Monotherapy Ivonescimab Achieved Clinically
Meaningful PFS Benefit Compared to Monotherapy Pembrolizumab in
HARMONi-2 Trial Conducted by Akeso
Ivonescimab Is the First Drug to Achieve
Clinically Meaningful Benefit over Pembrolizumab in Randomized
Phase III Clinical Trial in NSCLC
Additionally, Ivonescimab Phase II Data in
Perioperative Setting for Resectable NSCLC to be Presented
Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the
"Company") today announced that the primary analysis of the Phase
III HARMONi-2 trial featuring its novel, potential first-in-class
investigational bispecific antibody, ivonescimab, will be presented
as part of the Presidential Symposium at the International
Association for the Study of Lung Cancer’s (IASLC) 2024 World
Conference on Lung Cancer (WCLC 2024) in San Diego, California. The
presentation will take place on Sunday, September 8, 2024 at 8:37
am PT (11:37 am ET).
HARMONi-2 evaluated monotherapy ivonescimab against monotherapy
pembrolizumab in patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1
expression (PD-L1 TPS >1%). HARMONi-2 is a single region,
multi-center, double-blinded Phase III study conducted in China
sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX
Code: 9926.HK), with data generated and analyzed by Akeso.
There are no known Phase III clinical trials in NSCLC that have
shown a statistically significant efficacy improvement compared to
pembrolizumab in a head-to-head setting.
On May 30, 2024, Akeso announced that in HARMONi-2 ivonescimab
monotherapy achieved a statistically significant improvement in the
trial’s primary endpoint, progression-free survival (PFS), when
compared to monotherapy pembrolizumab. The PFS benefit was
demonstrated across clinical subgroups, including those with PD-L1
low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS
≥50%), squamous and non-squamous histologies, as well as other
high-risk patients.
The trial results will be presented by Dr. Caicun Zhou, Chief
Physician and Director of the Department of Medical Oncology at
Shanghai Pulmonary Hospital, Tongji University School of Medicine,
and President-Elect of IASLC.
A second presentation titled, “A Phase II Study of Perioperative
Ivonescimab Alone or Combined with Chemotherapy in Resectable
Non-Small Cell Lung Cancer” will include data from the Phase II
trial, AK112-205, which is conducted and sponsored by Akeso,
featuring data from ivonescimab in the perioperative, early-stage
NSCLC setting.
About the WCLC 2024 Presentations
First Presentation
Presentation Title: Phase 3 Study of Ivonescimab (AK112) vs.
Pembrolizumab as First-line Treatment for PD-L1-positive Advanced
NSCLC: Primary Analysis of HARMONi-2
Presenter: Caicun Zhou, MD, PhD
WCLC Presentation No.: PL02.04
Session Date & Time: Sunday, September 8, 8:37 am PT (11:37
am ET) Second Presentation
Presentation Title: A Phase II Study of Perioperative
Ivonescimab Alone or Combined with Chemotherapy in Resectable
Non-Small Cell Lung Cancer
Presenter: Xiaoliang Zhao, MD
WCLC Presentation No.: OA01.06
Session Date & Time: Sunday, September 8, 11:17 am PT (2:17
pm ET)
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
the United States, Canada, Europe, Japan, Latin America, including
Mexico and all countries in Central America, South America, and the
Caribbean, the Middle East, and Africa, 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 displays unique
cooperative binding to each of its intended targets with multifold
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, and over 4-times increased binding affinity to VEGF in
the presence of PD-1 in vitro (Zhong, et al, SITC, 2023). 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, together with a half-life of 6 to 7 days
(Zhong, et. al., SITC, 2023), is to improve upon previously
established efficacy thresholds, as well as to improve upon side
effects and safety profiles associated with these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK)
and is currently engaged in multiple Phase III clinical trials.
Over 1,800 patients have been treated with ivonescimab in clinical
studies globally.
Summit has begun its clinical development of ivonescimab in
non-small cell lung cancer (NSCLC), commencing enrollment in 2023
in two multi-regional Phase III clinical trials, HARMONi and
HARMONi-3.
HARMONi is a Phase III clinical trial which intends to evaluate
ivonescimab combined with chemotherapy compared to placebo plus
chemotherapy in patients with EGFR-mutated, locally advanced or
metastatic non-squamous NSCLC who have progressed after treatment
with a 3rd generation EGFR TKI (e.g., osimertinib).
HARMONi-3 is a Phase III clinical trial which is designed to
evaluate ivonescimab combined with chemotherapy compared to
pembrolizumab combined with chemotherapy in patients with
first-line metastatic squamous NSCLC.
In addition, Akeso has recently had positive read-outs in two
single-region (China), randomized Phase III clinical trials for
ivonescimab in NSCLC, HARMONi-A and HARMONi-2.
HARMONi-A was a Phase III clinical trial which evaluated
ivonescimab combined with chemotherapy compared to placebo plus
chemotherapy in patients with EGFR-mutated, locally advanced or
metastatic non-squamous NSCLC who have progressed after treatment
with an EGFR TKI.
HARMONi-2 is a Phase III clinical trial evaluating monotherapy
ivonescimab against monotherapy pembrolizumab in patients with
locally advanced or metastatic NSCLC whose tumors have positive
PD-L1 expression (PD-L1 TPS >1%).
Ivonescimab is an investigational therapy that is not approved
by any regulatory authority in Summit’s license territories,
including the United States and Europe. Ivonescimab was approved
for marketing authorization in China in May 2024.
About Summit Therapeutics
Summit Therapeutics Inc. is a biopharmaceutical oncology company
focused on the discovery, development, and commercialization of
patient-, physician-, caregiver- and societal-friendly medicinal
therapies intended to improve quality of life, increase potential
duration of life, and resolve serious unmet medical needs.
Summit was founded in 2003 and our shares are listed on the
Nasdaq Global Market (symbol "SMMT"). We are headquartered in
Miami, Florida, and we have additional offices in Menlo Park,
California, and Oxford, UK.
For more information, please visit https://www.smmttx.com and
follow us on X @SMMT_TX.
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., including the expected
benefits of the amendment to the collaboration and license
agreement, the intended use of the net proceeds from the private
placement, the Company's anticipated spending and cash runway, 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, potential acquisitions, statements about the
previously disclosed At-The-Market equity offering program (“ATM
Program”), the expected proceeds and uses thereof, 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 Company’s ability to sell shares of our
common stock under the ATM Program, the conditions affecting the
capital markets, general economic, industry, or political
conditions, including the results of our evaluation of the
underlying data in connection with the development and
commercialization activities for ivonescimab, 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, 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 ivonescimab. 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.
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.1
Avidity – Avidity is the accumulated strength of multiple
binding interactions.
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.2
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.3
Intracranial - Within the cranium or skull.
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.4
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.5
PD-L1 TPS – PD-L1 Tumor Proportion Score represents the
percentage of tumor cells that express PD-L1 proteins.
PFS – Progression-Free Survival.
RANO – Response Assessment in Neuro-Oncology, the
standard for assessing the response of a brain or spinal cord tumor
to therapy.
SQ-NSCLC – Non-small cell lung cancer tumors of squamous
histology.
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.6
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.7
VEGF – Vascular Endothelial Growth Factor is a signaling
protein that promotes angiogenesis.8
___________________
1
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
2
Stefan MI, Le Novère N. Cooperative
binding. PLoS Comput Biol. 2013;9(6)
3
US National Cancer Institute, a part of
the National Institutes of Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed April 2024.
4
Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar
1;10(3):727-742.
5
Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar
1;10(3):727-742.
6
Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
April 2024.
7
MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed April 2024.
8
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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240812145996/en/
Contact Summit Investor Relations: Dave Gancarz Chief
Business & Strategy Officer
Nathan LiaBraaten Senior Director, Investor Relations
investors@smmttx.com
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