On May 1, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported its financial results and provides an update on its operational progress for the first quarter ended March 31, 2024 (Press release, Summit Therapeutics, MAY 1, 2024, View Source [SID1234642544]).
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Operational & Corporate Updates
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 in the United States, Canada, Europe, and Japan, while Akeso retains development and commercialization rights for the rest of the world, including China. 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.
In January 2024, followed by a presentation at ELCC 2024 in March 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 NSCLC who 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 patients who 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 appointed Mostafa 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 the Stanford 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 from Royal Institute of Technology in Stockholm, Sweden.
Financial Highlights
Cash and Cash Equivalents, Restricted Cash, & Short-term Investments
Aggregate cash and cash equivalents, restricted cash, and short-term investments were $157.0 million and $186.2 million at March 31, 2024 and December 31, 2023, respectively. Research and development tax credits were $1.2 million and $1.8 million at March 31, 2024 and December 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.
GAAP and Non-GAAP Research and Development (R&D) Expenses
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
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
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 with Akeso.
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
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 U.S. generally accepted accounting principles ("Non-GAAP measures"). 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. For further information regarding these Non-GAAP measures, please refer to the tables presenting reconciliations of our Non-GAAP results to our U.S. GAAP results and the "Notes on our Non-GAAP Financial Information" at the end of this press release.
First Quarter 2024 Earnings Call
Summit will host an earnings call this morning, Wednesday, May 1, 2024, at 9:00am ET. The conference call will be accessible by dialing (888) 210-3702 (toll-free domestic) or (646) 960-0191 (international) using conference code 5785899. A live webcast and instructions for joining the call are accessible through Summit’s website www.smmttx.com. An archived edition of the webcast will be available on our website after the call.
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.
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.
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.