Oxford BioMedica Notes the Longer-Term Analyses from Pivotal Kymriah® Trials, Which Showed Durable Responses Are Maintained in Patients with Advanced Blood Cancers

OXFORD, England–(BUSINESS WIRE)–Oxford BioMedica plc (“Oxford BioMedica” or “the Group”) (LSE:OXB), a
leading gene and cell therapy group, today notes an announcement by
Novartis on the longer-term analyses of both the ELIANA and JULIET
pivotal trials in children and young adult patients with relapsed or
refractory (r/r) acute lymphoblastic leukaemia (ALL) and adult patients
with r/r diffuse large B-cell lymphoma (DLBCL), respectively. Kymriah®
(tisagenlecleucel) continued to demonstrate strong efficacy with durable
responses and maintained a consistent and well-characterised safety
profile. These data are being presented at the 60th American
Society of Hematology (ASH) annual meeting. Additionally, today, the New
England Journal of Medicine
published online the 14-month results
from JULIET, the study led by the Abramson Cancer Center at the
University of Pennsylvania 1.

In the 24-month follow-up analysis of the ELIANA study in children and
young adults with r/r B-cell ALL, Kymriah demonstrated deep and durable
responses without subsequent therapy in a significant portion of
patients in this population. Among 79 evaluable patients, who were
followed for at least three months or discontinued earlier, 82% (95%
confidence interval [CI], 72% – 90%) achieved complete response (CR) or
CR with incomplete blood count recovery (CRi) within three months of
infusion; and among these responding patients, 98% had negative minimal
residual disease (MRD). The relapse-free survival rate was 62% at 24
months; and the median duration of remission (mDOR) and median overall
survival (mOS) remained unreached, signifying responses are deep and
sustained, and further reinforcing the potential for Kymriah to be a
definitive therapy for many patients. The probability of OS was 76% (95%
CI, 65% – 85%) at 12 months and 66% (95% CI, 58% – 79%) at 24
months. The safety profile observed in this updated analysis was
consistent with previously reported results, with no emergence of new
safety signals. Grade 3/4 cytokine release syndrome (CRS) – as defined
by the rigorous Penn Grading Scale – occurred in 49% of patients. Within
eight weeks of infusion, 13% of patients experienced grade 3
neurological events, with no grade 4 events or cerebral oedema2.
These updated data will be presented in an oral session at the ASH
annual meeting (Abstract # 895; Monday, December 3, 4:30PM PST).

Results from the 19-month analysis from the JULIET study of Kymriah in
adult patients with r/r DLBCL (n=99) indicated prolonged durability of
response in patients who had previously been through multiple rounds of
chemotherapy and unsuccessful stem cell transplants (Abstract # 1684).
The overall response rate (ORR) after a median of 19 months of follow-up
was 54% (95% CI, 43% – 64%; CR, 40%; partial response [PR], 13%) among
patients who were followed for at least 3 months or discontinued
earlier. The mDOR was not reached at the time of analysis indicating
most responders were still experiencing a response at the time of
analysis; and the relapse-free probability, which was 66% (95% CI,
51%-78%) at 6 months, remained consistent at 64% (95% CI, 48%-76%)
between 12-month and 18-month analyses. Further, 54% (15/28) of patients
who had achieved a PR converted to CR. Median OS for all infused
patients was 11.1 months (95% CI, 6.6 months-NE) and not reached (95%
CI, 21 months-NE) for patients in CR. The OS probability was 48% (95%
CI, 38%-57%) at 12 months and 43% (95%CI, 33%-53%) at 18 months (max
follow-up, 29 months). Analyses of ORR, DOR and OS data showed
consistent results across all patient subgroups, regardless of
relapsed/refractory status, age and high-risk cytogenetics.

The safety profile observed in the 19-month follow-up from JULIET
continued to be consistent with previous reports and no deaths occurred
due to causes other than disease progression in this longer-term follow
up analysis. Within eight weeks of infusion with Kymriah, Grade 3/4 CRS,
as defined by the Penn Grading Scale, was reported in 23% of patients.
CRS management was conducted per the Penn CRS management algorithm,
which is specific to Kymriah. Tocilizumab and steroids were used in 16%
and 11% of patients, respectively, to treat CRS. Eleven percent of
patients had Grade 3/4 neurologic adverse events, which were managed
with supportive care3.

Oxford BioMedica is the sole manufacturer of the lentiviral vector used
in Kymriah. The Group signed an agreement with Novartis in July 2017 for
the commercial and clinical supply of lentiviral vectors used to
generate Kymriah and other undisclosed CAR-T products. This
collaboration has reached important milestones in 2018 with the US FDA
approval of Kymriah to treat adult patients with r/r DLBCL, and the
approval of Kymriah in these two distinct indications in the European
Union, Canada and Switzerland. These important achievements follow the
initial US launch of Kymriah in paediatric and young adult patients with
r/r B-cell ALL in 2017. Oxford BioMedica signed an agreement with
Novartis in July 2017 for the commercial and clinical supply of
lentiviral vectors used to generate CTL019 and other undisclosed CAR-T
products, for which Oxford BioMedica could potentially receive in excess
of $100m from Novartis over the next three years.

Notes for editors

About the ELIANA Trial

ELIANA is the first paediatric global CAR-T cell therapy registration
trial, examining patients in 25 centres in 11 countries across the US,
Canada, Australia, Japan and the EU, including: Austria, Belgium,
France, Germany, Italy, Norway and Spain, demonstrating effective
distribution of Kymriah across four continents using a global supply
chain. In 2012, Novartis and Penn entered into a global collaboration to
further research, develop and commercialize CAR-T cell therapies,
including Kymriah, for the investigational treatment of cancers.

About the JULIET Trial

JULIET is the first multi-centre global registration study for Kymriah
in adult patients with r/r DLBCL. JULIET, led by researchers at the
University of Pennsylvania, is the largest and only global registration
study examining a CAR-T cell therapy in DLBCL, enrolling patients from
27 sites in 10 countries across the US, Canada, Australia, Japan and
Europe, including Austria, France, Germany, Italy, Norway and the

About Kymriah

In August 2017, Kymriah became the first available chimeric antigen
receptor T cell (CAR-T) therapy when it received FDA approval for
children and young adults with B-cell acute lymphoblastic leukaemia
(ALL) that is refractory or has relapsed at least twice. Kymriah is a
novel immunocellular therapy and a one-time treatment that uses a
patient’s own T cells to fight cancer. Kymriah uses the 4-1BB
costimulatory domain in its chimeric antigen receptor to enhance
cellular expansion and persistence.

About Oxford BioMedica

Oxford BioMedica (LSE:OXB) is a leading gene and cell therapy group
focused on developing life changing treatments for serious diseases.
Oxford BioMedica and its subsidiaries (the “Group”) have built a sector
leading lentiviral vector delivery platform (LentiVector®),
which the Group leverages to develop in vivo and ex vivo
products both in-house and with partners. The Group has created a
valuable proprietary portfolio of gene and cell therapy product
candidates in the areas of oncology, ophthalmology and CNS disorders.
The Group has also entered into a number of partnerships, including with
Novartis, Bioverativ, Sanofi, Axovant, Orchard Therapeutics, Boehringer
Ingelheim/UK Cystic Fibrosis Gene Therapy Consortium/Imperial
Innovations and GC LabCell, through which it has long-term economic
interests in other potential gene and cell therapy products. Oxford
BioMedica is based across several locations in Oxfordshire, UK and
employs more than 360 people. Further information is available at www.oxb.com.