Summit Therapeutics Reports Financial Results and Operational Progress for the First Quarter Ended March 31, 2024
HARMONi and HARMONi-3 Enrollment Continues
Promising Intracranial Anti-Tumor Activity and Safety Data Featured at the 2024
Board of Directors Strengthened with the Addition of Dr.
Updated Guidance of Cash Runway for Operations through Q1 2025
Operational & Corporate Updates
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Our operational progress continues with ivonescimab (SMT112), an investigational, potentially first-in-class 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:
January 2024 marked the one-year anniversary of the close of our Collaboration and License Agreement with (Akeso Inc .Akeso ) for ivonescimab (SMT112), with which over 1,600 have been treated in clinical studies globally. Summit received rights to develop and commercialize ivonescimab inthe United States ,Canada ,Europe , andJapan , whileAkeso retains development and commercialization rights for the rest of the world, includingChina . Since in-licensing ivonescimab, we launched late-stage clinical development in non-small cell lung cancer (NSCLC) and are actively enrolling two registrational Phase III trials in the following proposed indications:-
HARMONi Phase III Trial: 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), with enrollment completion expected in the second half of 2024, and - HARMONi-3 Phase III Trial: Ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients, with the first patient having been treated in the fourth quarter of 2023.
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HARMONi Phase III Trial: Ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous NSCLC
-
In
January 2024 , followed by a presentation at ELCC 2024 inMarch 2024 ,Akeso announced updates from its Phase II AK112-201 trial data. Notably, in patients with first line advanced or metastatic squamous NSCLC without actionable genomic alterations (Cohort 1, n=63), a median PFS (mPFS) of 11.1 months (95% CI: 9.5 – 16.3 months) was observed; median overall survival (mOS) was not yet reached after a median follow-up time of 22.1 months. Additionally, in patients with advanced or metastatic NSCLC whose tumors are positive for EGFR mutations and have progressed following an EGFR TKI (Cohort 2, n=19), mPFS of 8.5 months (95% CI: 4.1 – 12.9 months) was observed, and a mOS of 22.5 months (95% CI: 10.4 - NE) was achieved after a median follow-up time of 25.8 months. Treatment-related adverse events leading to discontinuation of ivonescimab was 11% and 0% in the two populations, respectively; there were no treatment-related adverse events leading to a patient's death in either setting. AK112-201 is a study of Chinese subjects receiving ivonescimab plus chemotherapy conducted and analyzed by our partners,Akeso , of which the updated data supports Summit's HARMONi and HARMONi-3 Phase III clinical trials. -
Also at ELCC 2024, Summit and
Akeso highlighted promising ivonescimab Phase II data in NSCLC patients with brain metastases. The analysis consisted of 35 patients with advanced or metastatic NSCLCwho had asymptomatic brain metastases at baseline and received ivonescimab alone or in combination with chemotherapy. Across all patients analyzed, an intracranial response rate of 34% was achieved, including 23% complete responses, by response assessment in neuro-oncology (RANO) criteria and median intracranial progression-free survival was 19.3 months. All patientswho did not achieve a response demonstrated stable disease or non-progression; no patients experienced intracranial disease progression at the time of the initial follow-up scan. No cases of intracranial bleeding complications were observed in these patients. The data was from patients participating in AK112-201, described above, or AK112-202, in which ivonescimab was delivered as monotherapy. -
In
April 2024 , the Company appointedMostafa Ronaghi , PhD, to its Board of Directors.Dr. Ronaghi is the Co-Founder and Executive Board Member of Cellanome. He was previously the Chief Technology Officer at Illumina, Inc. from 2008 to 2021. While at Illumina, in 2016,Dr. Ronaghi co-founded GRAIL, a next-gen liquid biopsy platform for cancer detection. Prior to Illumina,Dr. Ronaghi was Principal Investigator at theStanford Genome Technology Center from 1999 to 2008. Throughout his prolific career,Dr. Ronaghi co-founded several companies which sought to increase the understanding of particular diseases through next-generation sequencing (NGS), advanced genotyping, or other advanced technology.Dr. Ronaghi holds a Ph.D. in Biotechnology fromRoyal Institute of Technology inStockholm, Sweden .
Financial Highlights
Cash and Cash Equivalents, Restricted Cash, & Short-term Investments
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Aggregate cash and cash equivalents, restricted cash, and short-term investments were
$157.0 million and$186.2 million atMarch 31, 2024 andDecember 31, 2023 , respectively. Research and development tax credits were$1.2 million and$1.8 million atMarch 31, 2024 andDecember 31, 2023 , respectively.-
Our short-term investments consist of
U.S. treasury securities. -
Operating cash outflow for the three months ended
March 31, 2024 and 2023 was$30.1 million and$13.1 million , respectively.
-
Our short-term investments consist of
-
R&D expenses according to generally accepted accounting principles in the
U.S. (“GAAP”) were$30.9 million for the first quarter of 2024, compared to$9.9 million for the same period of the prior year.
-
Non-GAAP R&D expenses were
$28.5 million for the first quarter of 2024, compared to$8.8 million for the same period of the prior year.
GAAP and Non-GAAP General and Administrative (G&A) Expenses
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GAAP G&A expenses were
$11.7 million for the first quarter of 2024, compared to$6.9 million for the same period of the prior year.
-
Non-GAAP G&A expenses were
$4.6 million for the first quarter of 2024, compared to$5.2 million for the same period of the prior year.
GAAP and Non-GAAP Operating Expenses
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GAAP operating expenses were
$42.6 million for the first quarter of 2024, compared to$537.7 million for the same period of the prior year. First quarter 2023 GAAP operating expenses included$520.9M in-process research and development expense that was primarily related to our upfront milestone payments pursuant to the License Agreement withAkeso .
-
Non-GAAP operating expenses were
$33.1 million for the first quarter of 2024, compared to$14.0 million for the same period of the prior year. The increase is primarily due to expansion of clinical study and development costs related to ivonescimab and increases in people cost as we continue to build out our R&D team.
GAAP and Non-GAAP Net Loss
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GAAP net loss in the first quarter of 2024 and 2023 was
$43.5 million or$0.06 per basic and diluted share, and$542.3 million or$1.43 per basic and diluted share, respectively.
-
Non-GAAP net loss in the first quarter of 2024 and 2023 was
$34.0 million or$0.05 per basic and diluted share, and$18.6 million or$0.04 per basic and diluted share, respectively.
Use of Non-GAAP Financial Results
This release includes measures that are not in accordance with
First Quarter 2024 Earnings Call
Summit will host an earnings call this morning,
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories,
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
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
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.
About Lung Cancer
Lung cancer is believed to impact approximately 600,000 people across
About
Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol "SMMT"). We are headquartered in
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
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GAAP Condensed Consolidated Statements of Operations |
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(in millions, except per share data) |
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Unaudited |
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Three Months Ended |
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Q1 2024 |
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Q1 2023 |
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Operating expenses: |
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Research and development |
$ |
30.9 |
|
|
$ |
9.9 |
|
|
General and administrative |
|
11.7 |
|
|
|
6.9 |
|
|
In-process research and development |
|
— |
|
|
|
520.9 |
|
|
Total operating expenses |
|
42.6 |
|
|
|
537.7 |
|
|
Other operating income, net |
|
0.2 |
|
|
|
0.6 |
|
|
Operating loss |
|
(42.4 |
) |
|
|
(537.1 |
) |
|
Other expense, net |
|
(1.1 |
) |
|
|
(5.2 |
) |
|
Net loss |
$ |
(43.5 |
) |
|
$ |
(542.3 |
) |
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|
|
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Basic and diluted loss per share |
$ |
(0.06 |
) |
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$ |
(1.43 |
) |
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GAAP Condensed Consolidated Balance Sheet Information |
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(in millions) |
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Unaudited
|
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Cash and cash equivalents, restricted cash, and short-term investments |
|
$ |
157.0 |
|
$ |
186.2 |
||
Total assets |
|
$ |
176.8 |
|
$ |
202.9 |
||
Total liabilities |
|
$ |
132.6 |
|
$ |
125.3 |
||
Total stockholders' equity |
|
$ |
44.2 |
|
$ |
77.7 |
||
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GAAP Condensed Consolidated Statement of Cash Flows Information |
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(in millions) |
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Unaudited |
||||||
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Three Months Ended |
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2024 |
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2023 |
||||
Net cash used in operating activities |
|
$ |
(30.1 |
) |
|
$ |
(13.1 |
) |
Net cash provided by (used in) investing activities |
|
|
19.8 |
|
|
|
(645.1 |
) |
Net cash provided by financing activities |
|
|
0.5 |
|
|
|
80.1 |
|
Effect of exchange rate changes on cash |
|
|
— |
|
|
|
0.4 |
|
Decrease in cash and cash equivalents |
|
$ |
(9.8 |
) |
|
$ |
(577.7 |
) |
|
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Schedule Reconciling Selected Non-GAAP Financial Measures |
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(in millions, except per share data) |
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Unaudited |
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Three Months Ended |
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2024 |
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2023 |
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Reconciliation of GAAP to |
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$ |
30.9 |
|
$ |
9.9 |
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Stock-based compensation (Note 1) |
|
(2.4 |
) |
|
(1.1 |
) |
||
|
$ |
28.5 |
|
$ |
8.8 |
|
||
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Reconciliation of GAAP to Non-GAAP General and Administrative Expenses |
|
|
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GAAP General and administrative |
$ |
11.7 |
|
$ |
6.9 |
|
||
Stock-based compensation (Note 1) |
|
(7.1 |
) |
|
(1.7 |
) |
||
Non-GAAP General and administrative |
$ |
4.6 |
|
$ |
5.2 |
|
||
|
|
|
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Reconciliation of GAAP to |
|
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GAAP In-process research and development |
$ |
— |
|
$ |
520.9 |
|
||
In-process research and development (Note 2) |
|
— |
|
|
(520.9 |
) |
||
Non-GAAP In-process research and development |
$ |
— |
|
$ |
— |
|
||
|
|
|
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Reconciliation of GAAP Net Loss to Non-GAAP Net Loss |
|
|
||||||
GAAP Net Loss |
$ |
(43.5 |
) |
$ |
(542.3 |
) |
||
Stock-based compensation (Note 1) |
|
9.5 |
|
|
2.8 |
|
||
In-process research and development (Note 2) |
|
— |
|
|
520.9 |
|
||
Non-GAAP Net Loss |
$ |
(34.0 |
) |
$ |
(18.6 |
) |
||
|
|
|
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Reconciliation of GAAP Net Loss to Non-GAAP Net Loss Per Common Share |
|
|
||||||
GAAP Net Loss Per Basic and Diluted Common Share |
$ |
(0.06 |
) |
$ |
(1.43 |
) |
||
Stock-based compensation (Note 1) |
|
0.01 |
|
|
0.01 |
|
||
In-process research and development (Note 2) |
|
— |
|
|
1.38 |
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Non-GAAP Net loss Per Basic and Diluted Common Share |
$ |
(0.05 |
) |
$ |
(0.04 |
) |
||
Basic and Diluted Common Shares |
|
701.8 |
|
|
378.2 |
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Schedule Reconciling Selected Non-GAAP Financial Measures |
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(in millions) |
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Unaudited |
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Three Months Ended |
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Reconciliation of GAAP to Non-GAAP Operating Expenses |
|
|
|
|
|
|
|
|
|
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||||||||||
GAAP Operating expenses |
|
$ |
42.6 |
|
|
$ |
36.4 |
|
|
$ |
20.8 |
|
|
$ |
15.8 |
|
|
$ |
537.7 |
|
Stock-based compensation (Note 1) |
|
|
(9.5 |
) |
|
|
(8.7 |
) |
|
|
(0.7 |
) |
|
|
(1.9 |
) |
|
|
(2.8 |
) |
In-process research and development (Note 2) |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
(520.9 |
) |
Non-GAAP Operating Expense |
|
$ |
33.1 |
|
|
$ |
27.7 |
|
|
$ |
20.1 |
|
|
$ |
13.9 |
|
|
$ |
14.0 |
|
|
|
|
|
|
|
|
|
|
|
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||||||||||
Reconciliation of GAAP Net Loss to Non-GAAP Net Loss |
|
|
|
|
|
|
|
|
|
|
||||||||||
GAAP Net Loss |
|
$ |
(43.5 |
) |
|
$ |
(36.6 |
) |
|
$ |
(21.3 |
) |
|
$ |
(14.7 |
) |
|
$ |
(542.3 |
) |
Stock-based compensation (Note 1) |
|
|
9.5 |
|
|
|
8.7 |
|
|
|
0.7 |
|
|
|
1.9 |
|
|
|
2.8 |
|
In-process research and development (Note 2) |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
520.9 |
|
Non-GAAP Net Loss |
|
$ |
(34.0 |
) |
|
$ |
(27.9 |
) |
|
$ |
(20.6 |
) |
|
$ |
(12.8 |
) |
|
$ |
(18.6 |
) |
|
|
|
|
|
|
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Notes on our Non-GAAP Financial Information
Non-GAAP financial measures adjust GAAP financial measures for the items listed below. These Non-GAAP measures should be viewed in addition to, and not as a substitute for Summit's reported GAAP results, and may be different from Non-GAAP measures used by other companies. In addition, these Non-GAAP measures are not based on any comprehensive set of accounting rules or principles. Summit management uses these non-GAAP measures for internal budgeting and forecasting purposes and to evaluate Summit’s financial performance. Summit management believes the presentation of these Non-GAAP measures is useful to investors for comparing prior periods and analyzing ongoing business trends and operating results.
Each of non-
Note 1: Stock-based compensation is a non-cash charge and costs calculated for this expense can vary year-over-year depending on the stock price of awards on the date of grant as well as the timing of compensation award arrangements.
Note 2: In-process research and development represents a one-time charge associated with the Company's in-licensing of ivonescimab from
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 |
|
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 |
8 |
US |
9 |
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 |
10 |
Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 |
11 |
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12 |
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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/20240501878504/en/
Contact Summit Investor Relations:
Chief Business & Strategy Officer
Senior Director, Investor Relations
investors@smmttx.com
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