Slides
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Corporate Over view For investors and analysts J a n u a r y 2 0 2 5
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Safe Har bor Statem ent 2 This presentation contains “forward-looking statements” within the meaning of the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by the use of terminology such as “will,” “may,” “expects,” “anticipates,” “believes,” “potential,” “plan,” “goal,” “estimate,” “likely,” “should,” and “intends,” and similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements, including statements regarding the timing and success of our clinical trials, enrollment of patients, type of clinical trials, presentation of data and our cash position and expenditures. Among these risks: Clinical development involves a lengthy and expensive process, with an uncertain outcome and Compugen may encounter substantial delays or even an inability to begin clinical trials for any specific product, or may not be able to conduct or complete its trials on the timelines it expects; Compugen relies and expects to continue to rely on third parties to conduct its clinical trials and these third parties may not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, and Compugen may experience significant delays in the conduct of its clinical trials as well as significant increased expenditures; Compugen’s business model is substantially dependent on entering into collaboration agreements with third parties and Compugen may not be successful in generating adequate revenues or commercializing aspects of its business model; Compugen’s approach to the discovery of therapeutic products is based on its proprietary computational target discovery infrastructure, which is unproven clinically; and Compugen does not know whether it will be able to discover and develop additional potential product candidates or products of commercial value. These and other factors, including the ability to finance the Company, are more fully discussed in the "Risk Factors" section of Compugen’s most recent Annual Report on Form 20-F as filed with the Securities and Exchange Commission (“SEC”) as well as other documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen’s views only as of the date of this presentation and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law. Certain studies and data presented herein have been conducted for us by other entities as indicated where relevant. Intellectual property, including patents, copyrights or trade secret displayed in this presentation, whether registered or unregistered, are the intellectual property rights of Compugen. Compugen's name and logo and other Compugen product names, slogans and logos referenced in this presentation are trademarks of Compugen Ltd. and/or its subsidiary, registered in the U.S.A., EU member states and Israel.
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3 Our Vision Transforming patient lives by developing first-in-class therapeutics based on Compugen’s computational target discovery platform UnigenTM From Code to Cure®
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4 1. AstraZeneca Investor Day May 21, 2024, presentation; PYR: AstraZeneca ‘s estimated non-risk adjusted peak year revenue for rilvegostomig inclusive of all indications and excludes non-registrational trials 2. Compugen is responsible for preclinical development and first- in-human Phase 1 trial evaluating the safety and tolerability of COM503. Thereafter, Gilead will have sole right to develop and commercialize COM503. IA: Interim analysis Fully owned clinical programs COM701 Potential 1st in-class anti-PVRIG antibody COM902 Potential best-in-class anti-TIGIT antibody Phase 3 AstraZeneca program Rilvegostomig AZ est. >$5bn PYR1 anti-PD1/TIGIT bispecific Ab, TIGIT component derived from COM902 Rich pipeline with validating partnerships - eligible >$1bn in milestones PLUS royalties Expected cash runway into 2027 Cash balance $113.2 M as of September 30, 2024 Phase 1 licensed to Gilead ➢ Expected COM701 platform trial initiation Q2 2025, projected IA H2 2026 ➢ COM503 Ph 1 initiation Q4 2024, advancement in clinic ➢ Discovery pipeline advancement COM5032 Potential first-in-class Anti-IL-18BP antibody Multiple assets in research undisclosed Foc us on novel im m uno -oncology antibodies D i s c o v e r e d b y C o m p u g e n ’s c o m p u t a t i o n a l e n g i n e- U n i g e nTM Research programs
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Immuno -oncology pipeline CT.gov; AstraZeneca Clinical Trial Appendix COM503: Compugen is responsible for preclinical development and the first- in-human Phase 1 trial evaluating the safety and tolerability of COM503. Thereafter Gilead will have the sole right to develop and commercialize COM503 . PSOC: Platinum sensitive ovarian cancer; PROC: Platinum resistant ovarian cancer *without AGA Program (mechanism of action) Indication Sponsor/ Partner Phase Achieved Research IND enabling 1 2 3 Milestone 2024 COM701 (anti-PVRIG) vs placebo Relapsed PSOC maintenance setting COM701 + COM902 + pembrolizumab (anti- PVRIG, TIGIT, PD-1) PROC with no alternative treatment options SITC-data rilvegostomig (anti-PD1/TIGIT)- TIGIT component derived from COM902 TROPION-Lung 12- stg 1 adenocarcinoma NSCLC TROPION-Lung 10 IL non-sq NSCLC PD-L1≥50%* TROPION-Lung 04 –NSCLC advanced or metastatic ARTEMIDE-01 –NSCLC advanced or metastatic WCLC- data ARTEMIDE-Lung 02-IL NSCLC PD-L1 >1% ARTEMIDE-Lung 03 – 1L non-sq NSCLC PD-L1>1% DESTINY-Lung 03- NSCLC HER2 overexpressing NeoCOAST-2-Early-stage resectable NSCLC ARTEMIDE-Biliary 01 – BTC with curative intent DESTINY-BTC01 – 1L HER2+ BTC GEMINI-HBP – HCC, BTC GEMINI-Gastric - gastric cancer ESMO-data DESTINY-Gastric03 – gastric HER2 overexpressing TROPION-PanTumor 03 – bladder Cancer BLUESTAR- Breast, biliary, endometrial, ovarian COM503 (anti-IL-18 binding protein) Solid Tumors Ph1 initiation Research Programs Undisclosed Q4 Q3 Q4 Q3 5 Stg 1: stage 1 NSCLC: Non-small cell lung cancer Non –sq: Non squamous BTC: Biliary tract cancer; HCC: Hepatobiliary cancer
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PV RIG and TIGIT – com plem entar y but distinc t pathways 6 PVRL2 more dominant than PVR in ovarian, endometrial and breast tumors PVRIG more dominant than TIGIT on stem like memory T cells Differentially expressed in the tumor microenvironment PVRL2 has higher expression than PVR on dendritic cells PVRIG preferentially binds PVRL2 TIGIT preferentially binds PVR Differentially expressed in tumors Differentially expressed on immune cells PVRIG blockade may lead to responses in tumors typically not responsive to immunotherapy
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7*Bi-specifics; Preclinical list of players is not exhaustive CO M 701 potential 1 st in c lass anti -PV RIG antibody PRE-CLINICAL PHASE 1 and 2 No data presented Simcere SIM-0348* Shanghai Junshi JS-209* GSK GSK-4381562 Biotheus PM-1009* COM701 POTENTIAL FIRST-IN-CLASS Phase 1 data presented; proof-of-concept studies ongoing COM701 IgG4 reduced Fc effector function Avoids CD8 + T cell depletion and potential associated risks NectinTx NTX2R13 TG ImmunoPharma NM1F Hengrui* SHR-2002 FutureGen FG-B902/T903* PHASE 1 Data presented
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CO M701 c linical benef it ac ross m ultiple tum ors typically unresponsive to im m unotherapy 8 BMS-986207 (Bristol Myers Squibb, anti-TIGIT); Pembro: pembrolizumab; Vibo: vibostolimab; ICI: Immune checkpoint inhibitor; bev: bevacizumab; PR: Partial Response; PD: Progressed Disease. *ongoing at time of data cut-off, ~patient had primary peritoneal cancer. 1. Matulonis et al ASCO 2022, 2. Holmes et al JCO ASCO 2022, 3. Perets et al ACCR 2022; 4 Oaknin et al J Immun of Cancer 2022; 5. Lheureux et al; J Immun of Cancer 2022; 6. Antill et al: J Immun of Cancer 2021. TUMOR TREATMENT MED PRIOR LINES BEST RESPONSE DESCRIPTION REFERENCE IO BENCHMARK Platinum resistant ovarian cancer COM701 6 across indications 1/6 ORR (16.6%) 4/6 DCR (66%) 1 PR >18 months~* in immune desert TME ASCO 2021 Pembro+ vibo: <10% ORR 0% ORR PD-L1 low 2 months mPFS 1-3 COM701 + nivolumab 6 2/20 ORR (10%) 9/20 DCR (45%) 1 PR in patient refractory to nivolumab ESMO IO 2022 COM701 + nivolumab + BMS-986207 4 4/20 ORR (20%) 9/20 DCR (45%) 3 PR >16 months* ESMO IO 2022 SITC 2023 COM701 +pembrolizumab +COM902 4 4/24 (17%) 11/24 (46%) 5 patients on treatment for >200 days SITC 2024 MSS CRC with liver metastases COM701 + nivolumab 4 2/17 ORR (12%) 4/17 DCR (24%) 1 PR in patient with immune desert TME 1 PR >11 months SITC 2022 ICI: 0% ORR COM701+ COM902+ pembrolizumab 3 1/15 ORR (7%) 6/15 DCR (40%) 1 PR > 9 months* in patient who had PD on chemo +bev (post data cut patient reassessed as non target liver lesion of uncertain etiology at baseline) 2 SD >7 months* ASCO 2024 ICI experienced NSCLC COM701 ± nivolumab 6, ≥ 2 prior ICI 5/7 DCR (71%) 3 SD on COM701 monotherapy ESMO IO 2022 Small study, no benchmark Recurrent metastatic MSS endometrial cancer COM701 + nivolumab + BMS-986207 2, 33% prior PD1x 2/9 ORR (22%) 4/9 DCR (44%) 1 PR in patient refractory to lenvatinib/pembro ASCO 2023 ICI in IO naive: ~10% ORR4-6 Metastatic breast cancer COM701 + nivolumab 5 2/17 ORR (12%) 5/17 DCR (30%) 1 CR > 21 months*, low immunogenic HER2 negative tumor SITC 2023 no benchmark heterogenous population
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Ovarian cancer
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~ Advanc ing CO M 701 to address unm et need in PSO C 10 mPFS ~ 10 m mPFS ~ 6 m mPFS ~ 5.6 m mPFS ~ 4.4 m mPFS ~ 4.1 m mPFS ~18 m Platinum doublet +/ - Bevacizumab Maintenance Bevacizumab or PARPi Platinum doublet +/- bevacizumab Maintenance Bev or PARPi COM701 target population: Women with complete/partial response post chemo not suitable for bevacizumab/PARPi median PFS ~ 6 months Platinum Sensitive Ovarian Cancer (PSOC) Platinum free ≥6-month before relapse Platinum Resistant Ovarian Cancer (PROC) Platinum free <6-month before relapse 1L 2L 3L 4L 5L 6L Standard of care Platinum doublet Maintenance none 4th Relapse 5th Relapse 3rd Relapse 2nd Relapse 1st Relapse PSOC: Platinum sensitive ovarian cancer; PROC: Platinum resistant ovarian cancer; PFS: Progression Free Survival Figure and Treatment algorithm adapted from: Hanker LC, et al. Ann Oncol. 2012;23(10):2605-12. González-Martín et al. Ann Oncol . 2023 Oct;34(10):833-848 Surgery B u i l d i n g o n d a t a g e n e ra t e d i n P R O C Immune system more compromised and challenging to see immunotherapy responses
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11 Strong biological rationale for targeting PV RIG in ovar ian canc er post c hem otherapy Tscm: Early differentiated stem like memory T cells TLS: Tertiary lymphoid structures MOA: Mechanism of action Alteber et al, Cancer Immunology Research, 2024 • Ovarian cancer identified as high priority indication for PVRIG blockade based on expression levels • PVRIG dominant expression in TLS & Tscm vs other checkpoints – potential to induce T cells in the tumor • Platinum based chemotherapy induces TLS and Tscm potential to sensitize tumor to unique MOA of COM701
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12 PD - L 1 n e g o v a r i a n c a n c e r p a t i e n t s u p p o r t e d b y i m m u n e a c t i v a t i o n CO M 701 single agent ac tivity: Par tial response >18 m onths* Ophir E et al SITC 2022; Alteber E et al Cancer Immunology Research 2024 * This patient was on study treatment for 24 months i.e., she completed her treatment course allowed per protocol ASCO, June 2021, Vaena et al., Oral presentation Pre C1D2 C2D1 C3D1 -100 0 100 200 300 % Change from Baseline Prim peritoneal 20 mg/kg IV Q4w (PR) IFNg IFNg Avr. all Mono Pts. CD8+ CM Ki67 CD8+ CM Ki67 Avr. all Mono Pts. CD8+ EM Ki67 CD8+ EM Ki67 Avr. all Mono Pts. NK-T Ki67 NK-T Ki67 Avr. all Mono Pts. Increase in IFNγ induction and immune activation in peripheral blood • Pre- treatment archival biopsy (>1 year) • Negative PD-L1 staining • PVRL2 expression found on tumor and endothelial cells • Immune “desert”: no immune cells detected in the biopsy PVRL2 PD-L1 COM701 single agent immune modulation of the tumor microenvironment also demonstrated P a t i e n t r e c e i v e d 3 p r i o r l i n e s o f a n t i c a n c e r t h e r a p y
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13TME: Tumor microenvironment CO M 701 suppor ts com bination approac h to overcom e im m unotherapy resistanc e DNAM-1 axis potential game changer in fight against cancer • PVRIG and TIGIT discovered by Compugen’s discovery platform • DNAM axis – two parallel and complementary inhibitory pathways (PVRIG & TIGIT) • Potential synergy in blocking PVRIG, TIGIT and PD-1 pathways • Blocking PVRIG is potentially unique in generating new waves of T cells to infiltrate the TME • PVRL2 broadly expressed in PD-L1 high and low tumors Anti- PD-1
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14 BMS-986207 (Bristol Myer’s Squibb, anti -TIGIT) TRAE: Treatment related adverse event AE: Adverse event Consistent ef f icac y & safety w ith CO M 701 tr iplet com bination I n p l a t i n u m r e s i s t a n t o v a r i a n c a n c e r p a t i e n t s w h o h a v e e x h a u s t e d a l l o p t i o n s Investigator assessed by RECIST v1.1 COM701+ nivolumab + BMS- 9862071 (N=20) COM701+ pembrolizumab+ COM9022 (N=24) Overall Response rate % (CR+PR) 4 (20%) 4 (17%) Disease control rate % (CR+PR+SD) 9 (45%) 11 (46%) Best response (%) Complete response – 1 (4%) Partial response 4 (20%) 3 (13%) Stable Disease 5 (25%) 7 (29%) Progressive Disease/Clinical PD/lack of clinical benefit 11 (55%) 13 (54%) • Most common reported AEs grade 1/2 fatigue, diarrhea and nausea • Grade ≥3 TRAEs 20% • No grade 4/5 TRAEs • Tx related discontinuations 4.4% • 1 patient in each study had grade 3 AE leading to drug discontinuation Efficacy The safety and tolerability profile generally consistent with approved anti-PD-(L)1s Activation of the immune system • Translational assessment of peripheral blood and on-treatment tumor biopsies showed a positive pharmacodynamic activation of the immune system Other investigational immune check point inhibitors: anti-PD-1 ± anti-TIGIT (ORR <10% in all-comers and 0% in PD-L1 <1)3,4,5 1. Moroney J, et al, ESMO IO 2022 Modified 2. Yeku O, et al, SITC 2024 Modified 3. Matulonis et al ASCO 2022, 4. Holmes et al JCO ASCO 2022, 5. Perets et al ACCR 2022
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14 22 36 37 41 43 43 43 43 44 58 64 76 85 86 113 120 127 176 203 207 227 246 262 0 50 100 150 200 250 300 Consistent durable responses dem onstrated ac ross studies 15 Platinum-Resistant Standard of Care: Single agent chemo (ORR ~ 12%, mPFS ~3-4 months, mOS ~ 13 months, with significant toxicity )3,4 Other investigational immune check point inhibitors: anti-PD-1 ± anti-TIGIT (ORR <10% in all-comers and 0% in PD-L1 <1)5,6,7 B. COM701 + pembrolizumb + COM9022 17% ORR 46% DCR180 days 23 31 41 42 52 52 54 54 56 57 58 59 63 106 107 222 232 505 538 566 0 50 100 150 200 250 300 350 400 450 500 550 600 A. COM701 + nivolumab + BMS-9862071 20% ORR 45% DCR 180 days Data cut: September 5, 2023 investigator assessed responses On Study Treatment RECIST v1.1 PD/ Clinical Progression/ Investigator Decision PR SD AE Treatment Ongoing PR SD CR PD 1. Gaillard S et al SITC 2023, modified 2. Yeku et al; SITC 2024 modified 3. Pujade-Lauraine et al JCI 2014, 4. Secord et al JCO 2007, 5. Matulonis et al ASCO 2022, 6. Holmes et al JCO ASCO 2022, 7. Perets et al ACCR 2022 BMS-986207 (Bristol Myer’s Squibb, anti-TIGIT). I n p l a t i n u m r e s i s t a n t o v a r i a n c a n c e r p a t i e n t s w h o h a v e ex h a u s t e d a l l o p t i o n s RECIST v1.1 PD/ Clinical Progression/Investigator Decision Data cut: August 29, 2024 investigator assessed responses Note: Earlier data cut in figure B
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COM701 + nivolumab + BMS-9862071 COM701 + pembrolizumab + COM9022 Consistent deep responses ac ross studies 16 Data cut off date 5 September 2023 2 patients with PD (clinical evaluation) not included. Best Percent Change from Baseline (%) 66 57 47 42 39 25 16 14 11 6 3 -2 -4 -18 -56 -61 -68 -100 -120 -100 -80 -60 -40 -20 0 20 40 60 80 Best Overall Response PD SD PR Best Percent Change from Baseline (%) 108 97.2 58.1 44 36.4 27.2 26.7 23.3 15.8 14.9 11.8 6.1 -2.1 -14.1 -17.1 -22.6 -22.9 -29.6 -41.7 -42.4 -73.8 -80.6 -100 -50 0 50 100 150 Best Overall Response PD SD PR CR I n p l a t i n u m r e s i s t a n t o v a r i a n c a n c e r p a t i e n t s w h o h a v e ex h a u s t e d a l l o p t i o n s 1. Gaillard, S. et al; SITC 2023 modified; 2. Yeku O, et al, SITC 2024, modified BMS-986207 (Bristol Myer’s Squibb, anti-TIGIT) Data cut off date 29 August 2024
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Clinical V ignette – CO M 701 + pem brolizum ab + CO M 902 com plete response in PRO C patient 17 69-year-old female with high grade serous adenocarcinoma platinum resistant ovarian cancer Baseline 20.6 x 23.36 mm 100 days from C1D1 3.02 x 11.64 mm 4 p r i o r l i n e s o f t h e r a p y i n c l u d i n g c h e m o t h e r a p y, b e v a c i z u m a b m a i n t e n a n c e a n d a n i n v e s t i g a t i o n a l a g e n t ( s m a c- m i m e t i c ) w i t h S D b e s t r e s p o n s e p r i o r t o s t u d y e n t r y Right common iliac node 2 Right external iliac node 1 Baseline 15.44 x 21.16 mm 100 days from C1D1 4.27 x 4.89 mm Yeku O et all SITC 2024, modified
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18 Modified from ASCO June 2021 Presentation Yeku e al, ESMO-IO 2022 Modified Clinical V ignette – CO M 701+nivolum ab par tial response in nivolum ab ref rac tor y PRO C patient R e c e i v e d 7 p r i o r l i n e s o ft h e r a p y i n c l u d i n g p r o g r e s s e d d i s e a s e o n n i v o l u m a b 6 53-year-old female with high grade serous adenocarcinoma (HGSC) platinum resistant ovarian cancer Increased CD8+ T cell infiltration On-treatment 7 prior lines of therapy include chemo, bevacizumab, nivolumab, lucitanib (TKI), niraparib (PARPi) Pre On % CD8 positive in tumor area 15.7% 25.7% Average CD8 density (CD8/mm2) 8.5 x 10-4 16 x 10-4 Pre-treatment On-treatment
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19 Definition: Clinical Benefit (CB)= CR+PR+SD>180 days on study; No Clinical Benefit (NCB) = PD +SD<180 days on study Cojocaru G, et al; SITC 2023, modified Clinical benef it and TM E T c ell c lonal expansion independent of baseline inf lam m ator y status 1 2 3 0 200 400 600 800 2000 2100 2200 2300 2400 2500 Patient unique TCRb CDR3 counts Pre On 55 394225361 14309930198 98690Patient 1 Patient 2 Patient 3 A B CB NCB 0 2 4 6 50 100 150 PD-L1 CPS ns CB NCB 0 10 20 30 40 50 %CD8 ns PD-L1 CPS CD8 % positive TME T cell clonal expansion in patients who derived clinical benefit from COM701 + nivolumab ± BMS-986207 Platinum Resistant Ovarian Cancer Patients Baseline inflammatory status Pre-treatment Pre-treatment Pre-treatmentPost -treatment Post -treatment Post -treatment TCR βclonesTCR βclones TCR βclones Total no. of clones Top 5 clones
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The safety and tolerability profile was generally consistent with approved anti-PD-(L)1s as monotherapy and in combination across tumors CO M 701 safety prof ile m ay provide c linically relevant dif ferentiation in ear lier canc er settings 1. Data Cutoff 30 Oct 2024 2. Alteber et al, Cancer Immunology Research, 2024 TRAE: treatment related adverse event; AE: Adverse event COM701 activity potentially occur mostly in the tumor microenvironment due to unique PVRIG biology2 COM701 ± anti-TIGIT ± anti-PD-11 20 • Majority of TRAEs ≤ Grade 2 • Most common reported AEs grade 1/2 fatigue, diarrhea and nausea • Grade ≥3 TRAEs 9.5% • No grade 4/5 TRAEs • Low rate of treatment related discontinuations 4.9%
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L ead program : CO M 701 adaptive platfor m tr ial in relapsed platinum sensitive ovarian canc er in m aintenanc e setting 21 Sub-study 1 Single agent activity of COM701 versus placebo (standard of care) Sub-study 2 and beyond COM701 combination studies e.g. anti-PD-1/TIGIT or bevacizumab or PARPi or others E n d p o i n t s Primary: Efficacy- mPFS Secondary: Safety Exploratory: Biomarkers K e y e l i g i b i l i t y c r i t e r i a Relapsed platinum sensitive ovarian cancer Complete or partial response following platinum-based chemo Post bevacizumab and/or PARP inhibitor maintenance or not a candidate for bevacizumab and/or PARP inhibitor Adaptive trial 2:1 Randomization E x p e c t e d t i m e l i n e s : s u b- s t u d y 1 Study initiation: Q2 2025 Projected Interim analysis: H2 2026 21 Evaluation of COM701 single agent activity, combinations and contribution of effects, represent a regulatory and commercial opportunity
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CO M 9 0 2- Po te nt i a l b e st- in - c l a s s a nt i- T I G I T a nt i b o d y
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CO M 902 potential best -in -c lass anti -TIGIT antibody GI: gastrointestinal, GU: genitourinary, GYN: gynecological, NSCLC: Non small cell lung cancer * isotype: hIgG1TM- triple mutations to reduce Fc effector functionality; ab: antibody 1. AstraZeneca Investor Day May 21, 2024, presentation; PYR: AstraZeneca ‘s estimated non -risk adjusted peak year revenue for rilvegostomig inclusive of all indications and excludes non-registrational trials Va l u e r e i n f o r c e d b y s t r a t e g i c c o l l a b o r a t i o n w i t h 23 Rilvegostomig AZ est. >$5bn PYR1 PD-1/TIGIT bispecific Ab COM902 potential best-in-class anti-TIGIT Compugen entitled to up to $200m milestone payments and mid-single digit tiered royalties AstraZeneca’s next generation IO bispecific to replace anti-PD-(L)1’s Plans to initiate up to 10 pivotal trials, novel combinations across NSCLC, GI, GU/GYN Higher affinity than other TIGIT antibodies Rilvegostomig* - TIGIT component derived from COM902 AstraZeneca has rights to develop TIGIT bispecifics AstraZeneca advanced to 6 Phase 3 studies across lung and liver cancerIgG4 reduced Fc functionality Compugen retains rights to PVRIG (PVRL2)/TIGIT bispecificsEncouraging data presented: ARTEMIDE-01 NSCLC, WCLC 2024 GEMINI GASTRIC, ESMO 2024
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Bladder Lung Liver Gastric Other O n g o i n g r i l v e g o s t o m i g p o t e n t i a l r e f l e c t > $ 5 B P Y R t a r g e t * 24 Study name Indication Rilvegostomig monotherapy or in combination Phase Next data anticipated 1 2 3 TROPION-Lung12 Stg 1 adenocarcinoma NSCLC ± TROP2 ADC(Dato-Dxd) vs SOC Randomized Not reported TROPION-Lung10 IL non-sq NSCLC PD-L1 ≥50%** ± TROP2 ADC (Dato-Dxd) vs pembro Randomized >2025 TROPION-Lung04 NSCLC advanced or metastatic + TROP2 ADC (Dato-Dxd) ± chemo Open label >2025 ARTEMIDE-01 NSCLC advanced or metastatic mono Open label >2025 ARTEMIDE-Lung 02 IL NSCLC PD-L1 >1% +chemo vs pembro + chemo Randomized Not reported ARTEMIDE-Lung 03 IL non-sq NSCLC PD-L1 >1% +chemo vs pembro + chemo Randomized >2025 DESTINY-Lung03 NSCLC, HER2 overexpressing + HER2 ADC (Enhertu) ± chemo Open label >2025 NeoCOAST-2 Early-stage resectable NSCLC ± TROP2 ADC(Dato-Dxd) Open label >2025 ARTEMIDE-Biliary01 BTC with curative intent + chemo vs chemo Randomized >2025 DESTINY-BTC01 1L HER2+ BTC ± HER2 ADC (Enhertu) vs SOC# Randomized >2025 GEMINI-HBP BTC and HCC + volrustomig+bevacizumab, or + chemo Open label >2025 GEMINI-Gastric Gastric cancer + chemo ± claudin ADC Open label H2 2025 DESTINY-Gastric03 gastric cancer HER2 overexpressing + chemo + HER ADC (Enhertu) Open label >2025 TROPION- Pan Tumor03 bladder cancer 1L, cis-ineligible/2L + TROP2 ADC (Dato-Dxd) Open label >2025 BLUESTAR breast, biliary, endometrial, ovarian + AZD8205 Open label >2025 Broad development strategy as monotherapy and part of ADC -IO combinations CT.gov; AstraZeneca Clinical Trial Appendix *AstraZeneca’s non-risk adjusted peak year revenue target inclusive of all indications and excludes non-registrational trials # SOC: Chemo + durvalamab ** without AGA Stg: Stage NSCLC: Non-small cell lung cancer Non-sq: non squamous BTC: Biliary Tract Cancer; HCC: Hepatobiliary Cancer Not comprehensive, does not include investigator-initiated studies
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25 Dumbrava E E, et al, SITC 2021, Modified Datacut 03 September 2021 DLT: Dose limiting toxicity PK: Pharmacokinetics ICI: Immune checkpoint inhibitor SD: Stable disease MTD: Maximum Tol erated Dose RDFE: Recommended Dose for Escalation CO M 902 m onotherapy showed a 50% disease control rate 21* 22*† 25* 37† 38 38* 40*† 41† 43 43† 70 81 83* 83† 131 291 302† 344† 0 50 100 150 200 250 300 350 400 1 mg/kg 1 mg/kg 3 mg/kg 1 mg/kg 0.3 mg/kg 0.01 mg/kg 10 mg/kg 0.03 mg/kg 10 mg/kg 3 mg/kg 3 mg/kg 10 mg/kg 1 mg/kg 0.1 mg/kg 1 mg/kg 0.01 mg/kg 0.01 mg/kg 1 mg/kg Days on Study COM902 Dose 1-On Study Treatment 2- RECIST v1.1 PD/Clinical Progression/Investigator DecisionDose Escalation DLT-Evaluable Population (N=18): SD *Subjects with Prior Treatment-refractory Disease † Subjects with Prior ICI Chordoma Adenoid-cystic CA trachea Rectal CA Ovarian CA Peritoneal CA Appendiceal CA Colon CA Esophageal CA Small cell lung CA Uterine sarcoma Mesothelioma Prostate CA Atypical carcinoid lung CA Colon CA Renal cell CA Colon CA Prostate CA Pancreatic CA
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1. Internal data as of data cut Oct 2024 2. DumBrava E,E, et al, SITC 2021 3. Hansen et al; Cancer Immunol Immunother, 2021 CO M 902 – well tolerated safety prof ile 1 Avoids depletion of anti-tumor CD8+ T-cells required for efficacy2 Potential to avoid infusion related reactions that active Fc may trigger Fc silent anti-TIGIT avoids peripheral Treg depletion that may lead to IrAEs3 Favorable safety and well tolerated as monotherapy and in combination COM902 ± COM701± pembrolizumab COM902 naturally reduced Fc effector function antibody (IgG4 backbone) chosen with efficacy and safety in mind 26 • Most commonly reported AEs were grade 1/2 • Grade ≥3 TRAEs 8.5%, fatigue – most common • No grade 4/5 TRAEs • Low treatment related discontinuations 4.2% • IrAE 17% all ≤Gr 3 all in triplet • IRR 5.3% all ≤ Gr 2 IRR – Infusion Related Reactions IrAE – Immune related Adverse Event TRAE: Treatment related adverse events
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CO M902 prevents depletion of m aj or TIGIT+ expressing lym phoc y tes - NK, CD4 and CD8 T c ells 27Dumbrava E,E, et al, SITC 2021, Modified S u p p o r t i n g r a t i o n a l e f o r s e l e c t i n g a h i g h a f f i n i t y a n t i- T I G I T a n t i b o d y w i t h a n I g G 4 b a c k b o n e a n d l o w F c e f f e c t o r f u n c t i o n- C O M 9 0 2 COM902 prevents CD8+ T Cell depletion and potential associated risks CD4+ NaiveCD4+ CMCD4+ CD4+ EM CD4+ EMRA Cycle/Day C1D1 C1D2 C1D8 C1D15 C2D1 C4D1 0 20 40 60 80 100% T I G I T + -103 0 103 104 105 TIGIT CD8+ NaiveCD8+ CMCD8+ CD8+ EM CD8+ EMRA Cycle/Day C1D1 C1D2 C1D8 C1D15 C2D1 C4D1 0 20 40 60 80 100% T I G I T + TIGIT -103 0 103 104 105 Cycle/Day C1D1 C1D2 C1D8 C1D15 C2D1 C4D1 0 20 40 60 80 100 % Changed from Baseline -100 -80 -60 -40 -20 C3D1 %CD8 EM %CD8 EM TIGIT+ %CD8 Total CD8 (cells/uL) %CD8 EMRA %CD8 EMRA TIGIT+ %NK Total NK (cells/uL) CD4+ Naive CD4+ CM CD4+ EM CD4+ EMRA CD8+ Naive CD8+ CM CD8+ EM CD8+ EMRA
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CO M 503 - Dif ferentiated approac h to har ness c y tokine biology for canc er therapeutic s
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CO M503 potential 1 st in c lass anti -IL -18BP antibody * less 15% tax withheld at source 29 L i c e n s e a g r e e m e n t w i t h up to $848M deal value Key Benefits Highlights potential of COM503 differentiated approach to harness cytokine biology to treat cancer Reflects quality of our computational discovery capabilities & ability to advance discoveries into drugs candidates Strengthens our balance sheet Expedites our goal to bring potential 1st in class therapies to patients Signed December 2023 $60 million upfront and $30 million milestone payment on achieving IND clearance, received* Up to additional $758M in additional development, regulatory and commercialization future milestone payment Single-digit to low double-digit tiered royalties on WW future net sales Compugen responsible for preclinical and ongoing Ph 1 trial initiated in Q4 2024. Thereafter, Gilead will have sole right to develop and commercialize COM503
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Cy tok ines power f ul potent ial lim ited by t herapeut ic w indow • Short half life • Pleiotropy • Vascular leak syndrome • Cardiotoxicity • Short half life • Short half-life • Systemic inflammation • Myelotoxicity • Hepatoxicity • Short half-life • Bound to IL-18BP inhibiting activity in TME Pleiotropy, toxicity, short half life severely limit the therapeutic use of cytokines 30Propper D J. et al, 2022
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DAMPs- Damage-associated molecular patterns . COM503 is licenced to Gilead, Compugen responsible for ongoing preclinical and future Phase 1 development, Thereafter, Gilead will have sole right to develop and commercialize COM503 CO M 503: Com pugen identif ied potential dom inant im m unosuppression m ec hanism and antibody therapeutic 31 I n t e r l e u k i n- 1 8 b i n d i n g p r o t e i n , a n e n d o g e n o u s i n h i b i t o r o f i n t e r l e u k i n- 18 IL-18 immune stimulatory cytokine upregulated in tumor microenvironment IL-18BP blocks IL-18 activity COM503 potential first-in-class high affinity antibody releases IL-18 to enhance T and NK cell activation in the tumor Pro-IL-18 IL-18 Inflammasome T/NK cells DAMPs IL-18R MγD88 Myeloid/ Cancer cells IFNγ IL-18BP COM503
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32 CO M 503: advantages of a dif ferentiated approac h COM503 anti-IL-18 binding protein Recombinant cytokines Novelty Novel antibody approach Multiple challenges, no FDA approval in last 30 years Anti-IL-18BP releases endogenous IL-18 in the TME Systemic administration of a recombinant protein Pharmacokinetics Slow elimination Requires modification/engineering to overcome pharmacokinetic limitations Immunogenicity Potentially low risk, human IgG antibody Modified/engineered recombinant cytokine, increases risk Therapeutic window Immune modulation selectively targets TME, potential for better tolerance Systemic immune modulation, potential for unmanageable side effects
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33 TILs- tumor infiltrating lymphocytes Ferre P, presentation, SITC, 2023, modified CO M 503, f ully hum an, high af f inity anti -IL -18B P antibody restores hum an TIL and NK c ell ac tivity in hum an assays COM503 restored TILs activity COM503 restored NK cell activity COM503 enhanced T cell activation in human dissociated tumor cells assay Treatment 0 200 400 600 800 IL-2 [pg/ml] 50% 29% Treatment 0 50 100 150 TNFa [pg/ml] 58 % 138% Treatment 0 5000 10000 15000 20000 GZMB [pg/ml] 25 % 56% IL-18 Isotype COM503 0 50 100 150 IFNg % of IL-18 alone ✱✱ IL-18+IL-18BP IL-18 Isotype COM503 0 50 100 150 TNFa % of IL-18 alone ✱✱ IL-18+IL-18BP IL-18 only + Isotype + COM503 0 1000 2000 3000 4000 IFNg [pg/ml] IL-18+IL-18BP aCD3+aCD28 Treatment 0 100 200 300 400 IFNg [pg/ml] 38 % 80% Media COM503 Pembro Pembro+COM503 Treatment 0 100 200 300 400 IFNg [pg/ml] 38 % 80% Media COM503 Pembro Pembro+COM503
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34Ophir E, presentation, CIMT 2023, modified Ant i-m ouse IL -18B P antibody dem onstrates m onotherapy ac tivity ac ross m urine syngeneic tum or m odels aIL-18BP Ab inhibits tumor growth in MC38ova mouse CRC tumor model aIL-18BP Ab inhibits tumor growth in B16F10-hmgp100 mouse melanoma model aIL-18BP Ab inhibits tumor growth in E0771 orthotopic mouse breast tumor model 5 10 15 20 25 30 0 500 1000 1500 Days post inoculation Tumor volume (mm3) Isotype control Isotype control aPD-L1 aIL-18BP ✱✱✱ ✱✱✱ 83% 61% 5 1 0 1 5 2 0 2 5 3 0 3 5 0 4 0 0 8 0 0 1 2 0 0 1 6 0 0 D a y s p o s t in o c u la tio n Tumor volume (mm3) Isotype control aIL-18BP ✱✱✱ 58% 5 1 0 1 5 2 0 0 3 0 0 6 0 0 9 0 0 1 2 0 0 1 5 0 0 1 8 0 0 2 1 0 0 D a y s p o s t in o c u la tio n Tumor volume (mm3) Isotype control anti-IL18BP ✱✱✱ 54%
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35 Anti -IL 18B P Ab is expec ted to have a better therapeutic window than recom binant c y tokines Administration of anti-mouse IL-18BP Ab to mice did not affect lymphocytes activation in contrast to engineered mouse IL-18 Administration of anti-mouse IL-18BP Ab to mice did not affect serum cytokines in contrast to engineered mouse IL-18* 0 4 24 0 50 100 150 200 IFNg Time after 4th treatment pg/ml 0 4 24 0 1000 2000 3000 4000 5000 IL6 Time after 4th treatment pg/ml Isotype control αIL-18BP Ab PBS Engineered IL-18 0 4 24 0 100 200 300 400 MCP1 Time after 4th treatment pg/ml 0 4 24 0 100 200 300 TNFa Time after 4th treatment pg/ml Isotype aIL-18BP Ab PBS IL15:IL15Ra 0 50 100 150 200 250 Spleen Weight mg **** *Engineered IL-18 does not bind to IL18BP but retains its binding to IL-18R Administration anti-mouse IL-18BP Ab to mice did not result in splenomegaly in contrast to rIL-15:IL15Ra Isotype αIL-18BP PBS Engineered IL18 0 10 20 30 40 CD4 CD69 % CD69+ out of CD4+ ✱✱✱✱ +221% Isotype αIL-18BP PBS Engineered IL18 0 10 20 30 40 CD8 CD69 % CD69+ out of CD8+ ✱✱✱✱ +794% Isotype αIL-18BP PBS Engineered IL18 0 5 10 15 20 CD19 CD69 % CD69+ out of CD19+ ✱✱✱✱ +283% Isotype αIL-18BP PBS Engineered IL18 0 10 20 30 40 NK CD107 % CD107+ out of NK ✱✱✱✱ +270% Isotype αIL-18BP PBS Engineered IL18 0 10 20 30 40 50 NKT CD69+CD107+ % CD69+CD107+ out of NKT ✱✱✱✱ +101%
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E xper ienc ed Team L eading Com pugen
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Diverse exper ienc ed leadership team 37 M a n a g e m e n t t e a m Eran Ophir, PhD Chief Scientific Officer Zurit Levine, PhD SVP, Strategic Collaborations Pierre Ferre, PhD, Dr. Vet. Med. SVP, Preclinical Development & Corporate Operations Paul Sekhri Chairman of the Board Anat Cohen-Dayag, PhD President & CEO, Director Mathias Hukkelhoven, PhD Director Gilead Halevy Director Kinneret Livnat Savitzky, PhD Director Eran Perry Director Sanford (Sandy) Zweifach Director Board Of Directors Yaron Turpaz, PhD SVP & Sr. Advisor Data and Informatics Solutions Dorit Amitay VP, Human Resources Eran Ben Dor General Counsel and Corporate Secretary Anat Cohen-Dayag, PhD President & CEO Michelle Mahler, MD Chief Medical Officer David Silberman Chief Financial Officer
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Nils Lonberg, PhD Former SVP, Oncology Discovery Biology Bristol Myers Squibb Miriam Merad, MD, PhD Elliott Sigal, MD, PhD Strategic Advisor Former CSO, EVP & Director, Bristol Myers Squibb Strategic advisors 38 Howard Soule, PhD Antoni Ribas, MD, PhD Drew Pardoll, MD, PhD Chairman Iain McInnes, FRCP, PhD I n d u s t r y v e t e r a n s , r e n o w n e d o n c o l o g i s t s a n d i m m u n o l o g i s t s Scientific Advisory Board
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Appendix
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CO M 701 and CO M 902 distinguishing proper ties 40 • Internally discovered and developed, potentially first-in-class asset • Issued and pending patents for PVRIG antibodies for use in cancer treatment, COM701 composition of matter, use and combinations worldwide Strong IP position COM701 • Humanized IgG4 (S241P) antibody • High affinity (2 pM KD by KinExA) • Blocks PVRIG/PVRL2 binding interaction • Enhances T and NK cell activation alone and in combination with TIGIT and PD1 blockade • Favorable PK in patients: Linear PK and PVRIG receptor occupancy > 90% threshold over 21 days from 1 mg/kg Antibody characteristics • Issued and pending patents for COM902 composition of matter, use and combinations worldwide Strong IP position • Fully human anti-TIGIT antibody, cross-reactive with cynomolgus and mouse • Femto-molar affinity to human TIGIT (626 fM KD by KinExA) • IgG4 (S228P) isotype, reduced Fc function prevents depletion of effector cells providing optimal anti-tumor response Antibody characteristics COM902
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CO M701 m onotherapy: par tial response in patient w ith PD -L1 negative ovarian ongoing treatm ent > 18 m onths 41Modified from ASCO June 2021 Presentation 63-year-old female with microsatellite stable platinum resistant primary peritoneal cancer PDL1 negative, MRE11 mutation; 3 prior lines of chemotherapy Study Treatment: COM701 20mg/kg IV Q 4 weeks Had 3 prior lines of SOC treatment • 1st line carboplatin/paclitaxel, SD (best response) • Carboplatin/paclitaxel, PD (best response) • Doxorubicin/Bevacizumab, PR (best response, d/c due to toxicity) • Enrolled into mono dose escalation (COM701 20 mg/kg IV Q4 wks) Baseline: 9/11/19 C2D28: 12/2/19 (PR) C6D28: 3/23/20 (PR)
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a flexible-loop platform for novel IO drug target discovery & development 42
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PV RIG and TIGIT – com plem entar y but distinc t pathways 43Tscm: Early differentiated stem like memory T cells; DC: Dendritic Cells; TLS: Tertiary Lymphoid Structures PVRL2 expression is more dominant than PVR on certain tumor types, including breast, endometrial and ovarian TIGIT and PVRIG are both expressed on T and NK cells PVRIG more dominant on Tscm TIGIT is highly expressed on Tregs relative to PVRIG Differentially expressed in the tumor microenvironment PVRL2 has higher expression on some myeloid lineage cells, particularly DC subsets PVRIG preferentially binds PVRL2 TIGIT preferentially binds PVR Differentially expressed in tumor types Differentially expressed on immune cell types PVRIG blockade may enhance Tscm activation by DCs in lymph nodes and TLS, potentially leading to T cell expansion and infiltration into cold tumors making them more sensitive to anti-PD-1 and anti-TIGIT