Slides
Page 1
FORTE BIOSCIENCES AUGUST 2025
Page 2
2 CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Certain statements contained in this presentation regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities and Exchange Act of 1934, as amended, and the Private Securities Litigation Act of 1995, known as the PSLRA. These include statements regarding management’s intention, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Forte Biosciences, Inc. (“we”, the “Company” or “Forte”) undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe- harbor provisions of the PSLRA. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, risks relating to the business and prospects of the Company; Forte’s plans to develop and potentially commercialize its product candidates, including FB102; the risk that results from preclinical studies and early- clinical trails completed by Forte and third parties may not be predictive of results from later-stage clinical trials; the timing of initiation of Forte’s planned clinical trials, including Forte’s planned Phase 2 celiac study and other future Phase 2 studies; the timing of the availability of data from Forte’s clinical trials, including Forte’s planned Phase 2 celiac study and Phase 1b vitiligo study; the timing of any planned investigational new drug application or new drug application; Forte’s plans to research, develop and commercialize its current and future product candidates; Forte’s projections of the size of the market in certain indications for FB102; the clinical utility, potential benefits and market acceptance of Forte’s product candidates; Forte’s commercialization, marketing and manufacturing capabilities and strategy; developments and projections relating to Forte’s competitors and its industry; the impact of government laws and regulations; Forte’s ability to protect its intellectual property position; Forte’s estimates regarding future revenue, expenses, capital requirements and need for additional financing; and the impact of global events on the Company, the Company’s industry or the economy generally. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs, and these statements represent our views as of the date of this presentation. We may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Information regarding certain risks, uncertainties and assumptions may be found in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” and elsewhere in our Quarterly Report on Form 10-Q for the period ending March 31, 2025, and other filings with the Securities and Exchange Commission. New risk factors emerge from time to time and it is not possible for our management team to predict all risk factors or assess the impact of all factors on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation.
Page 3
3 Mission Advance precision immunotherapies that target key drivers of autoimmune disease, delivering transformative outcomes for patients and long-term value for shareholders Strategy Leverage robust preclinical evidence and proprietary clinical study results to develop disease modifying therapies for multiple indications driven by IL-2/IL-15 axis dependent immune pathways Vision Lead in the development of a next generation biologic that inhibits CD122, addressing significant unmet needs in autoimmune and inflammatory diseases FORTE BIOSCIENCES, INC
Page 4
4 Investment Highlights FORTE BIOSCIENCES, INC CD122 is a subunit of the intermediate affinity IL-2/IL-15 receptor expressed on NK and certain subsets of T cells and is a subunit of the high affinity IL-2 receptor expressed on Tregs FB102 (Forte’s anti-CD122 antibody) is designed to mediate both IL-2 and IL-15 induced proliferation and activation of pathogenic NK and T cells while sparing beneficial Tregs Potential “pipeline in a product” Positive Phase 1b clinical data in celiac disease (CED). Phase 2 trial initiated 2H2025 with topline data expected 2026 Phase 1b trial in vitiligo enrolling with topline results expected 1H2026 Phase 1b trial in alopecia areata (AA) enrolling with topline results expected 2026 Experienced, focused team determined to make a difference
Page 5
5 Leadership Management Paul Wagner, Ph.D. Chief Executive Officer Tony Riley Chief Financial Officer Chris Roenfeldt, PMP Chief Operating Officer Barbara Finck, MD Senior Medical Clinician Scott Brun, MD David Gryska Barbera Finck, MD Steve Doberstein, PhD Steve Kornfeld Shiv Kapoor Rich Vincent Board of Directors FORTE BIOSCIENCES, INC
Page 6
6 Lodolce 2002 Cytokine Growth Factor Rev. PMID 12401478 Ross 2018 Annu Rev Immunol. PMID 29677473 Why Target CD122? CD122 = IL-2Rβ CD132 = IL-2Rγ CD25 = IL-2Rα CD215 = IL-15RαIL-15IL-2FB102 FB102 blocks medium affinity IL-2 binding to CD122/CD132 Kd ~ 1 nM Teff or NK cell IL-2 high affinity binding to CD25 and CD122/CD132 unaffected by FB102 Kd ~ .01 nM Treg cell FB102 blocks low affinity IL- 15 binding to CD122/CD132 Kd ~ 10 nM Teff or NK cell FB102 blocks medium affinity IL-15/IL15Rα binding to CD122/CD132 Kd ~ 1 nM TREG cell FB102 MOA CD122 Biology • Subunit of the intermediate affinity IL- 2/IL-15 receptor expressed on pathogenic T cell subsets and NK cells • Subunit of the high affinity IL-2 receptor critical for regulatory T cells (Tregs) FB102: Forte’s anti-CD122 antibody • Blocks IL-2 and IL-15 driven proliferation and activation of pathogenic T cells and NK cells • Preserves IL-2 signaling in Tregs, maintaining immune regulation and limiting toxicity • Designed for a differentiated therapeutic profile across autoimmune and inflammatory diseases
Page 7
7 FB102 Selectively Shuts Down IL-2/IL-15 Driven T cell and NK Cell Proliferation While Sparing Regulatory T cells RLU= Relative Light Units, a measure of cell viability FB102 IN VITRO DATA FB102 inhibits T cell and NK cell IL-2/IL-15 driven proliferation, while not inhibiting Treg proliferation Treg IL-2+CD3 Treg IL-2+CD3+Isotype Treg IL-2+CD3+FB102 Treg CD3+FB102 Treg CD3 Only 0 50000 100000 150000 RLU (Cell Titer Glo) IL-2 Only IL-2+Isotype IL-2+FB102 IL-15 IL-15+Isotype IL-15+FB102 Cells Only 0 20000 40000 60000 80000 RLU (Cell Titer Glo) IL-2 Only IL-2+Isotype IL-2+FB102 IL-15 IL-15+Isotype IL-15+FB102 Cells Only 0 50000 100000 150000 200000 250000 RLU (Cell Titer Glo) NK cell proliferation assay 100 nM FB102 or isotype control T cell proliferation assay 100 nM FB102 or isotype control T regulatory cells in proliferation assay with CD3 and IL2 +/- FB102
Page 8
8 FB102 Inhibits Anti-inflammatory Cytokines Induced by IL-2 and IL-15 Cell Only Donor006 IL-2 + Isotype Donor006 IL-15 + Isotype Donor006 IL-2 + FB102 Donor006 IL-15 + FB102 Donor006 Cell Only Donor55 IL-2 + Isotype Donor55 IL-15 + Isotype Donor55 IL-2 + FB102 Donor55 IL-15 + FB102 Donor55 Cell Only Donor47 IL-2 + Isotype Donor47 IL-15 + Isotype Donor47 IL-2 + FB102 Donor47 IL-15 + FB102 Donor47 0 50 100 150 % of Isotype Control Cell Only Donor06 IL-2 + Isotype Donor06 IL-15 + Isotype Donor06 IL-2 + FB102 Donor06 IL-15 + FB102 Donor06 Cell Only Donor55 IL-2 + Isotype Donor55 IL-15 + Isotype Donor55 IL-2 + FB102 Donor55 IL-15 + FB102 Donor55 Cell Only Donor47 IL-2 + Isotype Donor47 IL-15 + Isotype Donor47 IL-2 + FB102 Donor47 IL-15 + FB102 Donor47 0 50 100 150 % of Isotype Control Cell Only Donor06 IL-2 + Isotype Donor06 IL-15 + Isotype Donor06 IL-2 + FB102 Donor06 IL-15 + FB102 Donor06 Cell Only Donor55 IL-2 + Isotype Donor55 IL-15 + Isotype Donor55 IL-2 + FB102 Donor55 IL-15 + FB102 Donor55 Cell Only Donor47 IL-2 + Isotype Donor47 IL-15 + Isotype Donor47 IL-2 + FB102 Donor47 IL-15 + FB102 Donor47 0 50 100 150 % of Isotype Control Cell Only Donor06 IL-2 + Isotype Donor06 IL-15 + Isotype Donor06 IL-2 + FB102 Donor06 IL-15 + FB102 Donor06 Cell Only Donor55 IL-2 + Isotype Donor55 IL-15 + Isotype Donor55 IL-2 + FB102 Donor55 IL-15 + FB102 Donor55 Cell Only Donor47 IL-2 + Isotype Donor47 IL-15 + Isotype Donor47 IL-2 + FB102 Donor47 IL-15 + FB102 Donor47 0 50 100 150 % of Isotype Control FB102 IN VITRO DATA IL-6 IFN-γ TNF-α CSF-1
Page 9
9 FB102 Inhibits IL-2/IL-15 CD4+ and CD8+ T Cell Activation in an In Vitro Disease Model CD4+ and CD8+ T cells were treated with IL-2 for 24 hours then with IL-15 for 3 days, simulating disease activity in the presence or absence of FB102 CD8+ T Cells CD4+ T Cells FB102 IN VITRO DATA FB102 inhibits T cell activation FB102 Isotype +IL-2 / No IL-15 Cells Only 0 20 40 60 80 % CD25 Positive (CD8) FB102 Isotype +IL2 / No IL15 Cells Only 0 10 20 30 % CD25 Positive (CD4) P<0.0001 P<0.0001
Page 10
10 FB102 Proposed 12 Month Clinical Development Program Development Phase 1 Phase 2 Phase 3 Upcoming Milestones Celiac Disease Phase 1b Topline data readout June 2025 Phase 2 Initiated 2H25 Phase 2 Topline data expected in 2026 Vitiligo Phase 1b Initiated 1H25 Topline data expected in 1H26 Alopecia Areata Phase 1b initiated in 2H25 Topline data expected in 2026 Type 1 Diabetes Phase 1b in development FB102
Page 11
11 Yokoyama et al PNAS; 2009 (106) 15849-15854 Richmond et al Sci Transl Med. 2018 July 18; 10(450) Xing et al Nat Med 2014 Sep: 20 (9): 1043-9 Yuan et al JCI Insight. 2018;3(2):e96600 FB102 “Pipeline in a Product” Preclinical Validation Disease Species Outcome Reference Celiac disease Mouse Improved IL-15-induced mucosal damage PNAS, 2009 Vitiligo Mouse Enhanced repigmentation Sci Transl Med, 2018 Alopecia areata Mouse Prevented fur loss Nature Med, 2014 Type 1 diabetes Mouse Delayed disease onset JCI Insight, 2018 FORTE BIOSCIENCES, INC
Page 12
12 Celiac Disease: Large, Underserved Market Opportunity Disease Overview • Autoimmune disorder triggered by gluten ingestion • Causes immune-mediated small intestinal damage Epidemiology • Prevalence of ~1% of global population including 2.5M US • Bimodal onset: • Children: 6–8 years median age • Adults: 40–50 years median age • Female: Male = 2.5:1 (likely underdiagnosed in males) Symptoms • GI: Diarrhea, nausea, abdominal pain • Systemic: Fatigue, anemia, headaches • Skin: Dermatitis herpetiformis (itchy rash) Consequences of Untreated CD • Malnutrition, osteoporosis, infertility • Increased risk of lymphoma and other autoimmune diseases Unmet Need • No approved drug therapies • Gluten-free diet (GFD) is the only treatment • 10–30% fail to respond to GFD: • ~50% due to inadvertent gluten exposure (150-400 mg/day) • <10 mg/day considered safe threshold • <5% have true refractory disease CED Normal villi Celiac disease Lining of the small intestine Normal small intestine villi Villi damaged/ flattened by Celiac disease lamina propria lamina propria
Page 13
13 FB102 Blocks Gluten-induced Intestinal Damage by inhibiting IL-2 and IL-15 Proliferating and Activation of T Cells and NK Cells Adapted from Levescot 2022 Gut PMID 35879049 IELs=Intra-epithelial lymphocytes CED FB102 IL-2 • Clear genetic basis for involvement in CeD • Rapid serum peak within ~4h after gluten exposure • Correlates with symptom severity • Drives early activation/expansion of IELs (mainly CD8⁺ T cells) • Promotes Th1-type cytokines (e.g., IFN-γ) IL-15 • Clear genetic basis for involvement in CeD • Overexpressed in gut epithelium and immune cells upon gluten exposure • Tissue levels correlate with degree of mucosal injury • IL-15Rα overexpressed on IELs in CeD patients • Stimulates IEL proliferation, IFN-γ and TNF-α release • Activates pathogenic CD8⁺ T cells • Impairs Treg function and disrupts TGF-β-mediated mucosal protection healthy epithelium IL-2 lamina propria FB102 blocks IL-15 and IL-2 Gluten specific CD4+ T cell APC with gluten peptide IL-15 FB102 villous atrophy gluten CD8+ T cell damaged epithelium
Page 14
14 Gluten Modification Immunotolerance Gut Healing Immunomodulators Single targeting Multi targeting IMGX-003 CNP-101/TAK-101 IMU-856 IL-15 → CALY-002 CD122 (IL-2/IL-15)→FB102 TAK-062 TMP502 IL 15 → Ordesekimab IL15/IL-21→EQ-102 E40 KAN-101 IL 15 → TEV-53408 CD122 (IL-2/IL-15)→ANB033 TAK227/ZED1227 OX40L amlitelimab DONQ52 FB102 blocks both IL-2 and IL-15, Providing Potential Advantages Over Other Investigational Drugs in Celiac Disease CED
Page 15
15 1. Taavela J, PLoS One. PMID: 24146832; PMCID: PMC3795762. 2. Rostami K Gut. 2017 Dec; PMID: 28893865; PMCID: PMC5749338. 3. Adelman DC, Am J Gastroenterol. 2018 Mar;2018 Feb 20. PMID: 29460921 4. Syage J, et al. Clin Gastroenterolm Hepatol: 2024: 22: 1238-1244 Key Morphologic and Inflammatory Measurements in Celiac Disease CED In Celiac disease, IELs infiltrate the villus epithelium upon gluten exposure, driving villus atrophy IELs are measured as the density of CD3+ T cells per 100 enterocytes CeD patients typically have 20-30 IELs/100 enterocytes at baseline, which increases by >30%+ with gluten challenge1,2 Villus height to crypt depth (Vh:Cd) ratio Measures morphological damage due to IEL infiltration after gluten challenge in celiac disease Vh:Cd ratio in patients with CeD is ~2.0-3.0 on Gluten Free Diet3 Proposed VCIEL composite scale comprising individual subject values for Vh:Cd and IEL equally weighted Appears to offer better accuracy and statistical precision Potentially a broader measure of mucosal health 4
Page 16
16 FB102 Phase 1b Study in Celiac Disease Screening Includes BL Endoscopy Randomization 3:1 Ratio FB102:PBO Safety Follow-up Through day 122 Treatment Day 1 8 15 16 22 31 32 1st dose 2nd dose 3rd dose 4th Dose Endoscopy • 32 subjects, 9 sites • Progressive Gluten Challenge (GC) with 2 g on D16, 4 g on D17 and 8g on Ds 18 -31 • 3 of 4 weekly doses prior to 16-day gluten challenge followed by 4th dose on D22 • Safety and tolerability primary endpoint with endoscopy/biopsy at baseline and at end of gluten challenge (D32) • Central review of histology endpoints VCIEL, IELs and Vh:Cd change from baseline • Gluten challenge symptoms collected in patient diaries/AE reporting • All subjects completed day 32 biopsy VCIEL= Villus Height to Crypt Depth with Intraepithelial Lymphocytes, IELs = Intraepithelial Lymphocytes, VH:Cd = Villus Height to Crypt Depth ratio Gluten Challenge CED P1B STUDY DESIGN Follow-up FB102 10 mg/kg Placebo R Weekly dosing
Page 17
17 Baseline Demographics CED P1B STUDY DATA Parameter Placebo N=8 FB102 N=24 Overall N=32 Age (Years) Mean 38.3 40.8 40.1 Sex [n (%)] Female 5 (62.5%) 19 (79.2%) 24 (75.0%) Male 3 (37.5%) 5 (20.8%) 8 (25.0%) Ethnicity [n (%)] Hispanic or Latino 0 0 0 Not Hispanic or Latino 7 (87.5%) 23 (95.8%) 30 (93.8%) Not Reported 1 (12.5%) 1 (4.2%) 2 (6.3%) Unknown 0 0 0 Body Mass Index (kg/m2) at Screening Mean 25.61 24.8 25 Baseline Villus height to Crypt depth ratio Mean 2.756 2.818 Standard error of mean 0.1398 0.1099 Baseline CD3 positive IELs per 100 enterocyte Mean 25.6 23.5 Standard error of mean 3.83 1.68
Page 18
18 FB102 Demonstrates Statistically Significant Composite Histology (VCIEL) Benefit Compared to Placebo CED P1B STUDY DATA Placebo (n=8) FB102 (n=24) -3 -2 -1 0 1 Mean VCIEL Change (D32 VS Baseline) Day 32 vs baseline VCIEL composite score - 1.849 for PBO compared to 0.079 for FB102 treated subjects p=0.0099 Change in VCIEL Composite Histology Score
Page 19
19 Day 32 vs baseline mean IEL density increase of 13.3 for PBO compared to a decrease of 1.5 for FB102 treated subjects FB102 Demonstrates Statistically Significant Change in IEL Density Compared to Placebo CED P1B STUDY DATA p=0.0035 Change in IEL Density (Per 100 Enterocytes) Placebo (n=8) FB102 (n=24) -5 0 5 10 15 20 Mean Density Change (D32 vs Baseline)
Page 20
20 Increase of 8.6 for PBO compared to 2.5 for FB102 treated subjects Ki67 is a marker of T cell proliferation (inflammation) Increase of 3.9 for PBO compared to decrease of 1.5 for FB102 treated subjects Gluten interacts with receptors on TCR γδ IELs driving cytotoxic T cell expression and epithelial damage FB102 Demonstrates Statistically Significant Improvement in IEL Markers of Inflammation Compared to Placebo Based on analysis of covariance of changes from baseline to day 32, with baseline value as covariate, per 100 enterocytes CED P1B STUDY DATA Placebo (n=8) FB102 (n=24) -4 -2 0 2 4 6 Mean Density Change (D32 vs Baseline) Placebo (n=8) FB102 (n=24) 0 5 10 15 Mean Density Change (D32 vs Baseline) TCR γδ Positive IELs Ki67 Positive IELs p=0.0007 p=0.0006
Page 21
21 Vh:Cd Ratio Improvement Observed for FB102 vs Placebo CED P1B STUDY DATA Placebo (n=8) FB102 (n=24) -0.4 -0.3 -0.2 -0.1 0.0 Mean Change in Vh:Cd ratio (D32 v Baseline) Day 32 vs baseline Vh:Cd ratio improvement of 73% for FB102 (-0.046) compared to PBO (-0.173) Change in Vh:Cd Ratio
Page 22
22 FB102 Demonstrated Gluten Challenge Symptom Event Benefit Compared to Placebo Symptoms monitored: Nausea, diarrhea, vomiting, abdominal pain, abdominal bloating (patient diaries and AE collection) Outcome: FB102 reduced cumulative symptom events per subject by end of challenge by 42% • Placebo 6.9 events/subject • FB102: 4.0 events/subject Interpretation: Symptom separation between FB102 and placebo emerged early and widened through the 16-day Gluten Challenge Period CED P1B STUDY DATA Cumulative Symptom per Subject during the Gluten Challenge 0 1 2 3 4 5 6 7 8 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Cumulative Symptoms per Subject Study Day Placebo, n=8 FB102 10 mg/kg i.v, n=24
Page 23
23 1 8 15 16 22 32 70 1 8 15 16 22 32 70 0 50 100 150 Tregs (% of CD4 cells) day No Inhibition of Tregs with FB102 Treatment CED P1B STUDY DATA No statistically significant difference in Tregs with FB102 vs PBO at any timepoint 1st dose 2nd dose 3rd dose 4th dose Gluten Challenge Placebo (N=8) FB102 (N=24) 1st dose 2nd dose 3rd dose 4th dose Gluten Challenge Preserves Treg driven immune tolerance
Page 24
24 FB102 Generally Safe and Well Tolerated Subjects may be counted in more than one grade category CED P1B STUDY DATA Placebo N=8 FB102 N=24 Overall N=32 n % n % n % All Any Grade 8 100.0% 23 95.8% 31 96.9% Grade 1 (Mild) 8 100.0% 22 91.7% 30 93.8% Grade 2 (Moderate) 6 75.0% 9 37.5% 15 46.9% Grade 3 (Severe) 1 12.5% 0 0.0% 1 3.1% Subjects Experiencing ≥1 Treatment Emergent Adverse Event by Grade
Page 25
25 Subjects Experiencing ≥1 Treatment Emergent Adverse Event by Organ Class FB102 Generally Safe and Well Tolerated Subjects may be counted in more than one grade category CED P1B STUDY DATA System Organ Class Summary Placebo N=8 FB102 N=24 Overall N=32 n % n % n % Participants with at least one TEAE 8 100.0% 23 95.8% 31 96.9% Gastrointestinal disorders 7 87.5% 21 87.5% 28 87.5% Nervous system disorders 5 62.5% 10 41.7% 15 46.9% General disorders and administration site conditions 2 25.0% 5 20.8% 7 21.9% Infections and infestations 3 37.5% 4 16.7% 7 21.9% Metabolism and nutrition disorders 2 25.0% 2 8.3% 4 12.5% Musculoskeletal and connective tissue disorders 1 12.5% 2 8.3% 3 9.4% Blood and lymphatic system disorders 2 25.0% 0 0.0% 2 6.3% Psychiatric disorders 1 12.5% 1 4.2% 2 6.3% Respiratory, thoracic and mediastinal disorders 2 25.0% 0 0.0% 2 6.3% Ear and labyrinth disorders 0 0.0% 1 4.2% 1 3.1% Vascular disorders 0 0.0% 1 4.2% 1 3.1%
Page 26
26 Celiac Disease Phase 2 Design FB102-301 Topline data readout expected in 2026 • 14 sites AUS/NZ initially • Initiation in 2H25 • US IND expected late 2025/early 2026 • Men and women aged 18 to 70 years • Has documented diagnosis of CeD • Body mass index (BMI) 16.0 - 40.0 kg/m2, inclusive • Self-reported to be on a GFD for at least 12 months prior to Screening • Primary Endpoint: VCIEL change from baseline at D78 Study Day Amount of Gluten (grams per day) Day 1 to 22 0 Day 23 to 36 8 Day 37 to 77 3 Day 78 Endoscopy Screening (Up to 45 days) Including Endoscopy Randomization 2:2:1 Ratio Induction/Maintenance (N=100) Safety Follow-up Day 79 to Day 183 Follow-up Gluten Challenge day 23 to day 77 Induction Period Maintenance Period CED P2 STUDY DESIGN FB102 3 mg/kg Placebo FB102 10 mg/kg FB102 5 mg/kgFB102 10 mg/kgR Weekly dosing Dosing every other week 1 8 15 22 29Day 43 57 71 77 Endoscopy 127 18378
Page 27
27 Vitiligo: Autoimmune Skin Disease with High Unmet Need https://my.clevelandclinic.org/health/diseases/12419-vitiligo MACE: Major adverse cardiovascular events including stroke, heart attack, and cardiovascular death Disease Overview • Autoimmune condition in which pathogenic T cells destroy melanocytes resulting in depigmented (white) skin patches • Non-Segmental vitiligo: 85-90% of cases, bilateral • Segmental vitiligo: 10-15% of cases, unilateral Epidemiology • Estimated global prevalence: 0.5-2% globally, including US 2M • Age of onset: 10-30 years old, 50% before age 20 • Female:Male equal Symptoms and Consequences • Not just cosmetic • Associated photosensitivity, ocular abnormalities, emotional burden and increased risk of other autoimmune • Psychosocial stress and reduced quality of life Current Treatment • Limited and variably effective (topical steroids, phototherapy) • Long term safety concerns, especially JAK inhibitors, include black box warning for serious infections, death, cancer, MACE and blood clots Unmet Need • Disease modifying therapy that provides safe, accessible and durable response Vitiligo Skin Pigmentation Melanocyte Melanin Vitiligo
Page 28
28 IL-15 and IL-2 Drive Vitiligo via Activation of Pathogenic T Cells Adapted from Tokura, et al. Front Immunol. 2021 PMID: 33633737 1. Phan, et al. J Clin Oncol. 2001 PMID: 11481353 Activated pathogenic T cells kill melanocytes leading to loss of melanin and skin pigment FB102 blocks activation of pathogenic T cells, restoring melanocyte health and skin pigmentation Vitiligo has been observed in responders to high-dose IL-2 in melanoma, with multiple studies linking this to robust immune activation, reinforcing IL-2’s role in driving vitiligo1 Vitiligo Melanin Healthy melanocytes Dead melanocytes No melanin IL-15 T cell IL-2 IL-15 IL-2 IL-15 IL-2 IL-15 IL-2
Page 29
29 Anti-CD122 Antibody Reverses Disease in a Vitiligo Mouse Model i.p. = intraperitoneally Richmond, et al. Sci Transl Med. 2018 PMID 30021889 Note: Vitiligo induced in C57BL/6J (B6) mice via adoptive transfer of anti melanocyte antigen T cells with anti-mouse CD122 (surrogate molecule) antibody used Melanocyte reactive T cells eliminate tail pigmentation Vitiligo Baseline Week 8 Control (vehicle) CD122 Repigmentation study Anti-CD122 treatment restores pigmentation
Page 30
30 Short Course Anti-CD122 Demonstrates Durable Response i.d. = intradermal Richmond, et al. Sci Transl Med. 2018 PMID 30021889 Note: Vitiligo induced in C57BL/6J (B6) mice via adoptive transfer of anti melanocyte antigen T cells with anti-mouse CD122 (surrogate molecule) antibody used Comparable effect with systemic or local treatment Lower injection burden may improve patient adherence Vitiligo P=0.0017 P=0.0002 P=0.0105 P=0.0001 P=0.0143 3x weekly i.p. x 2 weeks 3x weekly i.d. x 4 weeks Control Anti-CD-122 Week 8Baseline Week 12Baseline Control Anti-CD-122 Systemic Local
Page 31
31 FB102: Dual IL-2/IL-15 Cytokine Inhibition A Novel MOA to Restore Immune Privilege in Vitiligo JAK based Carries Black Box Warning Reducing Autoimmune Response Single Cytokine Multi Cytokine JAK 3/TEC → ritlecitinib (LITFULO) IL-17A → aixekizumab (Taltz), CD122 (IL-2/IL-15) → FB102 JAK 1/3 → Tofacitinib (ZELJANZ) IL-17A → secukinumab (COSENTYX) IL-12/23 → ustekinumab (Stelara) JAK1/2/3 TYK2 → Upadacitinib IFNα → anifrolumab CD122 (IL-2/IL-15)→ INCA34460 JAK1 → povorcitinib (Incyte INCB54707) TNF-α → adalimumab (Humira), etanercept TNF-α, infliximab (Remicade), Vitiligo
Page 32
32 Vitiligo Phase 1b Design FB102-401 F-VASI: Facial Vitiligo Area Scoring Index Screening Up to 28 days Randomization 3:1 Ratio FB102:PBO (N=up to 32) Treatment (16 weeks) FB102 3 mg/kg Placebo R Day 1 8 15 22 43 64 85 113 169 1st dose 2nd dose 3rd dose 4th Dose 5th Dose 6th Dose 7th Dose • Currently enrolling • 10-12 sites in AUS/NZ • Males and females aged 18 to 75 years • Clinical diagnosis of non-segmental vitiligo • Primary endpoints: F-VASI at 16 and 24 weeks Topline data readout expected in 1H 2026 Vitiligo P1B Study Design Weekly dosing Dosing every 3 weeks FB102 10 mg/kg Safety and Efficacy Day 113 (week 16) Day 169 (week 24)
Page 33
33 www.naaf.org/ www.niams.nih.gov/health-topics/alopecia-areata Alopecia Areata (AA): Auto Immune Disease with Large Unmet Need Disease Overview • Common autoimmune disease that occurs when pathogenic T cells attack hair follicles causing hair loss • Sudden onset, affecting scalp, face and body Epidemiology • Prevalence: 2% of global population at some point in lifetime, including ~ US 6.5M, with 700K currently experiencing AA • Age of onset: <40 years • Females:Males equal Symptoms and Consequences • Unpredictable course, often relapsing and remitting • Emotional and psychosocial impact incl depression, anxiety and social isolation • Associated with other auto immune conditions Current Treatment • No cure, current treatments suppress immune response (topical/intralesional steroids or off label immunosuppressants e.g. methotrexate) or stimulate hair growth • JAK inhibitors FDA approved systemic therapy with durable efficacy but black box warnings and long-term safety concerns including serious infections, death, cancer, MACE, and blood clots Unmet Need • Safe effective and durable treatment across all severities Hair Follicle Lymphocytes attacking normally immune hair follicles Alopecia Areata Normal Hair Follicle AA
Page 34
34 • Healthy anagen (growth cycle) hair bulb is an immune privileged site – no MHC Class 1 expression and protected from immune attack1 • Poorly understood environmental triggers cause immune privilege collapse • Cytotoxic T cells infiltrate and attack follicular keratinocytes at the hair bulb base stopping hair growth • IL-2 and IL-15 cytokines drive autoimmune response and hair loss • Dense lymphocyte infiltration of 60– 80% CD4+ and 20–40% CD8+ T cells2 • IL-2 is elevated in AA patients3; IL-15 is overexpressed in AA hair follicles4 MHC: Major Histocompatibility Complex (code for cell surface proteins responsible for presenting antigens to T cells 1Bertolini Exp Dermatol. 2020 PMID: 32682334 2Ito Clin Dev Immunol. 2013 PMID: 24151515 3Ito Exp Dermatol. 2014 PMID: 25040075 4Xing Nat Med. 2014 PMID: 25129481, Supplementary material Alopecia Areta Driven by T Lymphocytes Invading Hair Follicles Healthy follicle - Immune privileged space - No MHC expression Alopecia follicle - Loss of immune privilege - Invasion of T and NK cells - Cytokines (e.g. IL-15, IL-2) - MHC expression - Hair loss Immune privileged AA CD122+ CD8+ T cells in follicles from AA patients4 IL-15/IL-15 RA Co-expression of IL-15 and IL-15 RA in alopecia areata (AA) but not normal control (NC) 4
Page 35
35 FB102 Anti-CD122 Antibody Potentially Restores Immune Privilege in AA IL-2 IL-15 IL-15 ? AA Hair loss due to IL-2/IL-15 driven immune attack on hair follicle FB 102 blocks CD122 and prevents T and NK cells from attacking the hair follicle Immune privileged healthy cell
Page 36
36 Anti-CD122 and Anti-IL-2 Antibodies Prevent Hair Loss • Spontaneous alopecia with ~20% penetrance with age • Grafting alopecic skin yields ~100% disease onset in successfully grafted recipient mice within 21-35 days1 • Pathology resembles human disease • Alopecia prevented with: • Anti-CD122 antibody, anti-IL-15Rβ, dosed 200 µg twice per week for 12 weeks • 2 combined anti-IL-2 antibodies, dosed 250 µg each three times per week2 Clone TM-β1= anti-IL-15Rβ used 1McElwee J Invest Dermatol. 1998 PMID: 9804341 2Xing Nat Med. 2014 PMI 25129481 P < 0.001 P < 0.05 C3H/HeJ Alopecia Areata Mouse Model AA PRECLINICAL DATA
Page 37
37 FB102: CD122 Blockade Offers Superior Multi Target Coverage vs Single Target Agents Under Investigation in Alopecia Areata JAK based Carries Black Box Warning Reducing Autoimmune Response Single Target Multi Target JAK 3/TEC → ritlecitinib (LITFULO) S1P → etrasimod (VELSIPITY) CD122 (IL-2/IL-15) → FB102 JAK 1/2 → baricitinib (Olumiant) OX40 → IMG-007 IL-4/13 → dupilumab (Dupixent) JAK 1/2 → deuruxolitinib (LEQSELVI) IL-2 → Rezpegaldesleukin IL7/TSLP → bempikibart JAK1/2/3 TYK2 → Upadacitinib IL-2/9/15 → EQ101 AA
Page 38
38 Alopecia Areata Phase 1b Design FB102-701 SALT: Severity of Alopecia Tool Screening Up to 28 days Randomization 3:1 Ratio FB102:PBO N=up to 32) Treatment (16 weeks) Follow-up FB102 5 mg/kg Placebo R Day 1 8 15 22 36 50 64 78 92 113 169 253 1st dose 2nd dose3rd dose 4th Dose 5th Dose 6th Dose 7th Dose 8th Dose 9th Dose • 10-12 sites in AUS/NZ • Primary endpoint: SALT at 16 and 24 weeks • Males aged ≥18 to 60 and females aged ≥18 to 75 years • Clinical diagnosis of severe to very severe AA with no other etiology for hair loss Topline data readout expected in 2026 Weekly dosing Dosing every 2 weeks FB102 10 mg/kg Follow-up Visit Day 253 (week 36) AA P1b STUDY DESIGN Safety and Efficacy Day 113 (week 16) Day 169 (week 24)
Page 39
39 https://beyondtype1.org/type-1-diabetes-statistics/ Type 1 Diabetes, an Autoimmune Disease that Targets Insulin-producing Pancreatic Beta Cells Disease Overview • Autoimmune disease driven by genetic susceptibility and environmental triggers • Chronic disease characterized by autoreactive T cells that destroy insulin producing pancreatic beta cells Epidemiology • Prevalence 7.4M globally, includes ~2M US • 64,000 people diagnosed with Type 1 diabetes annually1 Consequences • Eye, renal and cardiovascular disease Current Treatments 2 therapies approved to delay onset of TID Lantidra • Islet cell transplant from deceased donors • Variable response with some pts achieving insulin independence • Requires lifelong immunosuppression Tzield® • Monoclonal AB vs CD3 T cells • Delays progression by 2 years • Safety issues including immunosuppression and infection Unmet Need • Affordable, disease modifying therapy that cures or delays onset of disease Immune cells destroy beta cells in pancreas Pancreas Produces Insulin glucose Insulin moves glucose to cells Pancreas cannot produce Insulin Increased blood glucose Normal Type 1 diabetes T1D Eye, renal and CV disease
Page 40
40 The 2 approved products both carry significant challenges in their safety profile. • LANTIDRA • cell therapy that requires hospitalization for administration and cost $300K/cycle • 90% of subjects experience serious AEs • TZIELD® • IV infusion once daily for 14 consecutive days and Cost $190K/cycle • Severe AEs including lymphopenia Most drug candidates in development for Type 1 Diabetes work using indirect pathways FB102 offer the advantage of directly impacting the T cells that cause the damage that leads to Type 1 Diabetes www.tzieldhcp.com/safety-data/ LANTIDRA PI Type 1 Diabetes Clinical Competitive Space FB102 offers a unique MOA in potentially deactivating the autoreactive immune cells that lead to the destruction of the beta cells From LANTIDRA PI From TZIELD® PI T1D
Page 41
41 FB102 Blocks IL-2/IL-15 Signaling to Prevent Beta Cell Destruction Herold 2024 Nat Rev Immunol. PMID 38308004 Environmental stress causes beta cells to upregulate MHC and to express IL-15 and IL-15RA CD8+ T cells with receptors recognizing beta cell specific peptides are enriched in pancreatic islets of T1D patients FB102 blocks IL-2/IL-15 binding IL-15/IL15RA CD122/CD132 FB102 CD8+ T cell β cell with MHC + peptide IL-2 T1D
Page 42
42 *P < 0.05 NOD: Non-obese Diabetic ChMBC7 and TM-β1 are Anti-CD122 antibodies Yuan 2018 JCI Insight PMID 29367461 Anti-CD122 Antibody Delays Diabetes Progression T1D
Page 43
43 PPI 15–24 refers to amino acids 15 to 24 of the preproinsulin protein sequence, which act as β-cell autoantigens recognized by T cells in T1D. FB102 Inhibits Pathogenic T Cell Proliferation PPI 15-24 Reactive T cells FB102 inhibits beta cell induced proliferation of T1D T cells Autoreactive T cells obtained from Type 1 Diabetes patients co-cultured with IL-15 with and without FB102 T1D FB102 IN VITRO DATA
Page 44
44 FB102 Inhibits T1D T Cell Activation -13 -12 -11 -10 -9 -8 0 10 20 30 Log of IL15 Concentration (M) % CD25 Positive T Cells D1327 FB102 CD25D1327 Isotype CD25 -13 -12 -11 -10 -9 -8 0 10 20 30 40 50 Log of IL15 Concentration (M) % CD69 Positive T Cells D1327 FB102 CD69D1327 Isotype CD69 Donor 1327 (T1D) CD25 (T Cell Activation) Donor 1417 (T1D) CD69 (T Cell Activation) T1D FB102 IN VITRO DATA Activation of T cells is inhibited by FB102 but not by the (negative) control antibody Activated TID T cells are measured by an increase in % CD69 and CD25 T cells
Page 45
45 FACS (Fluorecence-Activated Cell Sorting) used to analyze beta cell survival FB102 Inhibits T1D T Cell Driven Killing of Beta Cells FB102 inhibits T1D donor T cell killing of beta cells T1D FB102 IN VITRO DATA D1327 Isotype GLUT2 D1327 FB102 GLUT2 0 200 400 600 800 Beta Cell Count FACS Analysis of Beta Cells Donor 1327 (T1D) p=0.0001 Beta cell killing by T1D reactive T cells is inhibited by FB102 vs isotype control
Page 46
46 Microscopy Shows FB102 Induced Inhibition of T Cell Attack on Beta Cells D1417 + Beta Cells with Isotype Control T cells are clustering to Beta Cells D1417 + Beta Cells with FB102 T cells are NOT clustering to Beta Cells T1D FB102 IN VITRO DATA
Page 47
47 FB102 Proposed 12 Month Clinical Development Program Development Phase 1 Phase 2 Phase 3 Upcoming Milestones Celiac Disease Phase 1b Topline data readout June 2025 Phase 2 Initiated 2H25 Phase 2 Topline data expected in 2026 Vitiligo Phase 1b Initiated 1H25 Topline data expected in 1H26 Alopecia Areata Phase 1b initiated in 2H25 Topline data expected in 2026 Type 1 Diabetes Phase 1b in development FB102
Page 48
48 Investment Highlights FORTE BIOSCIENCES, INC CD122 is a subunit of the intermediate affinity IL-2/IL-15 receptor expressed on NK and certain subsets of T cells and is a subunit of the high affinity IL-2 receptor expressed on Tregs FB102 (Forte’s anti-CD122 antibody) is designed to mediate both IL-2 and IL-15 induced proliferation and activation of pathogenic NK and T cells while sparing beneficial Tregs Potential “pipeline in a product” Positive Phase 1b clinical data in celiac disease (CED) with Phase 2 trial initiated 2H2025 with topline data expected 2026 Phase 1b trial in vitiligo enrolling with topline results expected 1H2026 Phase 1b trial in alopecia areata (AA) enrolling with topline results expected 2026 Experienced, focused team determined to make a difference