Slides
Page 1
Corporate Over view For investors and analysts J a n u a r y 2026
Page 2
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.
Page 3
3 Our Vision Transforming patient lives by developing first-in-class therapeutics based on Compugen’s AI/ML-powered predictive computational target discovery platform UnigenTM From Code to Cure®
Page 4
4 * Not including $65m upfront payment due from AstraZeneca as part of the 2025 amendment to the 2018 agreement 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 responsible for preclinical development and first- in-human Phase 1 trial evaluating the safety and tolerability of GS-0321. Thereafter, Gilead will have sole right to develop and commercialize GS-0321. Fully owned clinical programs COM701 Potential 1st in-class Fc reduced-anti-PVRIG antibody COM902 Potential best-in-class Fc-reduced anti-TIGIT antibody Phase 3 AstraZeneca program Rilvegostomig AZ est. >$5bn PYR1 anti-PD1/TIGIT bispecific Ab, TIGIT component derived from COM902 Rich clinical pipeline with validating partnerships >$1bn in milestones PLUS royalties Phase 1 licensed to Gilead GS-0321 (previously COM503)2 Potential first-in-class Fc reduced 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 d i s c o v e r y p l a t f o r m- U n i g e nTM Early-stage pipeline Cash balance $86.1M* as of September 30, 2025 COM701 MAIA-ovarian randomized interim analysis projected Q1 2027Expected cash runway into 2029 to support operations
Page 5
Immuno -oncology pipeline focus on novel antibodies 5 CT.gov ; AstraZeneca Clinical Trial appendix GS-0321: Compugen responsible for preclinical development and the first- in-human Phase 1 trial evaluating the safety and tolerability of GS-0321. Thereafter Gilead will have the sole right to develop and commercialize GS-0321. Programs (mechanism of action) Stage and Indication Sponsor/ Partner MAIA-ovarian COM701 maintenance therapy (anti-PVRIG antibody) Adaptive platform trial: relapsed platinum sensitive ovarian cancer, sub-trial 1 randomized vs. placebo COM701 + COM902 + pembrolizumab (anti-PVRIG, TIGIT, PD-1 antibodies) Proof of Concept: platinum resistant ovarian cancer Rilvegostomig monotherapy and combination trials (anti-PD1/TIGIT antibody) TIGIT component derived from COM902 5 Phase 3: non-small-cell-lung-cancer (NSCLC) 5 Phase 3: gastrointestinal cancer (GI) 1 Phase 3: endometrial cancer 14 Phase 1 or 2: NSCLC, GI cancer, others GS-0321 ongoing (anti-IL18BP antibody) Phase 1: solid tumors Early-stage pipeline ongoing (potential first-in-class drugs/new mechanism of actions) Undisclosed
Page 6
Differentiated TIGIT strategy
Page 7
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 * Rilvegostom ig broad developm ent strategy as m onotherapy and par t of AD C -IO com binations 7 Study name Indication Rilvegostomig monotherapy or in combination Data anticipated by AstraZeneca Primary endpointPHASE 1 PHASE 2 PHASE 3 Lung ARTEMIDE-Lung02 squamous NSCLC 1L PD-L1 ≥1% + chemo vs pembro + chemo >2026 PFS & OS ARTEMIDE-Lung03 non-sq NSCLC 1L PD-L1 ≥1% + chemo vs pembro + chemo >2026 PFS & OS ARTEMIDE-Lung04 metastatic NSCLC 1L PD-L1 ≥50% mono vs pembro >2026 PFS & OS TROPION-Lung10 non-sq NSCLC 1L PD-L1 ≥50% w/o AGA ± TROP2 ADC (Datroway) vs pembro >2026 PFS & OS TROPION-Lung12 stg 1 adenocarcinoma NSCLC ± TROP2 ADC (Datroway) vs SOC >2026 DFS TROPION-Lung04 advanced or metastatic NSCLC + TROP2 ADC (Datroway) ± chemo H1 2026** DLT & safety ARTEMIDE-01 advanced or metastatic NSCLC mono H2 2026 Safety RP2D, ORR DESTINY-Lung03 NSCLC, HER2 overexpressing + HER2 ADC (Enhertu) ± chemo H2 2026** Safety & RP2D NeoCOAST-2 early-stage resectable NSCLC ± TROP2 ADC (Datroway) >2026 pCR & safety ALTAIR metastatic NSCLC + AB248 (anti-IL2) or + CTx + anti-VEGF (Cyramza) >2026 Safety & OR LIBRA locally advanced/metastatic NSCLC ± anti-VEGF (Cyramza) or Data-DXd + Cyramza ± rilvegostomig >2026 Safety & ORR Gastrointestinal ARTEMIDE-Biliary02 1L advanced BTC +chemo vs durvalumab + chemo OS in PDL1≥ 1% ARTEMIDE-Biliary01 adjuvant BTC + chemo vs chemo >2026 RFS ARTEMIDE-Gastric01 gastric cancer 1L HER2 positive + Enhertu +chemo vs + Herceptin + chemo vs pembro + Herceptin + chemo >2026 PFS & OS ARTEMIDE-HCC01 1L HCC + anti-VEGF ( Avastin) ± anti-CTLA4 (Imjudo) vs Avastin +atezo >2026 OS DESTINY-BTC01 1L HER2+ BTC Enhertu ± rilvegostomig vs chemo + durvalumab >2026 OS DESTINY-Gastric03 HER2+ gastric cancer, GEJ & esoph. AC + chemo + HER2 ADC (Enhertu) H2 2026** Safety, RP2D & ORR GEMINI-Gastric gastric cancer + chemo ± claudin 18.2 ADC >2026 Safety, ORR, PFS6 GEMINI-PeriOp GC perioperative LA resectable gastric, GEJ, or esoph AC +claudin 18.2 ADC + CTx or + Enhertu +CTx or + FLOT CTx H2 2026 Safety, pCR rate GEMINI-Hepatobiliary HCC, BTC + anti-VEGF (Avastin) ± volrustomig or + chemo H2 2026** Safety & ORR Bladder TROPION-Pan Tumor03 bladder cancer 1L, cis-ineligible/2L + TROP2 ADC (Datroway) ESMO 2025 ORR & safety Other DESTINY- Endometrial01 stg III/IV/recurrent endometrial cancer +Enhertu vs pembro + Enhertu vs pembro+chemo >2026 PFS BLUESTAR breast, biliary, endometrial, ovarian Top1i B7 H4 ADC (AZD8205) ± rilvegostomig >2026 Safety NCT07115043 Advanced or metastatic solid tumors AZD6750, a CD8 guided IL-2 ± rilvegostomig >2026 Safety & efficacy ARTEMIDE-subQ Advanced solid tumors post SOC bioavailability Trials announced by AstraZeneca- CT.gov; AstraZeneca Clinical Trial Appendix., not comprehensive, does not include investigator -initiated studies *AstraZeneca’s non-risk adjusted peak year revenue target inclusive of all indications and excludes non -registrational trials ** data may not be from a rilvegostomig cohort AGA: actionable genomic alterations; esoph AC: esophageal adenocarcinoma; Stg: Stage; NSCLC: Non-small cell lung cancer; Non-sq: non squamous; BTC: Biliary Tract Cancer; HCC: Hepatobiliary Cancer; GEJ: gastroesophageal junction.. FPD: First patient dosed DFS: disease free survival; PFS: progres sion free survival; RP2D: recommended Phase 2 dose; ORR: overall response rate; OS: overall survival; pCR: pathological complete response; DLT: disease limiting toxicities
Page 8
CO M 902 potential best -in -c lass anti -TIGIT 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 * isotype: hIgG1TM- triple mutations to reduce Fc effector functionality; ab: antibody 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 8 Rilvegostomig AZ est. >$5bn PYR1 PD-1/TIGIT bispecific Ab COM902 potential best-in-class anti-TIGIT Compugen entitled to up to $225m milestone payments & tiered royalties up to mid-single digit AZ next generation IO bispecific: to replace anti-PD-(L)1’s and be the backbone for future combinations AZ 11 pivotal trials: novel combinations across NSCLC, GI, Endometrial Cancers Higher affinity than other TIGIT antibodies Rilvegostomig* - TIGIT component derived from COM902 AstraZeneca has rights to develop TIGIT bispecifics IgG4 reduced Fc functionality One of only two clinical stage Fc-reduced anti-TIGIT monoclonal antibodies Compugen retains rights to PVRIG (PVRL2)/TIGIT bispecifics Promising Phase 2 data presented: ARTEMIDE-01, GEMINI Gastric, TROPION-Lung04 GEMINI-Hepatobiliary TROPION-PanTumor 03 ~$30m in milestones received, remain eligible to receive up to $195m in regulatory and commercial milestones
Page 9
F o r m a t m a t t e r s Not all ant i -TIGIT antibodies are c reated equally 9 • Bispecific approach: differentiated coordinated inhibition of PD-1/TIGIT induces greater ex vivo activity than its components1 • Fc attenuated triple -mutant IgG1 potentially maintaining and enhancing immune responses, and conferring improved safety 1 • Fc-reduced functionality important for efficacy - unmodified or enhanced Fc-functionality appears to be detrimental to rilvegostomig anti-tumour activity in NSCLC explants1 Program by: (PD-1/TIGIT) Rilvegostomig* (IgG1-mut Fc reduced) Anti-PD-1 Fab from COM902 Anti-TIGIT Fab * Rilvegostomig, an Fc-reduced, monovalent, bispecific humanized IgG1 monoclonal antibody targeting PD-1 and TIGIT. The anti-TIGIT component of rilvegostomig is derived from COM902 developed by Compugen *Compugen is eligible for milestone and up to mid single digit tiered royalty payments 1. https://www.astrazeneca.com/content/dam/az/Investor_Relations/events/AZN-2025-ESMO-brochure.pdf Rilvegostomig aPD-1 + aTIGIT (bivalent) aPD-1 + aTIGIT (monovalent) Pembrolizumab aPD-1 (bivalent) aTIGIT (bivalent) PD-L1 TPS PD-L1 TPS <1 1-49 ≥50 Pending 54 43 39 39 37 9 Log2(Fold Change – IFNy) -2.5 0.0 2.5 5.0 1 5 10 15 20 25 30 35 40 45 Patient P=0.15 P=0.09 P=0.15 P=2.6e-5 % tumors with activity 0 20 40 60
Page 10
COM701 - potential first-in-class anti-PVRIG antibody
Page 11
CO M 701 potent ial 1st in c lass Fc reduc ed ant i -PV RIG antibody 1 1 PRE-CLINICAL PHASE 1 and 2 No data presented BioNtech BNT3213* (formally PM1009 acquired from Biothesus) COM701 IgG4 reduced Fc effector function Avoids CD8 + T cell depletion and potential associated risks Simcere SIM-0348* TG ImmunoPharma NM1F Hengrui SHR-2002* Shanghai Junshi JS-209* FutureGen FG-B902/T903* COM701 Fc Reduced POTENTIAL FIRST-IN-CLASS Phase 1 data presented; proof-of-concept studies ongoing PHASE 1 Data presented *Bi-specifics The preclinical list of players is not exhaustive
Page 12
12 Strong biological rationale to target PV RIG in ovar ian canc er Alteber et al, Cancer Immunology Research, 2024 • High PVRIG pathway expression levels in ovarian cancer • PVRIG pathway differentially expressed on early differentiated stem like memory T cells and dendritic cells compared to other immune checkpoints • PVRIG blockade with COM701 alters the tumor microenvironment including in less inflamed tumors like ovarian cancer
Page 13
13 Encouraging durable responses as monotherapy and in combination Patient characteristics Safety and tolerability profile in combination consistent with anti-PD-(L)1s7-8 Single agent COM701 activity4-6 PR >18 months in immune desert patient Immune modulation of the TME Triple combination blocking PVRIG, TIGIT, PD-17-9 ORR 17-20%* DCR 45-46% (n=44) mPFS in patients with CB 10.5 months Responses across PD-L1 levels, supportive of COM701 mediated effect Platinum resistant ovarian cancer Heavily pretreated Some patients failed ADCs Across PD-L1 tumor expression level Most common adverse events grade 1/2 fatigue, diarrhea, nausea Grade ≥3 treatment related adverse events 20% No grade 4/5 treatment related adverse events Treatment related discontinuations 4.4% CO M701 showed c linical benef it in patients with hard -to -treat platinum resistant ovar ian canc er Ty p i c a l l y, n o t r e s p o n d i n g t o i m m u n o t h e ra p y1 - 3 1. Matulonis et al, ASCO 2022, 2. Holmes et al, JCO ASCO 2022, 3. Perets et al, ACCR 2022 4. Ophir E et al, SITC 2022 5. Alteber E et al, Cancer Immunology Research 2024 6. Vaena et al, ASCO 2021 7. Gaillard S et al, SITC 2023 8. Yeku et al, SITC 2024 9. Yeku et al, ESMO 2025 PR: Partial Response; CR: Complete Response; ORR: Overall Response Rate; DCR: Disease Control Rate; ADCs: Antibody Drug Conjugates TME: Tumor Microenvironment CB: Clinical Benefit *anti-PD-1 ± anti-TIGIT (ORR <10% all-comers, 0% PD-L1 <1)1-3
Page 14
14 Platinum sensitive ovarian cancer represents a less competitive landscape to platinum resistant ovarian cancer Strong c linical and biological rationale to advanc e CO M701 developm ent to platinum sensitive ovar ian canc er 1. Alteber et al, Cancer Immunology Research, 2024 2. Vaena et al, ASCO 2021 3. Ophir E et al, SITC 2022 4. Gaillard S et al, SITC 2023 5. Yeku et al, SITC 2024 6. Yeku et al, ESMO 2025 7. Hanker LC, et al, Ann Oncol. 2012;23(10):2605-12. 8. González-Martín et al, Ann Oncol . 2023 Oct;34(10):833-848 9. Lanickova et al, Clin Cancer Res; 2025 High PVRIG pathway expression levels in ovarian cancer and PVRIG unique biology differentiated from other checkpoints supporting activity in less inflamed tumors1 COM701 showed clinical benefit in hard-to-treat platinum resistant ovarian cancer patients including PD-L1 low expressing tumors1-6 Platinum sensitive ovarian cancer patients are less heavily pre-treated, less immune compromised7-8 Platinum based chemotherapy may reduce disease burden and sensitize tumors to COM701’s unique mechanism of action9 COM701 is well tolerated and associated with durable responses especially important in a maintenance setting1-6
Page 15
M AIA -ovar ian : adaptive tr ial w ith m aintenanc e CO M 701 therapy in relapsed platinum sensitive ovar ian canc er 15 Sub-trial 1 Single agent activity of COM701 versus placebo (standard of care) Sub-trial 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- median progression free survival 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 chemotherapy Maintenance therapy post bevacizumab and/or PARP inhibitor or not a candidate for bevacizumab and/or PARP inhibitor Presence of liver metastases excluded Adaptive trial n= 60 2:1 Randomization T i m e l i n e s : s u b- t r i a l 1 Trial initiation: Q2 2025 First patient dosed: July 2025 Projected Interim analysis: Q1 2027 15 Evaluation of COM701 single agent activity, combinations and contribution of effects, represents a regulatory and commercial opportunity https://clinicaltrials.gov/study/NCT06888921?cond=COM701&rank=1
Page 16
~ Advanc ing CO M 701 to address unm et need in PSO C 16 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 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 Relapse2nd Relapse 1st Relapse Treatment journey 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 mPFS: medium progression free survival - measured from start of chemotherapy and includes 4-6 cycles of chemotherapy 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 immunotherapy response more challenging * mPFS measured following completion of chemotherapy ~ 6 months range based on historical data 1-4 1. Poveda A et al Lancet Oncol. 2021 May;22(5):620 -631 2. Mirza MR et al N Engl J Med. 2016 Dec 1;375(22):2154 -2164. 3. Aghajanian C J et al. Clin Oncol. 2012 Jun 10;30(17):2039 -45. 4. Coleman RL et al.Lancet. 2017 Oct 28;390(10106):1949 -1961 COM701 target population: Women with complete/partial response post chemo not suitable for bevacizumab/PARPi mPFS ~ 6 months (range:3.8-8.4mo)* PSOC: Platinum sensitive ovarian cancer; PROC: Platinum resistant ovarian cancer
Page 17
GS -0321 ( previously CO M 503) – potential f irst -in -c lass anti -IL 18BP antibody
Page 18
DAMPs- Damage-associated molecular patterns . GS -0321 is licenced to Gilead, Compugen responsible for ongoing preclinical and future Phase 1 development, Thereafter, Gilead will have sole right to develop and commercialize GS -0321 GS -0321 : Com pugen identif ied potential dom inant im m unosuppression m ec hanism and antibody therapeutic 18 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 GS-0321 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 GS-0321
Page 19
GS -0321 dif ferentiated approac h to harness c y tokine biology * less 15% tax withheld at source 19 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 GS-0321 differentiated approach to harness cytokine biology to treat cancer Reflects quality of our computational capabilities & ability to advance discoveries into drugs candidates Strengthens our balance sheet Advances our vision 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 GS-0321
Page 20
20 GS -0321 : advantages of a dif ferentiated approac h GS-0321 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
Page 21
Key eligibility criteria Advanced recurrent or metastatic solid tumor malignancy Part 2: dose expansion - GS-0321 monotherapy and in combination with zimberelimab* First in human dose escalation dose expansion trial Part 1: dose escalation - GS-0321 monotherapy and in combination with zimberelimab* (anti-PD-1) Clinicaltrials.gov identifier NCT06759649 *zimberelimab, Gilead’s anti-PD-1 21 GS -0321 f irst -in -hum an global Phase 1 trial in patients with advanc ed solid tum ors Endpoints Primary: safety and identify recommended dose for expansion Secondary: characterize GS-0321 pharmacology Exploratory: preliminary anti- tumor activity Trial initiated Q4 2024 First patient dosed January 2025 Trial in progress poster presented at SITC 2025
Page 22
Dif ferentiated by integrating pioneering com putational capabilities w ith im m uno -oncology dr ug developm ent
Page 23
a f lexible -loop AI/M L -powered validated com putational platfor m for target discover y & developm ent 23
Page 24
E xper ienc ed Team L eading Com pugen
Page 25
M a n a g e m e n t t e a m D iverse exper ienc ed leadership team 2 5 Eran Ophir, PhD President and Chief Executive Officer Anat Cohen-Dayag, PhD Executive Chair of the Board Eran Ophir, 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 Eran Ben Dor General Counsel and Corporate Secretary Michelle Mahler, MD Chief Medical Officer David Silberman Chief Financial Officer Dorit Amitay VP, Human Resources Zurit Levine, PhD SVP, Business Development Pierre Ferre, PhD, Dr. Vet. Med. Chief Operating Officer Sharon Kredo-Russo, PhD SVP, Research & Discovery
Page 26
Deep dive into CO M 701 data in platinum resistant ovar ian canc er
Page 27
CO M701 c linical benef it ac ross m ultiple tum ors typically unresponsive to im m unotherapy 27 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 ORR (17%) 11/24 DCR (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
Page 28
G u i d e d t h e d e s i g n o f o n g o i n g M A I A- o v a r i a n P S O C m a i n t e n a n c e p l a t f o r m t r i a l Charac ter iz ing PRO C responding pat ient s ac ross Phase 1 Yeku et.al. ESMO 2025 28 C1D1: Cycle 1 Day 1; CR: complete response; NA: not applicable; PD: progressive disease; POS: positive; PR: partial response; SD: stable disease. CB: clinical benefit; W/O: without. Patients derived clinical benefit irrespective of PD-L1 status Patients without liver metastases - more likely to derive clinical benefit 0 20 40 60 80 100 120 W/O liver metastases With liver metastases Percentage of patients CB no CB 62.2% (23/37) 37.8% (14/37) 91.3% (21/23) 8.7% (2/23) 100 200 300 400 500 600 700 1T 2M 3T 4T 5T 6T 7T 8D 9D 10T 11T 12T 13T 14T 18T 22D 0 PDL1_pos = Yes PDL1_pos = No PDL1_pos = NA/Other CR PR SD PD Ongoing (open arrow) M = Mono D = Double T = Triple Days COM701 alone and in combination was well tolerated and demonstrated consistent, durable responses in heavily pre- treated PROC patients, particularly in patients without liver metastases, as well as patients who were PD-L1 negative Data support advancing to a maintenance strategy in an earlier setting of ovarian cancer Ongoing MAIA-ovarian platform trial is evaluating COM701 maintenance therapy in relapsed PSOC without liver metastases, for which there is a significant unmet need
Page 29
29 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
Page 30
CO M 701 m onotherapy: par tial response in patient w ith PD -L 1 negative ovarian ongoing treatm ent >18 m onths 30Modified 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)
Page 31
31 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
Page 32
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 32 Data supports COM701 driven activity 1,2 versus historical data 5-7 B. COM701 + pembrolizumab + 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 Platinum-Resistant Standard of Care: Single agent chemo (ORR ~ 12%, mPFS ~3-4 months, mOS ~ 13 months, with significant toxicity )3,4 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
Page 33
COM701 + nivolumab + BMS-9862071 COM701 + pembrolizumab + COM9022 Consistent deep responses ac ross studies 33 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
Page 34
Clinical V ignette – CO M 701 + pem brolizum ab + CO M 902 com plete response in PRO C patient 34 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
Page 35
35 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
Page 36
36 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
Page 37
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 37 • 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%
Page 38
CO M 9 0 2- p o 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
Page 39
39 Dumbrava E E, et al, SITC 2021, Modified 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 Data cut 03 September 2021
Page 40
40Martinet & Smyth, 2015 (modified) Com pugen dif ferentiated in TIGIT spac e by unique proper ties of Fc reduc ed CO M 902 and c linical strategy DNAM-1 axis potential game changer in fight against cancer • One of only two clinical stage Fc- reduced anti-TIGIT monoclonal antibodies • Combination of TIGIT with PD-1 blockade may be effective in PD-1 high tumors • DNAM-1 axis: 2 parallel and complementary inhibitory pathways - TIGIT & PVRIG • Blocking PVRIG with COM701 may be disruptive in less inflamed tumors where TIGIT/PD-1 blockade alone is insufficient Anti- PD-1
Page 41
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 effector 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 IrAEs 3 Favorable safety and well tolerated as monotherapy and in combination COM902 ± COM701± pembrolizumab COM902 naturally Fc reduced antibody (IgG4 backbone) chosen with efficacy and safety in mind 41 • 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
Page 42
CO M902 prevents depletion of m aj or TIGIT+ expressing lym phoc y tes - NK, CD4 and CD8 T c ells 42Dumbrava 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
Page 43
Deep dive into GS -0321 data
Page 44
44 TILs- tumor infiltrating lymphocytes Ferre P, presentation, SITC, 2023, modified GS -0321 , 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 GS-0321 restored TILs activity GS-0321 restored NK cell activity GS-0321 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
Page 45
45Ophir 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%
Page 46
46 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%
Page 47
Appendix
Page 48
CO M701 and CO M 902 distinguishing proper ties 48 • 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 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 • Favorable linear PK and very large TIGIT receptor occupancy • 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
Page 49
PV RIG and TIGIT – com plem entar y but distinc t pathways 49Tscm: 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