EX-99.1 2 infi_guascoinvestorfinal.htm EX-99.1 infi_guascoinvestorfinal
Eganelisib Macrophage Modulator as 2L Combination Therapeutic Candidate for Metastatic Urothelial Cancer and Other Solid Tumors February 11, 2021 Exhibit 99.1


 
2 Cautionary Note Regarding Forward-Looking Statements This presentation contains forward-looking statements and information of Infinity Pharmaceuticals, Inc. (“we,” “us,” “our,” “Infinity” or the “Company”) within the meaning of The Private Securities Litigation Reform Act of 1995 relating to our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentation, including express or implied statements, regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. We often use words such as “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “milestone,” “goal,” “potential,” “will,” “would,” “could,” “should,” “continue,” and other words and terms of similar meaning to help identify forward-looking statements, although not all forward-looking statements contain these identifying words. You also can identify these forward-looking statements by the fact that they do not relate strictly to historical or current facts. Such forward-looking statements include those regarding the company’s expectations about: the therapeutic potential of PI3K-gamma selective inhibition and eganelisib, alone and in combination with other therapies; clinical trial plans, progress and enrollment projections; plans to present data; planning for a registration- enabling study in urothelial cancer; financial guidance; and the company’s ability to execute on its strategic plans. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the company’s current expectations. For example, there can be no guarantee that eganelisib will successfully complete necessary preclinical and clinical development phases or that any positive developments with eganelisib will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this presentation, could also be affected by risks and uncertainties relating to a number of other factors, including the following: Infinity’s results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; Infinity’s ability to obtain, maintain and enforce patent and other intellectual property protection for eganelisib; the content and timing of decisions made by the U.S. FDA and other regulatory authorities; Infinity’s ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; and development of agents by Infinity's competitors for diseases in which Infinity is currently developing or intends to develop eganelisib. These and other risks which may impact management’s expectations are described in greater detail under the caption “Risk Factors” included in Infinity’s annual report and quarterly reports filed with the Securities and Exchange Commission (SEC), and other filings filed by Infinity with the SEC, available on the SEC’s website at www.sec.gov. Any forward-looking statements contained in this presentation speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Infinity regularly uses its website to post information regarding its business, product development programs and governance.


 
3 Today’s Agenda Evolving Standard of Care in Metastatic Urothelial Cancer (mUC) and MARIO-275 Initial Results Brian Schwartz, MD, Consulting Chief Physician, Infinity Pharmaceuticals Q&A Discussion Brian Schwartz, MD; Adelene Perkins Eganelisib: Macrophage Modulating Therapeutic Candidate to Address High Unmet Medical Need Adelene Perkins, Chair & CEO, Infinity Pharmaceuticals Eganelisib Ongoing Development Brian Schwartz, MD, Consulting Chief Physician, Infinity Pharmaceuticals


 
4 Eganelisib is designed to address fundamental biologic mechanism of immune suppression in cancer Opportunity to Improve Patient Outcomes Over SOC in Areas of High Unmet Need Multiple Data Readouts Planned in 2021 Eganelisib is an oral, macrophage reprogramming therapeutic candidate Planning registration-enabling study in urothelial cancer Clinical and translational data presented in late 2020 demonstrate eganelisib patient benefit over standard of care therapies with UC data at ASCO GU Feb ‘21 and planned TNBC data in 1H & 2H ’21 Wholly-owned drug candidate with composition of matter IP through 2034 SOC, standard of care; UC, urothelial cancer; TNBC, triple-negative breast cancer


 
5 Population 2L Urothelial Cancer Study MARIO-2751 Combination Eganelisib + Nivolumab Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 ORR PD-L1 (-) PD-L1 (+) Combo Arm 26% (n=23) 80% (n=5) Control Arm 14% (n=7) 40% (n=5) CheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,3 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 3. Infinity calculation DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival


 
6 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 3. Infinity calculation Population 2L Urothelial Cancer Study MARIO-2751 Combination Eganelisib + Nivolumab Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 ORR PD-L1 (-) PD-L1 (+) Combo Arm 26% (n=23) 80% (n=5) Control Arm 14% (n=7) 40% (n=5) CheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,3 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival


 
7 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients Population 2L Urothelial Cancer 1L TNBC Study MARIO-2751 MARIO-33 Combination Eganelisib + Nivolumab Eganalisib + Tecentriq + Abraxane Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 Tecentriq + Abraxane (n=450) IMpassion130 ORR PD-L1 (-) PD-L1 (+) PD-L1 (-) PD-L1 (+) Combo Arm 26% (n=23) 80% (n=5) 50% (n=8) 100% (n=5) Control Arm 14% (n=7) 40% (n=5) Not Reported/ Not Approved (n=185) 58.9% (n=265) CheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,a 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 a. Infinity calculation 3. Hamilton E et al. SABCS 2020 DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival


 
8 Population 2L Urothelial Cancer 1L TNBC Advanced TNBC Study MARIO-2751 MARIO-33 ARC-24 Combination Eganelisib + Nivolumab Eganalisib + Tecentriq + Abraxane Eganelisib + Etrumadenant + Doxil Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 Tecentriq + Abraxane (n=450) IMpassion130 Etrumadenant + Doxil ORR PD-L1 (-) PD-L1 (+) PD-L1 (-) PD-L1 (+) 25% (n=8) Combo Arm 26% (n=23) 80% (n=5) 50% (n=8) 100% (n=5) Control Arm 14% (n=7) 40% (n=5) Not Reported/ Not Approved (n=185) 58.9% (n=265) 9% (n=11) CheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,a 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 a. Infinity calculation 3. Hamilton E et al. SABCS 2020 4. Gardner O et al. SABCS 2020 DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival TNBC, triple-negative breast cancer


 
9 Population 2L Urothelial Cancer 1L TNBC Advanced TNBC Advanced Ovarian Study MARIO-2751 MARIO-34 ARC-24 ARC-24 Combination Eganelisib + Nivolumab Eganalisib + Tecentriq + Abraxane Eganelisib + Etrumadenant + Doxil Eganelisib + Etrumadenant + Doxil Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 Tecentriq + Abraxane (n=450) IMpassion130 Etrumadenant + Doxil Etrumadenant + Doxil ORR PD-L1 (-) PD-L1 (+) PD-L1 (-) PD-L1 (+) 25% (n=8) 75% (n=4) Combo Arm 26% (n=23) 80% (n=5) 50% (n=8) 100% (n=5) Control Arm 14% (n=7) 40% (n=5) Not Reported/ Not Approved (n=185) 58.9% (n=265) 9% (n=11) 14% (n=7) CheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,a 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 a. Infinity calculation 3. Hamilton E et al. SABCS 2020 4. Gardner O et al. SABCS 2020 DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival TNBC, triple-negative breast cancer


 
10 Population 2L Urothelial Cancer 1L TNBC Advanced TNBC Advanced Ovarian Melanoma (< 2 lines) Study MARIO-2751 MARIO-34 ARC-24 ARC-24 MARIO-15 Combination Eganelisib + Nivolumab Eganalisib + Tecentriq + Abraxane Eganelisib + Etrumadenant + Doxil Eganelisib + Etrumadenant + Doxil Eganelisib + Nivolumab Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 Tecentriq + Abraxane (n=450) IMpassion130 Etrumadenant + Doxil Etrumadenant + Doxil Progression on immediate prior CPI ORR PD-L1 (-) PD-L1 (+) PD-L1 (-) PD-L1 (+) 25% (n=8) 75% (n=4) 21.1% (n=40) Combo Arm 26% (n=23) 80% (n=5) 50% (n=8) 100% (n=5) Control Arm 14% (n=7) 40% (n=5) Not Reported/ Not Approved (n=185) 58.9% (n=265) 9% (n=11) 14% (n=7) No response or DCR expectedCheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) 52.6% Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,a 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 a. Infinity calculation 3. Hamilton E et al. SABCS 2020 4. Gardner O et al. SABCS 2020 5. Postow et al. SITC 2020 CPI, checkpoint inhibitor; DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival; TNBC, triple-negative breast cancer


 
11 Population 2L Urothelial Cancer 1L TNBC Advanced TNBC Advanced Ovarian Melanoma (< 2 lines) SCCHN (< 2 lines) Study MARIO-2751 MARIO-34 ARC-2 ARC-2 MARIO-15 MARIO-16 Combination Eganelisib + Nivolumab Eganalisib + Tecentriq + Abraxane Eganelisib + Etrumadenant + Doxil Eganelisib + Etrumadenant + Doxil Eganelisib + Nivolumab Eganelisib + Nivolumab Control / Benchmark Therapy Nivolumab + Placebo Control Arm and CheckMate-275 Tecentriq + Abraxane (n=450) IMpassion130 Etrumadenant + Doxil Etrumadenant + Doxil Progression on immediate prior CPI Progression on immediate prior CPI ORR PD-L1 (-) PD-L1 (+) PD-L1 (-) PD-L1 (+) 25% (n=8) 75% (n=4) 21.1% (n=40) 20% (n=20) Combo Arm 26% (n=23) 80% (n=5) 50% (n=8) 100% (n=5) Control Arm 14% (n=7) 40% (n=5) Not Reported/ Not Approved (n=185) 58.9% (n=265) 9% (n=11) 14% (n=7) No response or DCR expected No response or DCR expectedCheckMate-275 Benchmark2 26% (n=124) DCR Combo Arm 57% (n=23) 80% (n=5) 52.6% 40% Control Arm 14% (n=7) 60% (n=5) CheckMate-275 Benchmark2,a 52% (n=124) PFS Combo over Control Arm PD-L1 (-) ITT 0.54 0.83 Strong Evidence of Eganelisib Activity vs Benchmarks Across Six Studies And Settings in Over 130 Patients 1. Tomczak et al. ASCO GU 2021 2. Sharma et al. AACR Annual Meeting 2018 a. Infinity calculation 3. Hamilton E et al. SABCS 2020 4. Gardner O et al. SABCS 2020 5. Postow et al. SITC 2020 6. Cohen et al. SITC 2020 CPI, checkpoint inhibitor; DCR, disease control rate; ITT, intention-to-treat; ORR, overall response rate; PFS, progression free survival; SCCHN, squamous cell carcinoma of the head and neck; TNBC, triple-negative breast cancer


 
12 Eganelisib Macrophage Reprogramming Therapeutic Candidate in Solid Tumors 1Acquisition completed on April 7, 2020 2Market Cap Data as of February 9, 2021 (www.finance.yahoo.com) CD-47 Heme Focused Market Cap: ~$1.4B2 Market Cap: ~$3.0B2 Eganelisib Solid Tumors Eganelisib • Only PI3K-gamma in the clinic • Activity in – Multiple Solid tumors: UC, TNBC, Melanoma, SCCHN and Ovarian – Monotherapy, Doublet & Triplets – With and without CPIs – 1L, 2L and 3L settings – PD-L1 high as well as PD-L1 low Acquired by Gilead for $4.9 Billion1


 
13 First-in-Clinic, Oral and Selective Inhibitor of PI3K-���� (Gamma) MDSC, myeloid-derived suppressor cell; PI3K, phosphoinositide 3-kinase; TAM, tumor‐associated macrophage. 1. De Henau O et al. AACR 2016. Abstract 554. 2. 4. Evans CA et al. ACS Med Chem Lett. 2016;7(9):862-867. Kaneda MM et al. Nature. 2016;539(7629):437-442. 3. Hirsch E et al. Oncogene. 2014;33(24):3083-3090. Eganelisib showed 100x selectivity for PI3K-���� over other PI3K isoforms4 PI3K-α PI3K-β PI3K-δ Ubiquitous Ubiquitous B cells and T cells • Mutated in solid tumors • Insulin signaling • PTEN-deleted solid tumors • Platelet activation • Insulin signaling • B-cell and T-cell activation and function • B-cell malignancies PI3K-���� is unique and distinct from all other PI3K isoforms PI3K-���� TAMs, MDSCs, endothelial cells • Macrophage reprogramming (M1→M2) • Immune cell trafficking • Vascular permeability Expression pattern1 Biologic functions1,2,3


 
14 Selective and Potent Inhibition of PI3K-γ at Doses ≥15mg QD IC50 PI3Kδ IC90 PI3Kγ E ga ne lis ib C on ce nt ra tio n( ng /m l) Sustained inhibition above PI3K-γ IC90 and below PI3K-δ IC50 at doses up to 40mg


 
15 Strong Scientific Foundation for Targeting PI3K-γ in Immune Oncology MSKCC, Memorial Sloan Kettering Cancer Center; PI3K phosphoinositide 3-kinase UCSD, University of California, San Diego., ; 1. Kaneda MM et al. Nature. 2016;539(7629);437-442. 2. De Henau O et al. Nature. 2016;539(7629);443-447. Megan Kaneda Judith Varner UCSD1 Olivier De Henau Taha Merghoub Jedd Wolchok MSKCC2


 
16 Eganelisib Mechanism of Action: Reprogramming Macrophages to Turn TME From Immune Suppressed to Immune Activated Suppressed T cells Tumor cells M2 PI3K-γ inhibitor, eganelisib Activated T cells 1 Eganelisib inhibition of PI3K-γ reprograms protumor (M2) macrophages/MDSCs to antitumor (M1) function to relieve macrophage suppression and expand activated T cells M1 CPI2 Expansion of activated T cells leads to IFN- γ mediated upregulation of PD-L1 to blunt T-cell response 3 Antitumor activity of expanded T cells maintained with addition of CPI M1 M2 TME, tumor microenvironment; IFN, interferon; MDSC, myeloid-derived suppressor cell; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; CPI, checkpoint inhibitor


 
17 MARIO-1: Monotherapy Translational Data Support MOA Decrease in MDSCs and Increase in T-Cell Reinvigoration and IFN-���� Signaling Following Treatment With Eganelisib C, cycle (28 days); CD, cluster of differentiation; D, days; FCGR1B, Fc gamma receptor 1B; GBP, guanylate-binding protein; HLADR, human leukocyte antigen – DR isotype; IFN, interferon; MDSC, myeloid-derived suppressor cell; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1. Sullivan R et al. ASCO 2018. Abstract 3013. Decreased Immune Suppression Following Treatment Increased Immune Activation Following Treatment Decrease in blood myeloid- derived suppressor cells (N=15) Increase in T-cell reinvigoration (N=17) Increased IFN-���� Responsive Genes Including PD-L1 140 120 100 80 60 40 20 0 -20 -40 -60 -80 -100 M D S C C D 14 + C D 11 b+ C D 33 +H LA D R - (% o f C 1D 1) C1D1 C2D1 140 120 100 80 60 40 20 0 -20 -40 -60 -80 -100 K i6 7+ o f P D -1 +m C D 8+ (% o f C 1D 1) C1D1 C2D1 2197% 332% 319% IFN-γ- responsive genes Fold increase at C2D1 P value PD-L1 2.4 3.5 × 10-5 FCGR1B 1.8 1.5 × 10-3 GBP2 1.5 5.6 × 10-4 GBP5 2.3 1.3 × 10-4 GBP1 2.0 1.9 × 10-4 GBP4 1.7 9.4 × 10-4


 
18 PHASE 1 PHASE 1B PHASE 2 Data Presented at SITC Nov 2020 Data Presented at SABCS Dec 2020 Data Presented at SABCS Dec 2020 Updated Data Planned 1H & 2H 2021 Data at ASCO GU Feb.11, 2021 Planning Registration-Enabling Study MACROPHAGE REPROGRAMMING IN IMMUNO-ONCOLOGY MARIO-275 2nd Line Urothelial Cancer in combination with nivolumab ARC-2 Triple-Negative Breast Cancer (TNBC) in combination with etrumadenant and Doxil® MARIO-1 Checkpoint inhibitor refractory Melanoma & SCCHN in combination with nivolumab MARIO-3 Front-Line Triple-Negative Breast Cancer (TNBC) in combination with atezolizumab and nab-paclitaxel Late-2020 & 2021 MILESTONES


 
Evolving Standard of Care in Metastatic Urothelial Cancer


 
20 Unmet Need: Metastatic Urothelial Cancer 5-Year Survival Rate of 5% aEstimated cases based on 2013-2017 cases. *5-Year relative survival percent, UC by SEER Summary Stage 2000. mUC, metastatic urothelial cancer; PD-L1, programmed death-ligand 1; SEER, Surveillance, Epidemiology, and End Results; UC, urothelial cancer. 1. National Cancer Institute. Accessed December 16, 2020. https://seer.cancer.gov/statfacts/html/urinb.html 2. National Cancer Institute. Accessed December 16, 2020. https://www.cancer.gov/types/bladder/patient/bladder-treatment-pdq#Keypoint2 3. Bellmunt J et al. Ann Oncol. 2015;26(4):812-817. Majority of mUCs are PD-L1 negative3 In 2020, it is estimated that there were 81,400 of urothelial cancer1,a new cases UC Is the Most Common Type of Bladder Cancer1 95% of bladder cancers are urothelial cancer 5-Year Survival Rate by Stage at Diagnosis of UC2,* P er ce nt 5% 0 20 40 60 80 100 Localized Regional MetastaticMet tatic 36% 70%


 
21 Five Checkpoint Inhibitor Approvals in mUC Either Limited to PD-L1 Positive Patients Or Showing Less Benefit for PD-L1 Negative Patients https://www.accessdata.fda.gov/drugs Reference IDs: 1: Ref ID 4405558 2: Ref ID 4446499 3: Ref ID 4634014 (data: pfizer.com/news/press-release/press-release-detail/fda-approves-bavencio- first-line-maintenance-treatment. Accessed July 1, 2020). 4: Ref ID 4703889 (data: Hahn NM, Powles T, Massard C, et al. Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC) [abstract no. 4525 plus poster]). J Clin Oncol. 2017;35(Suppl):286. 5. Ref ID 4156731 (data: Sharma et al. AACR Annual Meeting 2018) Checkpoint inhibitor Approval Limited to PD-L1 (+) Patients Tecentriq (atezolizumab)1 1L PD-L1 positive, cisplatin ineligible, advanced urothelial cancer patients (Imvigor 210) Keytruda (pembrolizumab)2 1L PD-L1 positive, cisplatin ineligible, advanced urothelial cancer patients (Keynote 045 & 052) Approved regardless of PD-L1 Levels, but PD-L1 Negative Patients Experience Less Benefit Bavencio (avelumab)3 1L maintenance treatment vs chemo (Javelin 100) ITT OS HR= 0.69 PD-L1(+) OS HR= 0.56 PD-L1(-) OS HR= 0.85 Imfinzi (durvalumab)4 2L Cisplatin refractory, advanced urothelial cancer patients (accelerated approval from Study 1108) ITT ORR 17.6% PD-L1(+) 27.4% PD-L1(-) 4.1% Opdivo (nivolumab)5 2L Cisplatin refractory, advanced urothelial cancer patients (accelerated approval from CheckMate-275) ITT ORR 21% PD-L1(+) 26% PD-L1(-) 16% Greatest Unmet Need in PD-L1 Negative Patients, the Majority of mUC Patients


 
22 Nivolumab + Eganelisib 40 mg QD* Nivolumab + Placebo Advanced Platinum Refractory 2nd Line Urothelial Cancer Patients • MDSC all comers (stratified) • PD-L1 status all comers (non-stratified) Primary objective: ORR in MDSC High Secondary objectives: DOR, PFS, OS, ORR in Total population + MDSC subset Leveraging MARIO-275 Data to Advance Eganelisib in UC FDA Fast-Track Designation, Addition of Eganelisib to Standard of Care in I/O Naïve Urothelial Cancer Patients C ro ss -o ve r R • Preliminary data from the Phase II trial, which enrolled 49 patients, demonstrate that the combination of nivolumab and eganelisib at 30mg was well tolerated and active, particularly in patients with low levels of PD-L1 expression • Based on this encouraging data, Infinity is planning a registration-enabling study PD *Infinity voluntarily paused enrollment in May 2020 and implemented a dose reduction of eganelisib from 40mg QD to 30mg QD to address reversible liver enzyme elevations. In September 2020, the ​Independent Data Monitoring Committee determined that there was a favorable benefit/risk ratio at 30mg. Findings presented include data up to November 30, 2020


 
23 Patient Demographics and Baseline Characteristics Parameter Eganelisib + Nivolumab(N = 33) Nivolumab + Placebo (N = 16) Age, mean ± SD 64.5 ± 8.9 68.1 ± 7.4 Male, n (%) 24 (72.7) 12 (75.0) Primary tumor location, n (%) Urinary bladder Renal pelvis Other 24 (72.7) 5 (15.2) 4 (12.1) 12 (75.0) 2 (12.5) 2 (12.5) ECOG performance status, n (%) 0 1 20 (60.6) 13 (39.4) 5 (31.3) 11 (68.8) Prior Systemic Therapies, median (range) 2.0 (1, 6) 2.0 (1, 5) Liver metastases, n (%) 8 (24.2) 5 (31.3) MDSC level, n (%) Low (< 22.3) High (≥ 22.3) 26 (78.8) 7 (21.2) 13 (81.3) 3 (18.8) PD-L1 Status, n (%) ≥1% <1% Unknown 5 (15.2) 23 (69.7) 5 (15.2) 5 (31.3) 7 (43.8) 4 (25.0) Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
24 Patient Disposition and Exposure Parameter Eganelisib + Nivolumab(N = 33) Nivolumab + Placebo (N = 16) Duration of exposure, median weeks (min, max) 15.9 (2, 45) 11.1 (2, 60) Eganelisib/placebo median average daily dose mg, (min, max) 31.5 (17.4, 39.9) 38.6 (14.2, 40.0) Ongoing treatment, n (%) 8 (24.2) 5 (31.3) Discontinued treatment, n (%) Progression of disease Adverse event, related to treatment Adverse event, unrelated to treatment Death Investigator decision Voluntary withdrawal 25 (75.8) 12 (48.0) 6 (24.0) 2 (8.0) 3 (12.0) 1 (4.0) 1 (4.0) 11 (68.8) 4 (36.4) 0 (0) 1 (9.1) 3 (27.3) 2 (18.2) 1 (9.1) Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
25 Safety and Tolerability Preferred Term Eganelisib + Nivolumab (N = 33), n (%) Nivolumab + Placebo (N = 16), n (%) All Causality Related to IPI-549 Related to Nivolumab All Causality Related to Placebo Related to Nivolumab Pyrexia 11 (33.3) 4 (12.1) 2 (6.1) 0 0 0 Decreased appetite 10 (30.3) 7 (21.2) 5 (15.2) 4 (25.0) 1 (6.3) 0 Disease progression 8 (24.2) 1 (3.0) 1 (3.0) 6 (37.5) 0 0 Pruritus 8 (24.2) 5 (15.2) 8 (24.2) 1 (6.3) 0 0 Rash 8 (24.2) 7 (21.2) 4 (12.1) 1 (6.3) 0 0 Alanine aminotransferase increased 8 (24.2) 7 (21.2) 7 (21.2) 2 (12.5) 0 0 Asthenia 7 (21.2) 6 (18.2) 5 (15.2) 4 (25.0) 2 (12.5) 1 (6.3) Treatment-Emergent Adverse Events (TEAEs) (>20% in Nivolumab + Eganelisib) Preferred Term Eganelisib + Nivolumab (N = 33), n (%) Nivolumab + Placebo (N = 16), n (%) All Causality Related to IPI-549 Related to Nivolumab All Causality Related to Placebo Related to Nivolumab Disease progression 8 (24.2) 1 (3.0) 1 (3.0) 6 (37.5) 0 0 Hepatotoxicity* 5 (15.2) 5 (15.2) 5 (15.2) 0 0 0 Alanine aminotransferase increased** 4 (12.1) 4 (12.1) 4 (12.1) 0 0 0 Aspartate aminotransferase increased* 4 (12.1) 4 (12.1) 4 (12.1) 1 (6.3) 0 0 Grade ≥3^ TEAEs (>10% in Nivolumab + Eganelisib) ^No Hy’s Law and No Grade 5 * 1 Grade 4 ** 2 Grade 4 Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
26 + ++ ++ + + + Reduction of Tumor Burden in 58% (11/19) of PD-L1(-) in Combination Arm Versus 17% (1/6) of PD-L1(-) in Control Arm C ha ng e fro m B as el in e (% ) Partial Response Disease Progression Placebo + NivolumabEganelisib + Nivolumab PD-L1 Negative Other: PD-L1 Positive+ or Unknown Best Percent Change in Tumor Volume of Target Lesion (N=40) Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
27 Reduction of Tumor Burden in 58% (11/19) of PD-L1(-) in Combination Arm Versus 17% (1/6) of PD-L1(-) in Control Arm Infinity Data on File Best Percent Change in Tumor Volume of Target Lesion (N=40) PD-L1 Negative C ha ng e fro m B as el in e (% ) Disease Progression Partial Response Placebo + NivolumabEganelisib + Nivolumab


 
28 46% Lower Probability of Progression on Combination Arm Versus Control Arm in PD-L1 Negative Patient Population 0.00 0.20 0.40 0.60 0.80 1.00 0 6 12 18 24 30 36 42 48 Pr og re ss io n Fr ee S ur vi va l P ro ba bi lit y Weeks PD-L1(-) PD-L1(+) ITT Eganelisib + Nivolumab Median PFS (wks) [95% CI] Patients with Events, n (%) N=23 9.1 [7.9, NE] 15 (65.2) N=5 NE [7.9, NE] 2 (40.0) N=33 9.1 [8.0, 22.3] 22 (66.7) Placebo + Nivolumab** Median PFS (wks) [95% CI] Patients with Events, n (%) N=7 7.9 [2.4, 8.0] 6 (85.7) N=5 16.4 [6.9, NE] 3 (60.0) N=16 8.5 [7.9, 16.4] 12 (75.0) Hazard Ratio [95% CI] 0.54 [0.21, 1.43] NE 0.83 [0.41,1.67] + Censored: Eganelisib + Nivolumab Censored: Placebo + Nivolumab Eganelisib + Nivolumab Placebo + Nivolumab Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
29 DCR 4X Greater in Combination Arm Versus Control Arm All Patients PD-L1 (-) Patients PD-L1 (+) Patients Eganelisib + Nivo N = 33 Nivo + Placebo N = 16 Eganelisib + Nivo N = 23 Nivo + Placebo N = 7 Eganelisib + Nivo N = 5 Nivo + Placebo N = 5 n % n % n % n % n % n % CR 4* 12% 1* 6% 2 9% 0 0% 2 40% 0 0% PR 6** 18% 3 19% 4 17% 1 14% 2 40% 2 40% ORR^ 10 30% 4 25% 6 26% 1 14% 4 80% 2 40% SD 8** 24% 1 6% 7 30% 0 0% 0 0% 1 20% DCR^^ 18 55% 5 31% 13 57% 1 14% 4 80% 3 60% PD 11 33% 7 44% 6 26% 5 71% 1 20% 1 20% NE 4 12% 4 25% 4 17% 1 14% 0 0% 1 20% *Confirmed CR **4 patients had PD at C3, then PR or SD at later cycles ^Unconfirmed overall response rate (ORR) (CR+PR) ^^Unconfirmed disease control rate (DCR) (CR,PR+SD) Note: Patients were stratified by MDSC level, but there was no meaningful difference between the DCR in the MDSC high combination arm (29%, n=7) versus the MDSC high control arm (33%, n=3);


 
30 Translational Data Consistent with MOA Decreased Immune Suppression and Increased Immune Activation Increased Immune Activation Eganelisib + Nivolumab Placebo + Nivolumab T C el l R ei nv ig or at io n K i6 7+ of P D 1+ m em or y C D 8 (% ) P<0.1 P<0.01 P-value is based on t-test assuming equal variance *MDSC = HLADR- of CD14+CD15-CD11b+CD33b+CD45+Lin-; Tomczak et al. ASCO Genitourinary Cancers Symposium 2021 C 1D 1 C 1D 15 C 2D 1 C 3D 1 C 1D 1 C 1D 15 C 2D 1 C 3D 1 C 1D 1 C 1D 15 C 2D 1 C 3D 1 C 1D 1 C 1D 15 C 2D 1 C 3D 1 PD-L1 Negative PD-L1 Positive Eganelisib + Nivolumab Placebo + Nivolumab Decreased Immune Suppression Lo g 2 fo ld c ha ng e *M D S C ( ce lls /m L) M D S C PD-L1 Negative PD-L1 Positive Eganelisib + Nivolumab Placebo + Nivolumab C 1D 1 C 1D 15 C 3D 1 C 1D 1 C 1D 15 C 3D 1 C 1D 1 C 1D 15 C 3D 1 C 1D 1 C 1D 15 C 3D 1 Eganelisib + Nivolumab Placebo + Nivolumab C 2D 1 C 2D 1 C 2D 1 C 2D 1


 
31 Conclusions and Next Steps in mUC • Preliminary data demonstrate that the combination of eganelisib at 30 mg + nivolumab was well tolerated • The combination demonstrated an improved ORR, DCR and PFS versus nivolumab, especially in PD-L1 negative patients, which represent approximately 70% of the combination arm patients • Translational data demonstrate decreased immune suppression and increased immune activation with eganelisib + nivolumab versus nivolumab + placebo, including in PD-L1 low patients • Given the magnitude of unmet need and the magnitude of the benefit seen in PD-L1 low mUC patients, Infinity is planning a registration-enabling study in the PD-L1 low mUC population Tomczak et al. ASCO Genitourinary Cancers Symposium 2021


 
32 High Unmet Need for PD-L1 Negative Patients in Many Tumor Types https://www.accessdata.fda.gov/drugs Reference IDs: 1. 4405558 2. 4446499 3. 4156731 Approved Label 1st Line Approved Therapy 2nd Line+ Approved Therapy PD-L1 positive, advanced TNBC  Tecentriq1 with nab-paclitaxel (accelerated approval)  Keytruda2 with chemo PD-L1 positive, advanced NSCLC That does not have an abnormal "EGFR" or "ALK" gene  Keytruda  Tecentriq  Opdivo3 with ipilumimab That does have an abnormal "EGFR" or "ALK" gene and was treated with "EGFR" or "ALK" inhibitor medicine that did not work or is no longer working  Keytruda PD-L1 positive, advanced SSCHN  Keytruda PD-L1 positive, advanced Esophageal  Keytruda PD-L1 positive, advanced Gastric cancer  Keytruda PD-L1 positive, advanced Cervical cancer  Keytruda Large Indications for Which Checkpoint Inhibitor Approvals Are Limited to PD-L1 Positive Patients


 
33 PD-L1 High % O R R % Patients With PD-L1 Low Cancers Show Low Response Rates Across 29 Tumor Types ACC, adenoid cystic carcinoma; cSCC. cutaneous squamous-cell carcinoma; HCC, hepatocellular carcinoma; H&N, head and neck; MCC, Merkel cell carcinoma; MMRd, mismatch repair–deficient; NSCLC, non-small cell lung cancer; ORR, overall response rate; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RCC, renal cell carcinoma; SCLC, small cell lung cancer; UM, uveal melanoma. 1. Chen DS, Mellman I. Nature. 2017;541(7637):321-330. 2. Yarchoan M et al. JCI Insight. 2019;4(6):e126908. Higher response rates to anti–PD-1/PD-L1 therapy in PD-L1 high tumors have been reported1,2 The greatest unmet need is in patients with PD-L1 low tumors 29 tumor types or subtypes with ORR available There is a positive relationship between the PD-L1 expression positivity rate and the ORR for anti–PD-1 or anti–PD-L1 therapy2 10 20 30 40 50 60 10 20 30 40 50 Pancreatic BreastProstate ACC Biliary Sarcoma Glioblastoma Ovarian Esophagogastric Endometrial SCLC HCC Cervical UM H&N Mesothelioma Urothelial NSCLC - Squamous NSCLC - Nonsquamous Anal Colorectal - MMRd RCC Noncolorectal - MMRd Melanoma CSCC MCC Nasopharyngeal Thymic ORR (n) PD–L1 High (n) 50 100 500 1000 50 250 1000 0 0 Colorectal


 
Eganelisib Ongoing Development


 
35 PHASE 1 PHASE 1B PHASE 2 Data Presented at SITC Nov 2020 Data Presented at SABCS Dec 2020 Data Presented at SABCS Dec 2020 Updated Data Planned 1H & 2H 2021 Data at ASCO GU Feb.11, 2021 Planning Registration-Enabling Study MACROPHAGE REPROGRAMMING IN IMMUNO-ONCOLOGY MARIO-275 2nd Line Urothelial Cancer in combination with nivolumab ARC-2 Triple-Negative Breast Cancer (TNBC) in combination with etrumadenant and Doxil® MARIO-1 Checkpoint inhibitor refractory Melanoma & SCCHN in combination with nivolumab MARIO-3 Front-Line Triple-Negative Breast Cancer (TNBC) in combination with atezolizumab and nab-paclitaxel Late-2020 & 2021 MILESTONES


 
36 Potential of Eganelisib to Improve on Atezolizumab + Nab-Paclitaxel FDA Approval Only in PD-L1 High mTNBC Front-Line Regimen CR, complete response; DCR, disease control rate; ITT, intent-to-treat; ORR, overall response rate; PD, pharmacodynamics; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PK, pharmacokinetics; SOC, standard of care; mTNBC, metastatic triple-negative breast cancer; TNBC, triple-negative breast cancer. 1. Schmid P et al. N Engl J Med. 2018;379(22):2108-2121. Eganelisib FDA Fast Track Designation for TNBC MARIO-3 TNBC exploring the potential of eganelisib to improve on IMpassion130 results1 Addition of eganelisib to SOC, atezolizumab and nab-paclitaxel, in front-line TNBC • Inclusion/exclusion criteria per IMpassion130 study • Two prespecified cohorts: PD-L1(+) and PD-L1(-) • Primary objective: CR rate CR benchmark ≈7% ITT; 10% PD-L1(+) • Secondary objectives: PK, PD, ORR, DCR, and PFS; ORR for PD-L1(-) cohort Total enrollment (n≈60) TNBC PD-L1(-) (n=up to 30) TNBC PD-L1(+) (n=up to 30) eganelisib 30mg QD + atezolizumab + nab-paclitaxel


 
37 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 * ** F I D J C K B M H L G A E B es t P er ce nt C ha ng e in T ar ge t L es io n fr om B as el in e Patient PR SD PD CR PD-L1 positive PD-L1 negative + - + + + + + - - - - - - - - 69.2% (9/13) exhibited a complete or partial response 100% of Evaluable Patients Exhibited Tumor Reduction Regardless of PD-L1 Status * >40% decrease in target lesion, but PD due to new lesions ** 100% decrease in target lesions, but PR due to presence of non-target lesions Hamilton E et al. SABCS 2020. Abstract PS11-32.


 
38 0 5 10 15 20 25 30 A B C D E F G H I J K L M 92% (12/13) of Patients Derived Clinical Benefit Hamilton E et al. SABCS 2020. Abstract PS11-32. * - - + - + - + + - + - - - Patient PD-L1 Status (+/-) Duration on Treatment (Weeks) * PR SD PD CR On Study Off Treatment Due to AE* • Majority of patients achieved PR at 1st Scan • Majority of patients remained on study as of SABCS • 7 additional patients enrolled as of SABCS awaiting 1st scan


 
39 Overall Response Rates Show Improvement Over Standard of Care Benchmarks in ITT and PD-L1(+) PD-L1, programmed death-ligand 1; RECIST, Response Evaluation Criteria in Solid Tumors. 1. Hamilton E et al. SABCS 2020. Abstract PS11-32. a Unconfirmed BOR presented, but 2 PRs of PD-L1(+) and 2 PRs of PD-L1(-) are confirmed. 2. N Engl J Med 2018;379:2108-21. 3. Infinity estimate. MARIO-31 ITT n=13 PD-L1(+) n=5 PD-L1(-) n=8 Overall response ratea 69.2% 100% 50% IMpassion130 Atezolizumab + Nab-Paclitaxel Standard of Care ORR Benchmark in PD-L1(+) 56% 2 58.9%2 Not Reported2 IMpassion130 Nab-Paclitaxel Control Arm ORR Benchmark 45.9% 2 42.6%2 Not Reported; ~40-45%3 Benchmarks


 
40 PHASE 1 PHASE 1B PHASE 2 Data Presented at SABCS Dec 2020 Updated Data Planned 1H & 2H 2021 Data at ASCO GU Feb.11, 2021 Planning Registration-Enabling Study MACROPHAGE REPROGRAMMING IN IMMUNO-ONCOLOGY MARIO-275 2nd Line Urothelial Cancer in combination with nivolumab ARC-2 Triple-Negative Breast Cancer (TNBC) in combination with etrumadenant and Doxil® MARIO-1 Checkpoint inhibitor refractory Melanoma & SCCHN in combination with nivolumab MARIO-3 Front-Line Triple-Negative Breast Cancer (TNBC) in combination with atezolizumab and nab-paclitaxel Late-2020 & 2021 MILESTONES  Ovarian ORR: 75% vs. 14%*  TNBC ORR: 25% vs. 9*  Melanoma ORR (≤ 2 lines): 21%  SCCHN ORR (≤ 2 lines): 20% *Triplet Arm (Eganelisib + Etrumadenant + Doxil) versus Doublet Arm (Etrumadenant + Doxil)


 
41 PHASE 1 PHASE 1B PHASE 2 KEY STUDY DATA  PFS Hazard Ratio: 0.54  4x DCR compared to control arm Expansive and Consistent Body of Evidence Across Tumor Types, Combination Regimens and Lines of Therapy MARIO-275 2nd Line Urothelial Cancer in combination with nivolumab ARC-2 Triple-Negative Breast Cancer (TNBC) in combination with etrumadenant and Doxil® MARIO-1 Checkpoint inhibitor refractory Melanoma & SCCHN in combination with nivolumab MARIO-3 Front-Line Triple-Negative Breast Cancer (TNBC) in combination with atezolizumab and nab-paclitaxel  100% ORR PD-L1 (+)  50% ORR PD-L1 (-)  Ovarian ORR: 75% vs. 14%*  TNBC ORR: 25% vs. 9* *Triplet Arm (Eganelisib + Etrumadenant + Doxil) versus Doublet Arm (Etrumadenant + Doxil)  Melanoma ORR (≤ 2 lines): 21%  SCCHN ORR (≤ 2 lines): 20%


 
42 Eganelisib Macrophage Reprogramming Therapeutic Candidate in Solid Tumors 1Acquisition completed on April 7, 2020 2Market Cap Data as of February 9, 2021 (www.finance.yahoo.com) CD-47 Heme Focused Market Cap: ~$1.4B2 Market Cap: ~$3.0B2 Eganelisib Solid Tumors Eganelisib • Only PI3K-gamma in the clinic • Activity in – Multiple Solid tumors: UC, TNBC, Melanoma, SCCHN and Ovarian – Monotherapy, Doublet & Triplets – With and without CPIs – 1L, 2L and 3L settings – PD-L1 high as well as PD-L1 low Acquired by Gilead for $4.9 Billion1


 
Q&A Discussion


 
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46 Arcus Collaboration: ARC-2 Phase 1/1b Study Eganelisib (30 or 40 mg po qd) + Etrumadenant (150 mg po qd) + Doxil IV q4w (n=3-6) TNBC and Ovarian Cancer TNBC Triplet Arm Eganelisib (40 mg po qd) + Etrumadenant (150 mg po qd) + Doxil IV q4w (n=15-40) Etrumadenant (75 or 150 mg po qd) + Doxil IV q4w (n=3-6) Doublet Arm Etrumadenant (150 mg po qd) + Doxil IV q4w (n=15-40) Dose Escalation Dose Expansion IV, intravenous; RDE, recommended dose for expansion; TNBC, triple-negative breast cancer.


 
47 ARC-2 Etrumadenant and Doxil +/- Eganelisib Clinical Activity in Ovarian Cancer and TNBC Etruma + Doxil + Eganelisib ORR = 42% 12 evaluable patients: 1 CR (Ovarian), 4 PRs (2 TNBC, 2 Ovarian) Etruma + Doxil ORR = 11% 18 evaluable patients: 2 PRs (1 TNBC, 1 Ovarian) Doublet Arm Triplet Arm † Patient withdrew prior to first disease assessment. BOR, best overall response; CR, complete response; Etruma, etrumadenant; OvCa, ovarian cancer; PD, progressive disease; PLD, pegylated liposomal doxorubicin; PR, partial response; SD, stable disease; TNBC, triple-negative breast cancer. Gardner O et al. SABCS 2020. Abstract PS12-12.


 
48 MARIO-1: Combination of Eganelisib + Nivolumab in Patients Who Progressed on Immediate Prior CPI Therapy * 28 day cycles, continuous 40mg QD dosing ** Flat-dose 240 mg Q2W *** Must have de novo or acquired resistance to immediately prior anti-PD-1/anti-PD-L1 therapy CPI, checkpoint inhibitor. Postow et al. SITC 2020. Melanoma SCCHNCombination Dose Escalation/Expansion Eganelisib*+ Nivolumab** Stable Disease E ganelisib B enefit MARIO-1 Study Start*** PD A key objective of the study is to mount an effective anti-tumor immune response in combination with CPI to generate clinical responses in patients who would not be expected to respond to checkpoint inhibitor therapy alone, including those having progressed on immediate prior CPI therapy


 
49 -60 -50 -40 -30 -20 -10 0 -30 -10 10 30 50 70 90 110 130 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 -20 0 20 40 60 80 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 -40 -30 -20 -10 0 10 20 30 40 Time (weeks) Objective Responses in Melanoma Patients Who Progressed on Immediate Prior Checkpoint Inhibitor Therapy CPI, checkpoint inhibitor. Postow et al. SITC 2020. ORR of 21.1% and DCR of 52.6% in Melanoma Patients ≤ 2 prior lines of therapy % C ha ng e fr om b as el in e ta rg et le si on s Time (weeks) • Patient A with Stage III melanoma • Refractory to pembrolizumab after 3 mos • 57% tumor reduction in response to treatment with eganelisib + nivolumab • PFS: > 25 months • Patient C with Stage IV melanoma • Refractory to pembrolizumab (CR for 1 year; PD after 6 months of therapy) • 76% tumor reduction in response to treatment with eganelisib + nivolumab • PFS: 6 months • Patient B with Stage IV melanoma • Refractory to nivolumab after 5 mos • 79% tumor reduction in response to treatment with eganelisib + nivolumab • PFS: 14 months % C ha ng e fr om b as el in e ta rg et le si on s % C ha ng e fr om b as el in e ta rg et le si on s Time (weeks) Start of MARIO-1 Therapy After Progression on Immediate Prior CPI Start of MARIO-1 Therapy After Progression on Immediate Prior CPI Start of MARIO-1 Therapy After Progression on Immediate Prior CPI


 
50 Potential Next Step: Pro-Tumor Macrophages Driving CPI Resistance May Be Overcome by Eganelisib+CPI+CTLA4 Macrophage-Rich B16 GM-CSF Melanoma Model CPI, checkpoint inhibitor. De Henau et al. Nature, 2016 Nov;539:443-447. Enhanced Survival Eganelisib in combination with anti-PD1 and anti-CTLA4 therapies extends survival with 80% complete regression with statistical significance **** p < 0.0001 *** p < 0.001 * p < 0.05 Tumor Regression


 
51 • Patient A: stage IV disease at study entry • Refractory to pembrolizumab after 15 mos • 63% tumor reduction • PFS: 11 months Eganelisib + Nivolumab: Partial Response in Patients Who Progressed on Immediate Prior CPI Therapy CPI, checkpoint inhibitor. Cohen et al. SITC 2020. ORR of 20.0% and DCR of 40.0% in SCCHN Patients ≤ 2 prior lines of therapy Start of MARIO-1 Therapy After Progression on Immediate Prior CPI % C ha ng e fr om b as el in e ta rg et le si on s % C ha ng e fr om b as el in e ta rg et le si on s Start of MARIO-1 Therapy After Progression on Immediate Prior CPI Time (weeks) Time (weeks) • Patient B: stage IV disease at study entry • Refractory to pembrolizumab after 5 mos • 36% tumor reduction • PFS: 7 months


 
52 Next Step: Phase 2 Window of Opportunity Study of Eganelisib in Patients with Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma Protocol 172058: UCSD Moores Cancer Center Investigator Initiated Trial 3 weeks Therapy: eganelisib 40 mg QD PO days 1-21 • Baseline tumor measurement • Tumor biopsy (non-surgical) Surgical Tissue Specimen Standard Therapy, Survival, Toxicity Follow-Up • RNA profiling • Multiplex IHC • DNA isolation/TCR sequencing Patients with Locally Advanced, Previously Untreated HNSCC Amenable to Surgical ResectionObjectives: To detect a change in the PI3Kgamma regulated gene expression signature of immune suppression To detect change in myeloid, T cell composition and immune activation markers by IHC as well as TCR sequencing To determine safety and tolerability of eganelisib and change in tumor size in patients with locally advanced HNSCC 1 2 3


 
53 MARIO-275 Patient Disposition Randomized (n = 49) Nivolumab + Placebo (n = 16) Nivolumab + Eganelisib (n = 33) Response Evaluable (n = 5) Response Not Evaluable (n = 0) PD-L1 (+) (n = 5) PD-L1 (-) (n = 23) Unknown (n = 5) Response Evaluable (n = 19) Response Not Evaluable (n = 4) Response Evaluable (n = 5) Response Not Evaluable (n = 0) Response Evaluable (n = 4) Response Not Evaluable (n = 1) PD-L1 (+) (n = 5) PD-L1 (-) (n = 7) Unknown (n = 4) Response Evaluable (n = 6) Response Not Evaluable (n = 1) Response Evaluable (n = 2) Response Not Evaluable (n = 2)