New Biomarker Research Builds Further Understanding of Tebentafusp (IMCgp100) Mechanism of Action, Link to Clinical Activity in Advanced Melanoma

• New analyses from first-in-human clinical trial presented at the
  2019 ASCO Annual Meeting
• Pivotal trials in metastatic uveal melanoma are ongoing

OXFORDSHIRE, England & CONSHOHOCKEN, Pa. & ROCKVILLE, Md.–(BUSINESS WIRE)–Monotherapy treatment with the first-in-class ImmTAC® molecule
tebentafusp (IMCgp100) induced an immunologically potent response in
patients with advanced uveal and cutaneous melanoma, according to new
data presented today by Immunocore Limited at the 2019 American Society
of Clinical Oncology (ASCO) Annual Meeting. The biomarker research
provides additional insight into the mechanism of action of tebentafusp
in patients with advanced melanoma and demonstrates the potential
association with clinical outcomes.

“We are pleased to share new biomarker data from our tebentafusp
clinical trial programme, which add to the growing body of evidence
supporting the investigational agent’s clinical activity and reinforce
the potential applicability of our ImmTAC technology,” said Bahija
Jallal, Chief Executive Officer of Immunocore. “We recognise the
immediate need for new treatment options for people living with
metastatic uveal melanoma and are working to advance tebentafusp as
quickly and safely as possible.”

Tebentafusp is a novel bispecific protein comprised of a soluble T cell
receptor fused to an anti-CD3 immune-effector function. Tebentafusp
specifically targets gp100, a lineage antigen expressed in melanocytes
and melanoma, and is the first molecule developed using Immunocore’s
ImmTAC technology platform designed to redirect T cells to recognise and
kill tumour cells. Pivotal tebentafusp clinical trials are currently
underway in metastatic uveal melanoma, a rare form of eye cancer.

“Biomarker research is critical to informing the development of new
immunotherapy agents, particularly in difficult-to-treat cancers like
uveal melanoma,” said Mark R Middleton, MD, lead study investigator
and Head of the Department of Oncology at the University of Oxford.
“These data build a deeper understanding of how the immune system
responds to tebentafusp and provide insights needed to inform future
enhancements.”

ASCO Presentations

Researchers analysed data from the Phase 1 first-in-human clinical trial
assessing the safety and tolerability of tebentafusp in 84 HLA-A2+
patients with metastatic melanoma (n=61 cutaneous, n=19 uveal, n=4
other) resistant to standard treatment regimens or for which no standard
treatments exist.

Pharmacodynamic Effect of IMCgp100 (TCR–CD3 bispecific) on
Peripheral Cytokines and Association with Overall Survival in Patients
with Advanced Melanoma

The goal of this analysis was to understand the biological effects of
tebentafusp and an association with anti-tumour activity. The findings
showed an association between a greater increase in serum CXCL10, a
chemokine for T cells expressing CXCR3 receptor, and a greater transient
reduction in peripheral CXCR3+CD8+ T cells, tumour shrinkage and longer
overall survival (OS). A greater reduction in peripheral CXCR3+ CD8+ T
cells also appeared to be associated with tumour shrinkage and longer
OS, and changes in tumour biopsies were consistent with T cell
infiltration and immune activation.

Relationship Between Clinical Efficacy and AEs of IMCgp100, a
Novel Bispecific TCR–anti-CD3, in Patients with Advanced Melanoma

In this analysis, adverse events (AEs) were consistent with
tebentafusp’s proposed mechanism of action with most AEs relating to
on-target (gp100) off-tumour activity (e.g., rash, pruritus), or were
cytokine mediated (e.g., pyrexia, hypotension). There appears to be an
association between the timing of onset and resolution of these AEs and
certain cytokines in the blood. AEs were generally manageable with
standard clinical interventions. An association was also observed
between OS and LDH ≤ULN and any-grade rash occurring within 21 days.

“Further understanding of the potential association of mechanism of
action with safety and activity is important in the success of novel
immune therapies,” said Omid Hamid, MD, study investigator and Chief
of Translational Research and Immunotherapy at The Angeles Clinic.
“These data support the continued investigation of tebentafusp in
cutaneous melanoma in addition to the pivotal trials in metastatic uveal
melanoma already underway.”

More information about the tebentafusp clinical trials can be found at https://www.clinicaltrials.gov.

– Ends –

About Tebentafusp

Tebentafusp is a novel bispecific protein comprised of a soluble T cell
receptor fused to an anti-CD3 immune-effector function. Tebentafusp
specifically targets gp100, a lineage antigen expressed in melanocytes
and melanoma, and is the first molecule developed using Immunocore’s
ImmTAC technology platform designed to redirect T cells to recognise and
kill tumour cells. Tebentafusp has Fast Track Designation and Orphan
Drug Designation in the US and Promising Innovative Medicine designation
under the UK Early Access to Medicines Scheme for metastatic uveal
melanoma. For more information about enrolling tebentafusp clinical
trials for metastatic uveal melanoma, please visit ClinicalTrials.gov
(NCT03070392).

About Immunocore

Immunocore is a leading T cell receptor (TCR) biotechnology company
working to create first-in-class biological therapies that have the
potential to transform patients’ lives. The Company’s primary
therapeutic focus is oncology and it also has programmes in infectious
and autoimmune diseases. Immunocore has a pipeline of proprietary and
partnered programmes in development and the lead tebentafusp is being
investigated in pivotal clinical studies as a treatment for patients
with metastatic uveal melanoma. Collaboration partners include
Genentech, GlaxoSmithKline, AstraZeneca, Lilly, and the Bill and Melinda
Gates Foundation. Immunocore is headquartered at Milton Park,
Oxfordshire, UK, with offices in Conshohocken, PA and Rockville, MD, US.
The Company is privately held by a broad international investor base.
For more information, please visit www.immunocore.com.

About ImmTAC® Molecules

Immunocore’s proprietary T cell receptor (TCR) technology generates a
novel class of bispecific biologics called ImmTAC (Immune mobilising
monoclonal TCRs Against Cancer) molecules that can potentially enable
the immune system to recognise and kill cancerous cells. ImmTAC
molecules are based on soluble TCRs engineered to recognise
intracellular cancer antigens with ultra-high affinity and selectively
kill cancer cells via an anti-CD3 immune-redirecting effector function.
Based on the demonstrated mechanism of T cell infiltration into human
tumours, the ImmTAC mechanism of action holds the potential to tackle
solid “cold” low mutation rate tumours, the majority of tumours that do
not adequately respond to currently available immunotherapies.

About Uveal Melanoma

Uveal melanoma is an aggressive form of melanoma which affects the eye,
with a poor prognosis and no standard of care.¹ Although it
is the most common primary intraocular malignancy in adults, the
diagnosis is rare, with approximately 8,000 new patients diagnosed
globally each year (1,600-2,000 cases/year in the US).^1,2,3,4
Up to 50% of people with uveal melanoma will eventually develop
metastatic disease.¹ When the cancer spreads beyond the eye,
only approximately 40% of patients will survive for one year.¹

For more information, please contact:

¹ Carvajal, RD, Schwartz, GK, Tezel, T, et al., 2017.
Metastatic disease from uveal melanoma: treatment options and future
prospects. British Journal of Ophthalmology, 101(1),
38-44.

² Pandiani C, Béranger GE, Leclerc J, Ballotti R, Bertolotto
C. Focus on cutaneous and uveal melanoma specificities. Genes
Dev. 2017;31(8):724-743.

³ Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S,
Cekic S, Stefanovic V. Ocular melanoma: an overview of the current
status. Int J Clin Exp Pathol. 2013;6(7):1230-1244.

⁴ About ocular melanoma. Ocular Melanoma Foundation website. www.ocularmelanoma.org
/about-om.htm. Accessed May 2019.

Contacts

Immunocore
Louise Conlon,
External Affairs and Brand
Communications Manager
T: +44 (0) 1235 438600
E: [email protected]
Follow
on Twitter: @Immunocore

Syneos Health Communications
(Tebentafusp/IMCgp100)
Stephanie Bukantz
T: +973 477 1814
E:
[email protected]