Full Press Release Details
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; the timing of the availability of data from Forte's clinical trials; 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 September 30, 2024 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. 2
CLINICAL STAGE FB102 CD122 is a subunit of the intermediate
affinity IL-2/IL-15 receptor expressed on NK cells and 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 the IL-2 and the IL-15 induced
proliferation and activation of pathogenic NK cells and T cells without effecting the IL-2 induced proliferation of the immune modulating Tregs. Significant amount of proof-of-concept preclinical data across numerous indications supports
"Pipeline-in-a-Product" potential for FB102. 4 and 13-week NHP tox studies completed Healthy volunteer SAD/MAD completed Initiated celiac disease patient study with readout expected in 2Q25 3
FORTE BIOSCIENCES OVERVIEW Strong Board of Directors comprised
of leaders in industry including: Scott Brun, MD - Former head of Abbvie product development David Gryska - Former CFO of Incyte and Celgene Barbera Finck, MD - Led Enbrel development at Immunex and Humira
biosimilar development at Coherus Steve Doberstein, PhD - Former Chief Scientific Officer of Nektar Steve Kornfeld - Co-Managing Partner of Castle Peak Partners and former Healthcare Sector Team Leader and PM at Franklin
Templeton Shiv Kapoor - Co-Founder of Stonegate Healthcare and biotech veteran with over 25 years of experience in investments and therapeutics development Rich Vincent - Multiple biotech CFO roles, Deloitte & Touche,
EXPERIENCED MANAGEMENT Forte's management has extensive experience
in manufacturing, quality, regulatory and clinical development Paul Wagner, Ph.D., CFA - CEO Tony Riley - Chief Financial Officer Chris Roenfeldt, PMP - Chief Operating Officer Steven Ruhl - Chief Technical Officer Barbara
Finck, MD - Senior Medical Clinician 5 5
FB102 CD122 ANTAGONIST MECHANISM 6
CLINICAL STAGE FB102 OVERVIEW CD122 is a subunit of the
intermediate affinity IL- 2/IL-15 receptor expressed on NK cells, certain T cell subtypes 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 the IL-2
and the IL-15 induced proliferation and activation of pathogenic NK cells, certain T cell subtypes without effecting the IL-2 biology of beneficial Tregs. CONFIDENTIAL Lodolce 2002 Cytokine Growth Factor Rev. PMID 12401478 Ross 2018 Annu Rev
Immunol. PMID 29677473 7
FB102 IN VITRO DATA 8
FB102 INHIBITS CD4+ AND CD8+ T CELL PROLIFERATION Fold Reduction
Isotype/FB102 FB102 inhibits IL-2/IL- IL-2 4.1 15 signaling back to IL-15 4.6 baseline levels of the unstimulated cell only 9 IL2+Isotype IL2 Only IL2+FB102 IL15+Isotype IL15 IL15+FB102 Cells Only RLU (Cell Titer Glo)
FB102 INHIBITS NK CELL PROLIFERATION BACK TO BASELINE LEVELS Fold
Reduction Isotype/FB102 IL-2 5.6 FB102 inhibits IL-2/IL- IL-15 7.8 15 signaling back to baseline levels of the unstimulated cell only 10 IL2+Isotype IL2 Only IL2+FB102 IL15+Isotype IL15 IL15+FB102 Cells Only RLU (Cell Titer Glo)
FB102 DOES NOT INHIBIT REGULATORY T CELL PROLIFERATION FB102 does not
inhibit high affinity IL-2 signaling of Tregs In the absence of IL-2 stimulation, FB102 does not impact cell viability and is comparable to unstimulated cell 11 Treg IL2+CD3+Isotype Treg IL2+CD3 T e IL2 D3+F r g +C B102 Treg CD3+FB1 2 0 Treg CD3
FB102 INHIBITS IL-2 AND IL-15 INDUCTION OF IL-6, TNF-ALPHA, IFN- GAMMA,
AND CSF-1 WITH 3 DIFFERENT T CELL DONORS 12 Cell Only Donor06 r IL15 + FB102 Dono 06 IL2 + FB102 Donor06 IL2 + Isotype Donor06 IL15 + Isotype Donor06 Cell Only Donor55 IL15 + FB102 Donor55 IL2 + FB102 Donor55 IL2 + Isotype Donor55 IL15 + Isotype
Donor55 Cell Only Donor47 Cell Only Donor06 IL15 + FB102 Donor47 IL15 + FB102 Donor06 IL2 + FB102 Donor47 IL2 + FB102 Donor06 IL2 + Isotype Donor47 IL2 + Isotype Donor06 IL15 + Isotype Donor47 IL15 + Isotype Donor06 Cell Only Donor55 IL15 + FB102
Donor55 IL2 + FB102 Donor55 IL2 + Isotype Donor55 IL15 + so pe Don r 5 I ty o 5 Cell Only Donor06 Cell Only Donor47 IL15 + FB102 Donor06 IL15 + FB102 Donor47 IL2 + FB102 Donor06 IL2 + FB102 Donor47 IL2 + Isotype Donor06 IL2 + Isotype Donor47 IL15 +
Isotype Donor06 IL15 + Isotype Donor47 Cell Only Donor55 IL15 + FB102 Donor55 IL2 + FB102 Donor55 IL2 + Isotype Donor55 IL15 + Isotype Donor55 Cell Only Donor47 Cell Only Donor006 IL15 + FB102 Donor47 IL15 + FB102 Donor006 IL2 + FB102 Donor47 IL2 +
FB102 Donor006 IL2 + Isotype Donor47 IL2 + Isotype Donor006 IL15 + Isotype Donor47 IL15 + Isotype Donor006 Cell Only Donor55 IL15 + FB102 Donor55 IL2 + FB102 Donor55 IL2 + Isotype Donor55 I 1 + I otyp n 5 L 5 s e Do or 5 Cell Only Donor47 IL15 +
FB102 Donor47 IL2 + FB102 Donor47 IL2 + Isotype Donor47 I 1 + Isotyp n 4 L 5 e Do or 7 % of Isotype Control % of Isotype Control % of Isotype Control % of Isotype Control
FB102 IN PROOF-OF-CONCEPT AUTOIMMUNE PRECLINICAL DATA 13
GENERATING PRECLINICAL EFFICACY DATA IN A HUMANIZED MOUSE MODEL OF
ACUTE GVHD Humanized mouse model of graft vs host disease Aggressive, rapid-onset of GvHD (100% mortality within 30 days) due to both T and NK cell engraftment NCG (immunodeficient) Transplant with human 6 with human IL-15 expression PBMC (5x10 )
Huarte, Immunotherapy 2021 PMID: 34184542. 14
DOSE-RANGING INVESTIGATION OF FB102 IN A HUMANIZED MOUSE MODEL OF ACUTE
GVHD: THERAPEUTIC MODE Irradiation & End of PBMC transplantation treatment 1 2 3 4 5 6 8 10 12 13 14 Day 7 9 11 FB102 Once-daily IP administration Start dosing on Day 5, (75, 125, 175 mpk) once daily Vehicle Once-daily IP administration
Twice-daily oral administration Ruxolitinib Start dosing on Day 5, (60 mpk) twice daily Twice-daily oral administration Vehicle N=10 per cohort 15
FB102 SURVIVAL BENEFITS: THERAPEUTIC MODEL FB102 Start of daily
treatment superior to 1 1 1 1 10 0 0 0 00 0 0 0 0% % % % % FB102(75): 90% aGvHD FB102(175): 90% 8 8 8 8 80 0 0 0 0% % % % % FB102(125): 80% standard of care, 6 6 6 6 60 0 0 0 0% % % % % Ruxolitinib: 60% ruxolitinib, head to head 4 4 4 4 40 0 0 0 0%
% % % % 2 2 2 2 20 0 0 0 0% % % % % Vehicle: 0% 0 0 0 0 0% % % % % 1 1 1 1 1 3 3 3 3 3 5 5 5 5 5 7 7 7 7 7 9 9 9 9 9 1 1 1 1 11 1 1 1 1 1 1 1 1 13 3 3 3 3 1 1 1 1 15 5 5 5 5 Study day P=0.0001 for FB102 (75, 175) vs Vehicle on Day 14 P=0.0007 for
FB102 (125) vs Vehicle on Day 14 P=0.01 for Ruxolitinib vs Vehicle on Day 14 16
MONO VS COMBINATION THERAPIES WITH FB102, RUXOLITINIB OR
CORTICOSTEROIDS Irradiation & End of study PBMC injection (D18) Day 1 5 8 12 15 18 Ruxolitinib Twice-daily oral (60 mpk) FB102+Ruxolitinib Once-daily IP + twice-daily oral (75 mpk+60 mpk) Placebo Once-daily IP + twice-daily oral (Combination of
vehicles) N=10 per cohort 17
FB102 SURVIVAL BENEFITS: COMBINATION OF FB102 WITH RUXOLITINIB
SIGNIFICANTLY SUPERIOR TO RUXOLITINIB ALONE Start of daily treatment FB102/rux 100% 1 10 00 0% % combo FB102+Rux: 90% significantly 8 8 80 0 0% % % superior to standard of care 6 6 60 0 0% % % single agent, 4 4 40 0 0% % % ruxolitinib, Ruxolitinib:
30% head-to-head 2 2 20 0 0% % % Vehicle: 0% 0 0 0% % % 1 1 1 3 3 3 5 5 5 7 7 7 9 9 9 1 1 11 1 1 1 1 13 3 3 1 1 15 5 5 1 1 17 7 7 Study day p 0.0001 for FB102+Rux vs Vehicle on Day 18 p 0.02 for FB102+Rux vs Ruxolitinib Mono on Day 18 18
GLP TOXICITY STUDY DESIGN 29 day GLP Study (5 doses; once weekly)
3-Month GLP Study (14 Doses; Once Weekly) Dose Administration Number of Dose Administration Number of (mpk) Route Animals (mpk) Route Animals 0 SC/IV 10 0 IV 12 10 IV 6 30 IV 8 30 IV 6 100 IV 8 100 IV 10 300 IV 12 100 SC 10 Clean safety/tolerability
profile to date No dose limiting toxicity (DLT) No adverse events No infections 20
FB102 REDUCES NK CELLS IN NHP AFTER ONE DOSE Significant reduction in
NK cells in NHP after a single dose 21 Percent of pre-dose
FB102 DOES NOT REDUCE TREG CELLS IN NHP WHILE REDUCING THE NK CELLS 22
% of Predose Reduction
PHASE 1 HEALTHY VOLUNTEER STUDY 23
HEALTHY VOLUNTEER SUMMARY Cohort FB102 PBO Sample Size (n) (n)
FB102-101 is an ongoing study currently in the follow up period SAD A1 in healthy volunteers assessing single ascending dose (SAD) and 8 6 2 (3 mg/kg IV) multiple ascending dose (MAD) dosing. It has been conducted SAD A2 as a single-center,
randomized, double-blind, placebo-controlled 8 6 2 (7.5 mg/kg IV) study. Part A is the SAD portion of the study, and Part B is the MAD portion of the study. SAD A3 8 6 2 (15 mg/kg IV) 5 cohorts consisting of 3 SAD cohorts, FB102 doses 3, 7.5 and MAD
B1 3 mg/kg 8 6 2 15 mg/kg and 2 MAD cohorts, FB102 doses 3 and 10 mg/kg (IV Weekly for 4 Weeks) weekly for 4 weeks, have completed dosing. MAD B2 10 mg/kg 8 6 2 (IV Weekly for 4 Weeks) Total 40 30 10 24
HEALTHY VOLUNTEER SUMMARY FB102 was safe and generally well tolerated
in the SAD and MAD cohorts at single doses of FB102 up to 15 mg/kg and multiple doses of FB102 up to 10 mg/kg weekly for 4 weeks. There were no deaths, serious adverse events (SAEs) or discontinuation of the study due to an adverse event. The most
frequent treatment emergent adverse events (TEAEs) reported in both the SAD and MAD study parts were headaches. In addition, there were no clinically significant changes in other safety parameters including electrocardiogram (ECG), vital signs, and
clinical laboratory data. PK from healthy volunteer study demonstrates FB102 half-life of approximately 2-3 weeks. Based on the data from the 3 SAD and 2 MAD cohorts, Forte decided to evaluate the safety and tolerability in targeted patient groups
rather than enrolling additional healthy volunteer cohorts. The Safety Management Committee did approve proceeding to the next dose cohort at the meeting held on 11 June 2024 after reviewing the FB102 10 mg/kg 4 weekly doses IV cohort. Available
safety, tolerability, and PK data from healthy participants in Parts A and B support expanding the current study design to include assessment of safety, tolerability and PK following multiple doses of FB102 in participants with celiac disease (Part
C of current study). 25
HEALTHY VOLUNTEER SUMMARY 26
FB102 NK CELL REDUCTION IN HEALTHY VOLUNTEERS 40 subject SAD/MAD
healthy volunteer study supports FB102 safety and tolerability FB102 demonstrates ~70+% NK cell reduction (4 weekly doses) NK cell reductions compares favorably to anti-IL-15 antibody data in humans. 27
FB102 INDICATION REVIEW 28
PARTIAL LIST OF POSITIVE POC ANIMAL DATA FOR ANTI-CD122 HIGHLIGHTS
FB102 "PIPELINE-IN-A-PRODUCT" POTENTIAL Disease Species Outcome Reference Celiac disease Mouse Improved IL-15-induced PNAS, 2009 mucosal damage 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 GVHD Mouse Prolonged survival JN Bio patent, 2015 Skin and kidney transplant Mouse/Monkey Prolonged graft survival in J Clin Invest, 2018 rejection combination
NO APPROVED THERAPIES FOR CELIAC DISEASE; POTENTIAL FOR A SIGNIFICANT
MARKET OPPORTUNITY Celiac disease Celiac disease is an autoimmune disease that's triggered by consuming gluten and results in damage to the small intestine Symptom include diarrhea, fatigue, headaches, anemia, nausea,
dermatitis herpetiformis (an itchy skin rash) Significant patient population does not respond to gluten free diet Health consequence for not treating include malnourishment, cancer, other autoimmune conditions Patient Population
Estimated 1:133 in US (2.5 million people) with celiac disease (Fasano, Arch Intern Med. 2003 PMID: 12578508.) 0.3% to 0.5% of celiac disease patients are non-responsive (Malamut Gastroenterology. 2024 38556189) No approved
treatment options for celiac disease 31
IL-2 AND IL-15 IN CELIAC DISEASE (CED) IL-2 Clear genetic basis
for involvement of IL-2 in CeD Gluten-induced IL-2 production differentiates true CeD from non-gluten induced GI symptoms IL-2 strongly correlates with symptom severity and Serum IL-2 peaks within 4 hours after gluten exposure