Phase II 24-Month OS Rate of 64.8% in 1L
Squamous NSCLC Patients
Phase II mOS of 22.5 Months in 2L+ EGFRm,
TKI-progressed NSCLC Patients
Catalyst Events Expected in Q2 2024 for Two
Randomized Phase III Trials Evaluating Ivonescimab in China
Conducted by Akeso, including Head-to-Head vs. Pembrolizumab
Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the
“Company”) today announced substantial updates to the promising
development of ivonescimab, as well as near-term corporate
catalysts that it will present at the 42nd Annual J.P. Morgan
Healthcare Conference on Tuesday, January 09, 2024, at 1:30 PM PT
in San Francisco, CA.
AK112-201 (NCT04736823) is an open-label Phase II study
evaluating ivonescimab plus chemotherapy across three cohorts of
patients. In part, data generated from this trial has supported
Summit’s decision to advance ivonescimab into two global Phase III
clinical trials. Updated data includes patients from Cohorts 1
& 2 of this study:
- Cohort 1: Patients with first line advanced or metastatic
non-small cell lung cancer (NSCLC) without actionable genomic
alterations (i.e., patients’ tumors do not have actionable
mutations in endothelial growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK)).
- The updated data centers on the 63 patients whose tumors are of
squamous histology.
- Cohort 2: Patients with second or third line advanced or
metastatic NSCLC whose tumors are positive for EGFR mutations
(EGFRm) and have progressed following an EGFR tyrosine kinase
inhibitor (TKI) (n=19).
Notably, the estimated 1-year overall survival rate was 85.6%,
and the 2-year overall survival rate was 64.8% for patients in
Cohort 1 with squamous histology NSCLC. After a median follow-up
time of 21.0 months, the median overall survival (OS) was not
reached.1 The frequency of treatment-related adverse events (TRAEs)
leading to discontinuation of ivonescimab was 11%; there were no
TRAEs leading to the death of a patient. The most frequent
treatment-emergent adverse events were anemia, decreased neutrophil
counts, and decreased white-blood cell counts.
The 19 patients in Cohort 2, primarily second or third line
patients with EGFRm NSCLC, demonstrated a median overall survival
of 22.5 months. After a median follow-up time of 25.8 months, the
estimated 1-year overall survival rate was 74%.1 Ivonescimab had an
acceptable safety profile in combination with platinum-doublet
chemotherapy for patients with advanced or metastatic NSCLC who had
progressed following an EGFR-TKI. There were no TRAEs leading to
permanent discontinuation of therapy or patient death.
AK112-201 Phase II
Trial1
Cohort 1: 1L SQ-NSCLC only
(n=63)
Cohort 2: 2L / 3L+ EGFR-TKI
Progressors NSCLC (n=19)
Overall Response Rate
(ORR)*
67%
68%
Disease Control Rate
(DCR)*
95%
95%
Median Duration of Response
(DOR)*
12.8 months
8.7 months
Median PFS (95%
CI)
11.1 months (9.5 – 16.3
months)
8.5 months (5.5 – 13.3
months)
Median OS (95%
CI)
Not Reached (22.5 months –
NE**)
22.5 months (10.4 months –
NE**)
12-month OS Rate
85.6%
73.7%
24-month OS Rate
64.8%
40.9%
* Confirmed responses for patients with at least one
post-baseline scan; SQ-NSCLC n=60; EGFR-TKI n=19
** NE – Not Established
AK112-201 is a clinical trial that is sponsored and conducted in
China by our collaboration and licensing partner, Akeso, Inc. (HKEX
Code: 9926.HK). The aforementioned data related to AK112-201 was
generated and analyzed by Akeso.
Summit is enrolling patients in two global Phase III clinical
trials involving ivonescimab:
- HARMONi 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 (NCT05184712), and
- HARMONi-3 is designed to evaluate ivonescimab combined with
chemotherapy compared to pembrolizumab combined with chemotherapy
in patients with 1L metastatic squamous NSCLC (NCT05899608).
Near-Term Catalyst Events for Summit & the Development of
Ivonescimab
In addition to the ongoing Phase III clinical trials sponsored
by Summit, Akeso is sponsoring four Phase III clinical trials
investigating ivonescimab in China in NSCLC. Near-term catalyst
events for both Summit and Akeso include expected key milestones
for two of Akeso’s Phase III randomized clinical trials evaluating
ivonescimab in China:
- AK112-301, which reflects the patient population of Summit’s
HARMONi trial, was submitted for marketing approval to the Chinese
health authority in 2023, and a decision from the Chinese Center
for Drug Evaluation (CDE) is expected in Q2 2024, along with a
read-out of topline data from the study by Akeso, and
- AK112-303, which is evaluating monotherapy ivonescimab vs.
pembrolizumab in 1L NSCLC patients whose tumors have a PD-L1 TPS
>1%, has a planned interim analysis
by Akeso, which is expected to be completed in Q2 2024.
Both studies represent ivonescimab in randomized, pivotal
clinical trials against the standard of care in their respective
settings.
“As the data continues to mature in Phase II studies evaluating
ivonescimab, including data related to the survival of patients
impacted by these terrible diseases, our belief and conviction in
ivonescimab is reinforced,” stated Summit’s Chief Executive
Officers, Robert W. Duggan and Dr. Maky Zanganeh. “The speed and
purpose with which Team Summit acts reflect the opportunity to
accomplish our mission of making a significant difference in the
lives of patients facing difficult odds from a cancer diagnosis. We
believe that the potential created by the differentiated mechanism
of action and supporting trial data for ivonescimab deserves a
swift development plan to bring ivonescimab to those patients who
can benefit most. We are honored to work with our partners at Akeso
to continue to strive to achieve this common goal.”
In addition to live attendance at the JPM 2024 conference, the
audio presentation will be available live from our website:
www.smmttx.com.
Update Regarding Current Financial Position
As of December 31, 2023, the company’s preliminary unaudited
balance of cash, cash equivalents, and short-term investments was
no less than $186 million. This amount is preliminary and is
subject to completion of financial closing procedures. As a result,
this amount may differ materially from the amount that will be
reflected in the Company’s consolidated financial statements for
the year ended December 31, 2023.
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.2 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.
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,
commencing enrollment in 2023 in its two Phase III clinical trials.
Over 1,600 patients have been treated with ivonescimab in clinical
studies in China and Australia, with enrollment beginning in 2023
in Summit's license territories.
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.3 NSCLC is the most prevalent type of lung
cancer and represents approximately 80% to 85% of all incidences.4
Among patients with non-squamous NSCLC, approximately 15% have
EGFR-sensitizing mutations in the United States and Europe.5
Patients with squamous histology represent approximately 25% to 30%
of NSCLC patients. 6
About Summit Therapeutics
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.
Summit’s mission, in part, is to develop 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.
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,
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 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.7
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.8
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.9
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.10
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. 11
PD-L1 TPS – PD-L1 Tumor
Proportion Score represents the percentage of tumor cells
that express PD-L1 proteins.
PFS – Progression-Free
Survival.
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.12
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.13
VEGF – Vascular Endothelial Growth
Factor is a signaling protein that
promotes angiogenesis. 14
1 Akeso, Inc. Press Release, January 8, 2024.
2 Zhong, et al, SITC 2023
3 American Cancer Society:
www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
(Accessed Jan 2024); World Health Organization: International
Agency for Research on Cancer, Globocan data by country (UK, Spain,
France, Italy, Germany); Japan National Cancer Registry.
4 Schabath MB, Cote ML. Cancer Progress and Priorities: Lung
Cancer. Cancer Epidemiology, Biomarkers & Prevention.
(2019).
5 About EGFR-Positive Lung Cancer | Navigating EGFR
(lungevity.org)
6 Schabath MB, Cote ML. Cancer Progress and Priorities: Lung
Cancer. Cancer Epidemiology, Biomarkers & Prevention.
(2019).
7 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.
8 Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol.
2013;9(6)
9 US National Cancer Institute, a part of the National Institute
of Health (NIH).
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy.
Accessed October 2023.
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 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in
Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742.
12 Cleveland Clinic.
https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed
October 2023.
13 MD Anderson Cancer Center.
https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00-159460056.html.
Accessed October 2023.
14 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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Summit Investor Relations: Dave Gancarz Chief Business
& Strategy Officer investors@smmttx.com
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