#1CORBUS PHARMACEUTICALS Connecting Innovation to Purpose Corporate Presentation February 29, 2024 NASDAQ: CRBP CorbusPharma.com @CorbusPharma#22 Forward-Looking Statements This presentation contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's restructuring, trial results, product development, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors, including the potential impact of the recent COVID-19 pandemic and the potential impact of sustained social distancing efforts, on our operations, clinical development plans and timelines, which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward- looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this presentation. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. All product names, logos, brands and company names are trademarks or registered trademarks of their respective owners. Their use does not imply affiliation or endorsement by these companies.#3Investment Summary Focus on developing precision oncology + differentiated assets Fi y Nectin-4 targeting ADC for treatment of solid tumors CB1R inverse agonist to treat obesity TGFB blocker Anti-avß8 integrin mAb for treatment of solid tumors CRBP Ticker $127 Million Cash investments as of Feb 2, 2024 and 10.3M Common Shares Outstanding (11.1M Fully-Diluted Shares)#4A diversified pipeline with differentiated clinical risk profiles CRB-701 Next-generation Nectin-4 targeting ADC CRB-601 Anti-av38 mAb (TGF6-targeting) CRB-913 CB1R inverse agonist Nectin-4 positive solid tumors Next-Generation Nectin-4 targeting ADC Dose Escalation Cohorts 1-6 completed Cohort 7 added and recruiting CSPC (China) Corbus (US + Europe) avß8 enriched solid tumors Dose Escalation Obesity and related conditions Anti-Integrin mAb Highly peripherally-restricted CB1R inverse agonist Dose Confirmation / Expansion Cohort 6 expanding Dose Confirmation / Expansion IND Cleared in January 2024 IND Expected in Q4 2024#5CRB-701 Next Generation Nectin-4 Targeting ADC#6Padcev® projected to reach up to ~$5B in global sales by 2028 6 L PADCEV. enfortumab vedotin-ejfv Injection for IV infusion 20 mg & 30 mg vials Latest Padcev® 03 revenues ¹ 1 (dollars in millions) Total Net Product Sales ADCETRIS PADCEV TUKYSA TIVDAK Ⓡ Three months ended September 30, 2022 2023 % Change $ 571 $ 428 33 $ 246 $ 219 13 $ 200 $ 105 89 $ 102 $ 88 $ 23 $ 16 16 40 % % % % % Nine months ended September 30, % Change 27 25 2023 $ 1,583 $ 751 $ 479 $ 289 $ 64 2022 $ 1,243 $ 601 $ 329 $ 267 $ 45 46 Sources: 1. SGEN Q3 earnings report, 2. SGEN press release, October 2023, 3. Evaluate Pharma 8 42 % % % % % 22nd October 2023 ² Groundbreaking EV-302 Trial Significantly Extends Overall Survival and Progression-Free Survival in Patients Treated with PADCEV® (enfortumab vedotin-ejfv) and KEYTRUDAⓇ (pembrolizumab) in First-Line Advanced Bladder Cancer 2021 PADCEVⓇ Global Projected Revenues in UC/Bladder³ $5B 2022 2023 2024 2025 2026 2027 2028#7Does tolerability for Padcev® impact clinical adoption? PADCEVⓇ Prescribing Information HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PADCEV safely and effectively. See full prescribing information for PADCEV. PADCEV (enfortumab vedotin-ejfv) for injection, for intravenous use Initial U.S. Approval: 2019 WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. PADCEV can cause severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SIS) and Toxic Epidermal Necrolysis (TEN). Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions. (2.2), (5.1) (6.1) . RECENT MAJOR CHANGES Indications and Usage (1) Dosage and Administration (22) Warnings and Precautions (5.1). (5.2). (5.3). (5.4). (5.6) 4/2023 10/2022 4/2023 INDICATIONS AND USAGE PADCEV is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated: as a single agent for the treatment of adult patients with locally advanced or metastatic urothelial cancer who: 0 have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand I (PD-L1) inhibitor and platinum- containing chemotherapy, or O are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. (1) in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy. (1) This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. (14.1) DOSAGE AND ADMINISTRATION For intravenous infusion only. Do not administer PADCEV as an intravenous push or bolus. Do not mix with, or administer as an infusion with, other medicinal products. (23) The recommended dose of PADCEV as a single agent is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. (21) The recommended dose of PADCEV in combination with pembrolizumab is 1.25 mg kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. (2.1) Avoid use in patients with moderate or severe hepatic impairment (8.6) DOSAGE FORMS AND STRENGTHS For Injection: 20 mg and 30 mg of enfortumab vedotin-ejfv as a lyophilized powder in a single-dose vial for reconstitution. (3) None. (4) WARNINGS AND PRECAUTIONS . Hyperglycemia: Diabetic ketoacidosis may occur in patients with and without preexisting diabetes mellitus, which may be fatal. Closely /monitor blood glucose levels in patients with, or at risk for, diabetes. mellitus or hyperglycemia. Withhold PADCEV if blood glucose i e is >250 mg/dl. (22.5.2) . CONTRAINDICATIONS . Pneumonitis/Interstitial Lung Disease (ILD): Severe, life-threatening or fatal pneumonitis ILD may occur. Withhold PADCEV for Grade 2 pneumonitis/ILD and consider dose reduction Permanently discontinue PADCEV for Grade 3 or 4 pneumonitis/ILD. (2.2, 5.3) Peripheral Neuropathy: Monitor patients for new or worsening peripheral neuropathy and consider dose interruption, dose reduction of discontinuation of PADCEV. (2.2. 5.4) Infusion Site Extravasation: Ensure adequate venous access prior to administration. Monitor the infusion site during PADCEV administration and stop the infusion immediately for suspected extravasation. (5.6) . Embryo-Fetal Toxicity: PADCEV can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. (5.7. 8.1, 8.3) ADVERSE REACTIONS The most common adverse reactions, including laboratory abnormalities, (220%) were: PADCEV as a single agent: rash, aspartate aminotransferase increased. glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin. (6.1) PADCEV in combination with pembrolizumab: glucose increased, aspartate aminotransferase increased, rash, hemoglobin decreased, creatinine increased, peripheral neuropathy, lymphocytes decreased, fatigue, alanine aminotransferase increased, sodium decreased, lipase increased, albumin decreased, alopecia, phosphate decreased, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia. potassium decreased, neutrophils decreased, urinary tract infection, constipation, potassium increased, calcium increased, peripheral edema, dry eye, dizziness, arthralgia, and dry skin. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Ocular Disorders: Ocular disorders, including vision changes, may occur. Monitor patients for signs or symptoms of ocular disorders. Consider prophylactic artificial tears for dry eyes and treatment with ophthalmic topical steroids after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV when symptomatic ocular disorders occur. (5.5) DRUG INTERACTIONS Concomitant use of dual P-gp and strong CYP3A4 inhibitors with PADCEV may increase the exposure to monomethyl auristatin E (MMAE) (7.1) -USE IN SPECIFIC POPULATIONS . Lactation: Advise women not to breastfeed. (8.2) See 17 for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling Source(s): PADCEVⓇ Prescribing Information as of Apr 2023. Revised: 4/2023 Revised: 4/2023 1 T 61% Dose interruptions PADCEVⓇ enfortumab vedotin-ejfv Injection for IV infusion 20 mg & 30 mg vials Duration of Response ~5 months 47% Rate of Serious Adverse Events (SAES) T 34% Dose reductions T 17% Dose Discontinuations EV-301: The safety of PADCEV was evaluated as a single agent in EV-301 in patients with locally advanced or metastatic urothelial cancer (n=296] who received at least one dose of PADCEV 1.25 mg/kg and who were previously treated with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy#8● ● ● 8 Padcev® is associated with skin toxicities and peripheral neuropathy PADCEV.Ⓡ enfortumab vedotin-ejfv Injection for IV infusion 20 mg & 30 mg vials A Black Box warning 1 WARNING: SERIOUS SKIN REACTIONS PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later. Closely monitor patients for skin reactions. Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions (see Dosage and Administration (2.2), Warnings and Precautions (5.1) and Adverse Reactions (6.1)]. Greater than 25% of PADCEV® discontinuations are linked to peripheral neuropathy2 PADCEVⓇ + Keytruda® patients who experienced neuropathy: 13% complete resolution 87% patients had residual neuropathy (45% had Grade ≥2]¹ ● Source(s): 1. PADCEVⓇ Prescribing Information Dec 2023. 2.. Rosenberg et al., 2020 Adverse Events (% of patients) Skin Reactions NR = not reported PADCEVⓇ monotherapy¹ All Grades 58% Peripheral Neuropathy 53% > Gr 3 14% 5% PADCEVⓇ+ Keytruda Ⓡ1 All Grades 70% 67% > Gr 3 17% 7%#99 Is the 2nd generation Seagen linker the cause? Similar dose limiting toxicities seen across divergent ADCs that share same constellation of 'linker + payload' Val-Cit linker + vedotin (MMAE] payload ADC drug PadcevⓇ Enfortumab vedotin Adcetris®Ⓡ Brentuximab vedotin TivdakⓇ Tisotumab vedotin Polivy Ⓡ Polatuzumab vedotin AidixiⓇ Disitamab vedotin TAA Nectin-4 CD30 TF CD79B HER2 Average DAR 3.8 4 4 3.5 4 Skin Rash Peripheral Neuropathy E 0% 10% 20% 30% 40% 50% 60% 0% 10% 20% 30% 40% 50% 60% 70% All grades Padcev® Val-Cit linker + payload = mc-VC-PABC = Maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyl alcohol p-nitrophenyl carbonate Source(s): 1. Fu et al., Science. 2023 doi: 10.1016/j.isci.2023.107778. Padcev® Prescribing information, Adcetris® Prescribing Information, Tivdak® Pescribing Information, Polivy Ⓡ Prescribing Information. Shi et al., 2022 https://doi.org/10.1080/10717544.2022.2069883 Aidix® https://www.adcreview.com/drugmap/disitamab-vedotin#1028 days = Cycle length 10 Padcev® requires frequent dosing and real-world usage differs from label Day 1 Day 8 Day 15 Day 22 Day 28 N Monotherapy PadcevⓇ 1.25 mg/kg 1.25 mg/kg 1.25 mg/kg dose holiday 6 months of therapy: = 54 hours of total clinic time / patient Source(s): 1. PADCEVⓇ Prescribing Information as of Dec 2019, 2. Redacted from Tsingas et al., ASCO 2023 Real-world use, dose intensity, and adherence to PadcevⓇ Metric EV use Number of cycles (median, IQR) EV dose intensity Treatments per patient month (mean [SD]) Dosing frequency; treatments per cycle (mean [SD]) Dose (mean, mg/kg [SD]) Change in average dose (mg) from baseline (%) EV treatment adherence Received on average > 2 treatments per cycle (%) Result (N = 416) 5 (2,8) 2.6 [0.6] 2.4 [0.5] 1.1 [0.2] -9.6 [20.2] % 58.8 [34.4] %#11Emerging clinical-stage competition is not solving for existing challenges 11 Seagen astellas PadcevⓇ 1.25 mg/kg ¹ 1 D1, D8, D15/28 days 51% (n=155) ² 2 38% 25% 5% 3 Bicycle 34% 64% Limitation Upper dose limit Schedule ≥ Grade 3 AE rate Peripheral neuropathy Skin reactions Neutropenia (Gr 3) Dose reduction Dose interruptions 1 Rosenberg, et al., "EV-101 JCO, 2020 Apr 1; 38(10): 1041-1049, 2. Powles et al., EV-301 2021, 3. Zhang et al., ESMO 2023, 4 Rigby et al., 2023, 6 Bicycle corporate deck Nov 2023 # - combined frequency of Grade 3 neutropenia/ low neutrophil count BT8009 5 mg/m² Q1W 65% (n=20) 6 30% 10% 10% # 16% 24% Mabwell 迈威生物 4 9MW-2821 1.25 mg/kg ³ D1, D8, D15 /28 days 3 35% (n=85) ³ 17% 18% 19% 3.5% 28%#1212 Designing a Nectin-4 ADC intended to address Padcev® unmet needs M Toxicity: 3rd gen ADC w/stable linker →Reduce free circulating MMAE Compliance: Extend ADC half-life → Reduce dosing frequency Efficacy: Lower DAR + longer half-life → Dose higher than PadcevⓇ#1313 CRB-701: Next generation site-specific Nectin-4 targeting ADC Novel nectin-4 Antibody ADCC + CDC functionality Glutamine focused side chain conjugation MMAE = Monomethyl auristatin E ADCC = antibody-dependent cellular cytotoxicity CDC complement dependent cytotoxicity O H Cathepsin-B cleavage site H₂N NH Payload Monomethyl auristatin E [MMAE] Microtubule disruption NH OH Source(s): Modified image from Corbus data on file; Corbus data on file#1414 CRB-701: One dose every 21 days expected to offer advantages over more frequent dosing Day 1 Day 8 Clinical cycle comparison CRB-701 PadcevⓇ Day 15 Day 21 CRB-701 dose holiday dose holiday Source(s): Corbus data on file; PADCEV® Prescribing Information as of Dec 2019 Day 1 Day 8 Day 15 Day 22 Day 28 1.25 mg/kg 1.25 mg/kg 1.25 mg/kg dose holiday Li Patient / physician convenience Combination flexibility#1515 Phase 1 dose escalation study (China): ASCO-GU 2024 KEY ELIGIBILITY Age >18 years Advanced urothelial carcinoma or Nectin-4 positive Advanced solid tumors ECOG 0-1 Adequate organ function. No uncontrolled diabetes No active CNS metastasis ESCALATION DESIGN Bayesian Optimal Interval [BOIN] design with accelerated titration at DL-1 IV Q3W over a 21-day cycle 0.2 mg/kg 0.6 mg/kg 1.2 mg/kg 1.8 mg/kg 2.7 mg/kg 3.6 mg/kg 4.5mg/kg (recruiting) KEY END POINTS Safety/tolerability Pharmacokinetics Anti tumor activity NEXT STEPS Continue escalation PK expansion at 3.6mg/kg MTD or RP2D Specific expansion#1616 Demographics & Key Characteristics Characteristic Median Age (Range) Sex (M/F) ECOG PS of 1 Weight in kg (Range) Prior therapy (Range) Creatine Cl <60 μmol/L Visceral metastasis Value 58 (35-76) 5/13 18 (100%) 55 (36-84) 5 (1-10) 7 (39%) 15 (83%) Characteristic Primary tumor type Urothelial Cervical Breast TNBC CRC HbA1C levels ≤ 6.5% Value n=18 7 CO 6 4 3 of 4 1 18 (100%)#17Safety and Dose Modifications AST increase ALT increase Pruritus Creatinine increase Asthenia Urinary tract infection Hyponatremia Hypoalbuminemia Platelet decrease Hypertriglyceridemia Lymphocyte decrease Decrease appetite Proteinuria 17 Dry eye Corneal disorder Anemia 0 10 Grade 1 Grade 2 Grade 3 20 30 40 50 60 70 80 Events expressed as a % - TEAEs ≥ 20% of participants 90 100 Dose Modifications (n=18) Discontinuations Reductions Interruptions SYS6002 (CRB-701) was well tolerated with mainly grade 1 or 2 AEs No DLTS or Grade 4 or 5 AEs have been observed to date Anemia and eye-related adverse events were the most common treatment emergent AEs [TEAE) Four subjects reported 7 SAES, 3 of which were considered probably related to SYS6002 (CRB-701) Two Grade 3 SAES (ILD and pulmonary infection) were reported in a single participant One Grade 3 (ALT increase) reported in a separate participant To date no cases of skin rash or peripheral neuropathy have been observed Value 0 0 1 [5.5%)#1818 ● ● ● Clinical Pharmacology 21 Day PK Enfortumab vedotin (EV) 1.25 mg/kg Q1W x3 SYS6002 [CRB-701) 1.2 mg/kg Q3W SYS6002 (CRB-701) 2.7 mg/kg Q3W Comparison EV benchmark Matched ADC dose Matched MMAE dose Cmax 100% 79% 177% % ADC AUC 21d 100% 106% 183% Cmax 100% The half-lives of TAb, ADC, and MMAE were 4-6 days, 4-5 days and 5-10 days, respectively No obvious accumulation was observed on C3D1 33% 79% % Free MMAE AUC 21d 100% Time-to-peak concentration of MMAE was about 3-7 days When compared to EV exposures SYS6002 (CRB-701) consistently demonstrates lower free MMAE 29% After single IV infusion of SYS6002 (CRB-701), the exposure of TAb, ADC and MMAE generally increased in a dose proportional manner Clearance and volume of distribution were similar across doses 68%#19Best Percent Change from Baseline in Sum of Diameters (%) Phase 1 Dose Escalation - Disease Response 19 90 60 30 0 -30 -60 -90 DOSE mg/kg INDICATION NECTIN-4 PD 46.60 PD 28.57 PD 25.66 1.2 1.8 2.7 TNBC TNBC CRC 70 167 140 PD 24.69 3.6 UC PD 16.95 SD 0.00 SD -0.86 PD -0.95 SD -2.27 0.6 1.2 3.6 1.8 0.6 TNBC Cervical Breast UC Cervical 123 110 25 65 68 SD -2.70 2.7 UC 105 PD -7.50 0.2 UC 80 SD SD -23.33 -24.42 PR -30.46 PR -35.62 PR -39.81 1.8 3.6 3.6 0.6 2.7 UC Cervical Cervical Cervical UC 92 235 185 190 65 TNBC Breast CRC Cervical UC PR -64.22 1.2 UC 175 Disease response in 3.6 mg/kg and 2.7 mg/kg doses: ORR 43% DCR 71%#2020 Phase 1 Disease Responses 3.6 mg/kg 2.7 mg/kg 1.8 mg/kg 1.2 mg/kg 0.6 mg/kg 0.2 mg/kg 0 PD A 1 2 PD PD PD PD PD PR SD 3 SD PD PR PR SD T 5 SD SD PR 6 7 Cycle number (21 days/cycle) 8 Note: Of the 4 PRs reported, 2 PRs are confirmed and 2 remain unconfirmed TNBC Breast CRC Cervical UC Progressive Disease Stable Disease A Partial Response Treatment ongoing 10 11 SD 12#2121 Phase 1 Summary - Data cutoff December 2023 Predicted therapeutically relevant doses in Ph. 1 study Objective Response Rate Disease Control Rate Tumor shrinkage across all nectin-4 positive mUC and cervical patients in study Dose for first observed SD Dose for first observed PR Longest observed response duration to-date Participants still on CRB-701 First expansion dose chosen Seven patients treated at 2.7mg/kg and 3.6 mg/kg on Q3W schedule 43%: 3 out of 7 patients with PR's (2 unconfirmed) 71%: 5 out of 7 patients 9 out of 10 patients 0.6 mg/Kg 1.2 mg/Kg 11 cycles (still ongoing) 7/18 (38%) 3.6 mg/Kg (cohort 6)#2222 CRB-701: A differentiated clinical development approach to competitors Proprietary insights are driving indication selection for CRB-701 mUC Other Nectin-4 solid tumors New reality of Padcev® + Keytruda Ⓡ 1L therapy Emerging clinical data from current dose escalation is informative Under-served niche mUC populations remain and are attractive targets Focus on unexplored Nectin-4 solid tumors#2323 CRB-701-01 Study Design (Corbus) Dose escalation (IND open: FPI Expected Q1 2024) 1.8 mg/kg 2.7 mg/kg 3.6 mg/Kg 4.5 mg/Kg Project Optimus [dose optimization) Randomized to 2 doses of CRB-701 monotherapy Randomized to 2 doses of CRB-701+CPI Dose expansion at RP2D Bladder cancer niche population[s] Non-UC tumors: A B C Basket of nectin-4 positive tumors#24Log2 Expression (RNA Seq) 15- Validation of Nectin-4 as a Tumor Associated Antigen beyond mUC 24 | bunda : D Mhain wicked D ▬▬ | MAR I ملاحة 1 Source: Corbus data on file, Swiecicki et al., Abstract 6017., ASCO 2023 <---- Other highly expressing tumors ----> U HAN ▬▬ ther PE I ▬▬ H&NSCC UC JU H uvm acc lgg pcpg gbm kirp lihc laml kirc skcm sarc kich meso dlbc thym tgct ucs read coad stad thca ucec prad ov chol paad esca luad brca lusc hnsc cesc blca Elevated Nectin-4 expression: urothelial, breast, ovarian, cervical, colorectal, rectal, esophageal, gastric, lung, thyroid, prostate, cholangiocarcinoma, pancreatic cancer, testicular cancer T IL **** Parameter Confirmed ORR CR PR PADCEV. enfortumab vedotin-ejfv Injection for IV infusion 20 mg & 30 mg vials H&NSCC SD mPFS Patients (N=46) 11 [23.9%) 1 [2.2%) 10 (21.7%) 15 (32.6%) 3.94 months 2023 ASCO ANNUAL MEETING#25Expected Milestones First patient dosed in U.S. dose escalation study Clinical data update on China dose escalation study Complete U.S. dose escalation study Present U.S. dose escalation data 25 Q1-2024 Mid-2024 Fall-2024 Q4-2024/Q1-2025#2626 CRB-701: Summary M Emerging clinical safety and potential for superior therapeutic index Dose expansion has started (China); dose escalation in US Q1 2024 3rd generation ADC with improved linker stability-reduces MMAE in circulation#2728 CRB-913 Oral cannabinoid Type-1 inverse agonist for superior incretin therapy in obesity#28Incretin analogs have transformed the field of obesity and its commercial value But... 28 Muscle loss Tolerability Accessibility → Long-term compliance is ~ 27% Sales (2018-2022) and sales estimates (2023-2028) for Ozempic, Wegovy, and Mounjaro reflect significant uptake and expectations Sales ($B) 25 20 15 10 5 0 2018 2019 2020 2021 2022 2023E 2024E 2025E 2026E 2027E 2028E Ozempic Wegovy Mounjaro Source(s): RBC report Oct 2023#2929 The obesity landscape is evolving to address these issues IM Muscle loss: Degree of weight loss → Quality of weight loss Tolerability: Single MOA → Multiple orthogonal MOAS Accessibility: Injectables → Oral small molecules#3031 CB1 inverse agonism: The return of a clinically- validated obesity drug class#3131 CB1 contribution to "Diabesity” is well understood Hepatic tissue Lipogenesis Glucose production Insulin signaling Fatty acid oxidation Obesity Skeletal tissue Insulin resistance Diabetes mellitus ↑ CBIR ↑ Neuronal tissue Neuropeptide ↑ Appetite Lipogenesis Body weight Obesity Diabesity Pancreatic cells Insulin secretion Diabetes mellitus Adipose tissue Lipogenesis Adipogenesis Inflammation Adiponectin secretion Obesity Source(s): Targeting the endocannabinoid system in diabesity: Fact or fiction?, Drug Discovery Today, Deeba et al. Mar 2021.#32The CB1 MOA is clinically validated in obesity: data from 1st gen drugs MERCK Taranabant² Change in Body Weight (kg) 32 -6- -10- || SANOFI Rimonabant¹ RIO-Lipids Phase 3 study Placebo (n=342); 5 mg rimonabant (n=345); 20 mg rimonabant (n=346) Rimonabant at 20 mg Placebo + Rimonabant at 5 mg KH P<0.001 P<0.001 H 8 12 16 20 24 28 32 36 40 44 48 52 Week % weight loss -2.4% -4.4% -9.0% 2 Mean Change in Body Weight (kg) प -12- 0 12 Completed Phase 3 studies (2 and 4 mg) (2 yr) Placebo (n=417); 2 mg taranabant (n=414); 4 mg taranabant (n=415) 24 oooo 36 oooooooooooo 52 60 68 Week 80 92 Placebo Taranabant 2 mg Taranabant 4 mg 104 LS Means (LOCF) % weight loss -2.6% -6.6% -8.1% Source(s): 1. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia, Després et al, NEJM, Nov 2005. 2. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study, Aronne et al, Nature, Feb 2010.#3333 Rimonabant weight loss was not associated with reduction of lean mass in obese patients Rimonabant vs. placebo Phase 3 RIO study DEXA-scanned subgroup (n=146) Total body mass Total fat mass Fat mass/body mass Lean mass Unchanged Body composition was measured with body DEXA in a subset of patients in RIO Lipids. Decreases in the rimonabant 20 mg group relative to placebo were observed in the total body mass (p<0.001), the total body fat mass (p=0.001) and the fat mass/total body mass ratio (p=0.007). There was no statistically significant difference between the 20 mg and the placebo groups in lean mass loss between groups. Rimonabant NDA (page 21)