On May 1, 2025 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, 2025 (Press release, Summit Therapeutics, MAY 1, 2025, View Source [SID1234652466]).
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Operational & Corporate Updates
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:
In January 2023, we closed our Collaboration and License Agreement with Akeso Inc. (Akeso, HKEX Code: 9926.HK) for ivonescimab (SMT112), with which over 2,300 patients have been treated in clinical studies globally. Summit has rights to develop and commercialize ivonescimab in 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 while Akeso retains development and commercialization rights for the rest of the world, including China.
Since in-licensing ivonescimab, we have begun our development for ivonescimab in non-small cell lung cancer ("NSCLC"), specifically launching Phase III clinical trials in the following proposed indications:
HARMONi: 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)
HARMONi-3: Ivonescimab combined with chemotherapy in first-line metastatic NSCLC patients
HARMONi-7: Ivonescimab monotherapy in first-line metastatic NSCLC patients with high PD-L1 expression
In October 2024, we completed enrollment in our HARMONi clinical trial. We expect to disclose topline results from HARMONi in mid-2025. Enrollment continues in HARMONi-3 and the initial patients have been enrolled in the US in HARMONi-7.
On April 23, 2025, our partner, Akeso, announced that the HARMONi-6 Phase III clinical trial met its primary endpoint of progression-free survival (PFS) at a prespecified interim analysis conducted by an Independent Data Monitoring Committee. This trial evaluated ivonescimab combined with platinum-based chemotherapy against tislelizumab, a PD-1 inhibitor, with the same chemotherapy regimen in patients with locally advanced or metastatic squamous NSCLC, regardless of PD-L1 expression. Conducted in China by our partners at Akeso, the trial showed statistically significant and clinically meaningful improvement in PFS for ivonescimab plus chemotherapy. Akeso noted that no new safety signals were identified.
This study is the first known Phase III trial in NSCLC to show significant improvement over a PD-(L)1 inhibitor combined with chemotherapy in a head-to-head setting. Following the success of Akeso’s HARMONi-2 study, this is the second instance where ivonescimab-based regimens have demonstrated a significant PFS benefit in front-line treatment in NSCLC. The full data set for HARMONi-6 is planned to be presented at an upcoming major medical conference later this year.
On April 25, 2025, Akeso announced that ivonescimab was approved in China by the National Medical Products Administration (NMPA), the Chinese Health Authority, for a second indication based on the results of the HARMONi-2 trial. HARMONi-2 evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. HARMONi-2 is a single region, multi-center, Phase III study conducted in China sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso.
As a part of the review of the supplemental marketing application submitted by Akeso seeking a label expansion of ivonescimab in China, the NMPA requested that Akeso perform an interim analysis of overall survival (OS). Akeso announced that the results of this interim overall survival analysis included a clinically meaningful, strongly positive trend represented by a hazard ratio of 0.777. The analysis was conducted at 39% data maturity, with a nominal alpha level of 0.0001.
Ivonescimab clinical trial collaborations with leading organizations continue to progress and expand evaluating ivonescimab in solid tumor settings outside of metastatic non-small cell lung cancer.
As part of our strategic collaboration with MD Anderson, two clinical trials sponsored by MD Anderson began enrolling this past quarter in cutaneous squamous cell carcinoma and glioblastoma.
We continue to support investigator-sponsored trials (ISTs) beyond our work with MD Anderson; two ISTs have begun enrolling at the Memorial Sloan Kettering Cancer Center and the Dana Farber Cancer Institute.
As we announced in February, our clinical trial collaboration with Pfizer will evaluate multiple antibody drug conjugates (ADCs) in combination with ivonescimab in unique solid tumor settings. The studies combining ivonescimab with Pfizer’s vedotin ADCs are planned to begin later this year. We plan to review the data generated from these clinical trials as a part of our consideration for advancing our clinical development for ivonescimab beyond non-small cell lung cancer.
In March, we further strengthened our leadership team with the appointment of Robert LaCaze as Chief Commercial Officer. Prior to joining Summit, Mr. LaCaze has held senior positions at major pharmaceutical companies including Executive Vice President and Head of the Oncology Strategic Business Unit overseeing the global oncology franchise at Bayer Healthcare and Senior Vice President and Head of Global Oncology at Bristol-Myers Squibb. He is a seasoned biopharmaceutical executive with over 30 years of extensive leadership experience in commercial strategy and execution. He has a proven track record of launching multi-billion-dollar products, building and growing blockbuster drug franchises, and expanding market presence for various oncology products.
Financial Highlights
Cash and Cash Equivalents & Short-term Investments
Aggregate cash and cash equivalents and short-term investments were $361.3 million and $412.3 million at March 31, 2025 and December 31, 2024, respectively.
GAAP and Non-GAAP Research and Development (R&D) Expenses
GAAP R&D expenses according to generally accepted accounting principles in the U.S. ("GAAP") were $51.2 million for the first quarter of 2025, compared to $30.9 million for the same period of the prior year.
Non-GAAP R&D expenses were $47.1 million for the first quarter of 2025, compared to $28.5 million for the same period of the prior year.
GAAP and Non-GAAP General and Administrative (G&A) Expenses
GAAP G&A expenses were $15.6 million for the first quarter of 2025, compared to $11.5 million for the same period of the prior year.
Non-GAAP G&A expenses were $8.6 million for the first quarter of 2025, compared to $4.4 million for the same period of the prior year.
GAAP and Non-GAAP Operating Expenses
GAAP operating expenses were $66.8 million for the first quarter of 2025, compared to $42.4 million for the same period of the prior year.
Non-GAAP operating expenses were $55.7 million for the first quarter of 2025, compared to $32.9 million for the same period of the prior year. The increase is primarily related to the increase in R&D expenses due to expansion of clinical studies and development costs related to ivonescimab and increases in people costs as we continue to build out our team.
GAAP and Non-GAAP Net Loss
GAAP net loss in the first quarter of 2025 and 2024 was $62.9 million or $(0.09) per basic and diluted share, and $43.5 million or $(0.06) per basic and diluted share, respectively.
Non-GAAP net loss in the first quarter of 2025 and 2024 was $51.8 million or $(0.07) per basic and diluted share, and $34.0 million or $(0.05) per basic and diluted share, respectively.
Use of Non-GAAP Financial Measures
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" that accompany this press release.
First Quarter 2025 Earnings Call
Summit will host an earnings call this afternoon, Thursday, May 1, 2025, at 4:30pm ET. The conference call will be accessible by dialing (800) 715-9871 (toll-free domestic) or (646) 307-1963 (international) using conference code 4936739. 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, North America, South America, Europe, the Middle East, Africa, 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 multifold higher affinity to PD-1 when in the presence of 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 TME (Zhong, et al, SITC (Free SITC Whitepaper), 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 after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to 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 2,300 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, and the Company has begun to enroll patients in the United States for HARMONi-7.
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). Enrollment in HARMONi was completed in the second half of 2024, and top-line results are expected to be announced in the middle of this year.
HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC.
HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.
In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.
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.
HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.
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 initially approved for marketing authorization in China in May 2024, and its label was expanded in China in April 2025. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration ("FDA") for the HARMONi clinical trial setting.