Slides
Page 1
Presentation of Initial SGR-1505 Phase 1 Clinical Data June 12, 2025
Page 2
2 Cautionary Note and Disclaimer This presentation contains certain "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical fact, made by Schrödinger, Inc. (“we,” “us,” “our,” “Schrödinger,” or the “Company”) contained in this presentation, including, without limitation, statements regarding the potential advantages of our computational platform, our research and development efforts for our proprietary drug discovery programs and our platform, the clinical potential and favorable properties of our molecules, including SGR-1505, our MALT1 inhibitor, and other compounds discovered with our platform, the potential for SGR-1505 to be used for the treatment of relapsed/refractory B-cell malignancies, including chronic lymphocytic leukemia, small lymphocytic leukemia, and Waldenström’s macroglobulinemia, our plans to engage with regulators, the timing of clinical trials for our proprietary drug discovery programs and reporting of data from such trials, our plans to leverage the synergies between our businesses, are forward-looking statements. The words “aim,” “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” or the negative of these words or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Actual results may differ materially from those described in the forward-looking statements and are subject to a variety of assumptions, uncertainties, risks and important factors that are beyond our control, including the demand for our software solutions, the reliance upon our third-party drug discovery collaborators, the uncertainties inherent in drug development and commercialization, such as the conduct of research activities and the timing of and our ability to initiate and complete preclinical studies and clinical trials, whether results from preclinical and early clinical studies will be predictive of the results of later preclinical studies and clinical trials, whether initial data from clinical trials will be predictive of the final results of the clinical trials, uncertainties associated with the regulatory review of clinical trials and applications for marketing approvals, factors adversely affecting the life sciences industry, and other risks detailed under the caption "Risk Factors" and elsewhere in our Securities and Exchange Commission (“SEC”) filings and reports, including our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 7, 2025, as well as future filings and reports by us. Any forward-looking statements contained in this presentation speak only as of the date hereof. Except as required by law, we undertake no duty or obligation to update any forward-looking statements contained in this presentation as a result of new information, future events, changes in expectations or otherwise. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys, and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. We have not independently verified such third-party data, and we undertake no obligation to update such data after the date of this presentation.
Page 3
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 3 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President, Head of Therapeutics R&D and Chief Strategy Officer, Partnerships Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 4
1 Active customers (# of customers who had an ACV >$1,000) as of Dec. 31, 2024. 2 Cumulative number of collaborators since 2018. 4 Multi-Pronged Business Enabled by Highly Differentiated Computational Platform COMPUTATIONAL PLATFORM COLLABORATIONS• Life Sciences • Materials Design ~1,752 customers worldwide1 19 drug discovery collaborators2 8+ active programs • Drug Design • Materials Design • Drug Discovery & Development PROPRIETARY PIPELINE SOFTWARE LICENSING
Page 5
5 Schrödinger’s Vision for the Future of Drug Discovery If all properties can be calculated with perfect accuracy, designing drugs would have a much higher success rate, be much faster and cheaper, and would produce much higher-quality molecules. Select THE best molecule “All” synthesizable molecules (~1080) Potency Selectivity Solubility Bioavailability Clearance / Half-life Permeability Drug-Drug Interactions Synthesizability ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
Page 6
66 Platform Validated by Clinical Success(1)(2) 1Based on publicly available information or information disclosed to us. 2All of the programs being pursued under these collaborations are owned and controlled by each respective collaborator. 3Acquired from Nimbus. 4Acquired by Servier. 5Acquired from Morphic. Phase 1 Phase 2 Phase 3 Immuno-oncology Myelofibrosis Additional programs in discovery and preclinical development with: Inflammatory Bowel Disease5 Metabolic Diseases3 FDA-Approved Psoriasis3 TIBSOVO4 IDHIFA4 UndisclosedUndisclosed UndisclosedUndisclosed Obesity Hematologic Malignancies AML/MDS Solid Tumors
Page 7
7 Capturing Value from Collaborative and Proprietary Programs Acquired Acquired Acquired TKY2 20142010 2016 2018 2020 2022 20242012 2022 2024Proprietary Programs 20202018
Page 8
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 8 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President, Head of Therapeutics R&D and Chief Strategy Officer, Partnerships Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 9
9 MALT1: An Emerging Mechanism in a Validated Pathway Lymphoma cell survival is associated with dysregulated NF-κB signaling B-cell BTK inhibitors are standard-of-care in B-cell malignancies, but resistance develops
Page 10
10 MALT1 is a key regulator of NF-κB signaling in B-cells and T-cells BTK inhibitors are standard-of-care in B-cell malignancies, but resistance develops MALT1: An Emerging Mechanism in a Validated Pathway Lymphoma cell survival is associated with dysregulated NF-κB signaling B-cell
Page 11
8,214 compounds modeled 11 Rapid Design of a Best-in-Class MALT1 Inhibitor 78 Compounds synthesized in SGR-1505 series 10 Months ✓ Novel allosteric pocket inhibitor ✓ Optimized in vitro cellular potency ✓ Selective against common off targets ✓ Optimized in vivo anti-tumor monotherapy and combination activity ✓ Optimized IL-2 inhibition in human blood cells Human MALT1 Paracaspase 8.2 billion compounds enumerated
Page 12
Traditional Drug Design • 8.2 billion compounds scored with Physics+AI/ML • SGR-1505 identified in 10 months Hit Discovery Hit-to-Lead Lead Optimization Drug candidates with potential property issues Hit Discovery Hit-to- Lead Lead Op. Phase 1 package Optimized profile confirmed in global patient study SGR-1505 IND Enabling PIb Patients PIa HV ✓ • Manual molecule design • ~5,000 molecules synthesized and tested over ~4 – 6 years 12 Impact of Schrödinger Drug Discovery Approach
Page 13
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 13 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President, Head of Therapeutics R&D and Chief Strategy Officer, Partnerships Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 14
14 BTK Inhibitor Approvals in B-Cell Malignancies DLBCL 65,006MCLCLL/SLL 46,023 FL 35,618 MZL 10,700WM 8,2625,534 Indolent B-cell Malignancies 2023 diagnosed incident cases in Major Markets (U.S., EU, Japan) Aggressive B-cell Malignancies 2023 diagnosed incident cases in Major Markets (U.S., EU, Japan) First approval Sources: Product prescribing information; Decision Resources Group Clarivate NHL Market Analysis. ✓ ✓ ✓ ✓ Label expansion✓ ibrutinib acalabrutinib zanubrutinib pirtobrutinib
Page 15
Five-Year Survival Rate in CLL- IPI Risk Subgroups 15 Potential MALT1 Opportunity in Higher-Risk CLL Patients Risk subgroups are based on genetic, biochemical, and clinical parameters*1,2 Low Intermediate High Very High 93.2% 79.3% 63.3% 23.3% *Includes age, TP53 and/or 17p deletion mutation status, IGHV mutational status. 1International CLL-IPI Working Group. Lancet Oncol. 2016;17(6):779-790. 2Hallek M, Al-Sawaf O. Am J Hematol. 2021;96(12):1679-1705.
Page 16
MRD negative (cure) 16 • Minimal residual disease (MRD) being evaluated to monitor disease • Patients with CR who remain MRD positive may benefit from further treatment • Patients who revert from MRD negative to MRD positive may benefit from further treatment Adapted from Woyach JA, Byrd JC. NEJM 2023: 388(19). New Mechanisms and Combinations Needed to Achieve Minimal Residual Disease 10-0 10-1 10-2 10-3 10-4 10-5 10-6 0 Time MRD relapse Hematologic relapse Proportion of Malignant Cells
Page 17
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 17 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President, Head of Therapeutics R&D and Chief Strategy Officer, Partnerships Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 18
18 Successful Phase 1 Study: Key Findings • SGR-1505 was observed to have a favorable safety profile and was well-tolerated • Confirmed strong target engagement • Encouraging preliminary efficacy across range of B-cell malignancies • Monotherapy signal in CLL and Waldenström macroglobulinemia (WM) Spurgeon et al., EHA 2025. As of the data cut-off date (May 13, 2025).
Page 19
19 Study Design & Objectives Primary objectives: • Safety and tolerability • Identification of maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or recommended dose(s) (RD) Secondary objectives: • Pharmacokinetics (PK) • Preliminary anti-tumor activity Exploratory objective: • Pharmacodynamics (PD) • R/R B-cell neoplasms following ≥ 2 prior lines • Indolent forms and aggressive forms of NHL • Continuous dosing • 21-day cycles Arm A (QD) Arm B (Q12H) Cohort 6 (N=3-6) 400 mg Cohort 5 (N=3) 300 mg Cohort 4 (N=1) 200 mg Cohort 3 (N=1) 150 mg Cohort 2 (N=1) 100 mg Cohort 1 (N=1) 50 mg Cohort 6 (N=3-6) 200 mg Cohort 5 (N=3) 150 mg Cohort 4 (N=3) 125 mg Cohort 3 (N=3) 100 mg Cohort 2 (N=1) 75 mg Cohort 1 (N=1) 50 mg Spurgeon et al., EHA 2025; Clinicaltrials.gov ID: NCT05544019. QD: once daily dosing; Q12H: dosing every 12 hours
Page 20
20 Study Conducted in Highly Refractory Patient Population Median age, years (range) 64 (31 - 82) Male, n (%), female, n (%) 32 (65.3), 17 (34.7) ECOG PS, n (%) 0, 1 25 (51.0), 24 (49.0) Median prior lines of therapy (range) 4 (2 - 9) Histologies, n (%) Chronic lymphocytic leukemia/small lymphocytic leukemia Diffuse large B-cell lymphoma Waldenstrom macroglobulinemia Marginal zone lymphoma Mantle cell lymphoma Other (4 FL, 1 PMBCL, 1 THRLBCL) 18 (36.7) 9 (18.4) 6 (12.2) 5 (10.2) 5 (10.2) 6 (12.2) Select previous treatments, n (%) BTK inhibitor BCL-2 inhibitor BTK inhibitor + BCL-2 inhibitor Anti-CD20 27 (55.1) 9 (18.4) 9 (18.4) 46 (93.9) Demographics (N=49) Spurgeon et al., EHA 2025. FL: follicular lymphoma; PMBCL: primary mediastinal large b-cell lymphoma; THRLBCL: t-cell/histiocyte rich large b-cell lymphoma
Page 21
21 SGR-1505 Observed to Have a Favorable Safety Profile and Was Well-Tolerated Common (≥10%) TEAE/TRAEs TEAE TRAE Any grade (n, %) Grade ≥3 (n, %) Any grade (n, %) Grade ≥3 (n, %) Any TEAE 42 (85.7) 23 (46.9) 21 (42.9) 12 (24.5) Neutrophil count decreased 10 (20.4) 10 (20.4) 3 (6.1) 3 (6.1) Fatigue 8 (16.3) 0 (0.0) 6 (12.2) 0 (0.0) Rash* 7 (14.3) 3 (6.1) 6 (12.2) 3 (6.1) Blood bilirubin increased 5✝ (10.2) 4 (8.2) 4 (8.2) 4 (8.2) • 43% of patients experienced ≥1 treatment-related adverse event (TRAE) • Well-tolerated with no dose limiting toxicities or deaths due to treatment-emergent adverse events (TEAE) • No cases of Hy’s law • All blood bilirubin increased TEAEs were asymptomatic, from participants with UGT1A1 polymorphisms, and none were G4 *Includes rash, papular rash, and maculo-papular rash. ✝All were asymptomatic, from participants with UGT1A1 polymorphisms, and none were G4. One participant with G2 unrelated hyperbilirubinemia reported a G1 AST elevation 23 days later, when the participant was progressing radiographically. Spurgeon et al., EHA 2025.
Page 22
22 IL-2 Response at Steady State Confirms Inhibition of NF-κB Signaling • SGR-1505 inhibits T-cell derived IL-2 upon ex vivo stimulation – ~90% inhibition in the majority of PD-evaluable patients treated at ≥150 mg QD and all Q12H doses at steady state • Q12H dosing provided more sustained IL-2 inhibition compared to QD dosing • Approximately 90% inhibition of IL-2 was observed as early as Day 8 and 15 N = number of participants in the dose groups n = number of data points in the dose groups IL-2 inhibition through C2 D1 (steady state) by dose groups Spurgeon et al., EHA 2025.
Page 23
50 75 125 150 100 Encouraging Preliminary Efficacy Across Range of B-Cell Malignancies 23 Includes 40 subjects with ≥1 follow-up disease assessment with measurable disease or IgM assessment. Dose (mg) 50 QD Q12H 100 150 200 300 Treatment Ongoing Exposed to BTKi and BCL-2i Exposed to BTKi PMR = partial metabolic response PR-L= partial response with lymphocytosis L = prior lines of therapy Best Change (%) 350 50 0 -50 -100 2L PR WM (n=5) MR MR MR PR 2L 2L 6L 4L Non-GCB DLBCL (n=3) 3L PR 2L 2L 6L PR-L CLL/SLL (n=16) *Clinical PR-L (independently confirmed) that did not meet iwCLL PR criteria ✝This participant discontinued treatment post-database lock PR-L PR PR-L*6L 2L 6L 4L 8L 2L 5L 4L 2L 2L 3L 3L 7L 3L 4L MZL (n=5) 2L 7L 5L 5L 5L PMR 7L 9L GCB-DLBCL, DLBCL NOS, FL, MCL, PMBCL, THRLBCL (n=11) 9L 3L 6L 3L 2L 6L 6L 2L 3L 9L✝ Spurgeon et al., EHA 2025. ✝
Page 24
Preliminary Duration of Treatment in Indolent Lymphomas 24 3 6 9 18 21 24 Treatment Length (Months) CLL/SLL (N=18) WM (N=6) MZL (N=5) 0 FL (N=4) ✝ 50 mg QD 100 mg QD 150 mg QD 200 mg QD 300 mg QD 50 mg Q12h 75 mg Q12h 100 mg Q12h 125 mg Q12h 150 mg Q12h ✝This participant discontinued treatment post-database lock SD / NMR Minor response PR / PMR PD / PMD TEAE TRAE Subject withdrawal Not done Reason for treatment discontinuation Response Dose level Treatment ongoing Spurgeon et al., EHA 2025. N=33
Page 25
No prior BTK or BCL-2 35% of evaluable CLL/SLL participants were double-exposed to BTK and BCL-2 inhibitors (n = 17) Spurgeon et al., EHA 2025. BTK inhibitor exposed BTK and BCL-2 inhibitor exposed 25 Prior BTK Exposure in CLL/SLL Patients • More than half of the evaluable CLL/SLL patients had been previously exposed to a BTK inhibitor • 35% of evaluable CLL/SLL participants were double-exposed to both BTK and BCL-2 inhibitors – Encouraging preliminary efficacy signals in these evaluable CLL/SLL patients (2/6)
Page 26
26 Phase 1 Summary and Next Steps Key Study Findings • SGR-1505 observed to be well-tolerated with a favorable safety profile • Strong target engagement • Encouraging preliminary efficacy across range of B-cell histologies – Monotherapy signal in CLL and WM Study Status and Next Steps • Dose escalation is complete • Recommended Phase 2 dose to be discussed with FDA later this year Spurgeon et al., EHA 2025.
Page 27
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 27 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President, Head of Therapeutics R&D and Chief Strategy Officer, Partnerships Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 28
28 Emerging Mechanism in the Lymphoma Therapeutics Landscape venetoclax (BCL-2) ibrutinib (BTK) idelalisib (PI3K) daratumumab (CD38) zanubrutinib rituximab (CD20) acalabrutinib Bispecifics & Antibody Drug Conjugates Cell Therapies BTK PI3K BCL-2 New Class: Maltibs: SGR-1505 MALT1 pirtobrutinib CD20 BCL-2 degraders BTK degraders CD38 Small MoleculesBiologics 2025 CD3 CD19 CD22 1995
Page 29
29 MALT1 Opportunity in Relapsed Refractory Lymphoma Resistance Mechanisms Target MutationsBypass Pathway Activation Microenvironment Strategies to Prevent Resistance Drug Sequencing Drug HolidayDrug Combination Strategies to Overcome Resistance Next-gen SOC Inhibitors Drug Sequencing New Drug Targets Skånland, Mato; Overcoming resistance to targeted therapies in chronic lymphocytic leukemia. Blood Adv 2021; 5 (1): 334–343. Jiang, et al. J Clin Invest. 2023. Strong Mechanistic & Therapeutic Rationale • MALT1 is an escape mechanism in resistant patients with hyperactive NF-ΚB – SGR-1505-induced IL-2 decreases confirm pathway inhibition • SGR-1505 is safe and clinically active in double-exposed patients • Preclinical combination synergy for MALT1 plus BTK and/or BCL-2 activity confirmed in BTK resistant models
Page 30
SGR-1505 + Ibrutinib in LY2298 PDX (ABC-DLBCL) 30 Preclinical Proof of Concept for Combination Activity SGR-1505 + Venetoclax in OCI-LY10 (ABC-DLBCL) Yin et al., ASH 2021. • Deeper anti-tumor activity observed in patient-derived tumors after combining SGR-1505 with BTK and BCL-2 inhibitors • Expansion into clinical combinations supported by our current SGR-1505 clinical package SGR-1505 75mg/kg + Ibrutinib 25mg/kg
Page 31
MALT1 opportunity 18 🡪 BTK degraders and non-covalent BTKi pirtobrutinib BCL-2 inhibitors venetoclax (+/- CD20) 31 Limited Treatment Options for Patients with Resistance to BTK Agents Provides an Opportunity for MALT1 Inhibitors ibrutinib Ibrutinib BTK Inhibitor Sales ($ Million) 1. Based on Evaluate Pharma and Wall Street Research reports. 2. Earnings reports from Johnson & Johnson, Abbvie, AstraZeneca, Beigene, and Eli Lilly. 3. Evaluate Pharma assumes ROW ~44% of total based on ROW:US ratio of ~80%. 1st Line CLL Treatment Paradigm BTK inhibitors (2nd gen) acalabrutinib and zanubrutib New monotherapy and combination regimens 3rd Line 2nd Line $10.9B 2020 2021 2022 2023 2024 pirtobrutinibzanubrutibacalabrutinib
Page 32
32 SGR-1505 – Potential In Multiple Indications SGR-1505 (MALT1i) T-cell lymphoma Inflammatory and Immune disease Monotherapy B-Cell Malignancy Proof of Concept • All evaluable Waldenstrom macroglobulinemia participants achieved objective responses – All had prior BTKi therapy as the last therapy • Double-exposed CLL/SLL participants responded to monotherapy SGR-1505 SGR-1505 MALT1 inhibition B-cell lymphoma
Page 33
33 Realizing Schrödinger’s Vision Most molecular properties were calculated with near-experimental accuracy, leading to a potential best-in-class molecule SGR-1505 1010 synthesizable molecules ✓Novel allosteric pocket inhibitor ✓Optimized in vitro cellular potency ✓Selective against common off targets ✓Optimized in vivo anti-tumor monotherapy and combination activity ✓Optimized IL-2 inhibition in human blood cells Schrödinger Platform (Physics + AI/ML) Phase 1 development ✓Favorable safety profile, well tolerated ✓Confirmed IL-2 inhibition ✓Encouraging clinical monotherapy activity ✓Dose escalation complete – RP2D to be discussed with FDA
Page 34
Introduction — Ramy Farid Rationale for MALT1 Inhibition & Discovery of SGR-1505 — Karen Akinsanya Therapeutic Landscape — Margaret Dugan SGR-1505 Phase 1 Data Review — Margaret Dugan Opportunity and Next Steps — Karen Akinsanya Q&A 34 Today’s Agenda Ramy Farid, Ph.D. Chief Executive Officer, Board Member Karen Akinsanya, Ph.D. President of R&D, Therapeutics Richie Jain Chief Financial Officer Margaret Dugan, M.D. Chief Medical Officer
Page 35
Presentation of Initial SGR-1505 Phase 1 Clinical Data June 12, 2025