Phase 1

Autolus

Overview

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T-cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T-cell programming technologies, the company is engineering precisely targeted, controlled and highly active T-cell therapies that are designed to better recognise cancer cells, break down their defence mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of haematological malignancies and solid tumours.

Team

Management team with a strong track record of accomplishment in redirected T-cell therapies, gene therapy, transplantation and oncology.

  • Christian Itin, Chairman & Chief Executive Officer
  • Andrew Oakley, Chief Financial Officer
  • Chris Vann, SVP, Chief Operating Officer
  • Vijay Peddareddigari, SVP, Chief Medical Officer
  • Martin Pulé, SVP, Chief Scientific Officer
  • Matthias Alder, SVP, Chief Business Officer

Critical unmet medical need for improved T-cell therapies

  • Loss of target antigen reported for CD19, CD22 and BCMA-targeting Chimeric Antigen Receptor (CAR) T-cell products
  • Complexity of tumour biology greater in solid tumours vs. haematological cancers
  • Managing safety (toxicity, elimination of normal cells via on-target off-tumour recognition)
  • Upregulation of checkpoint inhibitors or other negative regulators of T-cell action
  • Lack of cost-efficient, scalable treatment delivery model and manufacturing
  • Lack of T-cell persistence

Market potential

CAR-T has had dramatic success in treating certain late-stage blood cancers and the first two CAR-T therapies (Novartis's Kymriah and Kite's Yescarta) were approved and launched in the US in H2 2017. The cell therapy market is forecast to grow to $10bn+ by 2024 (Source: Evaluate Pharma) and significantly beyond, as signalled by Gilead's $12bn acquisition of Kite (H2 2017) and Celgene's $9bn acquisition of Juno (H1 2018).

Novel technology

Autolus has developed a modular approach towards developing advanced CAR-T-cells, with tailored therapies to address specific cancers. The company has a wide array of programming modules relative to its peers within CAR-T, providing scope to improve the efficacy and durability of products currently on the market.

Advanced Programming ModulesKey intended Benefits
Advanced TargetingInnovative Binders
  • Improve activity and safety pf programmed T-cells
  • Improve ability to bind to target
Dual targeting
  • Reduce the risk of negative antigen relapse
  • Support a response in patients with low levels of target antigen
Pattern recognition
  • Enhance the selectivity for the tumour
  • Spare healthy cells and unwanted side effects
Pharmacological controlSafety switches
  • Remove the therapy in the event a patient suffers a severe adverse event or chronic toxicity
Tunable T-cells
  • Dampen activity of the therapy to manage patients through periods of acute toxicities such as cytokine release syndrome of neurotoxicity
Enhance T-cell activityImmune Checkpoint Blockade
  • Prevent shutdown of T-cell activity by tumour microenvironment
  • Acting across a range of immune checkpoint pathways
Enhanced T-cell Persistence
  • Enhance activity against solid tumours
  • Continued stimulation to help T-cells survive and persist for extended periods of time

Milestones achieved

Positive clinical progression:

  • Encouraging early data from AUTO3 supports Autolus's hypothesis that dual-targeting can result in less antigen escape and superior long term outcomes.
  • Initiated Phase 1 AUTO4 trial for T-cell Lymphoma (TCL), an aggressive cancer with very poor prognosis for patients
  • Updated AUTO1 data showed comparable to better persistence and comparable survival of patients comparable to Kymriah and with a better safety profile. This is despite the fact that the study included patients post CD19 and CD22 targeted therapies, which were excluded from the Kymriah trial
  • Successful NASDAQ IPO, raising $172m
  • Well financed, with approximately $217.5m at 31 December 2018. Cash runway projected to last into CY 2021

Pipeline

ProductIndicationTargetPreclinicalPhase 1/2Phase 2/3
B-Cell Malignancies
AUTO1Paediatric Acute Lymphoblastic Leukaemia (pALL)CD19

UCL – CARPALL

AUTO1Adult Acute Lymphoblastic Leukaemia (aALL)CD19

UCL – CARPALL

AUTO3Paediatric Acute Lymphoblastic Leukaemia (pALL)CD19 & CD22
AUTO3Diffuse Large B Cell LymphomaCD19 & CD22
AUTO3 NGB-Cell MalignanciesUndisclosed
Multiple Myeloma
AUTO2Multiple MyelomaBCMA & TACI
AUTO2 NGMultiple MyelomaUndisclosed
T-cell Lymphoma
AUTO4TRBC1+ Peripheral T-cell Lyphoma (TCL)TRBC1
AUTO5TRBC1+ Peripheral T-cell LymphomaTRBC2
GD2+ Tumours
AUTO6NeuroblastomaGD2

CRUK

AUTO6 NGNeuroblastoma; Melanoma; Osteeosarcoma; SCLCGD2
Prostate Cancer
AUTO7Prostate CancerUndisclosed

Expected milestones in 2019

  • First AUTO1 data presentation for adult ALL (Phase 1 data) in Q2 2019 and full Phase 1 data in Q4 2019
  • AUTO2 full Phase 1 data in Q4 2019
  • Further interim Phase 1 AUTO3 (DLBCL and pALL) data in Q2 2019 and full Phase 1 data in Q4 2019
  • Initial Phase 1 AUTO4 (TCL) in Q4 2019
  • Plan to start two registration trials in the second half of 2019