respond to AUTO3 in clinical trials and whether dual antigen targeting CAR-T cell therapy offers the possibility of deeper initial and more sustained responses.”