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January 2026 Corporate Presentation for JPM
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2 This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended (the “Act”). Forward-looking statements are statements that are not of historical fact and include, without limitation, statements regarding future events, our future financial condition, results of operations, business strategy and plans, prospective products (as well as their potential to achieve a differentiated, competitive, or favorable benefit or profile or trend, including on safety, tolerability, improvement, maintenance, clinical response, dosing, efficacy and/or convenience), planned or expected product approval applications or approvals, anticipated milestones, expected data readouts and enrollments, research and development plans and costs, potential future partnerships, expectations about existing partnerships, timing and likelihood of success, objectives of management for future operations, future results of anticipated product development efforts, and adequacy of existing cash and potential partnership funding to fund operations and capital expenditure requirements, as well as statements regarding industry trends. These statements are based on management’s current expectations of future events only as of the date of this presentation and are inherently subject to a number of risks, uncertainties and assumptions, someof which cannot be predicted or quantified and some of which are beyond our control, including, among other things: the ability of our clinical trials to demonstrate safety and efficacy of our product candidates and other positive results; whether we will need expanded or additional trials in order to obtain regulatory approval for our product candidates; our ability to obtain and maintain regulatory approval of our product candidates; existing regulations and regulatory developments in the U.S., the UK, the PRC, Europe and other jurisdictions; the ability of our current cash and investments position to support planned operations; our plans and ability to obtain, maintain, protect and enforce our intellectual property rights and our proprietary technologies, including extensions of existing patent terms where available; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for preclinical studies and clinical trials; and the degree of market acceptance of our product candidates, if approved, by physicians, patients, healthcare payors and others in the medical community. Words such as “aim,” “anticipate,” “believe,” “could,” “expect,” “feel,” “goal,” “intend,” “may,” “optimistic,” “plan,” “potential,” “promising,” “will,” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. The inclusion of forward-looking statements should not be regarded as a representation by Connect that any of its expectations, projections or plans will be achieved. Actual results may differ materially due to the risks and uncertainties inherent in Connect’s business and other risks described in Connect’s filings with the SEC. Further information regarding these and other risks is included under the heading “Risk Factors” in Connect’s annual and periodic reports filed with the SEC. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on the scientific data presented or these forward-looking statements, which speak only as of the date of this presentation. Except as required by law, Connect undertakes no obligation to publicly update any forward-looking statements, whether because of new information, future events or otherwise. Connect claims the protection of the safe harbor for forward-looking statements contained in the Actfor all forward-looking statements. This presentation discusses product candidates that are under clinical study, and which have not yet been approved for marketing by the U.S. Food and Drug Administration, the National Medical Products Administration or by any other regulatory agency. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Forward-Looking Statements
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3After Transformative 2025 Connect is Well Positioned for Success • Differences in binding to IL-4Rα provide a likely explanation for improved safety and potentially greater efficacy profile of rademikibart • Reduction in eosinophils observed with rademikibart vs increase with dupilumab linked to greater internalization of IL-4 receptors with rademikibart • Lower rate of conjunctivitis observed with rademikibart may be due to lower eosinophils • In vitro HASM cell experiments and hPCLS results from independent labs in the US and UK demonstrate clear differentiation between rademikibart and dupilumab with substantially greater improvement in responsiveness to β-agonist treatment observed with rademikibart in the presence of IL-13 • HASM cell and hPCLS experiments provide a potential basis for much faster clinical improvement in FEV1 and greater improvement in airway function observed with rademikibart compared to published results with dupilumab. • Rademikibart rapidly reverses IL-13-induced hyporesponsiveness to β-agonist treatment providing a strong foundation for using rademikibart in combination with SOC β-agonists to reverse acute exacerbations and for maintenance therapy to provide greater improvement in airway function • Focused clinical development on highest value opportunity by conducting Phase 2 studies in acute asthma and COPD; indications with no competition where rademikibart’s unique pharmacology and rapid onset could provide significant benefit to patients. Phase 3 development to follow in both acute and chronic settings in which rademikibart has demonstrated the potential to provide important benefits • Initiated clinical study with intravenous rademikibart to assess whether IL-13–driven bronchoconstriction can be reversed more rapidly than with subcutaneous dosing COPD = chronic obstructive pulmonary disease; FEV1 – forced expiratory volume in one second; HASM – human airway smooth muscle; hPCLS – human precision cut lung slice; IV = Intravenous; SOC = Standard of care
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4 Rademikibart anti-IL-4Rα mAb Indication Discovery/ Preclinical Phase 1 Phase 2 Pivotal or Phase 3 Status/Anticipated Milestones Planned & On-going Studies Phase 2 studies of rademikibart in acute COPD and asthma exacerbations started in 2Q2025 with topline data expected in mid-2026 These ongoing studies conducted by Simcere at no cost to Connect Simcere filed NDA in China for AD in July 2025 Completed Studies Based on the results from these studies, the U.S. FDA agreed that rademikibart was ready to move into Phase 3 for chronic treatment of asthma and AD Connect Biopharma has global development & commercialization rights outside of greater China for rademikibart Rademikibart Has Demonstrated Efficacy & Safety Across Multiple Indications aSimcere is Connect’s partner in Greater China who holds responsibility for future development, including for additional indic ations mAb = monoclonal antibody; COPD = chronic obstructive pulmonary disease; AD = atopic dermatitis Atopic Dermatitis (AD) – Global Atopic Dermatitis (AD) – Chinaa Chronic Asthma - Global Acute Asthma - Global Acute COPD - Global Chronic Asthma – Chinaa Atopic Dermatitis (AD) – China
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5Asthma and COPD are Associated with Severe Exacerbations that are Difficult to Treat and Often Require Hospitalization Asthma COPD POPULATION Affects >22M adults in US with 30-40% having at least one exacerbation per year Affects >16M adults in US with ~30-50% having at least one exacerbation per year CURRENT SoC Fast-acting inhaled bronchodilators and oral/IV corticosteroids; severe cases may require IV magnesium sulfate, heliox therapy, and noninvasive ventilation; intubation is considered if patients do not respond to initial therapies. Antibiotics are often added if a bacterial infection is suspected with COPD. PROGRESSION ~50% fail to improve on 1st Line treatments ~85% fail to improve on 1st Line treatments ADMISSIONS Persistent hypoxia, severe respiratory distress, poor response to initial treatment, altered mental status and/or a history of exacerbations drive admission decisions ~1 million ED visits or hospitalizations/yr 10-30% of Asthma patients are hospitalized LOS typically ranges from 2 to 3 days ~50% meet treatment failure criteria within 4 weeks of an exacerbation, with 20% requiring a re-visit to the ED ~1.3 million ED visits or hospitalizations/yr ~41% of COPD patients are hospitalized LOS typically ranges from 4 to 7 days ~50% fail treatment within 4 weeks of an exacerbation with >10% of patients requiring re-hospitalization LONG-TERM CARE As symptoms improve, hospital physicians coordinate care with PCPs or pulmonologists; asthma patients are most likely to get treated by a PCP in the outpatient setting COPD patients are typically older and have more comorbidities than asthma patients, and are therefore more likely to be referred to a pulmonologist upon discharge ED = emergency department; LOS = length of stay; PCP = primary care physician; SoC = standard of care
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6 Took Medication at Home 38% Went to Doctor's Office 19% Went to Urgent Care (not ED or hospital) 20% Emergency Department (not hospital) 15% Hospitalized (with or without UC or ED) 5% Treatment Location for Asthma Patients Experiencing an Exacerbation in the U.S.* Did Nothing Stayed Home 3% Treatment Location Projected U.S. Patients* Took Medication at Home 2,466,667** Went to Doctor's Office 1,266,667 Went to Urgent Care (not ED or hospital) 1,333,333 Emergency Department (not hospital) 1,000,000 Hospitalized (with or without UC or ED) 333,333 Did Nothing and Stayed Home 200,000 *Projections based on 1 million ED visits per year Total addressable annual market size for acute asthma exacerbations in U.S.: ~4 million patients *Gardner, et al. Ann Allergy Asthma Immunol 2025:1-7 **Future upside opportunity for use as rescue treatment at home. ED – Emergency Department; UC – Urgent Care
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7 • Studies report ~20% of asthma patients are hospitalized, and upwards of ~20% of patients returned to the ED within 30 days1-9 • Studies suggest the prevalence of COPD exacerbations in the EU closely mirrors that of the US 10-14 • Hospitalization rates for exacerbations among COPD patients range from ~32% to 61% across the EU, with ~24% of patients returning to the ED within 30 days10-14 Asthma and COPD are Global Problems: Projected 2024 European Union Asthma & COPD ED Visits / Hospitalizations Sources: 1. Suruki et al., 2017; 2. Engelkes et al., 2020; 3. Mazurek et al., 2018; 4. OECD 2018; 5. Mayers et al., 2022; 6. Skene et al., 2023; 7. Ayar et al., 2022; 8. Hardtstock et al., 2022; 9. Korn et al., 2022; 10. Kong et al., 2020; 11. Bergs et al., 2022; 12. Liew et al., 2023; 13. Ali et al., 2019; 14. Rochester et al., 2022. ED = emergency department Projected annual ED/hospital visits associated with asthma and COPD exacerbations are similar in the EU and US 809,700 1,349,500 2024 Projected Annual ED Visits in EU 161,940 627,518 2024 Projected Annual Hospitalizations in EU Asthma COPD Asthma COPD Key Statistics and Considerations
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Rademikibart: A Next Generation Anti-interleukin-4 -receptor alpha (IL-4Rα) Antibody
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9 Rademikibart: Next Gen IL-4Rα Blocker Shows Potential For Less Frequent Dosing, Greater Sustained Efficacy Data, and Faster Onset Observed in Asthma Trials AD=atopic dermatitis; COPD=chronic obstructive pulmonary disease; IC50=half -maximal inhibitory concentration; IL=interleukin; JA K=janus kinase; STAT=signal transducers and activators of transcription; TARC=thymus - and activation-regulated chemokine. aBased on head-to-head in vitro comparison with dupilumab. 1. Zhang L, et al. Sci Rep. 2023 ;13(1):12411. Rademikibart is a novel, human monoclonal IgG4 antibody directed against IL-4Rα, a common subunit for IL-4 and IL-13 receptors. Blockade of IL-4 and IL-13 binding to IL-4Rα results in inhibition of both IL-4 and IL-13 signaling. Rademikibart Characteristics • Engaging with distinct epitopes associated with a higher binding affinity to IL-4Rα1 • Highly potent IC50 in: – Reducing JAK-STAT signaling1,a – Cell proliferation1,a – TARC release1,a Clinical Results Demonstrate that Rademikibart has: • Faster onset of action • Greater clinical response (FEV1) • Potential for less frequent dosing with Q4W dosing producing equal benefit versus Q2W dosing in AD • Reduction of eosinophils vs increase with dupilumab (reduces risk of SAEs associated with hypereosinophilia)
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Rademikibart Forms a More Stable Complex with the IL-4Rα subunit 10 Rademikibart and Dupilumab Have Different Binding Orientation – Rotation angle between dupilumab and rademikibart bound to IL-4Rα is 59° – Rademikibart forms a more stable receptor complex • Rademikibart binds IL-4Rα across loops 2 and 3 on the D1 domain and loop 5 on the D2 domain (Fig B - red box) • Dupilumab binds only D1 (D2 binding is absent – (Fig A - red box) Rademikibart engages a larger surface on IL-4Rα compared to dupilumab – The rotation angle enables epitopes of rademikibart to overlap more closely with the conserved binding interface naturally utilized by IL-4 and IL-13 cytokines • Rademikibart closely mimics… – IL-4 (with 74% overlap) and IL-13 (60% overlap) • In contrast, dupilumab mimics… – IL-4 (with 47% overlap) and IL-13 (35% overlap) – Rademikibart’s larger binding interface, potentially enhances blockade of IL-4/IL-13 compared to dupilumab
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11 IL-4 and IL-13 Play Important Roles in Asthma Exacerbations In addition to producing contraction of airway smooth muscle and increasing mucus production, IL-13 also shifts the efficacy curve of β-agonists making them less effective Robinett; Koziol-White et al. Am J Respir Cell Mol Biol . 2013. 50678-683. Reduced Bronchodilation in Precision Cut Lung Slice
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MOA Activities • Explanation for Differential Effects on Eosinophils • HASM Cells Show Differential Effects on pHSP20, a Marker for Airway Relaxation • Human PCLS Experiments from Two Independent Labs Show Consistent β- Agonist Augmentation with Rademikibart Compared to no benefit with Dupilumab
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13Rademikibart Induces Higher Level of IL-4Rα Internalization Compared to Dupilumab • Rademikibart can efficiently remove Type I IL-4 receptors from eosinophil cell surface, confirmed by Flow Cytometry and IncuCyte (shown to the left) • Rademikibart induced stronger apoptosis of EOL-1 than dupilumab • The effects on internalization and apoptosis are likely the underlying mechanisms of clinical observations: • Identical results with Q2W and Q4W dosing in AD • Reduction in EOS compared to greater increase in EOS with dupilumab • Higher EOS observed with dupilumab is associated with SAEs and may be linked to higher rates of conjunctivitis • Dupilumab was associated with 10% conjunctivitis, compared to 2% in the placebo group in Phase 31, while only 3% conjunctivitis was observed with rademikibart in AD2 AD – Atopic Dermatitis; EOS – Eosinophils; SAE – Serious Adverse Event 1. Dupilumab USPI - www.regeneron.com/downloads/dupixent_fpi.pdf. Accessed 1 Jan 2025 2. Silverberg JI et al. J Allergy Clin Immunol 2024;153:1040-9. https://doi.org/10.1016/j.jaci.2023.11.924
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14 Although Both Target IL-4Rα, Rademikibart Lowers Eosinophils While Dupilumab Increases them in Asthma Patients Effect of rademikibart on change from baseline in mean eosinophil counts (patients with eosinophil counts at any point during the treatment period) At baseline, mean (standard deviation) eosinophil counts = 299 cells/µL (229) for placebo and 320 cells/µL (220) for rademikibart 300 mg. -9 -9 12 2 -5 -12 -23 -8 -19 -16 -25 -40 -53 -97 -140 -100 -60 -20 20 60 100 140 0 1 4 8 12 16 20 24 Mean (SE) Change from Baseline Blood eosinophils (cells/μL) Treatment Week Placebo (N=108) Rademikibart 300 mg (N=108) Effect of dupilumab on change from baseline in mean eosinophil counts (placebo groups behave similarly to rademikibart phase 2b study above At baseline, mean±SD eosinophil counts = 370±338 cells/µL (placebo 1.14 ml); 391±419 (placebo 2.00); 349±345 (dupilumab 200 mg) and 351±369 (dupilumab 300 mg). 0 -12 -23 117 84 -43 -32 86 54 -140 -100 -60 -20 20 60 100 140 0 12 24 Mean (SE) Change from Baseline Blood eosinophils (cells/μL) Treatment Week Dupilumab phase 3 (QUEST) Placebo 1.14 ml (N=313) Dupilumab 200 mg q2w (N=631) Placebo 2.00 ml (N=321) Rademikibart Phase 2
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15 Eosinophilia Related Adverse Events Reported to FDA Safety Database for Dupilumab • Patients may have more than one adverse event or serious outcome per individual case report • 765 cases with 913 Eosinophilia AEs • 448 cases with 626 serious outcomes All Eosinophilia Primary Terms with >4 Reports by Quarter All Eosinophilia Serious Outcomes by Quarter Elevated Eosinophils is Not Just a Lab Abnormality
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16Inhaled β2-Agonists are SOC for Asthma and COPD Because They Can Rapidly Reverse Airway Hyperreactivity via the HSP20 Pathway SOC – Standard of care; CCh – Carbochol (muscarinic receptor agonist); ASM – Airway Smooth Muscle; MLC – Myosin Light Chain; HSP – Heat Shock Protein M3 ASM shortening Gaq Ga12/13 b2AR Gas M2 CCh Ca2+ PI3K AKT p-AKT MLC p-MLC MLCK MLCP Gai ADCY PKA cAMP HSP20 pHSP20 ROCK b-agonists p-MLC p-AKT ASM shortening p-HSP20 p-MLC ASM relaxation p-HSP20
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17 Mean of N=3 donors. Increases in β-agonist Induced pHSP20 are Augmented with the Addition of Rademikibart, but Not Dupilumab Veh - Vehicle; Rad - Rademikibart; Dup - Dupilumab; ASM - Airway Smooth Muscle; MLC - Myosin Light Chain; HSP - Heat Shock Protein; CCh – Carbochol (muscarinic receptor agonist); Form – Fornoterol (β-agonist) • In primary human airway smooth muscle (HASM) cells a potent β–agonist, formoterol, increases pHSP20, consistent with its normal effect on airways • Formoterol in the presence of rademikibart increased pHSP20 further; this added benefit was not observed with the addition of dupilumab • Addition of IL-4+IL-13 reduced the expected increase in pHSP20 observed with formoterol (consistent with previously demonstrated shift in efficacy of β–agonists in the presence of IL-4/IL-13) • Rademikibart increased levels of pHSP20 in the presence of IL-4+IL-13, while dupilumab had no beneficial effect on pHSP20 • The enhanced effect of rademikibart compared to dupilumab may explain the faster onset of airway relaxation and greater improvement in FEV1 observed with rademikibart 0 20 40 60 80 100 120 Veh Rad Dup Veh Rad Dup Veh Rad Dup Veh Rad Dup CCh CCh+Form CCh CCh+Form Veh IL-13+IL-4 Fold change in pHSP20 levels relative to Veh + CCh + Veh baseline condition Fold change in pHSP20 levels
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18 VEH – Vehicle N= 1 donor, N090425; Mean ±SD of 2-4 slices per condition. IL-13+IL-4 Reduces the β-Agonist Effect in Human Precision Cut Lung Slice (hPCLS) Model -6 -5 -4 -3 -2 -1 0 1 0 25 50 75 100 125 Log [Form] μM Bronchodilation (%) Veh IL-13+IL-4 0 100 200 300 400 500 AUC AUC Veh IL-13+IL-4 351 272.4
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19 -6 -5 -4 -3 -2 -1 0 1 0 25 50 75 100 125 Log [Form] μM Bronchodilation (%) Veh IL-13+IL-4 IL-13/IL-4+ Test Ab 0 100 200 300 400 500 AUC AUC Veh Veh Test Ab IL-13+IL-4 351 272 314 Consistent with the HASM cell data rademikibart returned bronchodilation toward baseline in the presence of Th2 cytokines IL-4+IL-13 Mediated Hyporesponsiveness to β-Agonists is Substantially Reversed by Rademikibart in Human Lung Slice Model Veh = Vehicle; Test Ab = Rademikibart; Ref Ab = Dupilumab; HASM – Human Airway Smooth Muscle; hPCLS – human Precision Cut Lung Slice N= 1 donor, N090425; Mean ±SEM of 2-4 slices per condition. (rademikibart)
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20 -6 -5 -4 -3 -2 -1 0 1 -20 0 20 40 60 80 100 120 Log [Form] μM Bronchodilation (%) Veh IL-13+IL-4 IL-13/IL-4+ Test Ab IL-13/IL-4+ Ref Ab 0 100 200 300 400 500 AUC AUC Veh Veh Test Ab Ref Ab IL-13+IL-4 351 272 314 258 23%↓ 11%↓ 26%↓ % Reduction in bronchodilation Contrary to rademikibart, and consistent with HASM cell experiments, β2 agonist response is not augmented with dupilumab Veh = Vehicle; Test Ab = Rademikibart; Ref Ab = Dupilumab; HASM – Human Airway Smooth Muscle; hPCLS – human Precision Cut Lung Slice N= 1 donor, N090425; Mean ±SEM of 2-4 slices per condition. Unlike with Rademikibart, IL-4/IL-13 Mediated Hyporesponsiveness to β-Agonists is Not Reversed with Dupilumab (rademikibart) (dupilumab)
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21 PCLS Data from Second Laboratory Confirmed Rademikibart Reverses IL-13 induced Hyporesponsiveness to β-agonist, While Dupilumab had No Effect Treatment with Rademikibart at doses of 10, 30 and 100ng/mL partially reversed IL-13 induced hyporesponsiveness. PCLS – Precision Cut Lung Slices N = 6 patients -2 -1 0 1 2 3 0 20 40 60 80 100 120 Log [Fomoterol, nM] % Bronchodilation Formoterol Formoterol + IL-13 (50ng/mL) Rademikibart (100ng/mL) + Formoterol Rademikibart (100ng/mL) + Formoterol + IL-13 (50ng/mL) Dupilumab (100ng/mL) + Formoterol Dupilumab (100ng/mL) + Formoterol + IL-13 (50ng/mL) Treatment with dupilumab at the highest concentration tested had no effect.
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22 • Consistent with in vitro HASM cell experiments, hPCLS results from two independent labs demonstrate clear differentiation to dupilumab with substantially greater improvement in responsiveness to β-agonist treatment with rademikibart in the presence of IL-13. – note, all patients in Phase 2 chronic asthma study were receiving stable β-agonist therapy. • The ability of rademikibart to rapidly reverse IL-13 induced hyporesponsiveness to β-agonist treatment provides the scientific basis for: – Rapid improvement in FEV1 observed with rademikibart – Greater improvement in airway function observed with rademikibart compared to dupilumab1 • Both the preclinical and clinical data provide a strong foundation for using rademikibart in combination with SOC β-agonists to reverse acute exacerbations and for maintenance therapy where rapid onset, reduced eosinophil related side effects and greater improvement in FEV1 would be well received by healthcare providers and patients Preclinical Experiments Provide Explanation for Differences Observed Between Rademikibart and Dupilumab in Clinical Trials HASM – Human Airway Smooth Muscle; hPCLS – human Precision Cut Lung Slice 1. QUEST – Castro M et al. N Engl J Med 2018;378:2486 -96
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New Preclinical Data Reveals the Potential Mechanism for Results from Phase 2 Chronic Asthma Study that Provided the Basis for Evaluating Rademikibart in the Treatment of Acute Exacerbations
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24 Efficacy and Safety Study ofCBP-201 (rademikibart) in Patients With Moderate to Severe Persistent Asthma (NCT04773678) Robust Data from Completed Global Phase 2b Study in Moderate-to-Severe Asthma Patients Abbreviations: ACQ=Asthma Control Questionnaire; ECP = eosinophilic cationic protein; FENO = fractional exhaled nitric oxide; FEV1=Forced expiratory volume at 1 second; ICS = inhaled corticosteroids; LABA = long -acting ß- agonist; LTRA = leukotriene receptor antagonists; OCS = oral corticosteroids; TARC = thymus and activation -regulated chemokine. https://doi.org/10.1164/rccm.202409-1708OC Key Inclusion Criteria: • Moderate to severe uncontrolled asthma ‒ Existing treatment with medium to high dose ICS in combination with a second controller (e.g., LABA, LTRA, or theophylline) for at least 3 months with a stable dose ≥1month prior to the screening visit. ‒ Pre-bronchodilator FEV1 40 to 85% of predicted normal at Visits 1 and 2, prior to randomization. ‒ Screening or historical blood eosinophil count ≥150 cells/μL (amended to ≥300 cells/μL) o No eosinophil count requirement for patients on maintenance OCS ‒ ACQ score ≥1.5 at Visits 1 and 2, prior to randomization. ‒ At least 1 documented asthma exacerbation in the 12 months prior to the date of informed consent that required use of a systemic corticosteroid Primary Endpoints: • Change from Baseline in FEV1 at Week 12 (in clinic with central overread) Secondary Efficacy Endpoints: • Change from Baseline in FEV1 at other timepoints • Asthma Exacerbations • PROs (ACQ, symptom diary, at-home lung function) • PD markers (FENO, eosinophils, ECP, periostin, TARC) • Rescue medication use Screening/run in 28 Days Rademikibart, 600 mg LD D1 + 300 mg Q2W, n=108 Rademikibart, 600 mg LD D1 + 150 mg Q2W, n=106 Placebo, n=108 24 Weeks/Treatment Follow-up Follow-up Follow-up 8 Weeks 1:1:1 R322 patients Age ≥ 18 years old
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25 -50 50 150 250 350 450 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 LS Mean Change from Baseline in FEV1 (mL) Week Placebo (N=82) Rademikibart 150 mg Q2W (N=80) Rademikibart 300 mg Q2W (N=85) Rapidly Improved and Sustained FEV1 Values Observed with Rademikibart Treatment in Completed Phase 2b Study ***p<0.001, **p<0.01, *p<0.05. Data were analyzed with ANCOVA FEV1 = Forced expiratory volume in one second. Rademikibart treatment associated with rapid, significant changes in FEV1 as early as Week 1 clinic visit, which were sustained for the duration of the 24-week study Home daily lung function data demonstrated 73% of improvement seen on Day 7 was observed by the morning after the first dose, with 113% by Day 2: 73% 113% 0% 20% 40% 60% 80% 100% 120% Day 1 Day 2 Percent of Day 7 Change in FEV1 Change in Pre-bronchodilator FEV1 over time in Patients with an Eosinophil Count ≥150 cells/µL at Baseline 341 mL 276 mL 42 mL ****** ****** ****** ****** ****** ****** *********** ************
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26 Rademikibart exhibited best-in-class potential in lung function improvement Competitive Landscape of Placebo Adjusted Improvement from Baseline In Pre-bronchodilator FEV1 EOS=eosinophils; FDA=Food and Drug Administration; FEV1 = Forced expiratory volume in one second; IL=Interleukin; MoA=mechanism of action; Pbo=Placebo; TSLP=thymic stromal lymphopoi etin; Tx=treatment group. *EOS ≥150 cell/µL †Patients from Phase 2 asthma study with asthma onset age > 40 year and post−bronchodilator FEV 1/forced vital capacity < 0.7 at screening visit 1. QUEST – Castro M et al. N Engl J Med 2018;378:2486-96. 2. STUDY 1&2- Castro M et al. Lancet Respir Med. 2015 May;3(5):355-66. 3. SIROCCO – Bleecker ER et al. Lancet. 2016 Oct 29;388(10056):2115-2127. 4. NAVIGATOR – Menzies-Gow A et al N Engl J Med 2021;384:1800-9. 5. NOTUS – Bhatt et al N Engl J Med 2024;390:2274-2283; 6. CALIMA – FitzGerald JM et al. Lancet 2016 Sept 5; S0140-6736(16)31322-8 Source MoA Product FDA Approv. in last 10 yrs Study N (Pbo/Tx) % patients with EOS ≥300 cells/μL Week First response week Placebo adjusted improvement from baseline in FEV1 Placebo adjusted improvement from baseline in FEV1 (EOS ≥300 cells/μL) Phase 2b IL-4Rα Rademikibart -- Phase 2b Asthma 108/108 46.3% 12 1 270 mL* 328 mL 24 299 mL* 420 mL COPD-Like Patients† 27/19 31.6% 12 1 228 mL 500 mL 24 290 mL 620 mL Biologic Phase 3 trial results IL-4Rα Dupilumab 2018 Asthma: QUEST1 231/633 41.8% 12 2 130 mL 240 mL 2024 COPD: NOTUS5 465/470 60.8 12 2 82 mL 113 mL IL-5Rα Benralizumab 2017 SIROCCO3 Q4W 407/399 68.9% 48 4 -- 106 mL CALIMA Q4W6 440/425 -- 125 mL5667.5% IL-5 Reslizumab 2016 STUDY 12 244/245 -- 52 4 126 mL -- STUDY 22 232/232 -- 90 mL -- TSLP Tezepelumab 2021 NAVIGATOR4 528/531 41.5% 52 2 130 mL 230 mL For Illustrative Purposes Only: Not a head-to-head trial. Differences exist between trial designs, subject characteristics and geographical regions – caution should be exercised when comparing data across trials
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27Dupixent Website
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Results from AD Studies Provide Evidence for Moving to Q4W Dosing
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29Maintenance of IGA 0/1 and EASI-75 Responses Observed at Week 16 Through Week 52 Demonstrates the Sustained Benefit of Q4W Dosing in AD IGA 0/1 and ≥2-Point Reduction (Percentage of Week 16 vIGA 0/1 responders to rademikibart maintaining response) EASI-75 (Percentage of Week 16 EASI-75 responders to rademikibart maintaining response) 76.0 87.2 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 16 20 24 28 32 36 40 44 48 52 vIGA 0/1 Responders (%) Week Rademikibart Q2W (n=34) Rademikibart Q4W (n=40) 91.7 91.9 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 16 20 24 28 32 36 40 44 48 52 EASI-75 Responders (%) Week Rademikibart Q2W (n=76) Rademikibart Q4W (n=79) Q2W = Continued on Q2W dosing from Week 16. Q4W = Switched from Q2W to Q4W dosing at Week 16. Data were analyzed by NRI-MI (non-responder imputation for rescue medications and multiple imputation for remaining missing data). Abbreviations: EASI = Eczema Area and Severity Index. EASI-50 = at least 50% decrease from baseline. Q2W = every 2 weeks. Q4W = every 4 weeks. vIGA 0/1 = validated Investigator Global Assessment of 0 (clear skin) or 1 (almost clear).
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30 Rademikibart Durability - Comparison of Biologic Drugs in AD Maintenance of response from Week 16 to 52 among IGA0/1 or EASI-75 responders 30 • Q2W to Q2W = Continued on Q2W dosing in maintenance phase. Q2W to Q4W = Switched from Q2W to Q4W dosing in maintenance phase. • Dupilumab – Worm M et al., JAMA Dermatol. 2020;156(2):131-143. • Lebrikizumab – Blauvelt A et al., Br J Dermatol 2023; 188:740–748 • Tralokinumab – Wollenberg A et al., Br J Dermatol 2021; 184: 437–449 76.0% 54.0% 71.2% 55.9% 87.2% 43.9% 76.9% 42.4% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Rademikibart (SEASIDE China) Dupilumab (Solo Continue) Lebrikizumab (Advocate 1 & 2) Tralokinumab (ECATRA 1 & 2) Percent of patients maintaining IGA 0/1 – Wk16 to Wk52 Q2W to Q2W Q2W to Q4W 91.7% 71.6% 78.4% 57.3% 91.9% 58.3% 81.7% 50.4% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Rademikibart (SEASIDE China) Dupilumab (Solo Continue) Lebrikizumab (Advocate 1 & 2) Tralokinumab (ECZTRA 1 & 2) Percent of patients maintaining EASI 75 – Wk16 to Wk52 Q2W to Q2W Q2W to Q4W IL-4 IL-13 IL-4 IL-13
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31Summary of Observations with Rademikibart • At End-of-Phase 2 meeting FDA agreed that rademikibart can move into Phase 3 in chronic asthma (Phase 3 is on pause until acute studies below are completed, expected in mid-2026) • At Type C meeting FDA agreed that rademikibart can proceed into parallel Phase 2 studies for acute treatment of exacerbations in asthma and COPD patients • FDA also agreed that there is an unmet need for improved treatments for acute exacerbations • Faster onset of action than reported with other biologics • Greater improvement in FEV1 than observed with other biologics • Reduction of eosinophils vs increase with dupilumab (reduces risk of SAEs associated with elevated eosinophils and may explain lower rate of conjunctivitis observed with rademikibart) • 600 mg loading and chronic dosing was well-tolerated in both AD and asthma studies • Based on data from AD Phase 2b dosing Q4W may provide equal benefit versus Q2W dosing Clinical Experience Regulatory Engagement
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32Replicate Phase 2 Clinical Trials of Rademikibart for Treatment of Acute Exacerbations of Chronic Respiratory Disease Initiated *Interim analysis for sample size re-estimation after 50 subjects complete 4 -week assessment period SOC + Placebo SC Assessment of Treatment Failure Day 0 Single SC dose SOC + Rademikibart 600mg SC Primary endpoint Treatment Failure 4-week follow-up period Week 8 Study Completion 4-week assessment period STAT STUDY DESIGN Each study targets 160 subjects 1:1 R Population Primary Endpoint Secondary Endpoints Key Exploratory Endpoints Seabreeze ASTHMA STAT Adolescents and adults at urgent outpatient visit, ED or hospital Eosinophil count of ≥ 300 cells/µL, ≥1 exacerbation in prior 12 months Treatment Failure (28 days after randomization): includes death (any cause), (re)admission to hospital, urgent visit to outpatient/ED provider for symptom worsening, or necessity to intensify pharmacologic treatment. Rate of exacerbations and Time to new exacerbation; absolute change in post- bronchodilator FEV1; mean change in respiratory symptoms. Safety Time to ready for discharge in hospitalized patients, disease specific-PROs Seabreeze COPD STAT Adults at urgent outpatient visit, ED or hospital
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33 Recent Investigator-Initiated Trial Validated Acute Exacerbation Study Approach and Provides a Roadmap to Improve Our Planned Acute Trials • ~45% of SOC + placebo experienced treatment failure criteria by 4 weeks • Benralizumab reduced treatment failure at 30 days by 50% • Little separation in the first 3-weeks indicating slow onset of effect of benralizumab • Based on published data, rademikibart may be more effective than benralizumab at improving overall lung function (FEV1)
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34 A Phase 1, Multipart Trial to Evaluate a Single Intravenous Dose of Rademikibart at Varying Infusion Rates in Healthy Adult Participants and in Adult Participants With Asthma or Chronic Obstructive Pulmonary Disease • Study Design and Status – Part A - Single-dose, placebo-controlled and double-blind in 3 cohorts of healthy adult participants • Increasing rate of IV infusion of rademikibart (300 mg/30 min to 300 mg/2 min) - no adverse impact on safety/tolerability • 2-min IV infusion selected for rademikibart administration to asthma and COPD participants in Parts B – Part B - Single-dose, placebo-controlled and double-blind in stable asthma and COPD • Change in FEV1 is assessed frequently for first 12 hours • Study is currently enrolling; targeting 10 asthma and 10 COPD patients Phase 1 IV Infusion Study
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35US Market Research: Obtaining Acute Treatment Indications Results in Significantly Greater Penetration into Asthma and COPD Markets *DUPIXENT US Package Insert Revised September 2024, ** Ramakrishnan et al; Lancet Respir Med 2024; Published Online Nov 27, 2024 COPD=chronic obstructive pulmonary disease; WW = worldwide; EU = European Union; MOA = mechanism of action; COPD -like patients had asthma onset age > 40 year and post−bronchodilator FEV 1/forced vital capacity < 0.7 at screening visit • U.S. Clinicians believed the acute indication was a clear differentiator between rademikibart and other biologics approved for patients with eosinophilic phenotype • Once patients were successfully treated with rademikibart acutely, clinicians expected to maintain 75% of these patients on rademikibart chronically Clinician Perspectives Highlight Rademikibart’s Differentiated Profile • Dupixent not labeled for treatment of acute symptoms or acute exacerbations of asthma or COPD* • New high-yield manufacturing process for rademikibart will allow for hospital-friendly pricing in the acute setting Persistent Unmet Need with Opportunity to Penetrate Acute Setting • Acute and chronic asthma and COPD indications resulted in WW peak sales forecast of ~$5B • Upside opportunities exist for rademikibart to drive revenue even higher (e.g., acute use in clinics, steroid sparing opportunity) Significant Commercial Opportunity • Approval of dupilumab for chronic treatment of COPD in US and EU provides evidence for rademikibart’s MOA to treat chronic COPD, further confirmed in COPD-like patients from global asthma study WW002 • ABRA benralizumab study provides higher level of confidence in obtaining a positive outcome in planned Phase 2 acute asthma and COPD studies** Strong Rationale Supporting Rademikibart
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36 Rademikibart Expected Utilization in Asthma and COPD Clinicians considered Rademikibart to be differentiated from other biologics by the dual indication Source: US HCP and Payer Qualitative Primary Research, HCP N=20, Payer N=10, October 2024. NOTE: Percentages represent brand shares and do not account for earlier population cuts (e.g., pharmacologic treatment rate, biologic class share, progression rates, etc.) COPD = chronic obstructive pulmonary disease; LABA = long -acting beta-agonist; LAMA = long-acting muscarinic antagonist Steroids and LABAs/LAMAs work well for these acute patients, so I wouldn’t really use this up front. But for those patients that are refractory to those options and need something stronger, then I’d definitely use this. 1st Line 25% 2nd Line+ 30% Post-Acute Treatment 75% 40% NAÏVE (of those who progress on SOC) Prior Biologic Treatment 25% ASTHMA 45% NAÏVE (of those who progress on SOC) Prior Biologic Treatment 25% 1st Line 45% 2nd Line+ 55% Post-Acute Treatment 75% COPD ACUTECHRONIC If a patient was treated with Product X during their acute exacerbation and it worked, then I’d keep them on it for maintenance. If they responded, why would I switch?
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37Comprehensive Data Package Sufficient to Move Quickly into Phase 3 Once the Planned Phase 2 Studies are Completed CMC = chemistry manufacturing and controls; CMO = contract manufacturing organization; SOC = standard of care; FEV1 = Forced expiratory volume in one second Study Status Outcomes CMC & Improved Manufacturing Process Tech Transfer to US CMO Completed • Initial manufacturing process successfully transferred to US CMO. New high-yield cell-line developed and expected to be transferred starting in 2026 Phase 2b Asthma Completed • Significantly improved lung function at week 1 in patients with moderate-to-severe asthma maintained through 24 weeks • Rapidly improved and sustained FEV1 values observed with rademikibart treatment within 24 hours • Rademikibart produced >60% lower annualized rate of exacerbations compared to placebo Phase 2 Acute Asthma Started (Topline Data expected mid-2026) • Phase 2 study evaluating rademikibart + SOC against SOC + placebo that will enroll patients with asthma having an acute exacerbation • Primary Endpoint: treatment failure through 28 days Phase 2 Acute COPD Started (Topline Data expected mid-2026) • Phase 2 study evaluating rademikibart + SOC against SOC + placebo that will enroll patients with COPD having an acute exacerbation • Primary Endpoint: treatment failure through 28 days
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38Rademikibart Exclusivity Timeline Biologic Exclusivity Expiry 20404 Exclusive global development & commercialization rights (outside of greater China) supportive of substantial growth and value creation Regulatory Exclusivity Patent Exclusivity 20442020 2022 2024 2026 2028 2030 2032 20402034 2036 2038 2042 FDA Approval 20283 PTE ap Expiry 20425 1 U.S. 10,774,141 & U.S. 11,866,491 2 Pending U.S. patent application 3 Estimated date of FDA approval 4 12 years biologic exclusivity 5 14 years and 5 years maximum PTE 6 Pending U.S. provisional patent applications 2046 2048 Family 2 (Formulation)2 Expiry March 2040 Family 3 (MOT)6 Expiry September 2045 Family 1 (COM)1 Expiry June 2037 PTE Cap Expiry 20425
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39Financial Summary Cash, cash equivalents and short-term investments of $54.8 million expected to support planned operations into 2027 Strong Financial Position: Cash and cash equivalents of $110.2 million expected to support planned operations into at least the first half of 2027 SummaryStatementof Operationsand Net Cash Used in Operations (In thousands,expect per share data) Three Months Ended September 30, 2025 Nine Months Ended September 30, 2025 License and collaboration revenue $16 $64 Operating expenses1 ($17,693) ($42,612) Loss from operations1 ($17,677) ($42,548) Otherincome, net $538 $2,347 Income tax expense ($61) ($170) Net loss1 ($17,200) ($40,371) Basic and dilutednet loss per share2 ($0.31) ($0.73) Net cash used in operations ($17,406) ($39,956) CondensedBalanceSheet Data (In thousands) September 30, 2025 Cash, cash equivalents and short-term investments $54,781 Total assets $67,361 Totalshareholders’ equity $55,371 1 Includes $0.9 million and $2.8 million, respectively, of non -cash, share-based compensation expense for the three and nine mon ths ended September 30, 2025. 2 Based on 55.7 million and 55.5 million, respectively, weighted -average ordinary shares outstanding for the three and nine mont hs ended September 30, 2025.
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40Connect is Well Positioned for Success • Differences in binding to IL-4R provide an explanation for improved safety profile of rademikibart vs dupilumab • In vitro HASM cell and hPCLS experiments with rademikibart from two independent labs demonstrate clear differentiation to dupilumab with substantially greater improvement in responsiveness to β-agonist treatment in the presence of IL-13 • Focused clinical development on highest value opportunity by starting Phase 2 studies in acute asthma and COPD with no competition where rademikibart’s unique pharmacology and rapid onset could provide significant benefit to patients; Phase 3 in both acute and chronic settings will follow • Initiated pharmacology study with IV rademikibart to evaluate opportunity to reverse bronchoconstriction produced by IL-13 even more quickly than subcutaneous dosing Rademikibart is Differentiated from Dupilumab in Both Safety and Efficacy Catalysts Complete IV pharmacology study designed to evaluate time to airway improvement Complete preclinical studies providing the basis for the rapid FEV1 improvement observed in Phase 2b Complete Phase 2 acute asthma and COPD studies 1Q2026 Mid-2026 Expect NDA approval in China for AD indication HASM – human airway smooth muscle; hPCLS – human precision cut lung slice; FEV1 – forced expiratory volume in one second; COPD = chronic obstructive pulmonary disease; Strong Financial Position: Cash, cash equivalents, and short-term investments of $54.8 million as of September 30, 2025 expected to support planned operations, including the Phase 2 acute asthma and COPD studies, into 2027
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