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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
 
FORM 8-K
 
CURRENT REPORT
Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934
 
Date of Report (Date of Earliest Event Reported): September 8, 2024
 
Summit Therapeutics Inc.
(Exact Name of Registrant as Specified in Its Charter)
   
Delaware001-3686637-1979717
(State or Other Jurisdiction
of Incorporation)		(Commission
File Number)		(IRS Employer
Identification No.)
 
601 Brickell Key Drive, Suite 1000, Miami, FL
33131
(Address of Principal Executive Offices)(Zip Code)
 
Registrant’s Telephone Number, Including Area Code: (305) 203-2034
 
Not applicable
(Former Name or Former Address, If Changed Since Last Report)
 
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
 
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
 
☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
 
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
 
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) 
Securities registered pursuant to Section 12(b) of the Act:
Title of Each ClassTrading Symbol(s)Name of Each Exchange on Which Registered
Common stock, $0.01 par value per shareSMMTThe Nasdaq Stock Market LLC
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐


 
Item 7.01
Regulation FD Disclosure.

Summit Therapeutics Inc. (the “Company”) announced data relating to the HARMONi-2 trial, conducted in China and sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK) (“Akeso”), with data generated and analyzed by Akeso. The data was presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (“IASLC”) 2024 World Conference on Lung Cancer (“WCLC 2024”) by Dr. Caicun Zhou, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President-Elect of IASLC on September 8, 2024. A copy of the presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K.

Additionally, the Company announced data relating to the Phase II trial, AK112-205 (“AK112-205”), which was conducted and sponsored by Akeso, featuring data from ivonescimab in the perioperative, early-stage NSCLC setting. The data was also announced at WCLC 2024 by Dr. Xiaoliang Zhao, Deputy Chief Physician, Department of Lung Cancer at Tianjin Medical University Cancer Institute & Hospital, and Visiting Scholar at the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. A copy of the presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K.

Finally, data abstracts in three additional Phase II clinical trials were released by European Society of Medical Oncology (“ESMO”). This included Phase II data from clinical studies sponsored by Akeso in first-line triple negative advanced breast cancer, first-line advanced colorectal cancer, and first-line head-and-neck squamous cell carcinoma.

The Company will utilize slides during its conference call scheduled for 8:30am ET on September 9, 2024 discussing the datasets associated with HARMONi-2, AK112-205 and the additional Phase II clinical trials. A copy of the slides is furnished as Exhibit 99.3 to this Current Report on Form 8-K and is incorporated by reference into this Item 7.01 as if fully set forth herein.

In accordance with General Instruction B.2 of Form 8-K, the information set forth under Item 7.01 and in Exhibits 99.1, 99.2 and 99.3 shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, as amended, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01
Other Events.

On September 8, 2024, the Company issued a press release announcing the datasets associated with HARMONi-2 and AK112-205. A copy of the September 8, 2024 press release is attached as Exhibit 99.4 to this Current Report on Form 8-K and is incorporated by reference herein.

Item 9.01
Financial Statements and Exhibits.

(d) Exhibits



SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, hereunto duly authorized.
 SUMMIT THERAPEUTICS INC.
  
  
Date: September 9, 2024By:/s/ Manmeet S. Soni
  Chief Operating Officer and Chief Financial Officer
  (Principal Financial Officer)

Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: HARMONi-2 C. Zhou1,2, J. Chen3, L. Wu3, L. Wang1, A. Xiong1, B. Liu4, J. Yao5, H. Zhong6, J. Li7, Y. Cheng8, Y. Sun9, H. Ge10, Q. Shi11, M. Zhou12, Z. Han13, J. Wang14, Q. Bu15, Y. Zhao16, J. Chen17, J. Yang18, M. Xia18 1Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai/CN; 2East Hospital Affiliated To Tongji University, shanghai/CN; 3Hunan Cancer Hospital, Changsha/CN; 4Harbin Medical University Cancer Hospital, Harbin/CN; 5The First Affiliated Hospital of Henan University of Science and Technology, Luoyang/CN; 6Shanghai Chest Hospital, Shanghai/CN; 7The First Affiliated Hospital of Gannan Medical University, Ganzhou/CN; 8Jilin Cancer Hospital, Changchun/CN; 9Shandong Cancer Hospital and Institute, Jinan/CN; 10The Fourth Hospital of Hebei Medical University, Shijiazhuang/CN; 11Fuzhou Tuberculosis Prevention and Treatment Hospital, Fuzhou/CN; 12Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou/CN; 13The Affiliated Hospital of Xuzhou Medical University, Xuzhou/CN; 14The Fifth Medical Center of the General Hospital of Chinese People's Liberation Army, Beijing/CN; 15The First affiliated hospital of Guangxi Medical University, Nanning/CN; 16Henan Cancer Hospital, Zhengzhou/CN; 17Fujian Cancer Hospital, Fuzhou/CN; 18Akeso Biopharma, Inc., Zhongshan/CN 1Caicun Zhou | HARMONi-2 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
Caicun Zhou | HARMONi-2 • Honoraria as a speaker: Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics. • Advisor: Innovent Biologics, Hengrui, Qilu, TopAlliance Biosciences Inc. Disclosures Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 2 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
• Anti-PD-1/L1 monotherapy or in combination with chemotherapy has been the standard of care for the first- line treatment of PD-L1 positive aNSCLC without driver gene alterations. • Monotherapy with an immune checkpoint inhibitor provides limited clinical benefit for PD-L1 positive aNSCLC1-2. • Ivonescimab (AK112) is a novel bispecific antibody against PD-1 and VEGF and has shown promising clinical efficacy and safety as front-line therapy for patients with PD-L1-positive aNSCLC in the phase 2 study (AK112-202)3. • HARMONi-2 (AK112-303, NCT05499390) is a randomized, double-blind, phase 3 study to compare the efficacy of ivonescimab with pembrolizumab as first-line treatment in patients with PD-L1-positive aNSCLC. • A sample size of approximately 388 patients and 264 PFS events would provide 90% power to detect a hazard ratio (HR) of 0.67. • An interim analysis of PFS was planned when 185 (70%) IRRC-assessed PFS events occurred. Background 1. Mok TSK, et al. Lancet. 2019;393(10183):1819-1830. 2. Yang JC, et al.J Thorac Oncol. 2024;19(6):941-953. 3.Wang L, et al. J Thorac Oncol. 2024;19(3):465-475. Abbreviations: PD-1, programmed death receptor 1; PD-L1, programmed death ligand 1; aNSCLC, advanced non-small cell lung cancer; VEGF, vascular endothelial growth factor; PFS, progression-free survival; IRRC, independent radiology review committee. Caicun Zhou | HARMONi-2 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 3 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
A randomized, double-blind, phase 3 studya Stratification • Clinical stage (IIIB/C vs. IV) • Histology (SQ vs. non-SQ) • PD-L1 TPS (≥50% vs. 1-49%) HARMONi-2 (AK112-303) Study Design Patient Population • Stage IIIB-IV aNSCLC • No prior systemic therapy • No EGFR mutations or ALK rearrangements • ECOG PS 0 or 1 • PD-L1 TPS ≥1% R 1:1 Ivonescimab 20 mg/kg Q3W (N=198) Pembrolizumab 200 mg Q3W (N=200) Treatment until no clinical benefit, unacceptable toxicity or up to 24 months N=398 Endpoints Primary: PFS by blind IRRC per RECIST v1.1 Secondary: OS, PFS assessed by INVs, ORR, DoR, TTR and safety Exploratory: QoL Caicun Zhou | HARMONi-2 a Patients were randomized from November 2022 to August 2023. Data cut off: January 29, 2024. Abbreviations: aNSCLC, advanced non-small cell lung cancer; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; ECOG PS, Eastern Cooperative Oncology Group performance score; PD-L1, programmed death ligand 1; TPS, tumor proportion score; R, randomization; SQ, squamous cell carcinoma; Q3W, every three weeks; PFS, progression-free survival; IRRC, independent radiology review committee; OS, overall survival; INV, investigator; ORR, overall response rate; DoR, duration of response; TTR, time to response; QoL, quality of life. Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 4 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
Baseline Characteristics Characteristics, n (%) Ivonescimab (n = 198a) Pembrolizumab (n = 200a) Total (n = 398a) Age (years) <65 97 (49.0) 85 (42.5) 182 (45.7) ≥65 101 (51.0) 115 (57.5) 216 (54.3) Sex Male 164 (82.8) 169 (84.5) 333 (83.7) Female 34 (17.2) 31 (15.5) 65 (16.3) ECOG PS 0 25 (12.6) 26 (13.0) 51 (12.8) 1 173 (87.4) 174 (87.0) 347 (87.2) Smoker Never 39 (19.7) 38 (19.0) 77 (19.3) Current 39 (19.7) 42 (21.0) 81 (20.4) Former 120 (60.6) 120 (60.0) 240 (60.3) Clinical stage IIIB/C 15 (7.6) 16 (8.0) 31 (7.8) IV 183 (92.4) 184 (92.0) 367 (92.2) Pathology SQ 90 (45.5) 91 (45.5) 181 (45.5) Tumor centrally locatedb 65 (72.2) 57 (62.6) 122 (67.4) Tumor with cavitation/necrosisb 9 (10.0) 7 (7.7) 16 (8.8) Tumor encasing large blood vesselb 6 (6.7) 1 (1.1) 7 (3.9) Non-SQ 108 (54.5) 109 (54.5) 217 (54.5) PD-L1 TPS ≥50% 83 (41.9) 85 (42.5) 168 (42.2) 1-49% 115 (58.1) 115 (57.5) 230 (57.8) Liver metastases Yes 25 (12.6) 28 (14.0) 53 (13.3) No 173 (87.4) 172 (86.0) 345 (86.7) Brain metastases Yes 33 (16.7) 39 (19.5) 72 (18.1) No 165 (83.3) 161 (80.5) 326 (81.9) a Patients who received randomization. b In 181 patients with SQ. Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance score; PD-L1, programmed death ligand 1; TPS, tumor proportion score; SQ, squamous cell carcinoma. Caicun Zhou | HARMONi-2 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 5 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
9-mo: 40% (32, 48) Median Follow-up: 8.67 months 9-mo: 56% (47, 64) Primary endpoint: PFS per IRRC Abbreviations: mPFS, median progression-free survival; IRRC, independent radiology review committee; mo, month; NE, not estimable; HR: hazard ratio; CI, confidence interval. Caicun Zhou | HARMONi-2 Ivonescimab demonstrated a statistically significant improvement in PFS vs. pembrolizumab with HR = 0.51, and a 5.3 months improvement in mPFS. Ivonescimab (n = 198) Pembrolizumab (n = 200) mPFS, mos (95% CI) 11.14 (7.33, NE) 5.82 (5.03, 8.21) Stratified HR (95% CI) 0.51 (0.38, 0.69) p-value <0.0001 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 6 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
0.06 0.1 1 10 Ivonescimab Better Pembrolizumab Better PFS Subgroup Analyses Ivonescimab Pembrolizumab Events/Patients Events/Patients Overall 72/198 112/200 Age <65 37/97 50/85 ≥65 35/101 62/115 Sex Male 58/164 94/169 Female 14/34 18/31 ECOG PS 0 4/25 19/26 1 68/173 93/174 Smoking Status Never 13/39 22/38 Current smoker 12/39 20/42 Former smoker 47/120 70/120 Liver metastases Yes 12/25 18/28 No 60/173 94/172 Brain metastases Yes 14/33 25/39 No 58/165 87/161 Distant metastatic sites ≥3 25/49 33/51 <3 47/149 79/149 Clinical stage IIIB/C 5/15 5/16 IV 67/183 107/184 Pathology Squamous 35/90 56/91 Non-Squamous 37/108 56/109 PD-L1 TPS ≥50% 25/83 45/85 1-49% 47/115 67/115 Caicun Zhou | HARMONi-2 Abbreviations: PFS, progression-free survival; ECOG PS, Eastern Cooperative Oncology Group performance score; PD-L1, programmed death ligand 1; TPS, tumor proportion score; SQ, squamous cell carcinoma; CI, confidence interval; aNSCLC, advanced non-small cell lung cancer. Unstratified Hazard Ratio (95% CI) 0.51 (0.38, 0.69) 0.53 (0.34, 0.81) 0.52 (0.34, 0.79) 0.53 (0.38, 0.74) 0.49 (0.24, 0.99) 0.18 (0.06, 0.54) 0.60 (0.44, 0.82) 0.39 (0.19, 0.77) 0.51 (0.24, 1.07) 0.57 (0.39, 0.74) 0.47 (0.23, 0.98) 0.53 (0.39, 0.74) 0.55 (0.28, 1.05) 0.53 (0.38, 0.74) 0.58 (0.34, 0.97) 0.49 (0.34, 0.71) 1.01 (0.29, 3.51) 0.49 (0.36, 0.67) 0.50 (0.33, 0.76) 0.55 (0.36, 0.84) 0.48 (0.29, 0.79) 0.54 (0.37, 0.78) Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 7 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
Key PFS Subgroup Analyses Caicun Zhou | HARMONi-2 Abbreviations: PFS, progression-free survival; PD-L1, programmed death ligand 1; TPS, tumor proportion score; HR: hazard ratio; CI, confidence interval; NSCLC, non-small cell lung cancer. PD-L1 Low (TPS 1-49%) Ivonescimab showed meaningful improvement in PFS vs. pembrolizumab in patients with both low and high PD-L1, with squamous or non-squamous advanced NSCLC. Stratified HR (95% CI) 0.54 (0.37, 0.79) Stratified HR (95% CI) 0.48 (0.31, 0.74) Stratified HR (95% CI) 0.54 (0.36, 0.82) Non-SquamousSquamous NSCLC Histology PD-L1 expression Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 8 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA PD-L1 High (TPS ≥50%) Stratified HR (95% CI) 0.46 (0.28, 0.75)

 
Caicun Zhou | HARMONi-2 Data cut off: January 29, 2024. Abbreviations: ORR, overall response rate; DCR, disease control rate; DoR, duration of response; IRRC, independent radiology review committee; CI, confidence interval; mo, month; NR, not reached; NE, not estimable. Ivonescimab (n = 198) Pembrolizumab (n = 200) ORR, % (95% CI) 50.0 (42.8, 57.2) 38.5 (31.7, 45.6) DCR, % (95% CI) 89.9 (84.8, 93.7) 70.5 (63.7, 76.7) Median DoR, mos (95% CI) NR (NE, NE) NR (8.28, NE) ORR and DCR were higher with ivonescimab vs. pembrolizumab. ORR, DCR and DoR per IRRC Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 9 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
b a Patients who received ≥1 dose of study treatment. b The incidence of ≥grade 3 Hypertension was 0.5%. Abbreviations: AEs, adverse events; TRAEs, treatment-related adverse events; SQ, squamous cell carcinoma. TRAEs Safety Summary Caicun Zhou | HARMONi-2 Ivonescimab showed a manageable safety profile, which was consistent with previous studies. Safety Summary, n (%) Ivonescimab (n = 90a) Pembrolizumab (n = 91a) TRAEs (all grades) 77 (85.6) 73 (80.2) Grade≥3 20 (22.2) 17 (18.7) Serious TRAEs 17 (18.9) 17 (18.7) Leading to discontinuation 2 (2.2) 3 (3.3) Leading to death 0 1 (1.1) TRAEs in SQ Subgroup Ivonescimab also demonstrated a tolerable safety profile in SQ patients. Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) TRAEs (all grades) 177 (89.8) 163 (81.9) Grade≥3 58 (29.4) 31 (15.6) Serious TRAEs 41 (20.8) 32 (16.1) Leading to discontinuation 3 (1.5) 6 (3.0) Leading to death 1 (0.5) 2 (1.0) The differences in AEs were predominantly proteinuria, hypertension, and laboratory abnormalities. The Most Common TRAEs (incidence ≥10%) Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 10 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
Caicun Zhou | HARMONi-2 Immune-Related and Possible VEGF-Related AEs • All VEGF-related AEs were grades 1-3 in both arms. • Grade 3 haemorrhage was observed in two patients with non-SQ and was not reported in SQ patients in the ivonescimab arm. irAEs Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) Possible VEGF-Related AEs (all grades) 94 (47.7) 42 (21.1) Grade≥3 20 (10.2) 2 (1.0) Possible VEGF-Related AEs Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) irAEs (all grades) 59 (29.9) 56 (28.1) Grade≥3 14 (7.1) 16 (8.0) Serious irAEs 11 (5.6) 22 (11.1) Leading to discontinuation 0 5 (2.5) Leading to death 0 0 Safety Summary by Classification, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) All Grade Grade≥3 All Grade Grade≥3 Proteinuria 62 (31.5) 6 (3.1) 20 (10.1) 0 Hypertension 31 (15.7) 10 (5.1) 5 (2.5) 1 (0.5) Haemorrhage 29 (14.7) 2 (1.0) 22 (11.1) 1 (0.5) Arterial thromboembolism 2 (1.0) 2 (1.0) 1 (0.5) 0 Venous thromboembolism 0 0 1 (0.5) 0 a Patients who received ≥1 dose of study treatment. Abbreviations: VEGF, vascular endothelial growth factor; irAEs, immune-related AEs; AEs, adverse events; SQ, squamous cell carcinoma. Ivonescimab exhibited similar irAEs to that of pembrolizumab. Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) 11 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
a Deterioration of global health status/quality of life (QoL) refers to a decrease of 10 points or greater from the baseline in standardized score. Time to deterioration is defined as the time from the date of randomization to the date of first occurrence of deterioration. b Patients who completed EORTC QLQ-C30. Abbreviations: mo, month; NR, not reached; NE, not estimated; HR: hazard ratio; CI, confidence interval. Global Health Status – EORTC QLQ-C30 Median time to deterioration (mos): 9.92 (8.02, NE) Median time to deterioration (mos): NR (9.63, NE) b b Ivonescimab was associated with comparable, numerically better time to deterioration of global health status. Stratified HR (95% CI) 0.92 (0.63, 1.33) Time to deterioration of global health status – EORTC QLQ-C30a Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA)Caicun Zhou | HARMONi-2 12 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA

 
Conclusions Caicun Zhou | HARMONi-2 • First-line ivonescimab significantly improve IRRC-assessed PFS in patients with aNSCLC and PD-L1 TPS ≥1%, compared with pembrolizumab (median PFS (mos), 11.14 vs. 5.82; HR, 0.51; p<0.0001). • PFS benefit with ivonescimab were consistent across major clinical subgroups: ◼ TPS ≥50%, HR = 0.46 (0.28, 0.75); TPS 1-49%, HR = 0.54 (0.37, 0.79) ◼ SQ, HR = 0.48 (0.31, 0.74); non-SQ, HR = 0.54 (0.36, 0.82) • Higher ORR (50.0% vs. 38.5%) and DCR (89.9% vs. 70.5%) were observed with ivonescimab vs. pembrolizumab. • OS was not matured at this time; the OS analysis is event-driven and will be reported in the future. • The safety profile of ivonescimab was consistent with prior studies and well tolerated, including in patients with SQ-NSCLC. • HRQoL with ivonescimab was comparable to pembrolizumab. Ivonescimab is an investigational therapy in this setting worldwide; ivonescimab is approved in 2L EGFRm NSCLC in China. Abbreviations: IRRC, independent radiology review committee; PFS, progression-free survival; aNSCLC, advanced non-small cell lung cancer; PD-L1, programmed death ligand 1; TPS, tumor proportion score; mo, month; HR: hazard ratio; CI, confidence interval; SQ, squamous cell carcinoma; ORR, overall response rate; DCR, disease control rate; OS, overall survival. This is the first randomized phase 3 study to demonstrate a clinically significant improvement in efficacy with a novel drug compared to pembrolizumab in aNSCLC. Ivonescimab is a novel 1st line treatment for patients with aNSCLC and positive PD-L1(TPS ≥1%). 13 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA)

 
Acknowledgments Caicun Zhou | HARMONi-2 • We sincerely thank all the participants and their families. • Thank you to all of the investigators and study site personnel from 55 sites. • Thanks to all personnel of Akeso Biopharma, Inc. who supported the study. 14 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA)

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 1 A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer Changli Wang1, Xiaoliang Zhao1, Lianmin Zhang1, Dongsheng Yue1, Zhenfa Zhang1, Meng Wang1, Ziqiang Tian2, Shengguang Wang1, Chong Pang1, Bin Zhang1, Qiang Zhang1, Wei Wei1, Yu Zhang1, Xiaofei Wang1, Yue Li1, Huilai Lv2, Yu Xia3, Baiyong Li3, Zhongmin Maxwell Wang3, Wenting Li3 1.Tianjin Medical University Cancer Institute & Hospital, Tianjin, P. R. China; 2.The Fourth Hospital of Hebei Medical University, Shijiazhuang, P. R. China; 3.Akeso, Inc., Zhongshan, P. R. China.

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 2 Background • Recent phase III trials have demonstrated the efficacy of neoadjuvant PD-(L)1 inhibitors combined with chemotherapy followed by surgery and adjuvant PD-(L)1 inhibitors for resectable non-small cell lung cancer (NSCLC), including KEYNOTE 6711, CheckMate 77T2, AEGEAN3, Neotorch4, and RATIONALE 3155. • Ivonescimab is a first-in-class anti-PD-1/VEGF bispecific antibody. Ivonescimab, both as monotherapy and in combination with chemotherapy, showed promising antitumor activity and manageable safety profile in patients with advanced NSCLC6,7. • Here we report the efficacy and safety of a phase II study of perioperative ivonescimab alone or combined with chemotherapy in resectable NSCLC (NCT05247684). 1Wakelee H, et al. N Engl J Med. 2023 Aug 10;389(6):491-503. 2Cascone T, et al. N Engl J Med. 2024 May 16;390(19):1756-1769. 3Heymach JV, et al. N Engl J Med. 2023 Nov 2;389(18):1672-1684. 4Lu S, et al. JAMA. 2024 Jan 16;331(3):201-211. 5D. Yue, et al. 2023 ESMO LBA58. 6Fang W, et al. JAMA. 2024 Aug 20;332(7):561-570. 7Wang L, et al. J Thorac Oncol. 2024 Mar;19(3):465-475.

 
• Primary Endpoints: MPR, Safety • Secondary Endpoints: pCR, EFS, OS, ORR, the rate of R0 resection and downstaging Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 3 Key Eligibility Criteria • Resectable NSCLC (stage II- IIIB[N2], AJCC 8th) • No prior anticancer therapy • EGFR/ALK wild type • ECOG PS 0-1 *Chemotherapy: Cisplatin/Carboplatin + Paclitaxel Surgery Ivonescimab 20mg/kg or 30mg/kg + CT* Q3W, 3-4 cycles Neoadjuvant treatment Surgery (Within 4-6 weeks post-neoadjuvant treatment) Adjuvant treatment (Start within 3-8 weeks after surgery) Cohort 1 Cohort 2 Surgery Ivonescimab 20mg/kg Q3W, 3-4 cycles Ivonescimab 20mg/kg Q3W, 16 cycles Data cutoff date: Feb 01, 2024. As of Feb 01, 2024, 60 patients were enrolled in the study. NSCLC, non-small cell lung cancer; AJCC, American Joint Committeon cancer; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; ECOG PS, Eastern Cooperative Oncology Group Performance Status; Q3W, every 3 weeks; MPR, major pathological response; pCR, pathological complete response; EFS, event-free survival; OS, overall survival; ORR, objective response rate. Study Design Ivonescimab 20mg/kg or 30mg/kg Q3W, 16 cycles

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 4 60 patients were enrolled 11 were enrolled to Cohort 1 49 were enrolled to Cohort 2 1 did not complete surgery 1 Disease progression 10 did not complete surgery 6 Subject request 1 Disease progression 1 Adverse event 2 Other 1 remains on adjuvant treatment 9 end of treatment 24 remain on adjuvant treatment 12 end of treatment 39 completed R0 resection10 completed R0 resection 36 received ≥1 cycle of adjuvant treatment 3 were awaiting adjuvant treatment All received ≥1 cycle of adjuvant treatment Patient Disposition

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 5 Baseline Characteristics

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 6 Cohort 1 Cohort 2 (N=10) (N=39) MPR 60.0% 71.8% - RVT*＜5% 50.0% 69.2% pCR 30.0% 43.6% *RVT：residual viable tumor cells in both primary tumor and lymph nodes. Cohort 1 Ivonescimab monotherapy Cohort 2 Ivonescimab + CT P a th o lo g ic a l R eg re ss io n ( % ) P a th o lo g ic a l R eg re ss io n ( % ) Pathological Response

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 7 85.7% 68.8% 100.0% 70.3% 83.3% 33.3% 66.7% 71.4% 70.0% 73.7% 57.1% 40.6% 40.5% 53.3% 11.1% 22.2% 50.0% 40.0% 47.4% 0% 20% 40% 60% 80% 100% MPR pCR Stage II (n=7) Stage III (n=32) N0 Stage (n=2) N1/2 Stage (n=37) Squamous (n=30) Non-squamous (n=9) PD-L1≥1% (n=28) PD-L1<1% (n=9) Ivonescimab 20mg/kg (n=20) Ivonescimab 30mg/kg (n=19) The expression of PD-L1 was unknown in two patients. MPR and pCR by Subgroups in Cohort 2

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 8 E F S ( % ) Cohort 1 Ivonescimab monotherapy (n=11) Median Follow-up (95% CI) 17.64 (12.3, 21.2) No. of Events/No. of Patients (%) 4/11 (36.4%) Median EFS (95% CI) NR (6.9, NE) E F S ( % ) Cohort 2 Ivonescimab + CT (n=49) Median Follow-up (95% CI) 8.94 (6.6, 12.2) No. of Events/No. of Patients (%) 8/49 (16.3%) Median EFS (95% CI) NR (14.9, NE) EFS

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 9 ORR, objective response rate; DCR, disease control rate. 81.8% 81.6% 90.9% 95.9% Cohort 1 Cohort 2 Cohort 1 Cohort 2 ORR DCR Cohort 2 Ivonescimab + CT (n=49) Cohort 1 Ivonescimab Monotherapy (n=11) Tumor Response and Stage Change in Neoadjuvant Phase

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 10 TRAEs, n (%) Cohort 1 Ivonescimab monotherapy (N=11) Cohort 2 Ivonescimab + CT (N=49) Total (N=60) Any grade 9 (81.8) 42 (85.7) 51 (85.0) Grade≥3 4 (36.4) 16 (32.7) 20 (33.3) SAE 2 (18.2) 1 (2.0) 3 (5.0) Leading to treatment delay of ivonescimab 3 (27.3) 6 (12.2) 9 (15.0) Leading to discontinuation of ivonescimab 4 (36.4) 1 (2.0) 5 (8.3) Leading to death 0 0 0 Leading to delayed or cancelled surgery 0 0 0 Surgery related TRAE 1 (10.0) 7 (17.9) 8 (16.3) Grade≥3 irAE 4 (36.4) 1 (2.0) 5 (8.3) The median follow-up time was 17.64 months in cohort 1 and 8.94 months in cohort 2. TRAE, treatment-related adverse event (related to ivonescimab); irAEs were evaluated by investigators. The TRAEs leading to discontinuation of ivonescimab and grade≥3 irAEs were the same events. Surgery related TRAE defined as TRAE reported within 90 days after surgery or until the start of adjuvant treatment, whichever occurred first (in patients who completed the surgery). Safety Profile

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 11 • Perioperative ivonescimab monotherapy or combined with chemotherapy for resectable NSCLC demonstrated high rates of pCR and MPR in this phase II study. • Compared with ivonescimab monotherapy, rates of MPR and pCR in ivonescimab combined with chemotherapy were numerically higher, and across tumor stage and PD-L1 expression subgroups. - Ivonescimab + chemotherapy: pCR rate was 43.6%, MPR rate was 71.8% -As of Aug 30, 2024, 55 patients in cohort 2 completed surgery, pCR and MPR rates were improved to 52.7% and 72.7%, respectively. For squamous NSCLC, pCR and MPR rates were 63.6% and 84.1%, respectively. - Ivonescimab monotherapy: pCR rate was 30.0%, MPR rate was 60.0% • Although EFS is not mature yet, higher pCR rates relative to historic studies1-3 may predict longer EFS. Additional follow-up studies are planned to confirm these results. • The safety profile was manageable. There were no TRAEs that led to cancelled or delayed surgery or wound healing complications. 1Wakelee H, et al. N Engl J Med. 2023 Aug 10;389(6):491-503. 2Cascone T, et al. N Engl J Med. 2024 May 16;390(19):1756-1769. 3Lu S, et al. JAMA. 2024 Jan 16;331(3):201-211. Conclusions

 
Changli Wang | A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer 12 • Thanks to all patients, their families, and their caregivers for their participation • Thanks to all investigators who supported this clinical trail • Thanks to all staff members for their contributions Acknowledgements

 
Summit Therapeutics Update Call from WCLC September 9, 2024

 
Forward-Looking Statements 2 Any statements in this presentation 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., including the expected benefits of the amendment to the collaboration and license agreement, the intended use of the net proceeds from the private placement, 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 of 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 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, the audience should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this presentation represent the Company’s views only as of the date of this presentation 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 presentation. Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024

 
A double-blind, randomized Phase III study comparing ivonescimab with pembrolizumab for patients with advanced or metastatic PD-L1-positive NSCLC (PD-L1 TPS >1%)a Stratification • Clinical stage (IIIB/C vs. IV) • Histology (SQ vs. non-SQ) • PD-L1 TPS (≥50% vs. 1-49%) HARMONi-2: Study Design Patient Population • Stage IIIB-IV aNSCLC • No prior systemic therapy • No EGFR mutations or ALK rearrangements • ECOG PS 0 or 1 • PD-L1 TPS ≥1% R 1:1 Pembrolizumab 200 mg Q3W (N=200) Treatment until no clinical benefit, unacceptable toxicity or up to 24 months N=398 Ivonescimab 20 mg/kg Q3W (N=198) Endpoints Primary: PFS by blind IRRC per RECIST v1.1 Secondary: OS, PFS assessed by INVs, ORR, DoR, TTR and safety Exploratory: QoL a Patients were randomized from November 2022 to August 2023. Data cut off: January 29, 2024. Abbreviations: aNSCLC, advanced non-small cell lung cancer; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; ECOG PS, Eastern Cooperative Oncology Group performance score; PD-L1, programmed death ligand 1; TPS, tumor proportion score; R, randomization; SQ, squamous cell carcinoma; Q3W, every three weeks; PFS, progression-free survival; IRRC, independent radiology review committee; OS, overall survival; INV, investigator; ORR, overall response rate; DoR, duration of response; TTR, time to response; QoL, quality of life. Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso. 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-2 Akeso Sponsored Study Conducted in China 3 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024

 
HARMONi-2 Baseline Characteristics Characteristics, n (%) Ivonescimab (n = 198a) Pembrolizumab (n = 200a) Total (n = 398a) Age (years) <65 97 (49.0) 85 (42.5) 182 (45.7) ≥65 101 (51.0) 115 (57.5) 216 (54.3) Sex Male 164 (82.8) 169 (84.5) 333 (83.7) Female 34 (17.2) 31 (15.5) 65 (16.3) ECOG PS 0 25 (12.6) 26 (13.0) 51 (12.8) 1 173 (87.4) 174 (87.0) 347 (87.2) Smoker Never 39 (19.7) 38 (19.0) 77 (19.3) Current 39 (19.7) 42 (21.0) 81 (20.4) Former 120 (60.6) 120 (60.0) 240 (60.3) Clinical stage IIIB/C 15 (7.6) 16 (8.0) 31 (7.8) IV 183 (92.4) 184 (92.0) 367 (92.2) Pathology SQ 90 (45.5) 91 (45.5) 181 (45.5) Tumor centrally locatedb 65 (72.2) 57 (62.6) 122 (67.4) Tumor with cavitation/necrosisb 9 (10.0) 7 (7.7) 16 (8.8) Tumor encasing large blood vesselb 6 (6.7) 1 (1.1) 7 (3.9) Non-SQ 108 (54.5) 109 (54.5) 217 (54.5) PD-L1 TPS ≥50% 83 (41.9) 85 (42.5) 168 (42.2) 1-49% 115 (58.1) 115 (57.5) 230 (57.8) Liver metastases Yes 25 (12.6) 28 (14.0) 53 (13.3) No 173 (87.4) 172 (86.0) 345 (86.7) Brain metastases Yes 33 (16.7) 39 (19.5) 72 (18.1) No 165 (83.3) 161 (80.5) 326 (81.9) a Patients who received randomization. b In 181 patients with SQ. Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance score; PD- L1, programmed death ligand 1; TPS, tumor proportion score; SQ, squamous cell carcinoma. 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-24 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
9-mo: 40% (32, 48) Median Follow-up: 8.67 months 9-mo: 56% (47, 64) HARMONi-2 Primary endpoint: PFS per IRRC Abbreviations: mPFS, median progression-free survival; IRRC, independent radiology review committee; mo, month; NE, not estimable; HR: hazard ratio; CI, confidence interval. Ivonescimab (n = 198) Pembrolizumab (n = 200) mPFS, mos (95% CI) 11.14 (7.33, NE) 5.82 (5.03, 8.21) Stratified HR (95% CI) 0.51 (0.38, 0.69) p-value <0.0001 Ivonescimab is the first compound to demonstrate a statistically significant improvement in PFS vs. pembrolizumab with HR = 0.51, and 5.3 months improvement in mPFS. 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-25 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
HARMONi-2 PFS Subgroup Analyses Ivonescimab Pembrolizumab Events/Patients Events/Patients Overall 72/198 112/200 Age <65 37/97 50/85 ≥65 35/101 62/115 Sex Male 58/164 94/169 Female 14/34 18/31 ECOG PS 0 4/25 19/26 1 68/173 93/174 Smoking Status Never 13/39 22/38 Current smoker 12/39 20/42 Former smoker 47/120 70/120 Liver metastases Yes 12/25 18/28 No 60/173 94/172 Brain metastases Yes 14/33 25/39 No 58/165 87/161 Distant metastatic sites ≥3 25/49 33/51 <3 47/149 79/149 Clinical stage IIIB/C 5/15 5/16 IV 67/183 107/184 Pathology Squamous 35/90 56/91 Non-Squamous 37/108 56/109 PD-L1 TPS ≥50% 25/83 45/85 1-49% 47/115 67/115 Abbreviations: PFS, progression -free survival; ECOG PS, Eastern Cooperative Oncology Group performance score; PD-L1, programmed death ligand 1; TPS, tumor proportion score; SQ, squamous cell carcinoma; CI, confidence interval; aNSCLC, advanced non-small cell lung cancer. Unstratified Hazard Ratio (95% CI) 0.51 (0.38, 0.69) 0.53 (0.34, 0.81) 0.52 (0.34, 0.79) 0.53 (0.38, 0.74) 0.49 (0.24, 0.99) 0.18 (0.06, 0.54) 0.60 (0.44, 0.82) 0.39 (0.19, 0.77) 0.51 (0.24, 1.07) 0.57 (0.39, 0.74) 0.47 (0.23, 0.98) 0.53 (0.39, 0.74) 0.55 (0.28, 1.05) 0.53 (0.38, 0.74) 0.58 (0.34, 0.97) 0.49 (0.34, 0.71) 1.01 (0.29, 3.51) 0.49 (0.36, 0.67) 0.50 (0.33, 0.76) 0.55 (0.36, 0.84) 0.48 (0.29, 0.79) 0.54 (0.37, 0.78) 0.06 0.1 1 10 Ivonescimab Better Pembrolizumab Better 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-26 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
HARMONi-2 Key PFS Subgroup Analyses PD-L1 High (TPS ≥50%)PD-L1 Low (TPS 1-49%) Ivonescimab showed meaningful improvement in PFS vs. pembrolizumab in patients with both low and high PD-L1, with squamous or non-squamous advanced NSCLC. Stratified HR (95% CI) 0.54 (0.37, 0.79) Stratified HR (95% CI) 0.46 (0.28, 0.75) Stratified HR (95% CI) 0.48 (0.31, 0.74) Stratified HR (95% CI) 0.54 (0.36, 0.82) Non-SquamousSquamous NSCLC Histology PD-L1 expression 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-27 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
Data cut off: January 29, 2024. Abbreviations: ORR, overall response rate; DCR, disease control rate; DoR, duration of response; IRRC, independent radiology review committee; CI, confidence interval; mo, month; NR, not reached; NE, not estimable. Ivonescimab (n = 198) Pembrolizumab (n = 200) ORR, % (95% CI) 50.0 (42.8, 57.2) 38.5 (31.7, 45.6) DCR, % (95% CI) 89.9 (84.8, 93.7) 70.5 (63.7, 76.7) Median DoR, mos (95% CI) NR (NE, NE) NR (8.28, NE) ORR and DCR were higher with ivonescimab vs. pembrolizumab. HARMONi-2 ORR, DCR and DoR per IRRC 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-28 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
a Patients who received ≥1 dose of study treatment. Abbreviations: AEs, adverse events; TRAEs, treatment-related adverse events; SQ, squamous cell carcinoma. TRAEs HARMONi-2 Safety Summary Ivonescimab showed a manageable safety profile, which was consistent with previous studies. Safety Summary, n (%) Ivonescimab (n = 90a) Pembrolizumab (n = 91a) TRAEs (all grades) 77 (85.6) 73 (80.2) Grade≥3 20 (22.2) 17 (18.7) Serious TRAEs 17 (18.9) 17 (18.7) Leading to discontinuation 2 (2.2) 3 (3.3) Leading to death 0 1 (1.1) TRAEs in SQ Subgroup Ivonescimab also demonstrated a tolerable safety profile in SQ patients. Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) TRAEs (all grades) 177 (89.8) 163 (81.9) Grade≥3 58 (29.4) 31 (15.6) Serious TRAEs 41 (20.8) 32 (16.1) Leading to discontinuation 3 (1.5) 6 (3.0) Leading to death 1 (0.5) 2 (1.0) The differences in AEs were predominantly proteinuria, hypertension, and laboratory abnormalities. Most Common TRAEs (incidence ≥10%) 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-29 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
HARMONi-2 irAEs and Possible VEGF-Related AEs • All VEGF-related AEs were grades 1-3 in both arms. • Grade 3 haemorrhage was observed in two patients with non-SQ and was not reported in SQ patients in the ivonescimab arm. irAEs Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) Possible VEGF-Related AEs (all grades) 94 (47.7) 42 (21.1) Grade≥3 20 (10.2) 2 (1.0) Possible VEGF-Related AEs Safety Summary, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) irAEs (all grades) 59 (29.9) 56 (28.1) Grade≥3 14 (7.1) 16 (8.0) Serious irAEs 11 (5.6) 22 (11.1) Leading to discontinuation 0 5 (2.5) Leading to death 0 0 Safety Summary by Classification, n (%) Ivonescimab (n = 197a) Pembrolizumab (n = 199a) All Grade Grade≥3 All Grade Grade≥3 Proteinuria 62 (31.5) 6 (3.1) 20 (10.1) 0 Hypertension 31 (15.7) 10 (5.1) 5 (2.5) 1 (0.5) Haemorrhage 29 (14.7) 2 (1.0) 22 (11.1) 1 (0.5) Arterial thromboembolism 2 (1.0) 2 (1.0) 1 (0.5) 0 Venous thromboembolism 0 0 1 (0.5) 0 a Patients who received ≥1 dose of study treatment. Abbreviations: VEGF, vascular endothelial growth factor; irAEs, immune- related AEs; AEs, adverse events; SQ, squamous cell carcinoma. Ivonescimab exhibited similar irAEs to that of pembrolizumab. 2024 World Conference on Lung Cancer Presidential Symposium, 9/8/24, San Diego, CA Caicun Zhou | HARMONi-210 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
Additional Promising Phase II Data for Ivonescimab (Ivo) Perioperative Resectable NSCLC Ivonescimab (n=11) Ivo + Chemo (n=49) pCR (n = 10; n = 39; respectively) 30.0% 43.6% MPR (n = 10; n = 39; respectively) 60.0% 71.8% 12-month EFS 81.8% 80.3% No TRAEs led to cancelled / delayed surgery or wound healing complications. 1L MSS Metastatic Colorectal Cancer (mCRC) Ivo + Chemo (n = 22) Ivo + CD47 + Chemo (n = 17) Overall Response Rate 81.8% 88.2% Disease Control Rate 100% 100% 9-month PFS Rate 81.4% 86.2% TRAE-Led Discontinuations 0 1 1L PD-L1-positive Head-and- Neck SCC (R/M HNSCC) Ivonescimab (n =10) Ivo + CD47 (n=20) Overall Response Rate 30.0% 60.0% Disease Control Rate 80.0% 90.0% Median PFS Rate 5 mos 7.1 mos TRAE-Led Discontinuations 0 1L Triple Negative Advanced Breast Cancer (TNBC) Ivo + Chemo CPS <10% (n=23) Ivo + Chemo CPS >10% (n=6) Overall Response Rate 69.6% 83.3% Disease Control Rate 100% 100% 6-month PFS Rate 68.4% TRAE-Led Discontinuations 0 11 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 2024 IASLC World Conference on Lung Cancer European Society of Medical Oncology Annual Meeting 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso. Akeso Sponsored Phase II Studies Conducted in China – Study Designs Contained in Appendix

 
Indication Study Treatment Population Regimen Phase Status NSCLC 2L EGFRm+ + Chemo vs. Chemo Approved 1L PD-L1 TPS ≥1% Monotherapy vs. pembrolizumab (PD-1) III Primary Analysis 1L Squamous + Chemo vs. tislelizumab (PD-1) + chemo III Ongoing AK112-205 Neoadjuvant/Adjuvant +/- Chemo II Ongoing AK112-208 1L advanced or metastatic + PD-1/CTLA-4 bsAb + chemo II Ongoing Biliary Tract CA TBD 1L + Chemo III Planned Head & Neck CA TBD 1L PD-L1 CPS ≥1% + CD47 vs. pembrolizumab (PD-1) III Planned Pancreatic CA TBD 1L PDAC + Chemo III Planned Ovarian CA AK112-211 PSOC + Chemo +/- PARP inhibitor II Ongoing Colorectal CA AK112-206 Metastatic MSS CRC +/- CD47, +/- chemo II Ongoing Hepatocellular CA AK112-207 BCLC Stage B or C Monotherapy II Ongoing Ovarian CA AK104-221 Recurrent +/- Chemo, PD-1/CTLA-4 bsAb II Ongoing G/GEJ CA AK117-202 HER2 negative +/- CD47 + chemo II Ongoing Breast CA AK117-203 TNBC + Chemo, CD47 + chemo II Ongoing SCLC AK112-103 Extensive Stage + Chemo I Completed Ivonescimab Global Clinical Trials Ivonescimab More Than 25 Clinical Trials Across 17 Indications1 1,800+ Patients Treated in Clinical Trials 8 Phase III Trials Completed or Ongoing1 1 Approved Cancer Indication in China1 4 Head-to-Head Studies vs. PD-1 9 Dedicated Trials Outside NSCLC1 These ivonescimab clinical trials are being conducted in China and / or Australia and are fully sponsored and managed by Akeso. Indication Study Treatment Population Regimen Phase Status NSCLC 2L EGFRm+ + Chemo vs. chemo III Ongoing 1L Squamous + Chemo vs. pembrolizumab (PD-1) + chemo III Ongoing 1L PD-L1 TPS >50% Monotherapy vs. pembrolizumab (PD-1) III Planned 1. Akeso's 2024 First Half Interim Results (prnewswire.com) Ivonescimab is an investigational therapy not presently approved by any regulatory authority other than China’s National Medical Products Administration (NMPA) Abbreviations: Abbreviations: 1L=first-line; 2L=second-line; Adeno CA=adenocarcinoma; BCLC=Barcelona clinic liver cancer; BRAC=breast cancer gene; bsAb=bispecific antibody; Chemo=chemotherapy; CD47=cluster of differentiation 47; CTLA-4=cytotoxic T lymphocyte antigen-4; CPS=combined positive score; CRC=colorectal cancer; EGFRm+=epidermal growth factor receptor mutant positives; G/GEJ=gastroesophageal junction; HER2=human epidermal growth factor receptor 2; NSCLC=non-small-cell lung cancer; PARPi=poly(ADP-ribose) polymerase inhibitors; PD-L1=programmed cell death ligand 1; PD- 1=Programmed Cell Death Protein 1; TNBC=triple negative breast cancer; TPS=tumor proportion score; SCLC=Extensive Stage Small Cell Lung Cancer; PDAC=pancreatic ductal adenocarinoma12 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 China

 
Q&A

 
Summit Therapeutics Update Call from WCLC September 9, 2024

 
Appendix

 
• 1L MSS Metastatic Colorectal Cancer (mCRC): • This was an open-label, multicenter, phase II randomized study. Untreated mCRC patients (pts) were randomly assigned (1:1) to receive FOLFOXIRI + ivonescimab (group A) or FOLFOXIRI + ivonescimab + ligufalimab (CD47) (group B) for up to 8 cycles, followed by maintenance with 5-fluoruracil + ivonescimab with (group B) or without ligufalimab (group A). The primary endpoints were objective response rate (ORR) by RECIST v1.1 and safety. Deng, et. al., ESMO, 2024 • 1L Triple Negative Advanced Breast Cancer (TNBC): • This was an open-label, multicenter phase II study in patients (pts) with locally advanced unresectable or metastatic TNBC. Pts received ivonescimab at 20 mg/kg Q2W and paclitaxel at 90 mg/m2 or nab- paclitaxel at100 mg/m2 on the 1st, 8th, and 15th day of each four- week treatment cycle. The primary endpoints were safety and objective response rate (ORR) by RECIST v1.1. The secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Ouyang, et. al., ESMO, 2024 Study Designs for Additional Phase II for Ivonescimab (Ivo) Akeso Sponsored Phase II Studies Conducted in China • Perioperative Resectable NSCLC: • This was an open-label, multi-center phase II study, pts diagnosed with resectable stage II, IIIA or IIIB (N2) NSCLC per AJCC 8th edition were enrolled into two cohorts. Pts received neoadjuvant ivonescimab (20 mg/kg) monotherapy in cohort 1 or ivonescimab (20 mg/kg or 30 mg/kg) plus cisplatin/carboplatin and paclitaxel in cohort 2 once every 3 weeks for 3-4 cycles, followed by surgery and adjuvant ivonescimab once every 3 weeks for up to 16 cycles. Primary endpoints were safety and major pathological response (MPR). Wang, et. al., WCLC, 2024 • 1L PD-L1-Positive Head-and-Neck SCC (R/M HNSCC): • In this open-label, multi-center phase II study, eligible R/M HNSCC pts with PD-L1 positive disease (CPS≥1) were enrolled, including oropharynx, hypopharynx, larynx or oral cavity cancer. Patients were treated with ivonescimab (10 mg/kg Q3W) monotherapy or in combination with ligufalimab (CD47) (45 mg/kg Q3W). The primary endpoint was objective response rate (ORR) per RECIST v1.1 assessed by investigator. Chen, et. al., ESMO, 2024 16 Summit Confidential & Proprietary Information - Do Not Copy or Distribute Presentation Summit Update – September 2024 Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s National Medical Products Administration (NMPA). Data generated and analyzed by Akeso.

 
1 Ivonescimab Monotherapy Reduced the Risk of Disease Progression or Death by 49% Compared to Pembrolizumab Monotherapy in First-Line Treatment of Patients with PD-L1 Positive Advanced NSCLC in China Summit to Initiate HARMONi-7, a Phase III Trial in First-Line PD-L1 High, Advanced NSCLC, in Early 2025 Ivonescimab Is the First Drug to Achieve Clinically Meaningful Benefit over Pembrolizumab in a Randomized Phase III Clinical Trial in NSCLC Median PFS of 11.14 Months vs. 5.82 Months, Respectively, for Patients Receiving Ivonescimab vs. Pembrolizumab; PFS Improvement Was Observed Broadly in Patients Across Subgroups, including PD-L1 High and Low Expressing Tumors, Squamous and Non-Squamous Histologies Comparable Serious Treatment-Related Adverse Events and TRAE-Led Discontinuation Rates Were Observed; Serious TRAEs were 20.8% vs. 16.1%, Respectively, in Ivonescimab and Pembrolizumab Arms Encouraging Perioperative NSCLC Phase II Data Also Featured in an Oral Presentation at WCLC 2024 Three Additional Phase II Solid Tumor Settings beyond NSCLC Featuring Ivonescimab to be Presented at ESMO 2024 Conference Call to be Held at 8:30am ET on Monday, September 9, 2024 Miami, Florida, September 8, 2024 – Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") today announced data from the primary analysis of the Phase III HARMONi-2 trial featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab. The data was presented this morning as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2024 World Conference on Lung Cancer (WCLC 2024) in San Diego, California. The HARMONi-2 presentation, Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of 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 our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK), with data generated and analyzed by Akeso. The trial results were presented by Professor Caicun Zhou, MD, PhD, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President-Elect of IASLC. Clinically Meaningful Efficacy In the HARMONi-2 primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, progression-free survival (PFS) by Independent Radiologic Review Committee (IRRC), when compared to monotherapy pembrolizumab, achieving a hazard ratio (HR) of 0.51 (95% CI: 0.38, 0.69; p<0.0001). A clinically meaningful 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

 
2 non-squamous histologies, as well as other high-risk patients. Both the overall response rate (ORR) measured according to RECIST v1.1 criteria as well as the disease control rate (DCR) were higher in patients treated with ivonescimab compared to those treated with pembrolizumab. HARMONi-2 ITT (n=398); Median Follow-up: 8.67 mos Ivonescimab (n=198) Pembrolizumab (n=200) Median PFS 11.14 mos (95% CI: 7.33, NE) 5.82 mos (95% CI: 5.03, 8.21) PFS Stratified HR 0.51 (95% CI: 0.38, 0.69; p<0.0001) ORR 50.0% (95% CI: 42.8%, 57.2%) 38.5% (95% CI: 31.7%, 45.6%) DCR 89.9% (95% CI: 84.8%, 93.7%) 70.5% (95% CI: 63.7%, 76.7%) HARMONi-2 Subgroup Analyses Ivonescimab vs. Pembrolizumab PD-L1 High (PD-L1 TPS ≥50%) PFS stratified HR Ivonescimab n=83; Pembrolizumab n=85 0.46 (95% CI: 0.28, 0.75) PD-L1 Low (PD-L1 TPS 1-49%) PFS stratified HR Ivonescimab n=115; Pembrolizumab n=115 0.54 (95% CI: 0.37, 0.79) Squamous histology PFS stratified HR Ivonescimab n=90; Pembrolizumab n=91 0.48 (95% CI: 0.31, 0.74) Non-Squamous histology PFS stratified HR Ivonescimab n=108; Pembrolizumab n=109 0.54 (95% CI: 0.36, 0.82) Overall survival data was not yet mature at the time of the data cutoff and will be evaluated in the future. Manageable Safety Profile Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies. There were three patients (1.5%) who discontinued ivonescimab due to TRAEs compared to six patients (3.0%) who discontinued pembrolizumab due to TRAEs. There was one patient in the ivonescimab arm and two patients in the pembrolizumab arm who died as a result of TRAEs in this Phase III study. The most frequent treatment-related adverse events (TRAEs) for ivonescimab treatment were proteinuria (Grade 3+: ivonescimab, 3.0%; pembrolizumab 0.0%), hypertension (Grade 3+: ivonescimab, 5.1%; pembrolizumab 0.5%), and various laboratory abnormalities, including AST increases, hypercholesterolemia, anemia, and bilirubin increases. Grade 3 or higher immune-related adverse events occurred in 7.1% of patients receiving ivonescimab and 8.0% of patients receiving pembrolizumab. Grade 3 or higher adverse events that were possibly VEGF-related in the ivonescimab monotherapy arm were 10.2% vs. 1.0% for pembrolizumab, all of which were classified as Grade 3. Of note, Grade 3 hemorrhage events were observed in two patients in the ivonescimab arm (both were of non- squamous histology) compared to one patient in the pembrolizumab arm in this study.

 
3 HARMONi-2 (n=396) Ivonescimab (n=197) Pembrolizumab (n=199) TRAEs Grade 3+ 29.4% 15.6% Serious TRAEs (TRSAEs) 20.8% 16.1% TRAEs Leading to Drug Discontinuation 1.5% 3.0% TRAEs Leading to Death 0.5% 1.0% Grade 3+ Immune-related 7.1% 8.0% Grade 3+ Possibly VEGF-related* 10.2% 1.0% *All Grade 3+ adverse events that were possibly VEGF-related were classified as Grade 3 events in both arms; there were no Grade 4 or 5 adverse events that were possibly VEGF-related observed in either arm. “This is a historic moment for ivonescimab, Team Summit, our partners at Akeso, and most importantly, we believe this is the beginning of a landscape shift for treatment options for patients living with cancer,” stated Robert W. Duggan, Chairman and Chief Executive Officer of Summit. “We are incredibly proud of our partnership with Akeso and their accomplishment with HARMONi-2.” Based on the results of HARMONi-2, Summit announced its intention to initiate HARMONi-7 in early 2025. HARMONi-7 is currently planned as a multi-regional Phase III clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%). “HARMONi-2 clearly demonstrates that ivonescimab has the potential to be the next generation in PD-1 directed immunotherapy, and potentially make a significant difference in the lives of patients with lung cancer and prospectively other tumors,” added Dr. Maky Zanganeh, Chief Executive Officer and President of Summit. “We want to again congratulate Akeso for this incredible result and their work to advance the patient-friendly standards of care today and well into the future. We look forward to initiating HARMONi-7 and sharing additional details about our expanded clinical development plan in early 2025.” Phase II Perioperative NSCLC In addition to the HARMONi-2 data presentation, a second oral presentation featuring ivonescimab was presented by Xiaoliang Zhao, MD, Deputy Chief Physician, Department of Lung Cancer at Tianjin Medical University Cancer Institute & Hospital, and Visiting Scholar at the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. The presentation was entitled, A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer, presenting the results from AK112-205, a single-region (China), multi-center, open-label Phase II study of patients with Stage II or III resectable NSCLC. The study is designed to assess patients receiving either ivonescimab monotherapy or ivonescimab plus chemotherapy prior to surgical resection and then ivonescimab monotherapy after surgery. Due to the maturity of the data and the timing of the data cutoff, the results were limited to the neo-adjuvant, or pre-surgery, portion of the clinical trial. At the time of data cutoff, 49 patients had been enrolled into the ivonescimab plus chemotherapy arm in the neo-adjuvant setting; of these 49 patients, 39 went on to complete surgery.

 
4 Of the 39 patients who received ivonescimab plus chemotherapy in the neo-adjuvant stage and completed surgery, 71.8% of patients experienced a major pathological response (MPR) and 43.6% of patients experienced a pathological complete response (pCR). In the 49 patients enrolled in this cohort, median event-free survival (EFS) was not yet reached after 8.9 months of median follow-up time; the 12-month EFS rate was 80.3% (95% CI: 59.6, 91.1). These results are encouraging compared to the historical data that has been observed in global pivotal studies in a similar setting. The safety profile was manageable: of the 49 patients who received ivonescimab plus chemotherapy in the neo-adjuvant setting, Grade 3 or higher adverse events were observed in 32.7% of patients; there was one patient who experienced a treatment-related serious adverse event. There were no TRAEs leading to delayed or cancelled surgery or that led to the death of a patient. Additional Phase II Data to be Presented at ESMO 2024 Beyond the data recently featured at WCLC 2024, Phase II data featuring ivonescimab will be presented at the European Society of Medical Oncology (ESMO) Congress 2024. ESMO 2024 will take place in Barcelona, Spain, from September 13 – 17, 2024. These presentations, which will feature data from studies sponsored by Akeso including first-line treatment for triple-negative advanced breast cancer (TNBC), first-line treatment for advanced head and neck squamous cell carcinoma (HNSCC), and first-line treatment of advanced colorectal cancer (CRC). About the ESMO 2024 Presentations Presentation Title: The efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI (chemotherapy) as first-line treatment for metastatic colorectal cancer (mCRC) ESMO Presentation No.: 514MO Session Date & Time: Saturday, September 14, 3:50 to 3:55pm CET Presentation Title: The safety and efficacy of ivonescimab in combination with chemotherapy as first-line treatment for triple-negative breast cancer (TNBC) ESMO Presentation No.: 347MO Session Date & Time: Monday, September 16, 8:30 to 8:35pm CET Poster Title: Evaluation of the safety and efficacy of ivonescimab in combination with ligufalimab as first-line treatment for PD-L1 positive recurrent/metastasis head and neck squamous cell carcinoma (R/M HNSCC) ESMO Poster No.: 876P Poster Display Date & Time: Saturday, September 14, 12:00 to 1:00pm CET Conference Call Summit Therapeutics Inc. will host a conference call to discuss recent updates related to ivonescimab, including data released at WCLC, on Monday September 9, 2024, before the market opens. Summit will host a live webcast of the conference call at 8:30am ET, which will be accessible through our website www.smmttx.com, and can also be accessed via the following link: https://events.q4inc.com/attendee/904766612. The dial-in information for US attendees is toll-free at (800) 715-9871. Additionally, all attendees may access through the toll number, (646) 307-1963. The Conference ID is 9820029. An archived edition of the webcast will be available on our website later in the day on Monday.

 
5 About Ivonescimab Ivonescimab, known as SMT112 in Summit’s license territories, 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, 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 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 TME 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 (Zhong, et al, SITC, 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 (Zhong, et al, SITC, 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 1,800 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, with a plan to initiate HARMONi-7 in early 2025. 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). 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. HARMONi-7 is a planned 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 (PD-L1 TPS > 50%). In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2. 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.

 
6 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 (PD-L1 TPS >1%). 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 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 @SMMT_TX. Contact Summit Investor Relations: Dave Gancarz Chief Business & Strategy Officer Nathan LiaBraaten Senior Director, Investor Relations investors@smmttx.com 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., including the expected benefits of the amendment to the collaboration and license agreement, the intended use of the net proceeds from the private placement, 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 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

 
7 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.

 
8 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.1 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.2 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.3 Intracranial - Within the cranium or skull. Monotherapy – a medical treatment that consists of a single drug or therapy. 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.4 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.5 PD-L1 TPS – PD-L1 Tumor Proportion Score represents the percentage of tumor cells that express PD-L1 proteins. Perioperative – around the time of surgery, typically considered to mean both before and after a surgery. 1 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 2 Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol. 2013;9(6) 3 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. 4 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. 5 Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742.

 
9 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. RECIST v1.1 – A generally-accepted way to measuring and evaluating the response of a tumor in clinical trials. The criteria is designated by an international group of experienced physicians in drug development from academic research backgrounds, government backgrounds and industry backgrounds, as well as imaging specialists and statisticians, referred to as the RECIST Working Group.6 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.7 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.8 VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.9 Summit Therapeutics and the Summit Therapeutics logo are trademarks of Summit Therapeutics Inc. Copyright 2024, Summit Therapeutics Inc. All Rights Reserved. 6 Eisenhauer, et. al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1), Eur J Cancer. 2009 Jan;45(2):228-47. 7 Cleveland Clinic. https://my.clevelandclinic.org/health/body/24630-t-cells. Accessed April 2024. 8 MD Anderson Cancer Center. https://www.mdanderson.org/cancerwise/what-is-the-tumor-microenvironment-3-things-to-know.h00- 159460056.html. Accessed April 2024. 9 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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Sep. 08, 2024
Entity Addresses [Line Items]  
Document Type 8-K
Document Period End Date Sep. 08, 2024
Entity Registrant Name Summit Therapeutics Inc.
Entity Incorporation, State or Country Code DE
Entity File Number 001-36866
Entity Tax Identification Number 37-1979717
Entity Address, Address Line One 601 Brickell Key Drive, Suite 1000
Entity Address, City or Town Miami
Entity Address, State or Province FL
Entity Address, Postal Zip Code 33131
City Area Code (305)
Local Phone Number 203-2034
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Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Title of 12(b) Security Common stock, $0.01 par value per share
Trading Symbol SMMT
Security Exchange Name NASDAQ
Entity Emerging Growth Company false
Entity Central Index Key 0001599298
Amendment Flag false
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