Unprecedented: Ivonescimab Is the First Drug to
Achieve Clinically Meaningful Benefit over Pembrolizumab in
Randomized Phase III Clinical Trial in NSCLC
Monotherapy Ivonescimab Achieved Clinically
Meaningful PFS Benefit in HARMONi-2 Trial Conducted by Akeso
PFS Improvement Was Observed Broadly in
Patients Across Subgroups, including PD-L1 Low and PD-L1 High
Expressing Tumors, Squamous and Non-Squamous Histologies
Full Data Set to be Presented at an Upcoming
Major Medical Conference Planned for Later This Year
Conference Call to be Held at 8:00am ET on
Monday, June 3, 2024
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) today announced that the Phase III clinical trial,
HARMONi-2 or AK112-303, met its primary endpoint of
progression-free survival (PFS). 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 Akeso, Inc. (Akeso, HKEX Code: 9926.HK) with data
generated and analyzed by Akeso.
At a prespecified interim analysis conducted by an independent
Data Monitoring Committee, ivonescimab demonstrated a statistically
significant and clinically meaningful improvement in PFS by blinded
independent central radiology review committee (BICR) compared to
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.
There are no known Phase III clinical trials in NSCLC which have
shown a statistically significant improvement compared to
pembrolizumab in a head-to-head setting.
The Phase III HARMONi-2 study, along with the approval of
ivonescimab in China in combination with chemotherapy based on the
results of the HARMONi-A trial, provides clear evidence supporting
the purposefully engineered, differentiated mechanism of action of
ivonescimab, a PD-1 / VEGF bispecific antibody evidencing
cooperative binding characteristics, and its opportunity to improve
upon the existing standards of care for solid tumors.
“HARMONi-2 clearly demonstrates that ivonescimab is the next
generation in PD-1 directed immunotherapy, and its potential to
make a significant difference in the lives of patients with lung
cancer and prospectively other tumors,” stated Dr. Maky Zanganeh,
Chief Executive Officer and President of Summit. “We want to
congratulate our partners at Akeso for this incredible result and
their work to advance the patient-friendly standards of care today
and well into the future. This result validates Team Summit’s
present-time intention to execute a development plan worthy of
ivonescimab’s emergent potential – including clinical trials in
both NSCLC and other solid tumors where ivonescimab can improve
upon existing standards of care.”
“This is an historic moment for ivonescimab, Team Summit, our
partners at Akeso, and most importantly, we believe this is the
beginning of a paradigm change for treatment options for patients
living with cancer,” added Robert W. Duggan, Chairman and Chief
Executive Officer of Summit. “We are incredibly proud of our
partnership with Akeso and their accomplishment with the HARMONi-2
trial.”
Conference Call
Summit Therapeutics Inc. will host a conference call to discuss
recent updates related to ivonescimab, including data released at
ASCO, on Monday, June 3, 2024, before the market opens.
Summit will host a live webcast of the conference call at 8:00am
ET, which will be accessible through our website www.smmttx.com. An
archived edition of the session will be available on our
website.
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
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. 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, and over 4-times increased binding affinity to VEGF in
the presence of PD-1 in vitro.1 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,1 is to improve upon previously
established efficacy thresholds, in addition to side effects and
safety profiles associated with these targets.
Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK)
and is currently engaged in multiple Phase III clinical trials.
Over 1,600 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 Phase III clinical trials, HARMONi and
HARMONi-3.
The safety profile of ivonescimab is manageable and consistent
with known risks for PD-1 and VEGF inhibiting drugs. In the first
Phase III study to be presented at ASCO, “Ivonescimab combined with
chemotherapy in patients with EGFR-mutant non-squamous NSCLC who
progressed on EGFR TKI treatment (HARMONi-A): A randomized,
double-blind, multi-center, phase 3 trial,” 5.6% of patients
discontinued ivonescimab due to adverse events.
HARMONi is a Phase III clinical trial which intends to evaluate
ivonescimab combined with chemotherapy compared to a placebo plus
chemotherapy in patients with EGFR-mutated, locally advanced or
metastatic non-squamous NSCLC who have progressed after treatment
with a third-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.
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 Lung Cancer
Lung cancer is believed to impact approximately 600,000 people
across the United States, United Kingdom, Spain, France, Italy,
Germany, and Japan.2 NSCLC is the most prevalent type of lung
cancer and represents approximately 80% to 85% of all incidences.3
Among patients with non-squamous NSCLC, approximately 15% have
EGFR-sensitizing mutations in the United States and Europe.4
Patients with squamous histology represent approximately 25% to 30%
of NSCLC patients.5
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 @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 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
use 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.
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.6
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.7
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.8
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.9
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.10
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.11
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.12
VEGF – Vascular Endothelial Growth Factor is a signaling
protein that promotes angiogenesis.13
_______________ 1 Zhong, et al, SITC 2023. 2 American Cancer
Society:
www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html.
Accessed April 2024; World Health Organization: International
Agency for Research on Cancer, Globocan data by country (UK, Spain,
France, Italy, Germany); Japan National Cancer Registry. 3 Schabath
MB, Cote ML. Cancer Progress and Priorities: Lung Cancer. Cancer
Epidemiology, Biomarkers & Prevention. (2019). 4 About
EGFR-Positive Lung Cancer | Navigating EGFR (lungevity.org). 5
Schabath MB, Cote ML. Cancer Progress and Priorities: Lung Cancer.
Cancer Epidemiology, Biomarkers & Prevention. (2019). 6 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. 7
Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol.
2013;9(6). 8 US National Cancer Institute, a part of the National
Institute of Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed April 2024. 9 Han Y, et al. PD-1/PD-L1 Pathway: Current
Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. 10
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am
J Cancer Res. 2020 Mar 1;10(3):727-742. 11 Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
April 2024. 12 MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed April 2024. 13 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/20240530536730/en/
Summit Investor Relations: Dave Gancarz Chief Business
& Strategy Officer
Nathan LiaBraaten Senior Director, Investor Relations
investors@smmttx.com
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