Potential First-in-Class Tetravalent Bispecific
Antibody Demonstrates Enhanced Binding in the Simultaneous Presence
of PD-1 & VEGF
Cooperative Binding of SMT112 Enables Higher
Avidity in the Tumor Microenvironment with Over 18 Fold Increased
Binding Affinity to PD-1 in the Presence of VEGF in vitro
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) today announced that data for its novel, potential
first-in-class investigational bispecific antibody, ivonescimab,
will be presented at the 38th Annual Meeting of the Society for
Immunotherapy of Cancer (SITC) in San Diego, CA. The poster with
updated data describing ivonescimab’s mechanism of action will be
displayed on Saturday November 4, 2023, from 11:55am to 1:25pm
Pacific Time.
The poster is a collaborative effort between Summit and our
collaboration and licensing partner, Akeso, Inc. (HKEX Code:
9926.HK), who generated and analyzed the data. The senior author of
the poster is Jing Min, PhD, Senior Vice President Drug Discovery
and Preclinical Science at Akeso, and it will be presented at SITC
2023 by Betty Y. Chang, PhD, Head of Research at Summit.1
Ivonescimab, known as SMT112 in the United States, Canada,
Europe, and Japan, and as AK112 in China and Australia, is a novel,
potential first-in-class investigational bispecific antibody
combining the effects of immunotherapy via a blockade of PD-1 with
the anti-angiogenesis effects associated with blocking VEGF into a
single molecule. The poster describes how ivonescimab displays
unique cooperative binding to each of its intended targets with
higher affinity when in the presence of both PD-1 and VEGF.
This could differentiate ivonescimab as there is potentially
higher expression (presence) of both PD-1 and VEGF in tumor tissue
and the tumor microenvironment (TME) as compared to normal tissue
in the body. Ivonescimab’s tetravalent structure (four binding
sites) enables higher avidity (accumulated strength of multiple
binding interactions) in the tumor microenvironment with over 18
fold increased binding affinity to PD-1 in the presence of VEGF in
vitro,2 and over 4 times increased binding affinity to VEGF in the
presence of PD-1 in vitro.3 This tetravalent structure, the
intentional novel design of the molecule, and bringing these two
targets into a single bispecific antibody with cooperative binding
qualities have the potential to direct ivonescimab to the tumor
tissue versus healthy tissue. The intent of this design is to
improve upon previously established efficacy thresholds, in
addition to side effects and safety profiles associated with these
targets.
Summit has begun its clinical development of ivonescimab in
order to establish its efficacy and safety in two proposed NSCLC
indications:
- Ivonescimab combined with chemotherapy in patients with
epidermal growth factor receptor (EGFR)-mutated, locally advanced
or metastatic non-squamous NSCLC who have progressed after
treatment with a third-generation EGFR tyrosine kinase inhibitor
(TKI) (HARMONi trial)
- Ivonescimab combined with chemotherapy in first-line metastatic
squamous NSCLC patients (HARMONi-3 trial)
Earlier this year, the first patient was treated in Summit’s
license territories in the Phase III HARMONi clinical trial. Summit
has opened clinical trial sites in the HARMONi-3 trial and expects
to begin dosing patients in the current fiscal quarter.
Over 950 patients have been treated with ivonescimab across
multiple clinical studies in different proposed indications in
China and Australia, in addition to those recently enrolled in
Summit’s license territories.
Lung cancer is believed to impact approximately 238,0004 people
in the United States each year and approximately 477,0005 in
Europe. NSCLC is the most prevalent type of lung cancer and
represents approximately 80% to 85% of all incidences.6 Among
patients with non-squamous NSCLC, approximately 15% have
EGFR-sensitizing mutations in the United States and Europe.7
Patients with squamous histology represent approximately 25% to 30%
of NSCLC patients.8
Ivonescimab is an investigational therapy that is not approved
by any regulatory authority.
About the SITC 2023 Poster
Poster Title: Mechanism of Action of Ivonescimab (AK112/SMT112):
A First-in-Class Tetravalent Fc-silent Bispecific Antibody with
Dual Blockade of PD-1 and VEGF that Promotes Cooperative Biological
Effects
SITC Abstract No.: 1194
Session Date & Time: Saturday November 4, 2023, from 11:55am
to 1:25pm PT
Summit Therapeutics’ Mission Statement
To build a viable, long-lasting health care organization that
assumes full responsibility for designing, developing, trial
execution and enrollment, regulatory submission and approval, and
successful commercialization of patient, physician, caregiver, and
societal-friendly medicinal therapy intended to: improve quality of
life, increase potential duration of life, and resolve serious
medical healthcare needs. To identify and control promising product
candidates based on exceptional scientific development and
administrational expertise, develop our products in a rapid,
cost-efficient manner, and to engage commercialization and/or
development partners when appropriate.
We accomplish this by building a team of world class
professional scientists and business administrators that apply
their experience and knowledge to this mission. Team Summit exists
to pose, strategize, and execute a path forward in medicinal
therapeutic health care that places Summit in a well-deserved, top
market share, leadership position. Team Summit assumes full
responsibility for stimulating continuous expansion of knowledge,
ability, capability, and well-being for all involved stakeholders
and highly-valued shareholders.
About Ivonescimab
Ivonescimab, known as SMT112 in the United States, Canada,
Europe, and Japan (Summit’s license territories), and as AK112 in
China and Australia, is a novel, potential first-in-class
investigational bispecific antibody combining the effects of
immunotherapy via a blockade of PD-1 with the anti-angiogenesis
effects associated with blocking VEGF into a single molecule.
Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and
is currently engaged in multiple Phase III clinical trials. Summit
has begun its clinical development of ivonescimab in NSCLC,
enrolling the first patient in its license territory in 2023, with
the intent of initiating another Phase III clinical trial in 2023.
Over 950 patients have been treated with ivonescimab in clinical
studies conducted by Akeso in China and Australia, with enrollment
beginning recently in Summit’s license territories.
About Summit Therapeutics
Summit was founded in 2003 and our shares are listed on the
Nasdaq Global Market (symbol ‘SMMT’). We are headquartered in Menlo
Park, California, and we have additional offices in Oxford, UK.
For more information, please visit https://www.smmttx.com and
follow us on X (formerly Twitter) @summitplc.
Summit Forward-looking Statements
Any statements in this press release about the Company’s future
expectations, plans and prospects, including but not limited to,
statements about the clinical and preclinical development of the
Company’s product candidates, entry into and actions related to the
Company’s partnership with Akeso Inc., the therapeutic potential of
the Company’s product candidates, the potential commercialization
of the Company’s product candidates, the timing of initiation,
completion and availability of data from clinical trials, the
potential submission of applications for marketing approvals, the
impact of the COVID-19 pandemic on the Company’s operations and
clinical trials, potential acquisitions and other statements
containing the words "anticipate," "believe," "continue," "could,"
"estimate," "expect," "intend," "may," "plan," "potential,"
"predict," "project," "should," "target," "would," and similar
expressions, constitute forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important
factors, including the results of our evaluation of the underlying
data in connection with the development and commercialization
activities for SMT112, the outcome of discussions with regulatory
authorities, including the Food and Drug Administration, the
uncertainties inherent in the initiation of future clinical trials,
availability and timing of data from ongoing and future clinical
trials, the results of such trials, and their success, and global
public health crises, including the coronavirus COVID-19 outbreak,
that may affect timing and status of our clinical trials and
operations, whether preliminary results from a clinical trial will
be predictive of the final results of that trial or whether results
of early clinical trials or preclinical studies will be indicative
of the results of later clinical trials, whether business
development opportunities to expand the Company’s pipeline of drug
candidates, including without limitation, through potential
acquisitions of, and/or collaborations with, other entities occur,
expectations for regulatory approvals, laws and regulations
affecting government contracts and funding awards, availability of
funding sufficient for the Company’s foreseeable and unforeseeable
operating expenses and capital expenditure requirements and other
factors discussed in the "Risk Factors" section of filings that the
Company makes with the Securities and Exchange Commission. Any
change to our ongoing trials could cause delays, affect our future
expenses, and add uncertainty to our commercialization efforts, as
well as to affect the likelihood of the successful completion of
clinical development of SMT112. Accordingly, readers should not
place undue reliance on forward-looking statements or information.
In addition, any forward-looking statements included in this press
release represent the Company’s views only as of the date of this
release and should not be relied upon as representing the Company’s
views as of any subsequent date. The Company specifically disclaims
any obligation to update any forward-looking statements included in
this press release.
Appendix: Glossary of Critical Terms Contained Herein
Affinity – Affinity is the strength of binding of a
molecule, such as a protein or antibody, to another molecule, such
as a ligand.
Avidity – Avidity is the accumulated strength of multiple
binding interactions.
Angiogenesis – Angiogenesis is the development,
formation, and maintenance of blood vessel structures. Without
sufficient blood flow, tissue may experience hypoxia (insufficient
oxygen) or lack of nutrition, which may cause cell death.9
Cooperative binding – Cooperative binding occurs when the
number of binding sites on the molecule that can be occupied by a
specific ligand (e.g., protein) is impacted by the ligand’s
concentration. For example, this can be due to an affinity for the
ligand that depends on the amount of ligand bound or the binding
strength of the molecule to one ligand based on the concentration
of another ligand, increasing the chance of another ligand binding
to the compound.10
Immunotherapy – Immunotherapy is a type of treatment,
including cancer treatments, that help a person’s immune system
fight cancer. Examples include anti-PD-1 therapies.11
PD-1 – Programmed cell
Death protein 1 is a protein on the surface of T cells and other
cells. PD-1 plays a key role in reducing the regulation of
ineffective or harmful immune responses and maintaining immune
tolerance. However, with respect to cancer tumor cells, PD-1 can
act as a stopping mechanism (a brake or checkpoint) by binding to
PD-L1 ligands that exist on tumor cells and preventing the T cells
from targeting cancerous tumor cells.12
PD-L1 – Programmed cell
Death Ligand 1 is expressed
by cancerous tumor cells as an adaptive immune mechanism to escape
anti-tumor responses, thus believed to suppress the immune system’s
response to the presence of cancer cells. 13
T Cells – T cells are a type of white blood cell that is
a component of the immune system that, in general, fights against
infection and harmful cells like tumor cells.14
Tetravalent – A tetravalent molecule has four binding
sites or regions.
Tumor Microenvironment – The tumor microenvironment is
the ecosystem that surrounds a tumor inside the body. It includes
immune cells, the extracellular matrix, blood vessels and other
cells, like fibroblasts. A tumor and its microenvironment
constantly interact and influence each other, either positively or
negatively.15
VEGF – Vascular Endothelial Growth
Factor is a signaling protein that
promotes angiogenesis. 16
___________________________________ 1 Poster Authors: Tingting
Zhong, Zhaoliang Huang, Xinghua Pang, Chunshan Jin, Xinrong He,
Jose G. Montoya, Hugh Wang, Betty Y Chang, Michelle Xia, Baiyong
Li, Jing Min 2 Zhong, et al, SITC 2022 ; Zhong, et al, SITC 2023 3
Zhong, et al, SITC 2023 4 American Cancer Society:
https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html.
Accessed October 2023 5 World Health Organization:
https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf.
Accessed October 2023. 6 Schabath MB, Cote ML. Cancer Progress and
Priorities: Lung Cancer. Cancer Epidemiol Biomarkers Prev.
2019;28(10):1563-1579. 7 Choi WI, Jeong J, Lee CW. Association
between EGFR mutation and ageing, history of pneumonia and
gastroesophageal reflux disease among patients with advanced lung
cancer. Eur J Cancer. 2019 Nov;122:101-108. 8 Schabath MB, Cote ML.
Cancer Progress and Priorities: Lung Cancer. Cancer Epidemiol
Biomarkers Prev. 2019;28(10):1563-1579. 9 Shibuya M. Vascular
Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling
in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic
Therapies. Genes Cancer. 2011 Dec;2(12):1097-105. 10 Stefan MI, Le
Novère N. Cooperative binding. PLoS Comput Biol. 2013;9(6) 11 US
National Cancer Institute, a part of the National Instutite of
Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed October 2023. 12 Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. 13
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am
J Cancer Res. 2020 Mar 1;10(3):727-742. 14 Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
October 2023. 15 MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed October 2023. 16 Shibuya M. Vascular Endothelial Growth
Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A
Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes
Cancer. 2011 Dec;2(12):1097-105.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231031533380/en/
Contact Summit Investor Relations: Dave Gancarz Chief
Business & Strategy Officer investors@smmttx.com
Grafico Azioni Summit Therapeutics (NASDAQ:SMMT)
Storico
Da Ago 2024 a Set 2024
Grafico Azioni Summit Therapeutics (NASDAQ:SMMT)
Storico
Da Set 2023 a Set 2024